HER 2 status: tumors must be HER2 negative defined as HER2 0 or 1+ by immunohistochemical (IHC) assays and/or lack of gene amplification by fluorescence in situ hybridization (FISH) defined as a ratio < 2 on invasive tumor; a tumor is considered HER2+ if 3+ by IHC or ISH amplified >= 2.0
HER2 0, 1+, or 2+ by IHC if HER2 testing is performed
Her-2 negative, defined as:\r\n* In-situ hybridization (ISH) ratio of < 2.0 (if performed)\r\n* Immunohistochemistry (IHC) staining of 0-2 positive (+) (if performed) \r\n* Deemed to not be a candidate for Her-2 directed therapy
Patients must have histologically confirmed mantle cell lymphoma, with cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH) and with proliferation rate determination, using Ki-67 or MIB-1 immunohistochemistry (=< 30% versus > 30% versus “indeterminate” Ki-67 index)
Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization [FISH])
Newly diagnosed de novo ALL (B-ALL or T-ALL) with definitive evidence of BCR-ABL1 fusion by karyotype, fluorescence in situ hybridization (FISH) and/or reverse transcriptase (RT)-PCR
HER2-overexpressing breast cancer (3+ staining by immunohistochemistry or HER2 gene amplification by fluorescent in situ hybridization [FISH] or silver in situ hybridization [SISH] >= 2.0)
Pathologically confirmed mantle cell lymphoma (MCL) which is relapsed or refractory to at least one chemotherapy containing regimen\r\n* Presence of cyclin D1 expression and/or t(11;14) by fluorescence in situ hybridization (FISH) or cytogenetics is required
Participants must have histologically confirmed HER2+ invasive breast cancer (immunohistochemistry [IHC] 3+ and/or fluorescence in situ hybridization [FISH] positive [HER2/chromosome 17 centromere [CEP17] >= 2 and/or > 6 HER2 gene copies per nucleus]); note: central confirmation of HER2 status is not required
Known positivity for HER2 (as defined by a positive IHC test of 3+ or IHC of 2_ with fluorescent in situ hybridization [FISH])
To qualify for Part 1, the participant must be t(11;14) positive as determined by an analytically validated Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
HER2 negative metastatic breast carcinoma defined as 0 or 1+ by IHC or with a FISH ratio (HER2 gene copy/ chromosome 17) < 2 if IHC 2+ by local institution standard protocol
Histologically confirmed HER2-positive metastatic breast cancer (HER-2 3+ by immunohistochemistry); if immunohistochemistry (IHC) score of 2, fluorescence in situ hybridization (FISH) ratio must be greater than 2.0; if FISH less than 2.0, HER2 copy number must be greater than 6; NOTE: Brain lesions are not required to have pathologic confirmation; estrogen receptor (ER)-positive patients are allowed
Patients must harbor a tumor HER2/neu+ based upon IHC staining score of “3+” or 2+ with confirmed gene amplification by fluorescence in situ hybridization (FISH) to be included
Patients may have any of the following:\r\n* Myc-overexpression (> 40%) by immunohistochemistry (IHC)\r\n* Myc-amplification (> 4 copies), as determined by fluorescent in-situ hybridization (FISH)\r\n* MYC-rearrangement, as determined by FISH
The following results must be available or pending at time of registration, though results will not affect enrollment/treatment:\r\n* B-cell lymphoma (BCL)-2 rearrangement by FISH\r\n* BCL-6 rearrangement by FISH\r\nNOTE: although not required, it is encouraged that MYC and BCL-2 be measured by immunohistochemistry (IHC) and clearly documented
Primary and/or metastatic breast tumor must be negative for human epidermal growth factor receptor (HER-2/neu) over-expression based on immunohistochemistry (IHC) (0 or 1+, 2+ if fluorescence in-situ hybridization [FISH] test is negative) or FISH (HER2/copy number of centromere of chromosome 17 [CEP17] ratio < 2.0 or < 4 Her-2/neu signals per nucleus)
HER2 negative in the primary tumor as defined by:\r\n* Grade 0 or 1+ staining intensity (on a scale of 0 to 3) by means of immunohistochemistry (IHC) analysis OR\r\n* Grade 2+ staining intensity by means of IHC analysis with gene amplification on fluorescence in situ hybridization (FISH) < 2.0 OR\r\n* Gene amplification on fluorescence in situ hybridization (FISH) < 2.0
Tumor positive or negative for expression of hormone receptors (< 1% or > 1%) and overexpressing HER2 by immunohistochemistry (IHC) (3+), or, HER2-amplified by fluorescence in situ hybridization (FISH) or by alternative gene testing
Negative for HER2 amplification by in situ hybridization (ISH) for 2+ IHC disease.
Patients must have histologically confirmed, relapsed/refractory ALK+ ALCL (with ALK positivity defined by immunohistochemistry and/or fluorescence in situ hybridization [FISH]/cytogenetics from any prior biopsy), MCL, or BCL6+ DLBCL (with BCL6 positivity defined by immunohistochemistry from any prior biopsy) and meet the following criteria:
Histologically or cytologically confirmed HER2-negative (0 or 1+ by immunohistochemistry [IHC] or non-amplified by fluorescent in situ hybridization [FISH]) breast cancer that is stage IV
IHC 1+ or 0
In situ hybridization negative based on:
Cohort 1: HER2 IHC 2+/FISH negative breast cancer
Cohort 2: HER2 IHC 3+ or HER2 IHC 2+/FISH positive breast cancer
Cohort 3: HER2 IHC 2+/FISH negative gastric/GEJ cancer
Cohort 4: HER2 IHC 3+ or HER2 IHC 2+/FISH positive gastric/GEJ cancer
Cohort 5: Any other HER2 IHC 3+ or FISH positive cancer
HER2 IHC 1+ or IHC2+/FISH- breast cancer patients who have received at least 1 and no more than 3 prior systemic chemotherapy regimens
HER2 IHC 2+ or 3+ FISH+ or FISH- gastric/GEJ cancer patients who have received at least 1 and no more than 3 prior systemic chemotherapy regimens.
For subjects with MCL (confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)
Patients must have a diagnosis of mantle cell lymphoma confirmed at diagnosis by one of the following:\r\n* t(11;14) detected by fluorescence in situ hybridization (FISH), conventional cytogenetics, or other molecular evaluation\r\n* Expression of cyclin D1 confirmed by immunohistochemistry
PART I: Adults with malignant soft tissue and bone tumors and recurrent or progressive, metastatic solid tumors who have progressed on standard therapies with known benefit but for whom anti-HER2 therapy is not clinically indicated:\r\n* Patients with ovarian, cervical, colon, gastric/gastroesophageal junction, non-small cell lung, renal cell, bladder, malignant soft tissue and bone tumor, prostate cancer or other solid tumors that is known to be HER2 1+, 2+ or 3+ by immunohistochemistry (IHC) OR have a Vysis fluorescent in situ hybridization (FISH) result >= 1.8\r\n* Patients with breast cancer that is known to be HER2 1+ or 2+ by IHC or with a Vysis FISH result of 1.8 - < 2.2
Tumor negative for expression of hormone receptors (< 1%) and not over-expressing HER2 by immunohistochemistry (IHC) (0-1), or in case of IHC of 2, negative by fluorescence in situ hybridization (FISH) or by alternative gene testing
INCLUSION - ENROLLMENT: Her-2 3+ or fluorescence in situ hybridization (FISH) ratio of 2.2 or higher, background gene expression with normal copy number
Cohort #2: histologic confirmation of relapsed or relapsed/refractory MCL confirmed by presence of cyclin D1 by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
Human epidermal growth factor receptor 2 (HER2) negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+ according to National Comprehensive Cancer Network (NCCN) guidelines
History of biopsy-proven HER2-overexpressing breast cancer and radiographic evidence of metastatic disease, or locally recurrent unresectable disease; the HER2 status can be determined either by immunohistochemistry (IHC) (IHC score, 3+) or by fluorescence in situ hybridization (FISH) (as defined by HER2/CEP-17 ratio >= 2.0, or HER2 copy number >= 6); patients must have received prior trastuzumab, independent of response to prior trastuzumab, and a taxane (in any disease setting, e.g. neo-adjuvant, adjuvant, metastatic)
Patients must have HER2 status determined by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC); HER2 status of positive or negative are both eligible for the study
Positive for HPV by p16 immunohistochemistry (IHC) or in situ hybridization (ISH).
Histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC) (stage IV, American Joint Committee on Cancer [AJCC] v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA)-approved fluorescence in situ hybridization (FISH) test, using Vysis ALK Break apart FISH Probe, or the Ventana immunohistochemistry (IHC) test; diagnosis using next generation sequencing (NGS) via a local diagnostic test will be accepted for enrollment but will need to be confirmed with either FISH or IHC
HER2 negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
for subjects with MCL (confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)
Histopathologically or cytologically documented TNBC or TN-IBC. Tumors must have been confirmed negative for ER and PR by IHC (<1% positive tumor nuclei, as per ASCO-CAP guideline recommendations) and negative for HER2 by IHC or fluorescent or chromogenic in situ hybridization (FISH or CISH). Patients with equivocal HER2 results by IHC should have their negativity status confirmed by FISH.
Patients must have histologically confirmed HER2-negative breast cancer (defined as immunohistochemistry [IHC] 0 or 1+ and/or fluorescence in situ hybridization [FISH] < 2.0), that is metastatic in stage
Must be negative for Her-2 amplification; (either 1+ on semi-quantitative evaluation of immunostain or negative by fluorescent in-situ hybridization)
Subjects must not have amplification of Her-2 (either 3+ by semi-quantitative immunostain or positive by fluorescent in-situ hybridization [FISH])
MCL cohort: MCL (diagnosis must be confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization [FISH], or PCR) with relapsed or refractory disease after at least 1 prior line of MCL therapy
Human epidermal growth factor receptor 2 (HER2)-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+; if IHC is 2+ (i.e. indeterminate), a negative in situ hybridization (fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], or silver in situ hybridization [SISH]) test is required by local laboratory testing; (as per the ASCO-CAP guidelines)
Patients must have an ongoing complete cytogenetic response (CCyR) on a TKI (imatinib, dasatinib, nilotinib, or bosutinib), defined as follows:\r\n* 0% Ph+ cells in metaphase, in the bone marrow and/or a negative peripheral blood fluorescence in situ hybridization (FISH) analysis for BCR-ABL1 gene fusion
Is HER2 normal, defined as HER2 0 or 1+ by immunohistochemistry (IHC) and negative by fluorescence in situ hybridization (FISH) if performed; or HER2 is 2+ by IHC and negative by FISH; or HER2 negative by FISH if IHC is not performed.
Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
Patients must have a metastatic tumor negative for HER2; the lack of HER2 overexpression by immunohistochemistry (IHC), is defined as 0 or 1+ whereas hyperexpression is defined as 3+; if equivocal IHC, 2+, the tumor must be non-gene amplified by fluorescence in situ hybridization (FISH) performed upon the primary tumor or metastatic lesion (ratio < 2 and HER2 copy number < 4)
Patients must have negative HER2 expression on immunohistochemistry (IHC) (defined as 0 or 1+) or fluorescence in situ hybridization (FISH) analysis; if HER2 is 2+, negative HER2 expression must be confirmed by FISH (HER2/cep17 ration < 2, and/or copy number less than 6); ER and PgR expression should be less than 10%
The current cancer must over express HER2 as determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
Histologically confirmed adenocarcinoma of the breast that is Her2 negative (by DAKO Herceptest, fluorescence in situ hybridization [FISH], or other approved assay)
To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization (ISH) as defined in the relevant ASCO/CAP or local guidelines.
HER2-negative breast cancer based on local laboratory results (test to be used as per local practice); HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (fluorescence in situ hybridization [FISH]/chromogenic in situ hybridization [CISH]/silver-enhanced in situ hybridization [SISH]) defined as a HER2/CEP17 ratio < 2 or for single probe assessment a HER2 copy number < 4
The invasive cancer must be HER2-low, defined as immunohistochemistry (IHC) 0-1+, or with a fluorescence in situ hybridization (FISH) ratio of < 1.8 if IHC is 2+ or if IHC has not been performed
Histologically or cytologically confirmed diagnosis of lung adenocarcinoma that demonstrates ALK rearrangement as detected by the approved fluorescence in situ hybridization (FISH) test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); or the Ventana immunohistochemistry (IHC) test; evidence of rearrangement by gene sequencing tests such as FoundationOne or Caris will also be seen as evidence of ALK abnormality and meeting eligibility requirement
Documented human epidermal growth factor receptor 2 (HER2)-negative tumor based on local testing on most recent tumor biopsy: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (fluorescence in situ hybridization [FISH]/chromogenic in situ hybridization [CISH]/silver in situ hybridization [SISH]) defined as a HER2/centromeric probe for chromosome 17 (CEP17) ratio < 2 or for single probe assessment a HER2 copy number < 4
For Cohort 2 (subjects with relapsed/refractory synovial sarcoma only), the following tests must be available by local laboratory: Morphology consistent with synovial sarcomas, and cytogenetics or fluorescence in situ hybridization (FISH) and/or molecular confirmation (e.g., DNA sequencing) of SS18 rearrangement t(X;18)(p11;q11)
For phase II: ER negative (defined as expression of ER in =< 1% cells), PR negative (defined as expression of PR in =< 1% cells), HER2 negative (acceptable methods of HER2 analysis include IHC [0, 1+], fluorescence in situ hybridization [FISH] with HER2/centromere on chromosome 17 [CEN17] ratio < 2, and/or chromogenic in situ hybridization [CISH] with HER2/CEN-17 ratio < 2), as previously documented by histological analysis
Human epidermal growth factor receptor 2 (HER2) negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
Is HER2 normal, defined as HER2 0 or 1+ by immunohistochemistry (IHC) and negative by fluorescence in situ hybridization (FISH) if performed; or HER2 is 2+ by IHC and negative by FISH; or HER2 negative by FISH if IHC is not performed
The invasive cancer must have been confirmed to be human epidermal growth factor receptor 2 (HER2)-negative at some point in a given patient’s disease history (can be from any tumor specimen from a given patient, including archived primary, recurrent, or metastatic tumor), defined as immunohistochemistry (IHC) 0-1+, or with a fluorescent in situ hybridization (FISH) ratio of < 1.8 if IHC is 2+ or if IHC has not been performed
Human epidermal growth factor receptor (HER) 2 negative defined as 0 or 1+ using IHC or a ratio of less than 2.0 on fluorescence in situ hybridization (FISH) testing; HER 2 of 2+ on IHC should have a ratio of less than 2.0 on FISH testing to be considered HER2 negative
Human epidermal receptor 2 (HER2) negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
Human epidermal growth factor receptor 2 (HER2) negative by fluorescent in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
HER2 positive breast cancer, defined by immunohistochemical staining for HER2 protein of 3+ intensity and/or amplification of the HER2 gene on fluorescence in situ hybridization (FISH) >= 2.0 on breast specimen or biopsy of a metastatic site
HER2 overexpression of tumor by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH); tumors tested by IHC must be 3+ positive; tumors tested by FISH must have a ratio of HER2:CEP17 > 2.0; when both tests are performed, the FISH result must be positive
Diagnosis of multiple myeloma (MM) with deletion 17p (del17p) or monosomy 17 by fluorescence in situ hybridization (FISH) who have received at least one line of therapy
Bone marrow analysis demonstrating normal cytogenetics, and no more than 5% of cells with a single clonal abnormality by fluorescence in situ hybridization (FISH) for myelodysplastic syndrome (MDS) panel within 3 months of stem cell collection
Multiple myeloma (MM): patients who\r\n* Have received induction therapy for a minimum of 4 cycles\r\n* In addition, patients must meet at least one of the following criteria I-IX (I-VII at time of diagnosis or pre-autograft): \r\n** Any abnormal karyotype by metaphase analysis except for isolated t(11,14),\r\n** Fluorescent in situ hybridization (FISH) translocation 4:14,\r\n** FISH translocation 14:16,\r\n** FISH deletion 17p,\r\n** Beta2 (B2)-microglobulin > 5.5 mg/ml,\r\n** Cytogenetic hypodiploidy\r\n** Plasmablastic morphology (>= 2%)\r\n** Recurrent or non-responsive (less than partial remission [PR]) MM after at least two different lines of conventional chemotherapy\r\n** Progressive MM after a previous autograft (provided stored autologous cluster of differentiation [CD]34 cells are available)
Patients with histologically confirmed adenocarcinoma of the breast that does not over-express HER-2/neu; this is defined as fluorescent in situ hybridization (FISH) negative, or 0, 1+ or 2+ by immunohistochemistry (IHC); IHC 2+ tumors must be FISH negative with an amplification ratio of less than 2.0; patients must not be eligible for therapy of known curative potential for metastatic breast cancer if it is identified during the course of the study
Breast adenocarcinoma that is amplified for HER-2/neu gene expression by 2-fold or more by FISH analysis, or that is IHC 3+
Expansion cohort only: Plasma cell fluorescence in situ hybridization (FISH) test demonstrating presence of t(11;14)
Documented HER3-positive disease measured by immunohistochemistry (IHC)
HER2 overexpression by immunohistocytochemistry (IHC) of 2+ or 3+, in the primary tumor or metastasis; if overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by fluorescence in situ hybridization (FISH)
Subjects with diagnosis of HER2-negative breast cancer that was confirmed by IHC or in situ hybridization (ISH) assessment of tumor samples
Histologically or cytologically confirmed ER+ HER2- breast cancer; ER-positivity is to follow local guidelines; if immunohistochemistry (IHC) HER2 is 2+, a negative fluorescence in situ hybridization (FISH) test is required
Progesterone receptor negative – defined as less than 1% staining by IHC\r\n* HER2 negative defined as 0 or 1+ using IHC or a ratio of less than 2.0 on fluorescence in situ hybridization (FISH) testing; HER2 of 2+ on IHC should have a ratio of less than 2.0 on FISH testing to be considered HER2 negative
Documentation of HER2 negative breast cancer at the time of protocol registration; (Note: HER2 negativity is defined as 0 or 1+ by immunohistochemistry OR nonamplified or equivocal by fluorescence in situ hybridization [FISH]; status may be defined on the basis of historic results on the breast primary or a metastatic site, whichever is most recent; repeat biopsies are not required for participation in this protocol)
Participants with mature B-cell (Burkitt’s) ALL are excluded from study; mature B-cell is defined by the presence of surface immunoglobulin and/or the t(8;14)(q24;q32), t(8;22), or t(2;8) translocation and/or c-myc-gene rearrangement by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR); (FISH/PCR testing for c-myc rearrangements is not required prior to study entry, but it is suggested for patients with surface immunoglobulin expression or L3 morphology)
Completely resected unilateral or bilateral primary carcinoma of the breast without clinical evidence of disease, negative for estrogen receptor (ER) and progesterone receptor (PR) (cut-off for positivity is > 1% positive tumor cells with nuclear staining), and negative for HER2 as defined by one of the four situations delineated below: \r\n* HER2 immunohistochemistry (IHC) expression of 0 or 1+ and in-situ hybridization non-amplified\r\n* HER2 IHC expression of 0 or 1+ and in-situ hybridization not done\r\n* HER2 IHC expression of 2+ and in-situ hybridization non-amplified\r\n* IHC not done and in-situ hybridization non-amplified\r\n* Note: central review is not required
HER2+ as 3+ by IHC or in-situ hybridation (ISH) amplified.
Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing >= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
Note: patients with mature B-cell (Burkitt's) ALL are excluded from study; mature B-cell is defined by the presence of surface immunoglobulin and/or the t(8;14)(q24;q32), t(8;22), or t(2;8) translocation and/or c-myc-gene rearrangement by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)
Tumors must be HER2 negative defined as HER2 0 or 1+ by immunohistochemistry (IHC) assays and/or lack of gene amplification by fluorescence in situ hybridization (FISH) defined as a ratio < 2 on invasive tumor by local review
HER2-negative breast cancer defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+ or 2+; if IHC is 2+, a negative in situ hybridization (fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], or silver in situ hybridization [SISH]) test is required by local laboratory testing
Cytogenetics, fluorescence in situ hybridization (FISH) or mutational analysis confirming adverse risk features must have been done within 90 days prior to enrollment
Human epidermal growth factor receptor 2 (HER2)/neu-negative breast cancer by standard criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH] negative if IHC 2+) at primary diagnosis
HER2 positive disease as defined by 3+ IHC or positive FISH (both in primary and metastatic sites)
Patients with histologically confirmed, metastatic HER2+ (by immunohistochemistry [IHC] 3+ or fluorescence in situ hybridization [FISH] ratio >= 2.0) breast cancer
Patients with HER2+ (immunohistochemistry [IHC] 3+ or fluorescence in situ hybridization [FISH]+ R/G > 2.0 or silver-enhanced in situ hybridization [SISH]+ HER2/chromosome 17 centromere [CEP17] > 2.0) breast cancer with documented central nervous system (CNS) recurrence or progression (potential participants with newly diagnosed brain metastasis who have not received prior treatment for their lesions in the brain are eligible)
Patients have positive HER2 expression by immunohistochemistry (IHC) (3+) or fluorescence in situ hybridization (FISH) testing (> 2.0 ratio)
HER2 positive breast cancer (immunohistochemistry [IHC] 3+ or fluorescent in situ hybridization [FISH] ratio of >= 2.0)
Patients must harbor a tumor HER2/neu+ based upon IHC staining score of “3+” or 2+ with confirmed gene amplification by FISH to be included
Has sufficient tumor tissue (slides or blocks) available for central confirmatory testing of immunohistochemistry and/or cytogenetics/fluorescence in situ hybridization (FISH) and/or deoxyribonucleic acid mutation analysis (required for study entry but enrollment based on local results) For Dose Escalation Only:
Documented HER2 overexpression or gene-amplified tumor (immunohistochemistry [IHC] 3+ or IHC 2+ with confirmatory fluorescence in situ hybridization [FISH]+).
Histologically-confirmed metastatic adenocarcinoma of the breast with either invasive primary tumor or metastatic tissue confirmation of HER2+ status as defined by immunohistochemistry (IHC) with score of 3+, or, if 2+ with confirmatory fluorescence in situ hybridization (FISH) ratio of >= 2.0
Patients must have stage IV gastric or GEJ adenocarcinoma with HER2 overexpression and/or amplification as determined by next generation sequencing assay, (immunohistochemistry [IHC] 3+) or fluorescent in situ hybridization (FISH+ is defined as HER2:chromosome 17 centromere probe [CEP17] ratio >= 2.0); MSKCC confirmation of HER2 status is not mandatory prior to enrollment and treatment on study; for patients with outside HER2 testing, if sufficient tissue is available HER2 testing will be repeated at MSKCC for purpose of analysis and will not impact the patient's eligibility
Documented HER2+ breast cancer defined as: 3+ by immunohistochemistry (IHC) or with amplification by in situ hybridization with ratio >= 2.0; results from the local lab are acceptable; eligibility will not be affected by hormone receptor status
Human epidermal growth factor receptor 2 (HER2)-negative tumor by local laboratory testing (immunohistochemistry [IHC] 0, 1+ regardless of fluorescence in situ hybridization [FISH] ratio; IHC 2+ with FISH ratio lower than 2.0 or HER2 gene copy less than 6.0; FISH ratio of 0, indicating gene deletion, when positive and negative in situ hybridization [ISH] controls are present)
International Prognostic Index score ? 2 or DLBCL with double-positive for BCL2 and c-MYC by IHC (immunohistochemistry) or FISH (fluorescent in situ hybridization) based on local pathology lab assessment.
HER2-positive disease by local laboratory testing (immunohistochemistry 3 positive [IHC 3+] staining or in situ hybridization positive)
Must have evidence of MET expression by fluorescence in situ hybridization (FISH), MET immunohistochemistry (IHC) score of 2-3+, reverse-transcriptase polymerase chain reaction (RT-PCR) or a mutation
HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
Patients must have histological documented or cytological confirmed mantle cell lymphoma; cyclin D1 must be present as evidenced by either fluorescence in situ hybridization (FISH) or immunohistochemical staining
If IHC HER2 2+, a negative FISH test is required
Negative human epidermal growth factor receptor 2 (HER-2)/neu- disease defined as patients with fluorescence in situ hybridization (FISH) ratio < 2.0 or < 6.0 HER2 gene copies per nucleus, and IHC staining scores of 0, 1+, or 2+
HER2 negative breast cancer. Central testing (required for all subjects) must demonstrate that the tumor is HER2 negative by FISH or Immunohistochemistry (IHC).
Histologically confirmed untreated mantle cell lymphoma, with documented cyclin D1 (BCL1) by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescent in situ hybridization (FISH)
Documentation of amplified PDGFR by fluorescent in-situ hybridization (FISH), colorimetric in-situ hybridization (CISH), or quantitative polymerase chain reaction (PCR) from tumor tissue (>= 3 copy number), or over expression by immunohistochemistry (IHC)
HER2+ patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
Participants' primary and/or metastatic tumor is human epidermal growth factor receptor 2 (HER2)-negative by fluorescence in-situ hybridization (FISH) or chromogenic in-situ hybridization (CISH) or 0, 1+ overexpression by immunohistochemistry (IHC)
Molecular testing result from Clinical Laboratory Improvement Act (CLIA)-certified laboratory confirming that the tumor tissue has at least one of the following:\r\n* HER2 overexpression (3+ immunohistochemistry [IHC]); Note: HER2 2+ IHC is eligible if the tumor is amplified by fluorescence in situ hybridization (FISH)\r\n* HER2 amplification by in situ hybridization assay (FISH or chromogenic in situ hybridization [CISH] signal ratio >= 2.0 or gene copy number > 6)\r\n* HER2 amplification by CLIA-certified next generation sequencing (NGS) sequencing assay
Detection of one of the following must be present:\r\n* t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics\r\n* Breakpoint cluster region (BCR)-Abelson (ABL) positive status by molecular analysis with qualitative polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH)
Histologically confirmed mantle cell lymphoma with documented expression of cyclin D1 (BCL1) by immunohistochemical stains and/or t (11; 14) by cytogenetics or fluorescence in situ hybridization (FISH)
Histologically or cytologically confirmed invasive breast cancer that is HER2-positive (3+ by immunohistochemistry [IHC] and/or > 2.0 by fluorescence in situ hybridization [FISH]) if concurrent HER2-directed therapy is planned
Confirmed HER2-positive disease by local pathology, defined as immunohistochemistry (IHC) 3+ or amplification by fluorescent in situ hybridization (FISH) (HER2/chromosome 17 centromere [CEP17] ratio >= 2 or an average of >= 6 HER2 gene copies per nucleus) AND confirmed by Central Pathology Review (Mayo Clinic Rochester) prior to patient being registered to begin protocol therapy\r\n* NOTE: ductal carcinoma in situ (DCIS) components should not be counted in the determination of HER2 status
Subject has human epidermal growth factor receptor 2 negative (HER2-) breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
Histologically documented HER2 (+) breast cancer as defined as immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) amplification of >= 2.0 of primary or metastatic site; results from the local lab are acceptable
Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0-1+ by immunohistochemistry (IHC) or non-amplified fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH); if HER2 IHC is 2+, FISH/CISH must be performed and must not be positive (must be a ratio of < 2), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by institutional standards
Documented results of cytogenetics/ fluorescence in situ hybridization (FISH) obtained at any time before transplant, and International Staging System (ISS) staging at the time of diagnosis available.
Patients must have histologically or cytologically confirmed mantle cell lymphoma as defined by the World Health Organization; all patients must have either t(11;14) by karyotype or fluorescent in-situ hybridization (FISH) or positive immunohistochemistry for cyclin D1
Patients must have histologically-confirmed HER2-positive breast cancer that is locally advanced or metastatic; HER2-positive disease must be documented by one of the following results using Food and Drug Administration (FDA)-approved testing methods: \r\n* Fluorescence in situ hybridization (FISH)-positive (with an amplification ratio >= 2.0 indicating positive status) and/or \r\n* Immunohistochemistry (IHC) 3 + by local laboratory assessment
A cytogenetics or fluorescence in situ hybridization (FISH) analysis of the leukemic cells within 24 months of randomization is required to document the presence or absence of del(17p). Note: if a sample from within 24 months is not available, it should be evaluated as part of the screening laboratory evaluation to inform stratification
Human growth factor receptor 2 (HER2) positive tumors as defined by Food and Drug Administration (FDA) guidelines (3+ immunohistochemical staining, defined as uniform, intense membrane staining of more than 10% of invasive tumor cells, and for cases with 2+ staining showing gene amplification by fluorescence in situ hybridization [FISH], expressed as a ratio of more than 2 when comparing HER-2 gene and chromosome 17 fluorescent signals)
Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
HER2 overexpression and/or amplification as determined by immunohistochemistry (3+) or fluorescence in situ hybridization (FISH) (>= 2.0)
Documented HER2 overexpression (immunohistochemistry [IHC] 3+ or gene-amplified tumor with fluorescence in situ hybridization [FISH] ratio of >= 2.0)
Patients have HER2-positive breast carcinoma (IHC staining more than 3+ or HER2 gene amplification by fluorescent in situ hybridization [FISH])
HER2 overexpression by immunohistochemistry (IHC) of 2+ or 3+ in the primary tumor or metastasis; or documented gene amplification by fluorescent in situ hybridization (FISH) analysis; IHC =< 2+ must have HER2 gene amplification documented by FISH
Patients with histologically confirmed stage I-III, HER2-positive invasive breast cancer for which adjuvant/neoadjuvant chemotherapy is indicated based on physician judgment following National Comprehensive Cancer Network (NCCN) practice guidelines\r\n* HER2 overexpression or amplification will be based on local test results and is defined as either:\r\n** Immunohistochemistry (IHC) staining of 3+ (uniform, intense membrane staining) in >= 10% of invasive tumor cells or\r\n** Fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or\r\n** FISH ratio (HER2 gene signals to chromosome 17 signals) of >= 2.0
HER2 negative (IHC 0,1 or FISH HER2:CEP17 ratio < 2.0)
PRE-REGISTRATION INCLUSION CRITERIA: Histologically confirmed HER2-negative primary invasive ductal or invasive lobular breast carcinoma; for patients enrolling for neoadjuvant treatment, diagnosis must be clinical stage II or III; for patients enrolling for adjuvant treatment, diagnosis must be pathologic stage IIA to IIIC\r\n* Standard HER2 testing will be performed in the surgical specimen at Washington University according to the standard of care in the department of pathology; a HER2-negative primary breast cancer sample from a patient eligible for randomization should have a HER2 immunohistochemistry (IHC) score of 0 or 1+; those patients with IHC score of 2+ should be HER2 fluorescent in situ hybridization (FISH)-negative in standard testing\r\n* Patient will have undergone staging studies including a computed tomography (CT) of the chest/abdomen/pelvis and bone scan and/or positron emission tomography (PET) scan either prior to the initiation of treatment or prior to entry into the trial\r\n* In addition, patients with non-metastatic, HER2-negative, recurrent tumors who need chemotherapy are eligible
Expanded cohort only: Cohort 1: patients with predominant metastatic bone disease; Cohort 2: patients with primary squamous head and neck cancers; Cohort 3: patients presenting any molecular abnormality of interest, which can include an ALK translocation, ALK amplification, ALK mutation and overexpression as determined by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR), quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), array Comparative Genomic Hybridization or direct sequencing (aCGH); a c-MET abnormality, either c-MET amplification by FISH, overexpression by IHC or c-MET mutation; BRAF, DDR2 and CDKN2A mutations; and, finally, TRIM 16 expression and CCN2 expression
An adverse risk karyotype defined by:\r\n* Complex karyotype by cytogenetics, or\r\n* Deletion of all or part of chromosome 5, 7, 12, or 17 defined by fluorescence in situ hybridization (FISH) or cytogenetics, or\r\n* Somatic TP53 mutation
HER2 negative, defined as 0-1+ by immunohistochemistry or FISH-negative (ratio < 2.2); central confirmation is not required
Enrollment will be restricted to patients demonstrating NAD(P)H dehydrogenase, quinone 1 (NQO1) immunohistochemistry (IHC) overexpression; demonstration of NQO1 overexpression by IHC should be confirmed prior to conducting other study procedures (e.g., laboratory and imaging studies)
Note: patients with a negative or equivocal overall result (FISH ratio of < 2.0 or =< 6.0 HER2 gene copies per nucleus) and IHC staining scores of 0, 1+, 2+ are not eligible for enrollment
Tumors must be negative for HER2 (by FISH, CISH or IHC)
Previously untreated patients with a morphologic diagnosis of APL, confirmed by demonstration of t(15;17) using conventional cytogenetics OR fluorescence in situ hybridization (FISH), OR a positive reverse transcriptase (RT)-polymerase chain reaction (PCR) assay for promyelocytic leukemia (PML)-retinoic acid receptor, alpha (RAR-alpha) at the subject's local institution
Participants must have a diagnosis of chronic myelogenous leukemia as confirmed by fluorescent in situ hybridization (FISH) for BCR/ABL translocation and/or standard cytogenetics analysis
Her-2 normal as determined by fluorescence in situ hybridization (FISH) or 0 or 1+ by immunohistochemistry (IHC) staining.
Confirmed pathologic diagnosis of breast cancer which is metastatic and for which capecitabine is a reasonable treatment option\r\n*ARMS C & D: Histologically confirmed human epidermal growth factor receptor 2 (HER2) positive (+) breast cancer: immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) amplified; by clinical assay on either primary or metastatic tumor
Patients must have esophageal, gastric or gastroesophageal adenocarcinoma with HER2 overexpression and/or amplification as determined by next generation sequencing assay, immunohistochemistry (IHC 3+) or fluorescent in situ hybridization (FISH+ is defined as HER2:CEP17 ratio >= 2.0); MSKCC or enrolling institution confirmation of HER2 status is not mandatory prior to enrollment and treatment on study; for patients with outside HER2 testing, if sufficient tissue is available HER2 testing will be repeated at MSKCC or the enrolling institution for purpose of analysis and will not impact the patient's eligibility
For patients with evidence of minimal residual disease prior to vaccination, assessment of minimal residual disease status by cytogenetics or fluorescence in situ hybridization (FISH) will be followed post vaccination
HER2-positive breast carcinoma (IHC staining more than 3+ or HER2 gene amplification by fluorescent in situ hybridization [FISH])
Patients who have already received an allogeneic hematopoietic cell transplant and have either a documented relapse of leukemia or MDS or have recurrent persistent minimal residual disease as documented by at least 2 sequential testings, separated by 1 week, demonstrating molecular evidence of leukemia or MDS by fluorescence in situ hybridization (FISH), cytogenetics or fluorescent immunocytometry
Patients must have HER2-positive (fluorescence in situ hybridization [FISH]+ or immunohistochemistry [ICH] 3+) metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma to be eligible for trastuzumab; for the purposes of this protocol, FISH+ is defined as HER2:centromeric probe for chromosome 17 (CEP17) ratio >= 2.0; biopsy samples with cohesive IHC3+ or FISH+ clones are considered HER2 positive irrespective of size, i.e. < 10%; FISH+ defined as > 2 HER2:CEP17; Note: samples will be processed locally in the laboratory of investigational sites; the results of local laboratory HER2 analysis will be required and sufficient to start the study treatment; the Memorial Sloan-Kettering (MSK) laboratory will be used for subsequent confirmation of HER2 status; MSK pathology review will not be required to begin therapy on the protocol; samples provided to the MSK laboratory must either be HER2 IHC slides, or if FISH confirmation is necessary, a paraffin block(s) of adequate size to allow if possible for at least 5 slides with cuts that are 5-microns thick or if a paraffin block is not available, then if possible at least 5 slides with cuts that are 5-microns thick will be acceptable; archived or fresh tumor samples may be used
Documentation of complete cytogenetic response (CCR) by conventional cytogenetics or fluorescent in situ hybridization (FISH) analysis on a frontline TKI with stable dosing
Myc positive lymphoma is defined by:\r\n* Positive for Myc gene rearrangement by fluorescence in-situ hybridization (FISH) involving various breakpoints (e.g. 8-14, 8-22 and 2-8) AND concurrent gene rearrangements in bcl-2 and/or bcl-6 by FISH OR\r\n* Myc and Bcl-2 overexpression defined by >= 40% Myc and > 50% Bcl-2 expression by immunohistochemistry (IHC); patients may enroll in the study based on the local laboratory evaluation, but these should be confirmed by the University of North Carolina (UNC) Hematopathology Laboratory retrospectively
Patients meeting the above pathologic criteria will be eligible for therapy irrespective of their HER2/neu over expression status; immunohistochemical staining will be not be required for protocol entry but fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) studies for HER2/neu are preferred
Have negative HER2 expression by immunohistochemistry (IHC) (defined as 0 or 1+), or fluorescence in situ hybridization (FISH); if HER2 is 2+, negative HER2 expression must be confirmed by FISH
Tumor must be HER2 positive 3+ by immunohistochemistry or positive by fluorescence in situ hybridization (FISH) analysis if 2+ by immunohistochemistry
Double hit lymphoma is defined as B-cell lymphoma with genetic abnormalities involving A) and in addition, B) and/or C): A) v-myc myelocytomatosis viral oncogene homolog (avian) (C-MYC) arrangement or amplification by fluorescence in situ hybridization (FISH) study; B) B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL2) rearrangement or amplification by FISH study; C) BCL6 rearrangement or amplification by FISH study
Tumors must be HER-2/neu expression negative, as determined by local hospital laboratory (immunohistochemistry [IHC] =< 2+ or fluorescence in situ hybridization [FISH] negative)
c-MET positive (defined by c-MET IHC intensity score +2 in ? 50% of tumor cells and MET gene copy number ? 5 by FISH or IHC intensity score +3 in ? 50% of tumor cells) and K/NRAS WT status for mCRC patients only
Females with histologically or cytologically confirmed HER2-positive breast cancer. HER2-positive is defined as 3+ staining by immunohistochemistry or HER2 gene amplification by fluorescent in situ hybridization or silver in situ hybridization with HER2/CEP17 ratio ? 2.0
Presence of 17p deletion in CLL cells as demonstrated by fluorescence in-situ hybridization (FISH) testing
The invasive cancer must be HER2-negative (IHC 0-1+, or with a fluorescence based in situ hybridization [FISH] ratio of < 1.8 if IHC is 2+ or if IHC has not been done)
Any Her 2+ breast cancer (immunohistochemistry 3+; or amplified by fluorescence in situ hybridization [FISH])
Invasive breast cancer must be Her2-negative; if breast cancer is Her2 2+ by immunohistochemistry (IHC), then fluorescence in situ hybridization (FISH) must be negative for Her2 gene amplification
Tumor determined to be HER2-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (HER2/CEP17 amplification ratio >= 2.0); tumors determined to be ER or PR positive by immunohistochemistry (> 10% )
Patient has HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0 or 1+ as per local laboratory testing
HER2 positive as determined by score of 3 on immunohistochemistry (IHC) staining or gene amplification by fluorescence in situ hybridization (FISH).
3+ by IHC and/or
Local histologic or cytologic confirmation of HER2+ solid tumors by fluorescent in situ hybridization (FISH) amplification or immunohistochemistry (IHC) (3+)
HER2 Positive disease documented as FISH-positive and/or 3+ by IHC on previously collected tumor tissue.
Patients are required to have HER2+ breast cancer defined as a fluorescent in situ hybridization (FISH)- ratio of >= 2.0 or immunohistochemistry (IHC) 3+
For participants with lung cancer, centrally confirmed high expression of a sodium-dependent phosphate transporter (NaPi2b) by immunohistochemistry (IHC) is required (i.e., IHC 2+ or 3+).
Tumor negative for HER2 expression (0 or 1+ by immunohistochemistry [IHC]) or negative fluorescent in situ hybridization (FISH) testing
HER2-positive disease documented as in situ hybridization (ISH)-positive and/or 3+ by immunohistochemistry (IHC) on previously collected tumor tissue
Met diagnostic-positive status tested by immunohistochemistry (IHC)
HER2/neu-negative breast cancer by standard criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH]-negative if IHC 3+) at primary diagnosis
Progressive HER2 positive solid tumours (immunohistochemistry [IHC] positive or equivocal) with no available standard or curative treatment.
Currently on fish oil or has been on fish oil within the last 10 days
HER2 expression as defined by ISH positive and/or 3+ by immunohistochemistry (IHC)
Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer by local laboratory testing (immunohistochemistry [IHC] 3+ staining or fluorescent in situ hybridization [FISH] positive)
Patients with non-metastatic, node positive, HER2 negative breast cancer, confirmed by pathology report, who are in remission and defined as having no evidence of disease (NED); HER2 negative is defined as\r\n* 0-1+ HER2 expression by immunohistochemistry (IHC) OR\r\n* Fluorescence in situ hybridization (FISH) negative OR\r\n* HER2 2+ and FISH negative
Subjects with invasive breast cancer at least stage IIIA >= N2 (> 4 positive nodes) or have recurrent metastatic breast cancer rendered no evidence of disease (NED) by any means that are classic HER-2 3+ 10%, 2+ immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) positive or HER-2 2+ FISH negative that have completed chemotherapy and/or trastuzumab and have no evidence of disease
HER2/neu-expressing tumor (immunohistochemistry [IHC] 3+ and/or amplified fluorescence in situ hybridization [FISH] >2.2, or N0 (i+))
HER2/neu-expressing tumor (IHC 1-3+ and or positive FISH >1.2)
HER2 negative (HER2 1+ by IHC or HER2 2+ by IHC/FISH)
HER2 immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH) ordered on core biopsy, if biopsy indicates invasive cancer; Oncotype DX or other deoxyribonucleic acid (DNA) testing performed on core biopsy or not requested
History of HER2/neu positive cancer (IHC 3+ and/or fluorescence in situ hybridization [FISH] positive) as assessed by medical record review at screening
Pathologically or cytologically confirmed metastatic or primary esophagogastric cancer; HER2 positive status by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) as currently being implemented for patients with esophagogastric cancer; HER2 overexpression and/or amplification as determined by IHC (3+) or FISH (>= 2.0)
Two patients must be HER2 3+ by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) positive
The cancer must over express HER2 as determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH)
Cohort 1: Her2-positive (defined as 3+) or fluorescence in situ hybridization (FISH) HER2:Chromosome 17 centromere (CEP17) ratio > 2 biopsy-proven breast cancer
Cohort 2: Her2-positive (defined as 3+) or FISH HER2:CEP17 ratio > 2 OR HER2-negative (0 or 1+, 2+ and FISH negative) biopsy-proven breast cancer
Histologically confirmed HER2+ breast cancer: immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) amplified; by clinical assay on either primary or metastatic tumor
For patients with evidence of minimal residual disease prior to vaccination, assessment of minimal residual disease status by cytogenetics or fluorescence in situ hybridization (FISH) will be followed post vaccination
Histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC) (stage IV, American Joint Committee on Cancer [AJCC] v7.0) that carries (a) an ALK rearrangement, as determined by fluorescence in-situ hybridization (FISH), immunohistochemistry, or next generation sequencing (NGS) of either tissue or plasma, or (b) a ROS1 rearrangement as determined by FISH or reverse transcriptase-polymerase chain reaction (RT-PCR) or NGS via a local diagnostic test (LDT) or plasma analysis
Tumor HER2/neu expression must be determined (as part of standard clinical care) prior to study enrollment; HER2 may be tested by any Food and Drug Administration (FDA) approved HER2 testing method; if determination is intermediate by immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) or another alternate HER2 test must be performed
HER2/neu positive by IHC and/or another FDA approved HER2 testing method
The patient is receiving preoperative chemotherapy other than adriamyacin, cyclophosphamide, and a taxane (ACT) in standard or dose-dense fashion; herceptin may be added to the neoadjuvant chemotherapy regimen in cases where the tumor is Human Epidermal growth factor Receptor 2 (Her-2)/neu positive by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and must not be positive (HER2/CEP17 ratio must be < 2, and HER2 copy number < 6 signals/cell), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by institutional standards.
Estrogen receptor (ER) and progesterone receptor (PgR) status by immunohistochemistry must be known; ER positive tumors are allowed in patients for whom the treating investigator has determined neoadjuvant chemotherapy is appropriate
Any ER/progesterone receptor (PgR) status allowed
Estrogen receptor (ER) and/or progesterone receptor (PR) positive histologically confirmed adenocarcinoma of the breast with staining of >= 1% cells will be considered positive; receptor status may be based on any time during treatment prior to study randomization, and from any site (i.e. primary, recurrent, or metastatic)
* For patients who underwent initial surgery and received adjuvant chemotherapy\r\n** Triple negative breast cancer (TNBC) patients must have been axillary node-positive (>= pN1, any tumor size) or axillary node negative (pN0) with invasive primary tumor pathological size > 2 cm (>= pT2)\r\n** Estrogen receptor (ER) and/or progesterone receptor (PgR) positive/human epidermal growth factor receptor (HER) 2 negative patients must have had >= 4 pathologically confirmed positive lymph nodes\r\n* For patients who underwent neoadjuvant chemotherapy followed by surgery\r\n** TNBC patients must have residual invasive breast cancer in the breast and/or resected lymph nodes (non-pathological complete response [pCR])\r\n** ER and/or PgR positive/HER2 negative patients must have residual invasive cancer in the breast and/or the resected lymph nodes (non-pCR) AND a clinical pathologic stage (CPS) & estrogen receptor status nuclear grade (EG) score >= 3
Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) testing performed on the primary breast tumor; when applicable, testing must have been performed prior to neoadjuvant chemotherapy
Metastatic or locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression
Metastatic breast cancer with any evidence of estrogen receptor (ER) or progesterone receptor (PR) positivity in >= 1% cells in biopsy specimens from either a primary or metastatic site is eligible
Participants with locally advanced or metastatic, histologically documented TNBC (absence of human epidermal growth factor receptor 2 [HER2], estrogen receptor [ER], and progesterone receptor [PR] expression), not amenable to surgical therapy
SAFETY RUN-IN: Women diagnosed with pathologically confirmed metastatic triple negative invasive breast cancer (centrally confirmed immunophenotype negative for all three receptors estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2])
Histologically documented TNBC (negative human epidermal growth factor receptor 2 [HER2], estrogen receptor [ER], and progesterone receptor [PgR] status)
Invasive breast cancer between 0.5 cm and 5 cm in size diagnosed by needle core biopsy, estrogen receptor positive (ER+) or estrogen receptor negative (ER-), Her2neu positive or negative, tumor grade 2 or 3
Histologically confirmed estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor 2 (HER2)-negative adenocarcinoma of the breast with measurable metastatic or locally advanced disease
Patients enrolling in the triple negative breast cancer (estrogen receptor negative [ER-]/progesterone receptor negative [PR-]/human epidermal growth factor receptor 2 negative [Her2-]) group, cohort 3, must have a negative family history of HBOC syndrome, or negative gBRCA1/2m test; a family history of HBOC is defined by National Comprehensive Cancer Network (NCCN) Genetic/Familial High-Risk Assessment: Breast and Ovarian guideline
Patients must have histologically confirmed clinical stage II or III estrogen receptor negative (ER-) progesterone receptor (PR) - HER2 positive (+) (per College of Pathologists [CAP] criteria) invasive ductal carcinoma of the breast
Estrogen receptor (ER) and progesterone receptor (PR) < Allred score of 3 or =< 5% positive staining cells in the invasive component of the tumor (provided the patient is being treated as triple negative breast cancer)
Documentation of estrogen receptor positive ((ER+), human epidermal growth factor receptor 2 (HER2 negative (HER2-)) tumor.
Histologically-proven metastatic or locally-advanced relapsed/refractory HER2+ breast cancer based on the most recently available tumor biopsy collected from the patient. Tumors may be estrogen receptor (ER)/progesterone receptor (PgR) positive or negative.
Human epidermal growth factor 2 (HER2) positive and estrogen receptor (ER) or progesterone receptor (PR) positive tumors: must be refractory to hormonal therapy (e.g. aromatase inhibitor, tamoxifen or fluvestrant) and previously treated with at least 2 regimens containing at least two anti-HER2 agents (e.g. trastuzumab and pertuzumab).
Any estrogen receptor (ER), progesterone receptor (PR), HER2 status
Estrogen receptor (ER) and progesterone receptor (PR) less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor
Subjects must be estrogen receptor (ER) positive
Has positive estrogen receptor (ER) or progesterone receptor (PR) status. ER or PR >= 10%.
Estrogen receptor (ER)+ Her2- breast cancer
Estrogen receptor (ER)+ Her2- breast cancer
Primary, invasive, estrogen receptor (ER) and/or progesterone receptor (PR)-positive, HER2 negative breast cancer; ER-and/or PR–positive breast cancer is defined by > 10% staining by immunohistochemistry
Dose Expansion Cohort Group 1 and 2: Patients must have a diagnosis of histologically confirmed metastatic TNBC defined as negative for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2); patients must have received either adjuvant chemotherapy or first line chemotherapy for metastatic disease; negative for estrogen and progesterone receptor includes the following:\r\n* Local pathology report classifies them as negative\r\n* Allred score of 2 or below\r\n* < 1% positive staining
Estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive tumor (? 1% positive stained cells) based on local laboratory results
Breast cancer determined to be estrogen receptor (ER)-negative and progesterone receptor (PgR)-negative defined for this study as < 10% tumor staining by immunohistochemistry (IHC)\r\n* Note: Eligibility should be based on the ER and PgR status reported at the time of the most recent biopsy or resection
Patient must have histologically or cytologically confirmed breast cancer that is now metastatic; any estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status is allowed
PHASE II STUDY COHORT 5 TRIPLE NEGATIVE BREAST CANCER ELIGIBILITY CRITERIA (MEDI+O ONLY)\r\nPatients must have histologically confirmed persistent or recurrent triple-negative breast cancer (TNBC) for which standard curative measures do not exist or are no longer effective; estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) status needs to be documented either by an outside source or at National Cancer Institute (NCI)
Estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) (HER2 status is not required for women diagnosed with DCIS)
Estrogen receptor (ER) and progesterone receptor (PR) less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor
Estrogen receptor (ER) and progesterone receptor (PR) less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor; patients not meeting this pathology criteria, but have been clinically treated as having triple negative breast cancer (TNBC), can be enrolled at principal investigator (PI) discretion
Patients must have estrogen receptor (ER) analysis performed prior to study entry. If ER analysis is negative, then progesterone receptor (PgR) analysis must also be performed. (Patients are eligible with either hormone receptor-positive or hormone receptor-negative tumors.)
COHORT II: Core biopsy demonstrating breast cancer and receptors that are estrogen receptor (ER) or progesterone receptor (PR) positive
COHORT II: Patients must have estrogen receptor (ER) and progesterone receptor (PR) analysis performed on core biopsy
Patients with progesterone receptor positive (PR+) tumors are allowed
Patients must have had histologically confirmed stage I-III breast carcinoma that is positive for estrogen receptor (ER) and/or progesterone receptor (PR)
Estrogen receptor (ER), progesterone receptor (PR), and HER2/neu status documented by core needle biopsy of the primary tumor and/or regional lymph node must be known prior to beginning systemic therapy
Step 2 subjects only: newly diagnosed, operable, triple negative breast cancer, i.e. estrogen receptor (ER)/progesterone receptor (PR)-negative, human epidermal growth factor receptor (her2)/neu-negative, with tumor size between 2–5 cm (T2) as measured by either clinical breast exam, mammogram, ultrasound or magnetic resonance imaging (MRI), with or without ipsilateral axilla node involvement (N0 or N1)
Subjects must not have been diagnosed with estrogen receptor negative (ER-) AND progesterone receptor negative (PR-) breast cancer (patients must have either an ER or PR positive status)
Patient has disease that is hormone-receptor positive (estrogen receptor [ER] and/or progesterone receptor [PR] positive [+], HER-2/neu negative [-]) or triple-negative (ER/PR/HER-2/neu -).
Immunohistochemical studies must demonstrate the invasive component of the tumor to be estrogen receptor positive (ER+) (>= 10%) or progesterone receptor positive (PR+), human epidermal growth factor receptor 2 negative (HER2-) and grade 1 or 2
Pathologically confirmed squamous cell carcinoma of the head and neck OR pathologically confirmed invasive breast adenocarcinoma with documented estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) status and radiographic evidence of distant metastatic disease
Estrogen receptor (ER) and progesterone receptor (PgR) status by IHC must be known; tumor must be ER and PR negative (=< 5% staining) by local review
Histologically and/or cytologically confirmed diagnosis of ER+ and/or progesterone receptor positive (PR+) breast cancer by local laboratory
Any estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2neu) status as long as the patient will receive nab-paclitaxel alone
Histologically confirmed diagnosis of recurrent or residual epithelial ovarian cancer, primary peritoneal carcinoma or fallopian tube carcinoma, OR histologically confirmed metastatic breast cancer, that is estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)/neu negative (as determined by local pathology laboratory)
Estrogen receptor (ER) and progesterone receptor (PgR) negative.
Estrogen receptor (ER)/progesterone receptor (PR) determination is required; ER- and PR-assays should be performed by immunohistochemical methods according to the local institution standard protocol
Histologic confirmation, from the A011203 pre-registration biopsy, by institutional/local pathologist of either locally advanced or metastatic breast cancer that is estrogen receptor positive and HER2 negative; those patients with bone only disease with either no tumor or insufficient tumor for ER/progesterone receptor (PR) and HER2 staining after the bone biopsy are still eligible to participate in this study
Estrogen Receptor (ER)-, Progesterone Receptor (PR)-, and Human Epidermal Growth Factor Receptor (HER)2-negative (triple-negative) cancer of the breast.
Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) testing in progress (i.e. on outside or MSKCC biopsy report)\r\n* HER2-positive pathology is permitted
Patients may have any molecular status (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]) and must have failed at least 1 systemic regimen after their diagnosis of locoregional disease
Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) Breast Cancer by local laboratory testing, based on last available tumor tissue.
Known Human Epidermal Growth Factor Receptor 2 (HER2) positive, erythrocyte receptor (ER) positive, or progesterone receptor (PR) positive breast cancer
All positive or negative ER (estrogen receptor), PR (progesterone receptor), and HER-2 subjects are eligible for this study.
Documentation of ER-positive and/or progesterone receptor (PR)-positive tumor.
Breast tumors with hormone receptor positive disease (estrogen receptor [ER]+/progesterone receptor [PR]+, ER+/PR- regardless of HER2 status)
Men and women with advanced malignancies for which no standard therapy is available\r\n* Dose escalation: Patients with any solid tumor malignancies \r\n* Dose expansion: \r\n** Patients with advanced malignancies that have germline and/or somatic BRCA mutations (cohort gBRCA) or\r\n** Triple negative (TN) metastatic breast cancer without known BRCA mutation (cohort TNBC); tumors will be considered TN when:\r\n*** Estrogen receptor (ER) expression < 1%\r\n*** Progesterone receptor (PR) expression < 1%\r\n*** Human epidermal growth factor receptor 2 (Her2) negative as per the American Society of Clinical Oncology (ASCO) guidelines\r\n** Paclitaxel expansion: any solid tumor malignancy with potential benefit from this combination and paclitaxel (ASP)
Tumors must be estrogen and/or progesterone receptor positive according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2010 guidelines as either estrogen receptor (ER) or progesterone receptor (PR) >= 1% positive nuclear staining by immunohistochemistry; estrogen and/or progesterone receptor results by Oncotype Dx will not be accepted
Histologically confirmed invasive breast carcinoma, stage I-III\r\n* Note: estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status must be known; in newly diagnosed patients planning neoadjuvant treatment, a formal assessment of axillary lymph nodes is not required
Patients must have histologically or cytologically confirmed metastatic invasive breast cancer that is negative for the estrogen receptor (ER), progesterone receptor (PR) and HER2 by institutional guidelines
Patients have positive estrogen receptor (ER) expression in the primary tumor site by immunohistochemistry (IHC) (defined as >= 10%) (progesterone receptor [PR] status is not required)
Histologically documented HR+ breast cancer in either the primary or metastatic setting, as defined by estrogen receptor (ER) + or progesterone receptor (PR) +; results from the local lab are acceptable; eligibility will not be affected by human epidermal growth factor 2 (HER2) status
Histologically or cytologically confirmed estrogen/progesterone receptors (ER/PR) +/-; human epidermal growth factor receptor 2 (HER2)-, metastatic breast cancer.
Histological or cytological confirmation of estrogen-receptor positive (ER+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer
Histologically or cytologically confirmed estrogen receptor (ER) and/or progesterone receptor (PgR) positive carcinoma of the breast with unresectable, locally advanced and/or metastatic (American Joint Committee on Cancer [AJCC] Stage IV) disease
At the recommended phase II dose level, a total of 20 patients with triple-negative breast cancer defined as estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative, will be enrolled and another 10 patients with a solid malignancy who would benefit from a paclitaxel and carboplatin-based regimen, will also be enrolled
Patient must have histologically or cytologically-confirmed metastatic breast cancer; any estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (Her2) status is allowed
Histopathological diagnosis of triple negative breast cancer (ductal, lobular, mixed or metaplastic), defined as estrogen receptor (ER) < 1%, progesterone receptor (PR) < 1%, and human epidermal growth factor receptor 2 (HER2) negative according to American Society of Clinical Oncology/College of American Pathologists guidelines by local testing according to institutional standards; for tumors with equivocal interpretation of receptor status (e.g. “weak” or “faint” staining), the principal investigator will have final determination of triple negative status
Documented pathological evaluation of the breast cancer for hormone receptor (estrogen receptor [ER] and progesterone receptor [PR]) status and HER-2 status
Known human epidermal growth factor 2 (HER2)-positive, estrogen receptor (ER)-positive, or progesterone receptor (PgR)-positive breast cancer
Estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer
Women with ER+/progesterone receptor positive (PR+) human epidermal growth factor receptor 2 (HER2)-negative breast cancer initiating neoadjuvant endocrine therapy with curative intent OR initiating endocrine therapy for the treatment of metastatic breast cancer with a biopsy accessible primary breast tumor
Triple negative breast cancer (TNBC) Cohort: Participants with histologically confirmed incurable, advanced estrogen receptor (ER)-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2 (HER2)-negative adenocarcinoma of the breast (triple-negative) not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)
For Stage 2: Participants with human epidermal growth factor receptor 2 (HER2) negative, estrogen-receptor (ER) negative, and progesterone-receptor (PR) negative breast cancer
Estrogen receptor (ER)-positive disease and human epidermal receptor 2 (HER2)-negative disease
Estrogen receptor (ER)/progesterone receptor (PR) positive tumor (as confirmed by City of Hope Pathology Department if done on the outside) or
The following receptor status:\r\n*Expansion: Triple negative (estrogen receptor [ER] < 1%, progesterone receptor [PR] <1%, and Her-2/neu negative)\r\n* Phase I (closed): Negative Her-2/neu status
Candidate for hormonal therapy (estrogen receptor [ER] and/or progesterone receptor [PR]-positive at primary diagnosis and at metastatic diagnosis where tissue is available)
Have stage I-III estrogen receptor positive (ER+) breast cancer
If receiving neoadjuvant chemotherapy, must not be triple negative (estrogen receptor [ER]-/progesterone receptor [PR]-/HER2-)
Must have BOTH estrogen receptor (ER) and progesterone receptor (PR)-positive tumors and BOTH must be >= 26% positive; alternatively, if ER and PR are determined by Allred score, the score needs to be 5 or higher
Patients must be women with histologically confirmed estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive invasive carcinoma of the breast (Stage I-III) with no evidence of metastatic disease (M0)
The invasive tumor must be hormone receptor-poor, defined as both estrogen receptor (ER) and progesterone receptor (PgR) staining present in =< 10% of invasive cancer cells by immunohistochemistry (IHC)
Patients must be positive for either estrogen receptor (ER) and/or progesterone receptor (PgR) as determined by institutional standard
Diagnosed with triple negative (negative for estrogen receptor, progesterone receptor and not human epidermal growth factor receptor 2 [Her2] amplified) breast cancer at 60 or younger
Patients with triple negative breast cancer (estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and human epidermal growth factor receptor 2-negative (Her2-) must also meet the following criteria: a. Must have received at least one prior chemotherapy regimen for locally advanced or metastatic disease; b. Must have received prior taxane therapy.
Primary tumor and/or metastatic site must be ER+ and may be progesterone-receptor positive (PgR+) or progesterone-receptor negative (PgR-) by IHC; patients with a history of an estrogen-receptor negative (ER-) primary tumor and a documented ER+ metastatic site are eligible
Estrogen receptor (ER) receptor positive on core needle biopsy, or if receptor negative, have evaluable ER receptor with positive internal control on core biopsy
Progesterone receptor (PR) positive on core needle biopsy if biopsy indicates invasive cancer, or if receptor negative on biopsy indicating invasive cancer, have evaluable PR receptor with positive internal control on core biopsy
Adult patients with a history of pathologically confirmed estrogen receptor positive (ER+) breast cancer
High risk ductal carcinoma in situ (DCIS) or invasive stage I and II estrogen receptor (ER) positive (+)/progesterone receptor (PR)+ breast cancer with negative clinical lymph node exam
Participants must have biopsy proven invasive breast carcinoma stages T1cN0 to T3N0, estrogen receptor (ER) or progesterone receptor (PR) positive with tumors greater than 1 cm without lymph node spread
Tumors must be estrogen and/or progesterone receptor positive according to ASCO/CAP 2010 guidelines as either ER or PR ? 1% positive nuclear staining by immunohistochemistry based on local laboratory results.
Triple-negative disease (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) negativity confirmed on a histological biopsy of a metastatic tumor lesion (receptor conversion not allowed).
Documented history of prior tamoxifen, aromatase inhibitor, or raloxifene in last 6 months
1-2 prior regimens (including primary therapy); hormonal therapies (e.g., tamoxifen, aromatase inhibitors) will not count toward the prior regimen limit
Patients who have had hormonal therapy (e.g., tamoxifen, aromatase inhibitor) within 1 week prior to entering the study
Tamoxifen and aromatase inhibitors within 14 days prior to the first dose of study drug.
Participants who are receiving other concurrent chemotherapies or immunotherapies for their cancer (except for patients who will receive letrozole, anastrozole, exemestane, tamoxifen, fulvestrant, trastuzumab, bisphosphonates, or ovarian suppression therapy)
Patients must not have received any prior chemotherapy, radiation therapy, or endocrine therapy for their current breast cancer; patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer may be included as long as the patient has discontinued the treatment at least one month prior to baseline study biopsy
For Part C (LY2835219 + tamoxifen): The participant may have received prior systemic endocrine therapy for metastatic disease and may be receiving ongoing therapy with tamoxifen.
Use hormone replacement therapy (including systemic or topical estrogen, progesterone, or testosterone based medication) or/and phytoestrogen supplements (i.e. black cohosh) or has been on progestin (including progestin containing IUD), tamoxifen or aromatase inhibitor within the prior 3 months
Women who have received treatment with Selective Estrogen Receptor Modulators (SERMs) (e.g. tamoxifen, raloxifen) or aromatase inhibitors
Have never used tamoxifen, raloxifene, or other antiestrogen compounds
PART I: Stable, concurrent use of tamoxifen or aromatase inhibitors for hormone receptor positive breast cancer
PART II: Stable, concurrent use of tamoxifen or aromatase inhibitors for hormone receptor positive breast cancer are allowed
Patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for prevention or treatment of breast cancer or for other indications (e.g., osteoporosis, prior ductal carcinoma in situ [DCIS]), or who receive aromatase inhibitors for prevention or treatment of breast cancer, are eligible; patients who are hormone-receptor positive and who have received other hormonal agents for the treatment of breast cancer (e.g., Fulvestrant) are also eligible; tamoxifen therapy or other hormonal agents should be discontinued at least 1 week before the patient is enrolled on this study
Currently treated with hormone therapy-based regimen, including selective estrogen receptor modulators (SERMs), aromatase inhibitors, selective estrogen receptor down regulators (SERDs), CYP17A1 inhibitors, gonadotrophin releasing hormone (GnRH) agonists/antagonists, and antiandrogens; concurrent anti-HER2 therapy and other targeted therapy (e.g., CDK4/6 inhibitor, mTOR inhibitor) is permitted; must have started the current regimen at least 4 weeks prior to enrollment
HER2 negative and either ER or PR positive tumors: must be refractory to hormonal therapy (e.g. aromatase inhibitor, tamoxifen or fulvestrant) and previously treated with at least 2 chemotherapy containing regimens.
FOR ALL PHASES (Ib AND II): Current therapy with raloxifene, tamoxifen, aromatase inhibitor, or other selective estrogen receptor modulator (SERM), either for osteoporosis or prevention of breast cancer; subjects must have discontinued therapies for at least 28 days prior to first baseline biopsy
Patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for the prevention or treatment of breast cancer or for other indications (e.g., osteoporosis, prior ductal carcinoma in situ [DCIS]), or who receive aromatase inhibitors for prevention or treatment of breast cancer, are eligible; patients who are hormone-receptor positive and who have received other hormonal agents for the treatment of breast cancer (e.g., Fulvestrant) are also eligible; tamoxifen therapy or other hormonal agents should be discontinued at least 1 week before the patient is started on study therapy
Patients are not eligible if they have previously received endocrine therapy within 5 years prior to diagnosis of the current malignancy; this includes use for prophylactic reasons, including treatment of osteoporosis or cancer prevention with tamoxifen, raloxifene, or aromatase inhibitors (AI)
Prior treatment or preventative use of any hormonal agent such as aromatase inhibitors (AI), fulvestrant, raloxifene, tamoxifen or other SERM, or with any other hormonal agent used for the treatment or prevention of BC or for any other indication (e.g. osteoporosis).
Patients with a history of tamoxifen and/or aromatase inhibitor use for treatment or prevention are eligible but should discontinue these medications at least 2 weeks prior to starting this trial
Any prior treatment with radiation therapy or chemotherapy for the currently diagnosed breast cancer prior to registration; endocrine therapy may be given but not within 28 days prior to study entry and must be stopped if the patient will be receiving chemotherapy until completion of chemotherapy; patients must discontinue any hormonal agents such as raloxifene, tamoxifen, or other selective estrogen receptor modulators prior to registration
For subjects enrolled in the Anastrozole Arm, prior hormonal therapy (including, but not limited to, tamoxifen, megestrol acetate, fulvestrant, and GnRH analogs) for the treatment of recurrent/advanced endometrial cancer are not allowed
Current use of selective estrogen receptor modulators (SERMS) or aromatase inhibitors
Patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for prevention or for other indications (e.g., osteoporosis, prior ductal carcinoma in situ [DCIS]) are eligible; tamoxifen therapy or other SERMs should be discontinued at least 1 week before the patient is enrolled on this study
Taken tamoxifen or other selective estrogen/progesterone receptor modulators (SERMs/SPRMs) within two years prior to entering study or been required to discontinue SERM therapy due to thromboembolic or uterine toxicity
Willing to accept oral endocrine therapy with a third generation aromatase inhibitor (AI) or selective estrogen receptor modifier (SERM)
Current use of tamoxifen, aromatase inhibitors, or SERMs for a breast cancer indication for at last six months
Patients who have received more than 4 weeks of tamoxifen therapy for this malignancy; patient who have received tamoxifen or raloxifene for purposes of chemoprevention (e.g. breast cancer prevention trial or for other past indications (including previous breast cancer) are eligible; tamoxifen or raloxifene therapy will be discontinued at least one month before the patient is enrolled on this study
Women may have been taking tamoxifen or raloxifene as a preventive agent prior to study entry but must have discontinued the drug for at least 21 days prior to study enrollment
1 week for non-cytotoxic agents, such as interferon, tamoxifen, & cis-retinoic acid
Previous endocrine therapy such as raloxifene or tamoxifen (or other selective estrogen receptor modulator [SERM]) or an aromatase inhibitor for any malignancy
Any patients with a history of tamoxifen or raloxifene use within two years of current DCIS diagnosis are not eligible
Tamoxifen or other preventive measures within 6 months
Patients must not have received an aromatase inhibitor (AI) or a selective estrogen receptor modulator (SERM) such as tamoxifen or raloxifene within 5 years prior to registration
Prior treatment with tamoxifen, raloxifen or aromatase inhibitors for reduction in risk (chemoprevention) of breast cancer and/or treatment for osteoporosis within last 2 years
Previous treatments with hormonal therapy (tamoxifen, aromatase inhibitors) and signal transduction agents (e.g., erlotinib, gefitinib, everolimus, bevacizumab) are allowed and are not counted towards the prior line of therapy.
Major surgery within <30 days of starting treatment or received chemotherapy, investigational agents, or other cancer therapy, except hormonal therapy (eg, tamoxifen, aromatase inhibitors), <14 days prior to the initiation of investigational products
? 14 days elapsed from administration of any non-cytotoxic agent (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid)
Part 2, Cohort 3: Histologically and/or cytologically confirmed diagnosis of breast cancer with hormone receptor-positive status (ER and/or PgR positive) and HER2-negative status with prior exposure to tamoxifen and/or an aromatase inhibitor and/or an aromatase inhibitor plus palbociclib. Prior treatment with tamoxifen in the neoadjuvant setting is allowed but must have been discontinued for at least 1 year prior to the first dose.
Concurrent treatment with hormone replacement therapy is permitted at the discretion of the treating physician; patients who have been taking hormonal/hormone blocking agents for breast cancer or breast cancer prevention or other indication are eligible; use of anti-hormonal agents (tamoxifen, medroxyprogesterone, aromatase inhibitors) is permitted at the discretion of the treating physician; documentation of concurrent medications is required
At least 2 months must have elapsed from the use of tamoxifen
Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Subjects must have discontinued use of such agents prior to beginning study treatment.
Tamoxifen therapy less than 14 days before first dose of study treatment
Disease that progressed during treatment or within 12 months of completion of adjuvant therapy with tamoxifen and/or an aromatase inhibitor (AI).
No use of selective estrogen receptor modulators (SERM) such as raloxifene or similar agents in the past 2 years
Hormonal therapies used as single agents (i.e. tamoxifen, aromatase inhibitors) will not count towards line limit considerations
Minimum of 6 months since last chemotherapy, biologic therapy (i.e., trastuzumab), radiation therapy, and/or breast surgery and no evidence of recurrent disease; minimum of 6 months since completion of adjuvant tamoxifen; current use of a third generation aromatase inhibitor [AI] (i.e., anastrozole, letrozole, exemestane) is permitted, provided that the participant has been on a stable dose for the past 6 months
Receiving hormone replacement therapy, tamoxifen, or raloxifene within 6 months of trial entry; patients on non-systemic hormone replacement therapy are eligible
Breast cancer patients must be currently on adjuvant aromatase inhibitors
Current therapy with endocrine agents (tamoxifen, raloxifene, toremifene and all aromatase inhibitors) and/or bisphosphonates and/or tumor necrosis factor (ligand) superfamily, member 11 (RANK)-ligand inhibitors is permitted
Prior adjuvant therapy with an AI and/or tamoxifen is allowed, provided treatment ended at least 2 weeks prior to the first dose of MEDI-573
Patients who have received agents that modulate or downregulate the estrogen receptor for breast cancer prevention (e.g. tamoxifen, raloxifene, fulvestrant) or bone health (raloxifene) are eligible if they were on treatment for at least 6 months, did not have a diagnosis of breast cancer on the medication, and have discontinued the agents 6 months prior to study registration
Prior aromatase inhibitors (e.g. anastrozole, letrozole, exemestane, aminoglutethamide) are allowed in the adjuvant setting
Prior tamoxifen as adjuvant treatment is allowed as long as the patient did not have disease relapse or progression while on adjuvant tamoxifen or within 4 weeks of last dose
The participant has previously received endocrine therapy for breast cancer prevention (tamoxifen or raloxifene or aromatase inhibitors).
Women currently on tamoxifen and raloxefene for prevention are not eligible
1 week for non-cytotoxic agents (e.g., interferon, tamoxifen, & cis-retinoic acid)
Patient has been treated with all FDA approved endocrine therapies or has been treated with all FDA approved endocrine therapies except for tamoxifen (tamoxifen is excluded from the trial)
For phase I patients only: Current therapy with hormone replacement therapy, or any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators
Prior treatment with tamoxifen, raloxifen or aromatase inhibitors for reduction in risk (chemoprevention) of breast cancer and/or treatment for osteoporosis within last 2 years
Patients must not have received prior AI therapy with exemestane, letrozole, or anastrozole as preoperative/adjuvant therapy or for prevention of breast cancer; prior tamoxifen is allowed
For breast cancer patients only, endocrine therapies are allowed (such as aromatase inhibitors, but not current tamoxifen. Prior tamoxifen is permitted with a 30 day wash out period)
Prior use of selective estrogen receptor modulator (SERMS) and aromatase inhibitors (AIs) including tamoxifen, raloxifene, anastrozole, letrozole, or exemestane for prevention or therapy within 5 years
7 days from administration of non-cytotoxic agents [e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count)]
No prior use of a selective estrogen receptor modulator (SERM) or aromatase inhibitor (AI) for chemoprevention
Women diagnosed with breast cancer stages I-III initiating first line adjuvant aromatase inhibitor (AI) therapy with any of the Food and Drug Administration (FDA)-approved AIs (anastrozole, exemestane, letrozole)
Prior tamoxifen use is allowed
Participants must self-identify as being at least 90 days post final chemotherapy, biologic therapy, or radiation therapy treatment and/or breast surgery; current use of hormonal therapy is permitted (e.g., tamoxifen and aromatase inhibitors)
Women who have been diagnosed with stage I-IIIA breast cancer will be recruited 1-8 years after the completion of all primary cancer treatment except for longer-term hormonal therapies (tamoxifen, aromatase inhibitors); recruit women who have received one of the two most common stage I-IIIA chemotherapy regimens, either docetaxel/cyclophosphamide or doxorubicin/cyclophosphamide followed by paclitaxel to provide uniformity of prior treatment
Concurrent use of tamoxifen, raloxifene, or any of the aromatase inhibitors
Cases with stage I-IIIB breast cancer that have completed neoadjuvant or adjuvant treatment with anthracyclines and/or taxanes + or – radiation therapy within past 6 months (+/- 7 days) (subjects on concurrent endocrine therapy [tamoxifen (TAM), aromatase inhibitors] are also eligible to participate)
Eligible to receive AHT (tamoxifen or an aromatase inhibitors [AI]) for the first time
All the female breast cancer survivors will be at least two months from receiving cancer treatment (surgery, adjuvant therapy or radiation) and within three years from completing cancer treatment, except for tamoxifen/aromatase inhibitors
Subjects must be on current treatment with tamoxifen or an aromatase inhibitor for at least two months prior to study enrollment (defined as the date of consent) and should not be planning to discontinue treatment or to change dose or type of endocrine treatment during the duration of the study
Was prescribed adjuvant therapy with an AI (prior chemotherapy or tamoxifen OK) in past 2 to 4 weeks (Randomized Trial only)
Breast cancer (stage 0, I, II, III), 18 months to 5 years post oncologic therapies of surgery, chemotherapy, and/or radiation therapy (does not exclude current selective estrogen receptor modulators or aromatase inhibitors)
Tamoxifen, raloxifene, or aromatase inhibitors are allowed, but the patient must have been on a constant dose for >= 4 weeks and ust not be expected to stop the medication during the study period
Must be more than six months from ingestion of antihormonal therapy (tamoxifen, raloxifene, other selective estrogen receptor modulators [SERMs], aromatase inhibitors)
Currently receiving tamoxifen or raloxifene
Women eligible to take tamoxifen must be offered tamoxifen prevention as part of their clinical care and have refused tamoxifen treatment
Current treatment with tamoxifen or aromatase inhibitors
Prior use of selective estrogen receptor modulators (SERMS) and aromatase inhibitors (AIs) for prevention or therapy, except for a maximum of 3 months and at least 12 months prior
Current use or < 6 months since use of selective estrogen receptor modulator (SERMS) or aromatase inhibitors or any other investigational treatment for breast cancer prevention or therapy
Is taking risk reduction therapy with tamoxifen
Patients currently on endocrine therapy (tamoxifen, ralozifene or an aromatase inhibitor)
Medications:\r\n* Current anticoagulant use (must discontinue for 3 weeks prior to fine needle aspirate [FNA])\r\n* Taking systemic hormones within two months (eight weeks) prior to screening RPFNA\r\n* Taken tamoxifen, raloxifene, or an aromatase inhibitor within the past 6 months\r\n* Participation on any chemoprevention trial within 6 months
Patients on treatment with tamoxifen
Use of any selective estrogen receptor modulator or aromatase inhibitor within 6 months of randomization, including, but not limited to: tamoxifen, raloxifene, arzoxifene, acolbifene, anastrozole, exemestane, and letrozole
Participants must not have received either chemotherapy or radiotherapy within the previous 6 months; Note: participants receiving long-term adjuvant hormonal therapy (such as tamoxifen or aromatase inhibitors for breast cancer) are allowed
Elevated risk of breast cancer as defined by at least one of the following categories and have declined tamoxifen and/or raloxifene therapy:
Prior tamoxifen or raloxifene use in the past 1 year.
Prior history or current use of tamoxifen or anti-estrogen therapy
Use of any selective estrogen receptor modulator or aromatase inhibitor (tamoxifen, raloxifene, arzoxifene, acolbifine, anastrozole, exemestane, letrozole) within the previous 6 months
Use of tamoxifen, raloxifene, or chemotherapy within the previous 6 months
Hormonal therapy (tamoxifen, an aromatase inhibitor, or Lupron) is not permitted during radiation or during the subsequent 4 weeks (the entire dose-limiting toxicity [DLT] window)
Participants must have been on adjuvant endocrine therapy, either tamoxifen or aromatase inhibitor (AI), for at least 6 months without any significant adverse events leading to drug interruption for more than 1 month, and must not have had any change in endocrine therapy in the past 6 months; ongoing use of any AI, including letrozole, anastrozole or exemestane, or tamoxifen is allowed; concurrent gonadotrophin releasing hormone (GNRH) agonist is allowed
Women who are receiving endocrine therapy for breast cancer treatment or chemoprevention including tamoxifen, letrozole, anastrozole, fulvestrant, or exemestane at the time of screening
Use of selective estrogen receptor modulators (SERMS) in the past 6 months, including tamoxifen and raloxifene
If undergoing adjuvant therapy (e.g. tamoxifen or aromatase inhibitors) willing and able to remain on current regimen for entire 6-month study period
No history of receiving endocrine therapy, tamoxifen, and or aromatase inhibitors for therapeutic measures; these agents used previously as chemoprevention are allowed
Patient is a postmenopausal woman, man, or premenopausal woman for whom standard endocrine therapy alone (tamoxifen, aromatase inhibitor [AI], with or without ovarian suppression or fulvestrant) is planned after FES-PET/CT is completed
Postmenopausal women, men, or premenopausal women for whom endocrine therapy (tamoxifen, aromatase inhibitor [AI] with or without ovarian suppression or fulvestrant), with or without a CDK4/6 inhibitor is planned after FES-PET/CT is completed.
Patients must have been off tamoxifen or other estrogen receptor blocking agents for at least 6 weeks and off chemotherapy for 3 weeks for the initial baseline FES
Received prior or ongoing local (e.g radiation) or systemic treatment (chemotherapy or endocrine therapy) for the current breast cancer; patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer may be included as long as the patient has discontinued the treatment at least one month prior to baseline study biopsy
Patients must not have received hormonal therapy (i.e., tamoxifen, raloxifene, and/or aromatase inhibitors) for prevention of breast cancer within 3 months of the biopsy documenting DCIS
Has had hormonal cancer therapy (e.g., tamoxifen, leuprolide). within 4 weeks prior to the first dose of study treatment
TREATMENT GROUP: Elect to undergo, but have not yet started tamoxifen therapy
Current use of aromatase inhibitor as prevention or treatment for breast cancer
Histologically proven stage 0-III carcinoma of the breast, status/post (s/p) surgical resection; radiation therapy and chemotherapy can have been administered, as indicated; concurrent aromatase inhibitor, tamoxifen, trastuzumab, and/or bisphosphonate therapy are permitted
Prior exposure to cisplatin, 5-fluorouracil, tamoxifen, and/or MEK inhibitors within 3 months of enrollment and/or ethambutol and/or hydroxychloroquine within 12 months.
Current or recent use of reproductive hormone therapy, tamoxifen, aromatase inhibitor or other estrogen inhibitors within the last 90 days, which may affect biomarkers
ER(+) and/or PR(+) by IHC (? 10% staining or Allred score ? 4)
Eligible tumor-node-metastasis (TNM) stages include:\r\n* Estrogen receptor (ER) and progesterone receptor (PR) negative (defined as < 1% staining for ER and PR by IHC): T2 or T3 N0, T0-3N1-3\r\n** Note: Patients with T1, N1mi disease are NOT eligible\r\n* ER and/or PR positive (defined as >= 1% staining for ER and/or PR on IHC): T0-3N1-3 or T3N0\r\n** Note: Patients with T0N0, T1N0 and T1, N1mi disease are NOT eligible\r\n* ER and/or PR positive (defined as >= 1% staining for ER and/or PR on IHC): T0-3N1-3 or T3N0\r\n** Note: Patients with T0N0, T1N0, T2N0 and T1-2, N1mi disease are NOT eligible\r\n* The eligibility of neo-adjuvant subjects can be assessed on the basis of clinical (c)TNM or pathologic (yp)TNM; the same eligible TNM combinations apply; patients may be eligible if they meet eligibility requirements at either time point, as long as they do not have T4 disease prior to therapy
Invasive breast cancer is estrogen receptor (ER) positive with an Allred score of 6, 7 or 8 by local institution standard protocol; if an Allred score is not reported on the diagnostic pathology report, ER positivity in > 66% cells is eligible; if ER positivity is =< 66%, the staining intensity (weak, intermediate, strong) is needed to calculate the Allred score to determine eligibility
Tumor ER Allred score between 0-5 or HER2 positive by IHC (3+) or amplified by FISH > 2.0
Patients must have histologically confirmed estrogen receptor (ER)-, progesterone receptor (PR)- and HER2-negative (triple-negative, TNBC) or ER, PR, and HER2 equivocal status and must not have received and not be planning to receive adjuvant anti-HER2 or endocrine therapies after completion of neoadjuvant chemotherapy; patients who are HER2 positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines are ineligible; HER2 negative and HER2 equivocal cases as per ASCO CAP guidelines that do not receive HER2-targeted therapy are eligible; patients with weekly ER or PR positive disease, defined as ER and/or PR < 5% by immunohistochemistry, are eligible if the treating physician considers the patient not eligible for adjuvant endocrine therapy; residual disease must be >= 1 cm in greatest dimension, and/or have positive lymph nodes (ypN+) observed on pathologic exam\r\n* NOTE: Immunohistochemistry (IHC)-positive isolated tumor cells in the lymph node (N0 [i+]) are not considered node-positive and these patients also must have >= 1 cm residual invasive cancer in the breast in order to be eligible
Patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer are eligible if all histopathologically examined tumors meet pathologic criteria for ER+ and/or PR+ and HER2-.
SAFETY RUN-IN: Patients with hormone-receptor positive breast cancer (ER and/or PR > 5%), and with HER-2 positive breast cancer (by means of immunohistochemistry with 3+ indicating positive status or fluorescence in situ hybridization with amplification ratio >= 2.0 indicating positive status)
RANDOMIZED PHASE II CLINICAL TRIAL: Patients with hormone-receptor positive breast cancer (ER and/or PR > 5%), and with HER-2 positive breast cancer (by means of immunohistochemistry with 3+ indicating positive status or fluorescence in situ hybridization with amplification ratio >= 2.0 indicating positive status)
Evidence of hormone sensitive, ER rich primary tumor defined by an Allred score of >= 6
Local testing on the diagnostic core must have determined the tumor to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP guidelines. (If local testing has determined a tumor to be HER2 equivocal or to have a borderline ER/PgR status (% IHC staining < 10% for both) and other eligibility criteria are met, material may be submitted for central testing to determine eligibility.)
Central testing for ER, PgR, and HER2 will be performed, and the tumor must be determined to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP Guidelines Recommendations. Material from either the diagnostic core biopsy or the research biopsy can be used for central testing depending on local preferences and standards.
Patients with synchronous bilateral or multicentric HER2-negative breast cancer are eligible as long as the highest risk tumor is ER-negative and PgR-negative and meets stage eligibility criteria. All of the other invasive tumors must also be HER2-negative by ASCO/CAP Guidelines based on local testing. Central testing to confirm TNBC status is only required for the highest risk tumor.
Histologically confirmed metastatic ER positive (+) and/or PR+ and HER2 negative (-) breast cancer who are candidates for palbociclib in combination with either letrozole or fulvestrant per treating physician
Part E) ER-positive and/or PR-positive/HER2- disease and received no more than 1 prior non-hormonally-directed or cytotoxic therapy in the MBC setting.
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED BY WASH U GPS LABORATORY): To be eligible for the Part II fulvestrant-naive ER+ cohort, prior treatment with fulvestrant is not allowed; in addition, ER and/or progesterone receptor (PR) positivity by institutional standard is required on pathology from the most recent tumor specimen if biopsy was done unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED BY WASH U GPS LABORATORY): To be eligible for the Part II fulvestrant-treated ER+ cohort, prior disease progression on fulvestrant is required; in addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): To be eligible for the Part II fulvestrant-naive ER+ cohort, prior treatment with fulvestrant is not allowed; in addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen if biopsy was done unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): To be eligible for the Part II fulvestrant-treated ER+ cohort, prior disease progression on fulvestrant is required; in addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required
Newly diagnosed ER-positive, HER2-negative breast cancer. ER-positive is defined as ? 1% immunohistochemical (IHC) staining of any intensity. HER2 test result is negative if a single test (or both tests) performed show:
Known HER2-, ER-positive, or PR-positive breast cancer by local laboratory assessment
Histologic confirmation of invasive breast cancer with any measures of ER, PR and HER2neu
Tumor assay profile must include on of the following: MammaPrint High, any ER status, any HER2 status, or MammaPrint Low, ER negative (<5%), any HER2 status, or MammaPrint Low, ER positive, HER2/neu positive by any one of the three methods used (IHC, FISH, TargetPrint™)
Have a diagnosis of ER+ breast cancer (defined as ER > 1% by IHC)
Women diagnosed with pathologically confirmed HER2-overexpressing breast cancer, that is locally recurrent, unresectable or metastatic (negative or positive for ER/PR, and positive for HER2)
Histologic confirmation of ER+ breast cancer
Patients must have histologically or cytologically confirmed ER and/or PR positive, HER-2/neu negative metastatic breast cancer; they can be enrolled in any line of therapy without investigational agents and should have stable disease or a partial response (which can be determined clinically) on current systemic treatment; patients must also have pathologic OR radiographic evidence of bone metastases and >= 5 CTCs; (Note: the pathology report that is used by the physician to determine diagnosis, will be used to determine patient eligibility; ER and PR status should be available at the time of registration)
Known ER, PgR and HER2 statuses.
Patients must have histologically or cytologically confirmed invasive breast cancer that is estrogen receptor positive (ER+) (> 1% staining) with radiographical or clinical evidence of metastatic disease \r\n* Measurable and/or non-measurable disease
History of ER positive (+) (>= 10% of cells positive on hematoxylin and eosin stain [H&E]), HER2 negative (?) breast cancer disease, either as a\r\n* History of primary, operable ER+/HER2? invasive breast cancer OR\r\n* History of de novo metastatic breast cancer that is ER+/HER2?\r\n** Note: HER2? (negative) disease defined as one of the following:\r\n*** HER2 immunohistochemistry (IHC) expression of 0, 1+ and in-situ hybridization (ISH) non-amplified\r\n*** HER2 IHC expression of 0, 1+ and ISH not done\r\n*** HER2 IHC expression of 2+ and ISH non-amplified\r\n*** IHC not done and ISH non-amplified; Note: supporting documentation such as a pathology report from their primary diagnosis that indicates ER+/Her2- invasive breast cancer or a biopsy report of de novo metastatic breast cancer that is ER+/HER2? should be submitted through the RAVE database
Central ER determination on pre-registration biopsy completed
The invasive cancer must be estrogen receptor alpha (ER)-positive, defined as having ER staining by IHC in >= 10% of malignant tumor cells
Patients with histologically confirmed diagnosis of locally-advanced, inoperable, metastatic and/or treatment-refractory triple negative breast cancer (TNBC). *Treatment refractory disease is defined as the persistence of tumor lesions following at least one intervention that may include chemotherapy, radiation and/or surgery, or any combination thereof. *Patients must have both ER and PR staining < 5% and be HER2-negative. Patients with ER or PR staining of 5-10%, but who have historically been treated as TNBC may also be enrolled. *Patients must not have disease that, in the opinion of the investigator, is considered amenable to potentially curative treatment.
ER+ status
Disease must be ER+ and HER2-
Women with previously untreated, unilateral stage II-III breast cancer, ER/PgR/HER2 negative (ER =< 5%, PgR =< 5%, HER2 0-1+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] =< 2.0); if clinically negative lymph nodes, tumor size should be minimum 1.0 cm and identifiable under office-based ultrasound guidance
Estrogen receptor (ER) less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor
Must have ER positive disease with ER/PR report available.
Addition inclusion for Part A (A6 & A7) Has a histological confirmation of either metastatic breast (ER+ve for Arm A6, 50% ER +ve and 50% HER2+ve metastatic breast cancer patients for Arm A7) or castrate-resistant prostate cancer
ER+ve tumours defined as ?1% of tumour cells positive for ER on IHC staining or an IHC score (Allred) of ?3
ER with <1% of cells positive on IHC or an IHC score (Allred) of ?2
PR with <1% of tumour cells positive on IHC or an Allred score of ?2
Part E3 dose expansion: must have advanced or metastatic ER-negative, PR-negative, and HER-2 non-overexpressing breast cancer
The tumor specimen obtained at the time of diagnosis used for HER2 testing must also have central testing for estrogen receptor (ER) and progesterone receptor (PgR) according to current ASCO/CAP guideline; patients with < 1% ER and PgR staining by IHC will be classified as negative
The tumor specimen obtained at the time of diagnosis used for HER2 and ER/and PgR testing must also have central testing for PD-L1 status; patients who are negative or positive are eligible
Patients who will participate in the endocrine therapy cohort must have invasive breast cancer that is estrogen receptor (ER)+ (? 1% ER staining by immunohistochemistry [IHC])
Head and neck cancer OR metastatic breast for which standard therapy is not curative\r\n* NOTE: Patients with ER/PR positive, HER2 negative breast cancer must have progressed through at least one prior cytotoxic regimen for advanced disease and no longer be candidates for standard endocrine therapy; patients with HER2 positive breast cancer irrespective of ER/PR status must have received or no longer be candidates for standard HER2 directed therapy (i.e., trastuzumab, pertuzumab, trastuzumab emtansine, and lapatinib); patients with ER/PR/HER2 negative breast cancer must have progressed through at least one prior cytotoxic regimen for advanced disease; ER/PR and HER2 status are defined by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
Patients must have known ER, PR, and HER2 status defined as either:\r\n* Triple-negative breast cancer, defined as: ER and PR < 10% by immunohistochemistry, and HER2-negative (defined as IHC 0 or 1+, or FISH ratio < 2.0)\r\n* Or, inflammatory breast cancer with any ER, PR, HER2 status
Estrogen (ER) and/or progesterone (PR)-positive at primary diagnosis and at metastatic diagnosis where tissue is available (defined as > or = 1% of staining nuclei)
National Comprehensive Cancer Network (NCCN) guidelines recommend for metastatic breast cancer “…biopsy documentation of first recurrence, if possible, and determination of hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]) and HER2 status….”; therefore, histologic and/or cytologic confirmation of metastatic disease is encouraged whenever feasible, but not required; in some circumstances, histologic confirmation may not be feasible (eg, bone metastases not amenable to biopsy and elevated cancer antigen [CA]27-29 tumor marker); for patients who have had histologic confirmation of metastatic disease, it is required that the biopsy confirm that the metastatic tumor is ER and/or PR positive, and HER2/neu negative; for patients in whom biopsy confirmation of metastatic disease is not feasible, it is required that the primary tumor be ER and/or PR-positive and HER2/neu negative
Centrally confirmed hormone-receptor-positive (?1% ER and/or PR positive stained cells) and HER2-normal (IHC score 0-1 or FISH negative (in-situ hybridization (ISH) ratio) <2.0 status) assessed preferably on tissue from post-neoadjuvant residual invasive disease or core biopsy of the breast, or if no other tissue is available the residual tumor of the lymphnode can be assessed. In case of bilateral breast cancer hormonreceptor positivity and HER2-normal status has to be centrally confirmed for both sides.
Histological or cytological confirmation of ER+ BC as assessed by a local laboratory using slides, paraffin blocks, or paraffin sample or by medical history: ER+ (confirmed as ER expression more than or equal to 1% positive tumor nuclei)
Willing to provide tissue samples for ER and retinoblastoma (RB) staining
Primary tumor was negative for ER, PR (cut-off for positivity is >10% positive tumor cells with nuclear staining) and negative for Her2-neu (0 or 1+ on immunohistochemistry and/or normal gene copy number by in-situ hybridization); Central review is not required.
ER-positive tumor, HER2-negative breast cancer
Women who agree to undergo a standard of care core biopsy of recurrent or metastatic breast cancer to confirm the ER+ (>= 10% nuclear staining) and HER2 negative status
Documentation of ER positive (? 1% positive stained cells by local standards) based on the most recent tumor biopsy, unless bone-only disease
ER/PgR negativity to follow local guidelines
Pre and postmenopausal women or men with stage IV estrogen receptor positive (ER+) breast cancer histological or cytological confirmation\r\n* ER-positive tumors\r\n** Progressed after at least one line of hormonal therapy\r\n** Any number of prior chemotherapy in the metastatic setting\r\n** Any number of prior hormonal therapies\r\n* ER-negative tumors\r\n** PD-L1 low, high or unknown\r\n** Progression after prior PD-1 or PD-L1 inhibitors allowed\r\n** HER2 positive or negative
Confirmed diagnosis of ER positive breast cancer
ER positive breast cancer. Central testing (required for all subjects) must demonstrate that the tumor is ER+ with low expression (H-score [1-159]).
Confirmed diagnosis of ER positive breast cancer
Concomitant active malignancy other than ER+ breast cancer.
Invasive breast cancer must be estrogen receptor-positive (ER+) in > 66 % of the cells or ER allred score 6-8; if ER is positive in >= 66%, the staining intensity (weak, intermediate, strong) is needed to calculate the allred score to determine eligibility; in institutions where ER expression is classified only by < 1%, 1-10%, and > 10% cut-offs, > 10% expression is required for inclusion
Estrogen receptor (ER)+ (ER- DCIS meeting other eligibility criteria are eligible)
ER/PR determination assays performed by IHC methods according to the local institution standard protocol
Patients with both ER positive and ER negative breast cancer are eligible for this study; patients with human epidermal growth factor receptor 2 (HER2) positive disease will be excluded from participation in this study
Must have histologically or cytologically confirmed triple negative (ER-/PR-/HER2-) invasive breast cancer, clinical stage I-III at diagnosis (AJCC 6th edition) based on initial evaluation by physical examination and/or breast imaging prior to study registration. NOTE: ER, PR and HER2 status will be confirmed by central pathology review prior to randomization. ER and PR will be considered negative if ? 1% of cells stain weakly positive. HER2 will be considered negative if scored 0 or 1+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of < 2.0 or < 6 copies per cell.
Patient must have histologically confirmed (by routine hematoxylin and eosin [H&E] staining) estrogen receptor (ER)-negative invasive adenocarcinoma of the breast
Participants must have histologically or cytologically confirmed inoperable locally advanced or metastatic ER+ breast cancer; to fulfill the requirement for ER+ disease, a breast cancer must express, by immunohistochemistry (IHC), ER in >= 10% of cells, on the most recent biopsy; central confirmation of ER status is not required
ER/progesterone receptor (PR) determination is required; ER- and PR-assays should be performed by immunohistochemical methods according to the local institution standard protocol
Confirmed pathologic diagnosis of triple negative breast cancer (TNBC), OR estrogen receptor (ER) positive with immunohistochemistry (IHC) staining of 1-9%, irrespective of progesterone receptor (PR) staining, and human epidermal growth factor receptor (HER)2 negative, OR prior diagnosis of ER positive (>= 10%) (HER2 negative) breast cancer that is demonstrated to be ER < 10% on the patient’s most recent biopsy\r\n* NOTE: patients with a diagnosis of TNBC who are found to have ER or PR positive staining on any additional biopsies since diagnosis remain eligible
Tumors are positive for ER, PgR, or both
Patients with the following types of histologically documented solid tumors:\r\n* Estrogen receptor (ER) positive (+)/progesterone receptor (PR)+, ER+/PR negative (-), or ER-/PR+ breast cancer\r\n* Gynecologic tumors (endometrial, ovarian, uterine, fallopian tube, peritoneal, etc.)\r\n* Desmoid tumors\r\n* Tumors that are ER+ or PR+ by immunohistochemistry (including low-level expression) such as non-small cell lung, colorectal, and prostate
Patients enrolled based on tumor ER/PR status must have ER/PR status confirmed by the Laboratory of Pathology, National Institutes of Health (NIH); ER/PR status will be determined on a metastatic site, if possible; otherwise, the original site or available tissue will be acceptable
Patients must have tumors that demonstrate ER/PR+ (positivity by immunohistochemistry [IHC] staining >= 1%)
Invasive carcinoma should be ER alpha receptor positive
The invasive cancer must be estrogen receptor alpha (ER)-positive, with ER staining present in greater than 50% of invasive cancer cells by immunohistochemistry (IHC)
Estrogen receptor (ER)/progesterone receptor (PR) status (ER or PR defined as positive if >= 1%; ER/PR is defined as negative if 0%): \r\n* PHASE I: Patients may have ER/PR(+) or negative (-) breast cancer; ER(+) patients must have progression of disease following 1 prior line of endocrine therapy; progression of disease within 6 months of adjuvant endocrine therapy will be considered 1 line of prior endocrine therapy\r\n* PHASE II: Patients must have ER/PR(-) breast cancer
Tumors must express ER positivity by immunohistochemistry (ER expression >10% by immunohistochemistry).
Diagnosis of TNBC: < 1% cells positive for ER/progesterone receptor, and HER2 IHC score of 0 or 1, or FISH HER2+ ratio of less than 1.8; patients with low ER IHC (> 1% but < 10% cells positive), but negative by genomic assay are eligible
Patients who are ER+ and/or PR+ and who are receiving anti-hormone therapy for at least three months may continue to receive such therapy during the course of the trial
Patients must have histologically confirmed HR+ breast cancer; HR+ is defined as either ERa or PgR being positive, or both; positivity is defined for the purposes of this protocol as:\r\n* Allred >= 4\r\n* IHC 1+, 2+, 3+\r\n* Percentage of positive staining > 10%\r\n** When there is discrepancy between the metastatic and primary tumor results with respect to ERA or PgR status, the metastatic results will hold precedence; when there is discrepancy between the local and University of Wisconsin (UW) pathology results with respect to ER? or PgR status, the UW results will hold precedence
ER and/or PR-positive disease. Tumors must be HER-2/neu negative or equivocal.
Patients must be ER >= 1% and HER2 negative on local testing
Biopsy proven ER/PR positive tumor
Screen-detected, estrogen receptor (ER) positive DCIS of the breast proven on core needle biopsy, defined as 10% ER positive cells; the presence of a focus suspicious for microinvasion will be allowed; the size of the DCIS in the core biopsy sample must total 5 mm (multiple cores can be summed) and must be estimated on the deepest step section (if step sections are taken)
The study will be conducted in women who have been diagnosed with a first primary invasive estrogen receptor (ER) positive (+) breast cancer (stages I-IIIa) who are within the first 3 years post-treatment
The patient was proven to have TNBC, defined from standard pathologic assays as negative for ER and PR (< 10% tumor staining) and negative for HER2 (immunohistochemistry [IHC] score < 3, gene copy number not amplified)
HR (ER and/or PgR) positive disease based on local testing: ASCO/CAP guidelines should be utilized for assessing HR status.
Confirmed histologic diagnosis of operable HER2 overexpressing (ER < 10%, progesterone receptor [PR] < 10%, and HER2 2+ or fluorescence in situ hybridization [FISH] amplified) OR triple negative (ER < 10%, PR < 10%, and HER2 0/1+ or 2+/FISH not amplified) OR ER positive invasive ductal breast cancer, including Memorial Sloan Kettering Cancer Center (MSKCC) pathology confirmation
Histologically confirmed estrogen receptor positive (ER+) breast cancer either from a metastatic biopsy or from a primary breast tumor with imaging evidence of metastatic disease. The pathology report and either (1) tumor tissue (blocks or unstained slides) or (2) a photomicrograph of the ER immunohistochemistry (IHC) slide from at least one site of metastatic disease and/or from primary breast cancer must be available for review and analysis.
No or equivocal ER, PR or HER2 testing performed prior to surgery if biopsy indicates invasive cancer
Patient must have any one of the following types of breast cancer (primary or metastatic): estrogen receptor (ER)+/PgR+/human epidermal growth factor receptor 2 negative (HER2-) or ER+/PgR-/HER2-\r\n* ER+ is defined as Allred score of at least 4 and greater\r\n* PgR+ is defined as Allred score of at least 4 and greater\r\n* IHC is the primary assay methodology for HER2; HER2- refers to HER2 of 0, 1+ by IHC or negative by fluorescence in situ hybridization (FISH)
History of ER+ pathology (ER+ may be confirmed from surgery or biopsy of primary breast cancer or lymph nodes, and/or surgery or biopsy of a metastatic site, metastatic biopsy is not required)
Patients with histologic/immunochemical proof of estrogen receptor (ER)+ primary or metastatic malignancy (positive staining in >= 1% of cells by immunohistochemistry)
Patients who are to be treated with clinically approved or experimental regimens where ER has an important role
Breast cancer from ER+ primary that is seen on other imaging tests; tumor ER expression must have been confirmed by immunohistocytochemistry of primary tumor or recurrent disease
PHASE II: Women with a first primary ER+, HER2-, LN-, breast cancer < 3 cm immediately after their initial surgical consultation
Patients must have estrogen receptor (ER) positive, HER2 negative metastatic breast\n             cancer (MBC) with at least one non-irradiated distant site of metastasis.
Patients must have had estrogen receptor, progesterone receptor and HER2 status (by immunohistochemistry [IHC] and/or in situ hybridization [ISH]) evaluated on diagnostic core biopsy prior to start of neoadjuvant chemotherapy\r\n* Note: If HER2 status has not been clearly determined (i.e. equivocal/indeterminate), then patients should not be enrolled
Known estrogen, progesterone, and HER2 status of either primary tumor or metastasis; \r\n* Note: estrogen, progesterone and HER2 status of metastasis preferred for stratification
For Cohort E only: Patients must have histologically confirmed HER2+ (IHC 3+ and/or FISH positive [HER2/CEP17 >= 2 and/or > 6 HER2 gene copies per nucleus]) and hormone receptor positive (estrogen receptor [ER]+ and/or progesterone receptor [PR]+ >= 1%), metastatic breast cancer
Estrogen receptor positive (ER+) breast cancer patients must have received and progressed on fulvestrant and be post-menopausal
Participants with histologically or cytologically confirmed hormone receptor (HR)-positive, Her2-negative metastatic breast cancer; central confirmation of HR positivity is not required
Primary and/or metastatic breast tumor must be negative for over-expression of estrogen and progesterone receptors; patients with weak estrogen receptor and/or progesterone receptor expression (< 10% on immunohistochemistry [IHC]) will be eligible
Estrogen receptor positive, progesterone receptor positive, HER2 negative
Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (triple-negative breast cancer; TNBC);
Participant has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor (ER) positive breast cancer by local laboratory.
Biopsy proven neuroendocrine tumor, which is somatostatin receptor positive as demonstrated on somatostatin receptor PET\r\n* All sites or origin are eligible\r\n* Functional and nonfunctional tumors are allowed
Oral estrogen, progesterone, testosterone therapy within last 3 months
COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: Patients must have measurable disease, per RECIST 1.1
COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: HR+BC patients must have received prior treatment with at least 2 lines of hormonal treatment (selective estrogen receptor modulator [SERM], adriamycin-ifosfamide [AI], or fulvestrant) and deemed ineligible for further hormonal therapy; patients may have received prior chemotherapy and there is no limit to the number of prior chemotherapy
COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: Absolute neutrophil (ANC) >= 1,500/mm^3 (>= 1.5 X10^6/L)
COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: Platelet count >= 75,000/mm^3 (>= 75 X 10^6/L)
COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: Patients who have undergone radiotherapy within 4 weeks of first dose of study treatment
Any receptor status (estrogen receptor, progesterone receptor, HER2 receptor); patients who are hormone receptor (HR)+ should also no longer be candidates for hormonal-based therapy; patients who are HER2+ should have progressed on or no longer be candidates for available HER2 directed therapy; hormonal therapy must be stopped prior to day 1 of treatment
COHORT 2 (HORMONE RECEPTOR POSITIVE [HR+])
DISEASE SPECIFIC EXPANSION COHORTS: Breast cancers patients enrolled on this study must have:\r\n* Metastatic or advanced (incurable and unresectable) HER2 negative breast cancer regardless of estrogen receptor status (both hormone receptor positive and triple negative patients are eligible)\r\n* Received hormonal therapy, as appropriate based on their hormone receptor status; hormone receptor positive patients who have not received endocrine therapy for recurrent/metastatic disease are eligible, permitted their physician feels they are not appropriate for first line endocrine therapy, for example for high risk visceral metastatic disease
Tumor is hormone receptor (HR)+ (estrogen receptor and/or progesterone receptor positive with at least 10% expression of either receptor by local immunohistochemical staining) and HER2 negative based on local assessment
Patients can have hormone receptor (HR)+ or HR-negative disease
Breast cancer determined to be hormone receptor-positive or hormone receptor-negative defined as follows:\r\n*  Hormone receptor-positive: >= 10% staining by IHC for either estrogen receptor (ER) or progesterone receptor (PgR)\r\n* Hormone receptor-negative: < 10% staining by IHC for both ER and PgR
Locally advanced breast cancer defined as any of the following per American Joint Committee on Cancer (AJCC) staging criteria:\r\nNote: imaging methods that may be used for tumor measurement to determine eligibility include breast ultrasound and breast magnetic resonance imaging (MRI); mammography may not be used\r\n* T2 based on tumor measurements by physical examination or imaging with clinically positive regional lymph nodes (cN1 or cN2), irrespective of hormone receptor status\r\n* Hormone receptor-negative patients with tumor size of 3-5 cm measured by physical examination or imaging with clinically negative regional lymph nodes (cN0)\r\n* Any T3 based on tumor measurements by physical examination or imaging, irrespective of hormone receptor status\r\n* Any T4 (including inflammatory breast cancer), irrespective of hormone receptor status
Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
Estrogen receptor negative invasive breast carcinoma as defined as less than 10% stained cells
Estrogen Receptor-positive pathology
Documentation of estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive tumor (>= 1% positive stained cells) based on most recent tumor biopsy (unless bone-only disease, discuss with the Study Chair if results in different biopsies are discordant in terms of hormone receptor positivity) utilizing an assay consistent with local standards
Clinically node negative, hormone receptor positive (+). HER2 negative (-), with <25% intraductal component in the aggregate.
Estrogen and/or progesterone receptor positive
HER2-negative and hormone receptor-positive status (common breast cancer classification tests)
Have brain metastases secondary to hormone receptor positive breast cancer, NSCLC, or melanoma.
Has documented hormone (estrogen and/or progesterone) receptor (HR)-positive disease
Known hormone receptor status at the time of protocol registration; (Note: estrogen receptor [ER] and/or progesterone receptor [PgR] status are considered positive with a cut-off of >= 1% invasive tumor cells; status may be defined on the basis of historic results on the breast primary or a metastatic site, whichever is most recent; repeat biopsies are not required for participation in this protocol)
Subject has hormone-receptor positive metastatic breast cancer with disease progression following antiestrogen therapy
Estrogen receptor positive tumor and/or progesterone receptor positive tumor
Estrogen receptor negative and progesterone receptor negative tumor
DCIS must express estrogen and/or progesterone receptor, as determined by immunohistochemical methods on the diagnostic pathology sample, according to the local institution’s standard protocol; greater than or equal to 1% cells will be considered to be positive
Folate receptor alpha positive tumor expression as defined in the protocol
Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast cancer
Patients with advanced or metastatic breast cancer must have disease that is HER2-negative, estrogen receptor-negative, and progesterone receptor-negative (ie, TNBC). Patients with advanced or metastatic disease may have up to 4 lines of cytotoxic therapy. Neoadjuvant and adjuvant therapies are not counted towards lines of therapy.
Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive breast cancer by local laboratory and has HER2 negative breast cancer
Subject has received zero to one prior cytotoxic chemotherapy regimen for metastatic disease, regardless of prior targeted therapy (eg. everolimus, palbociclib or lapatinib), biologic (eg. trastuzumab) or hormonal therapy treatment (eg. aromatase inhibitors, selective estrogen receptor modulators, or estrogen receptor down-regulators).
Tumors must stain positive for estrogen receptor (>= 10%) by immunohistochemistry (IHC)
Estrogen receptor positive disease is defined as > 10% nuclear staining
Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory and has HER2-negative breast cancer.
Patients that are estrogen receptor positive (ER+) will take anti-estrogen therapy for treatment of their DCIS during vaccinations
Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer
Known hormone receptor status of the primary tumor
Known hormone receptor status (estrogen receptor and progesterone receptor)
Estrogen receptor and/or progesterone receptor positive disease
Estrogen and/or progesterone receptor positive breast cancer (> 10% staining), as determined by pathology from either primary or metastatic site(s); central confirmation is not required
Subject has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive breast cancer by local laboratory (based on most recently analyzed biopsy).
Patients with a hormone receptor-positive, HER2-negative invasive cancer that meets study criteria may have ductal carcinoma in situ in another quadrant of the same breast or in the contralateral breast even if the DCIS is hormone receptor-negative
Histologic proof of metastatic or locally advanced, unresectable breast cancer which is estrogen receptor positive and/or progesterone positive per institutional standards
Centrally determined HER2-positive, hormone receptor status, breast molecular subtype by Prediction Analysis of Microarray 50 (PAM50) on the pre-treatment biopsy of metastatic lesion obtained during screening
Postmenopausal, Hormone receptor positive (HR+), HER2 negative breast cancer
Metastatic breast cancer patients who are hormone receptor positive at baseline must be hormone refractory or have indications for emergent treatment with chemotherapy (e.g., visceral crisis)
Known hormone receptor status of the primary tumor
Pathological tumor-node-metastasis staging (Union for International Cancer Control-American Joint Committee on Cancer [UICC/AJCC] 7th edition): eligible participants must have either: Node-positive disease (pN more than or equal to [>/=] 1), any tumor size except T0, and any hormonal receptor status; or Node-negative disease (pN0) with pathologic tumor size >2.0 centimeters by standard local assessment and negative for estrogen receptor (ER) and progesterone receptor (PR) determined by a central pathology laboratory
Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
Patients with hormone receptor +/- and HER2 +/- breast cancer are eligible
Known hormone-receptor status
Estrogen and/or progesterone receptor positive breast cancer, as determined by pathology from either primary or metastatic site(s); central confirmation is not required
Hormone-receptor positive defined as estrogen receptor-positive and/or progesterone receptor-positive
Part G: Breast Cancer that is not only advanced and/or metastatic but also hormone receptor positive
Must have estrogen and/or progesterone receptor positive histologically confirmed adenocarcinoma of the breast; receptor status may be based on any time during treatment prior to study registration, and from any site (i.e. primary recurrent, or metastatic)
For invasive cancers, the tumor must be estrogen receptor positive (defined as 10% or greater expression of estrogen receptor)
Participants with hormone-receptor positive tumors must have failed available lines of hormonal therapy unless hormone therapy was not tolerated or not clinically appropriate
Unknown hormone-receptor status
Hormone receptor status\r\n* Estrogen or progesterone receptor positive or\r\n* Estrogen and progesterone receptor negative and clinical tumor size =< 1.0 cm
Estrogen receptor and progesterone receptor negative tumor with clinical size > 1 cm
Patient has a confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory and has HER2-negative breast cancer
Patient has estrogen-receptor and/or progesterone positive breast cancer as per local laboratory testing
Inoperable estrogen receptor positive and HER2 negative breast cancer.
Subjects with a primary tumor that is hormone (estrogen, progesterone, or both) receptor-positive or receptor-negative are eligible.
Group 2: Post-menopausal women with advanced stage estrogen receptor positive breast cancer who are candidates for exemestane or fulvestrant
Patients with estrogen receptor positive (ER+) breast cancer being treated with hormonal therapy (selective estrogen receptor modulator or aromatase inhibitor) who have rising tumor markers as evidence of disease progression or metastatic disease on scans may continue on hormonal therapy while being treated with vaccine
Patients with estrogen receptor (ER)+ breast cancer must have received prior treatment with at least one hormone therapy
Patients must have histologically or cytologically diagnosed locally advanced or metastatic triple-negative breast cancer defined as negative for estrogen receptor, progesterone receptor and HER2.
HER2 negative disease, and a known positive hormone receptor status (common breast cancer classification tests)
Patients with hormone receptor-positive disease must have progressed on or following hormone therapy
Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast cancer
Patients must have estrogen and/or progesterone receptor positive histologically confirmed stage I-III adenocarcinoma of the breast
PHASE I: Hormone receptor positive tumor defined as any positivity of estrogen or progesterone receptor
PHASE II: Hormone receptor positive tumor defined as any positivity of estrogen or progesterone receptor
Low grade disease positive for estrogen and progesterone receptors
Patients with a known hypersensitivity reaction to 5-HT3 receptor antagonists or NK1 receptor antagonists
Any receptor status
Stage I-III estrogen receptor positive breast cancer (positive for estrogen receptor [ER] with positivity defined as immunohistochemical staining in >= 10% of cells) on adjuvant hormonal therapy with aromatase inhibitors (anastrozole, letrozole or exemestane)
Folate receptor alpha positive tumor expression as defined in the protocol
Hormone receptor status not specified
Use of any chemopreventive agents (selective estrogen receptor modulators [SERM]) in the last 3 months
Prior diagnosis of stage 0 to III breast cancer that is estrogen receptor negative, progesterone receptor negative with completion of definitive surgery, radiation therapy and/or chemotherapy
Taken tamoxifen or other selective estrogen/progesterone receptor modulators (selective estrogen receptor modulators[SERMs]/selective progesterone receptor modulators [SPRMs]) within two years prior to entering study or been required to discontinue SERM therapy due to thromboembolic or uterine toxicity
Histologically confirmed advanced solid tumors with HR-positivity defined as > 1% on immunohistochemistry (estrogen receptor-positive with or without positivity for the progesterone receptor) and HER2/neu positivity (3+ on IHC and/or 2+ on IHC and FISH amplified, or by v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 [ERBB2] mutation on next generation sequencing)
Postmenopausal, Estrogen-receptor positive and/or Progesterone-receptor positive breast cancer
Estrogen receptor- or progesterone receptor-negative disease
Estrogen receptor positive breast cancer
Diagnosed with hormone receptor-positive breast cancer and prescribed endocrine hormonal treatment (EHT)
Patients must have a histologically confirmed diagnosis of invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2, for whom standard adjuvant endocrine therapy is planned; estrogen and progesterone receptor positivity must be assessed according to American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guidelines as either estrogen receptor (ER) or progesterone receptor (PR) >= 1% positive nuclear staining; HER-2 test result negativity must be assessed as per ASCO/CAP 2013 guidelines using immunohistochemistry (IHC), in situ hybridization (ISH) or both; HER-2 is negative if a single test (or all tests) performed in a tumor specimen show: a) IHC negative (0 or 1+) or b) ISH negative using single probe or dual probe (average HER-2 copy number < 4.0 signals per cell by single probe or HER-2/chromosome enumeration probe [CEP] ratio < 2.0 with an average copy number < 4.0 signals per cell by dual probe); if HER-2 IHC is 2+, evaluation for gene amplification (ISH) must be performed and the ISH must be negative; ISH is not required if IHC is 0 or 1+; HER-2 equivocal is not eligible
The tumor must have been determined to be human epidermal growth factor receptor 2 (HER2)-negative as follows:\r\n* Immunohistochemistry (IHC) 0-1+; or\r\n* IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to centromere enumerator probe 17 (CEP17) < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells; or\r\n* ISH non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells
Female and male patients must have histologically confirmed invasive breast cancer that meets the following criteria:\r\n* Clinical stage II-III (American Joint Committee on Cancer [AJCC] 7th edition) at diagnosis, based on initial evaluation by clinical examination and/or breast imaging; no metastatic disease allowed\r\n* ER- and PR- should meet one of the following criteria:\r\n** =< 10% cells stain positive, with weak intensity score (equivalent to Allred score =< 3)\r\n** =< 1% cells stain positive, with weak or intermediate intensity score (equivalent to Allred score =< 3)\r\n* HER2 negative (not eligible for anti-HER2 therapy) will be defined as:\r\n** Immunohistochemistry (IHC) 0, 1+ without in situ hybridization (ISH) HER2/neu chromosome 17 ratio OR\r\n** IHC 2+ and ISH HER2/neu chromosome 17 ratio non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells OR\r\n** ISH HER2/neu chromosome 17 ratio non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells without IHC\r\n** NOTE: patients that originally present with synchronous bilateral tumors are eligible provided both tumors are TNBC, and at least one of them fulfills the remainder eligibility criteria of the protocol; multifocal or multicentric breast cancers are eligible as long as all tumors fulfill eligibility criteria\r\n** NOTE: patients that have a discrepancy in ER/PR/HER2 status between original diagnosis and surgical specimen (only applicable if ER/PR/HER2 status were repeated; repeating it is not mandatory) are not eligible for study participation (i.e. ER/PR/HER2 has to fulfill above criteria in both scenarios)
Invasive breast cancer is human epidermal growth factor receptor 2 (HER2) negative; a patient is considered to have HER2 negative breast cancer if one of the following if one of the following applies: \r\n* 0 or 1+ by immunohistochemistry (IHC) and in situ hybridization (ISH) not done\r\n* 0 or 1+ by IHC or ISH ratio (HER2 gene copy/chromosome 17) < 2\r\n* 2+ by IHC and ISH ratio (HER2 gene copy/chromosome 17) < 2
Patients whose tumors have HER2 immunohistochemistry (IHC) 3+, in situ hybridization (ISH) >= 2.0, or average HER2 copy number >= 6.0 signals per cell are not eligible; receptor status may be based on any time during treatment prior to study randomization, and from any site (i.e. primary, recurrent, or metastatic)
Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that is one of the two following phenotypes:\r\n* TNBC defined as:\r\n** ER and PgR negative defined as immunohistochemistry (IHC) nuclear staining < 1%\r\n** HER2 negative (not eligible for anti-HER2 therapy) defined as:\r\n*** IHC 0, 1+ without in situ hybridization (ISH) OR \r\n*** IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells OR \r\n*** ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells (without IHC)\r\n* ER and/or PgR positive, HER2 negative breast cancer defined as:\r\n** ER and/or PgR positive defined as IHC nuclear staining >= 1%; AND\r\n** HER2 negative (not eligible for anti-HER2 therapy) defined as:\r\n*** IHC 0, 1+ without ISH OR\r\n*** IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells OR\r\n*** ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells (without IHC)
Primary tumors and/or metastatic lesions must demonstrate HER2-neu overexpression by immunohistochemistry (IHC 3+) or amplification by in situ hybridization based on the following:\r\n* Single-probe average HER2 copy number >= 6.0 signals/cell\r\n* Dual-probe HER2/chromosome enumeration probe 17 (CEP17) ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell\r\n* Dual-probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell\r\n* Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number > 6.0 signals/cell\r\nPatients may be estrogen and/or progesterone positive (>= 1%) or negative (< 1%); hormone receptor status will be a stratification factor
Evidence of HER2 positive metastatic breast cancer in either a primary or metastatic site, if 3+ by an immunohistochemistry (IHC) method defined as uniform membrane staining for HER2 in 10% or more of tumor cells or demonstrate HER2 gene amplification by an in situ hybridization (ISH) method (single probe, average HER2 copy number >= 6.0 signals/cell; dual probe HER2/chromosome enumeration probe [CEP] 17 ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell; dual probe HER2/CEP 17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell; and HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell) or amplified by fluorescence in situ hybridization (FISH) > 2.0; high average copy number of HER2 (>= 6.0 signals/cell) is considered positive regardless of the HER2/CEP17 ratio
Participants must NOT have HER2 positive status based on American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines defined as:\r\n* Immunohistochemistry (IHC) 3+ based on circumferential membrane staining that is complete, intense -AND/OR – \r\n* Fluorescence in situ hybridization (FISH) positive based on one of the three following criteria:\r\n** Single-probe average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/CEP17 ratio >= 2.0
Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0) from toxicities related to any prior treatments, unless adverse event(s) (AE[s]) are clinically nonsignificant and/or stable on supportive therapy:\r\n* Cohort 1: HER2-positive, defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines: \r\n** IHC 3+ based on circumferential membrane staining that is complete, intense OR\r\n** FISH positive based on one of the three following criteria:\r\n*** Single-probe average HER2 copy number >= 6.0 signals/cell; OR\r\n*** Dual-probe HER2/chromosome 17 centromere (CEP17) ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell; OR\r\n*** Dual-probe HER2/CEP17 ratio >= 2.0\r\n* Cohort 2: Hormone receptor positive (estrogen receptor [ER]-positive and/or progesterone receptor [PR]-positive, defined as >= 1% staining by immunohistochemistry) and HER2-negative\r\n* Cohort 3: Triple negative (ER-negative, PR-negative, HER2-negative)
Pathologically confirmed HER2-positive MBC by local laboratory with the following requirements: HER2 overexpressed or amplified (immunohistochemistry of 3+ or HER2 gene amplification by in situ hybridization with a ratio of HER2-gene signals to centromere 17 signals ? 2.0 or average HER2 copy number ? 6.0 signals/cells)
Single-probe average HER2 copy number < 4.0 signals/cell
Dual-probe HER2/CEP17 ratio < 2 with an average HER2 copy number < 4.0 signals/cell.
Metastatic triple negative breast cancer (TNBC), as defined by: \r\n* Estrogen receptor (ER) and progesterone receptor (PR) negative as defined as ER < 10% and PR < 10% by immunohistochemistry according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing\r\n* Human epidermal growth factor receptor 2 (HER2) non-amplified per ASCO/CAP guidelines, defined as: \r\n** immunohistochemistry (IHC) score 0/1+\r\n** IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells; or\r\n** ISH non-amplified with a ratio of HER2 to chromosome enumeration probe 17 (CEP17) < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells
Has confirmed HR+ and HER2 negative breast cancer with known metastatic disease. HR defined as positive if expression greater than 10% by immunohistochemistry (IHC). HER2 negative or non-amplified is determined by the current American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) criteria which are as follows: HER2 testing by IHC as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be performed. HER2 is positive if: i. IHC 3+ based on circumferential membrane staining that is a. complete, intense ii. ISH positive based on: a. single-probe average HER2 copy number >= 6.0 signals/cell. b. Dual-probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell c. Dual-probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell d. Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell.
COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: Patients must have histologically confirmed persistent or recurrent invasive metastatic hormone receptor positive, HER2 normal breast cancer for which standard curative measures do not exist or are no longer effective; hormone receptor positive is defined as estrogen receptor (ER) positive >= 10% by immunohistochemistry (IHC) and/or progesterone receptor (PR) positive >= 10% by IHC; HER2 will be considered negative per American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines (HER2 test result as negative if a single test (or both tests) performed show: 1) IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within >10% of the invasive tumor cells; 2) IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =< 10% of the invasive tumor cells; or 3) in situ hybridization (ISH) negative based on: a) single-probe average HER2 copy number < 4.0 signals/cell or b) dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell)and HER2 testing must have been performed in a laboratory accredited by the College of American Pathologists (CAP) or another accrediting entity
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Patients must have histologically or cytologically confirmed persistent or recurrent invasive, metastatic triple negative breast cancer (TNBC) for which standard curative measures do not exist or are no longer effective; TNBC, defined as ER negative (ER < 10%), PR negative (PR < 10%); HER2 will be considered negative per ASCO-CAP guidelines (HER2 test result as negative if a single test (or both tests) performed show: 1) IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of the invasive tumor cells; 2) IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =< 10% of the invasive tumor cells; or 3) ISH negative based on: a) single-probe average HER2 copy number < 4.0 signals/cell or b) dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell) and HER2 testing must have been performed in a laboratory accredited by the College of American Pathologists (CAP) or another accrediting entity
Hormone receptor positive (defined as estrogen receptor [ER] and/or progesterone receptor [PR] positive), HER2 negative breast cancer that is clinically staged II-III with no known metastatic disease. ER and/or PR defined as positive if expression > 10% by immunohistochemistry (IHC). HER2 negative or non-amplified as determined by the current American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) criteria which are as follows: HER2 testing by immunohistochemistry (IHC) as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be performed. HER2 is positive if: IHC 3+ based on circumferential membrane staining that is complete, intense ISH positive based on: 1) Single-probe average HER2 copy number >= 6.0 signals/cell, 2) Dual-probe HER2/CEP17 ratio >= 2.0; c,e with an average HER2 copy number >= 4.0 signals/cell, 3) Dual-probe HER2/CEP17 ratio >= 2.0; c,e with an average HER2 copy number < 4.0 signals/cell, 4) Dual-probe HER2/CEP17 ratio < 2.0; c,e with an average HER2 copy number >= 6.0 signals/cell
HER2 status confirmed positive by means of immunohistochemistry (IHC) or in situ hybridization (ISH) according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2013 guidelines; it is considered positive if scored as 3+ by an IHC method defined as uniform membrane staining for HER2 in 10% or more of tumor cells or demonstrate HER2 gene amplification by an ISH method (single probe, average HER2 copy number >= 6.0 signals/cell; dual probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell; dual probe HER2/chromosome enumeration probe (CEP)17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell; HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell)
Cohort 1: Phase 1b: subject must have HER2 + (regardless of hormonal receptor status) primary metastatic or locally advanced breast cancer (IBC or Non-IBC); HER2 positive status is defined as strongly positive (3+) staining score by immunohistochemistry (IHC), or gene amplification using fluorescence in situ hybridization (FISH), if performed; if IHC is equivocal (2+), assays using FISH require gene amplification based on recent American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guideline: dual-probe HER2/CEP17 ratio is >= 2.0 and/or an average HER2 copy number >= 6.0 signals/cell; IBC is determined by using international consensus criteria: onset: rapid onset of breast erythema, edema and/or peau d’orange, and/or warm breast, with/without an underlying breast mass; duration: history of such findings no more than 6 months; extent erythema occupying at least 1/3 of whole breast; pathology: pathologic confirmation of invasive carcinoma
Cohort 2 patient must have HER2-/HR+ stage III IBC; HER2 negative status, which determined by assays using IHC require negative (0 or 1+) staining score; if IHC is equivocal (2+) staining score, assays using FISH require the absence of gene amplification: dual-probe HER2/CEP17 ratio is < 2.0 and an average HER2 copy number < 4.0 signals/cell; if HER2 testing result is confirmed at M D Anderson Cancer Center (MDACC), it does not require centralized repeat testing; hormone receptor (HR) positivity is determined by estrogen receptor (ER) >= 10% and /or progesterone receptor (PR) >= 10% by IHC staining
Breast cancer determined to be HER2-negative per current American Society of Clinical Oncologists/College of American Pathologists (ASCO/CAP) HER2 guidelines (if immunohistochemistry [IHC] was performed, IHC 0 or 1+; if fluorescence in situ hybridization [FISH] or other in situ hybridization test, dual probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell)
Estrogen receptor (ER) and progesterone receptor (PR) expression both < 10% by immunohistochemistry (IHC) and human epidermal growth factor receptor 2 (HER2) negative or non-amplified as determined by the current American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) criteria which are as follows: HER2 testing by IHC as 0 or 1+; if HER2 is 2+, ISH (in situ hybridization) must be performed; HER2 is positive for gene amplification if: - IHC 3+ based on circumferential membrane staining that is complete, intense - ISH positive based on: \r\n* Single-probe average HER2 copy number >= 6.0 signals/cell\r\n* Dual-probe HER2/chromosome enumeration probe (CEP)17 ratio >= 2.0; with an average HER2 copy number >= 4.0 signals/cell\r\n* Dual-probe HER2/CEP17 ratio >= 2.0; with an average HER2 copy number < 4.0 signals/cell\r\n* Dual-probe HER2/CEP17 ratio < 2.0; with an average HER2 copy number >= 6.0 signals/cell
Hormone receptor positive and HER2 negative breast cancer; patients with HER2/neu positive tumors irrespective of their hormone receptor status will be excluded; at least 10% of tumor cell nuclei should be immunoreactive for hormone receptors (ER and/or PR) to be deemed eligible for the study; Her2/neu negative is defined as:\r\n* Immunohistochemistry (IHC) score of 0 (no staining is observed or membrane staining that is incomplete and is faint/barely perceptible and within =< 10% of tumor cells) OR\r\n* IHC score of 1 (incomplete membrane staining that is faint/barely perceptible and within < 10% of tumor cells) OR\r\n* Fluorescence in situ hybridization (FISH) HER2/chromosome enumeration probe 17 (CEP17) ratio of < 1.8 or average HER2 gene copy number of < 4 signals/nucleus for test systems without an internal control probe\r\n* Equivocal results for HER2/neu (defined as: IHC 2+ or FISH HER2/CEP17 ratio of 1.8-2.2 or average HER2 gene copy number 4-6 HER2 signals/nucleus for test systems without an internal control probe) should prompt reflex test (same specimen using an alternative method) or order a new test (new specimen if available, using IHC or FISH)
The tumor specimen obtained at the time of diagnosis of locally recurrent or metastatic disease must have been demonstrated to be HER2-positive based on central testing; HER2-positive is defined as HER2/chromosome enumeration probe 17 (CEP17) ratio >= 2.0 or >= 6 average HER2 copy number per cell by in situ hybridization (ISH) or IHC 3+ by current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines; sites must send biopsy specimens for central testing which have been determined to be HER2-positive or HER2-equivocal on local testing
HER2 negative in the primary or metastatic tumor tissue defined as:\r\n* Immunohistochemistry (IHC) grade 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =< 10% of the invasive tumor cell; OR\r\n* IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of the invasive tumor cell; OR\r\n* IHC grade 2+ staining intensity by means of IHC analysis with no gene amplification below; OR\r\n* No gene amplification on in situ hybridization (ISH) based on:\r\n** Single-probe average HER2 copy number < 4.0 signals/cell OR\r\n** Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell
The tumor must have been determined to be HER2-postive as follows:\r\n* Immunohistochemistry (IHC) 3+ or\r\n* In situ hybridization (ISH)-positive (defined by ratio of HER2 to circulating endothelial progenitors [CEP]17 >= 2.0 or HER2 gene copy number >= 6 per nucleus)
Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes) invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2 status; estrogen and progesterone receptor positivity must be assessed according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as either estrogen receptor (ER) or progesterone receptor (PR) >= 1% positive nuclear staining; HER-2 test result negativity must be assessed as per ASCO/CAP 2013 guidelines using immunohistochemistry (IHC), in situ hybridization (ISH) or both; HER-2 is negative if a single test (or all tests) performed in a tumor specimen show: a) IHC negative (0 or 1+) or b) ISH negative using single probe or dual probe (average HER-2 copy number < 4.0 signals per cell by single probe or HER-2/CEP ration < 2.0 with an average copy number < 4.0 signals per cell by dual probe); if HER-2 IHC is 2+, evaluation for gene amplification (ISH) must be performed and the ISH must be negative; ISH is not required if IHC is 0 or 1+; HER-2 equivocal is not eligible
HER-2 positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines, confirmed by central testing confirmed by central testing (NeoGenomics Laboratories): \r\n* Immunohistochemistry (IHC) 3+ based on circumferential membrane staining that is complete, intense AND/OR\r\n* FISH positive based on one of the three following criteria:\r\n** Single-probe average HER2 copy number >= 6.0 signals/cell OR\r\n** Dual-probe HER2/chromosome 17 centromere (CEP17) ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell OR\r\n** Dual-probe HER2/CEP17 ratio >= 2.0\r\n* NOTE: HER-2 status must be confirmed to be positive by central review prior to patient starting protocol therapy; patients previously having had HER2 testing at NeoGenomics Laboratories, Inc. (formerly Clarient Laboratories) do not need to undergo retesting for central confirmation of HER2 status; ductal carcinoma in situ (DCIS) components should not be counted in the determination of HER2 status
Documented HER2-negative tumor based on local testing on most recent tumor biopsy (immunohistochemistry score 0/1+ or negative by in situ hybridization HER2/CP17 ratio < 2 or for single probe assessment HER2 copy number < 4)
Invasive breast cancer must be HER2 negative; HER2 negative is defined as a single test or both tests used to determine HER2 status (in situ hybridization [ISH] and immunohistochemistry [IHC]) show:\r\n* IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of the invasive tumor cells\r\n* IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =< 10% of the invasive tumor cells\r\n* ISH single-probe average HER2 copy number < 4.0 signals/cell\r\n* ISH dual-probe HER2/chromosome 17 centromere probe (CEP17) ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell
HER2 negative, defined as 0-1+ by immunohistochemistry or fluorescence in situ hybridization (FISH)-negative (HER2 copy number < 6 and HER2/chromosome enumeration probe [CEP]17 ratio < 2.0); central confirmation is not required
HER2 positive breast cancer (3+ by immunohistochemistry or Her2 gene amplification by in situ hybridization with a ratio of HER2 gene signals to centromere 17 signals > 2.0 or average HER2 copy number > 6.0 signals/cell)
Participants must have invasive primary tumor or metastatic tissue confirmation of HER2-positive status, defined as presence of one or more of the following criteria: HER2-positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines\r\n* Immunohistochemistry (IHC) 3+ based on circumferential membrane staining that is complete, intense OR\r\n* Fluorescent in situ hybridization (FISH) positive based on one of the three following criteria:\r\n** Single-probe average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/chromosome 17 centromere (CEP17) ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/CEP17 ratio >= 2.0\r\n* Note: participants with a negative or equivocal overall result (FISH ratio of < 2.0 or =< 6.0 HER2 gene copies per nucleus) and IHC staining scores of 0, 1+, 2+ are not eligible for enrollment
HER-2 positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines, confirmed by central testing (Clarient laboratories [labs]):\r\n* IHC 3+ based on circumferential membrane staining that is complete, intense OR\r\n* Fluorescence in situ hybridization (FISH) positive based on one of the three following criteria:\r\n** Single-probe average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/chromosome 17 centromere (CEP17) ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/CEP17 ratio >= 2.0\r\n* NOTE: ductal carcinoma in situ (DCIS) components should not be counted in the determination of HER2 status\r\n* NOTE: HER-2 status must be confirmed to be positive by central review prior to patient starting protocol therapy; patients previously having had HER2 testing at Clarient Laboratories do not need to undergo retesting for central confirmation of HER2 status; a pathology report documenting testing at Clarient should be provided at time of patient registration
HER2-positive breast cancer, defined as by American Society of Clinical Oncology College of American Pathologists (ASCO CAP) 2013 guidelines\r\n* Immunohistochemistry (IHC) 3+ based on circumferential membrane staining that is complete, intense AND/OR\r\n* Fluorescence in situ hybridization (FISH) positive based on one of the following three criteria: \r\n** Single-probe average HER2 copy number >= 6.0 signals/cell OR\r\n** Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0signals/cell; OR \r\n** Dual-probe HER2/CEP17 ratio >= 2.0
Histologically proven diagnosis HER2-positive breast cancer; Her2-positive is defined as follows:\r\n* Validated immunohistochemistry (IHC) assay score of 3+ (defined as uniform, intense staining of > 30% of invasive tumor cells)\r\n* Average HER2 gene copy number of > 6\r\n* Gene amplified (HER2:D17Z1 ratio > 2.20)
Patients must have either:\r\n* Estrogen receptor (ER) negative/progesterone receptor (PR) negative (< 10% by immunohistochemistry [IHC] staining) and HER-2 negative breast cancer OR\r\n* ER negative/PR negative (< 10% by IHC staining) and HER-2 positive tumors\r\n* HER2 status will be determined per the 2013 American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines:\r\n** HER2 is considered positive if a) there is IHC 3+ staining or b) positive using either single probe in situ hybridization (ISH) or dual probe ISH\r\n** HER2 is considered negative if a) there is IHC 0 or 1+ staining or b) ISH negative using either single probe ISH or dual probe ISH\r\n* For patients enrolling after neoadjuvant therapy, the ER, PR, and HER2 markers are based on assessment prior to initiating neoadjuvant treatment
Clinical stage IV ER, PR, HER2 negative invasive mammary carcinoma, previously documented by histological analysis and that meets the following criteria:\r\n* HER2 negativity is defined as any of the following by local laboratory assessment: in-situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell), or IHC 0 or IHC 1+ (if more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the protocol chair to establish eligibility of the patient)\r\n* ER and PR negativity are defined as =< 10% of cells expressing hormonal receptors via IHC analysis
or c-MET amplification; FISH c-MET to chromosome 7 (CEP 7) ratio ? 2.2; NGS copy number variation ? 4
c-MET amplification; FISH c-MET to chromosome 7 (CEP 7) ratio ? 2.2; NGS copy number variation ? 4
Patients must have histologically documented unresectable stage III or IV triple negative breast cancer (TNBC) and a known BRCA 1/2 mutation present; TNBC patients must be Her-2 negative, estrogen receptor (ER) negative (defined as less than 3% ER by immunohistochemistry [IHC]) and progesterone receptor (PR) negative breast cancer (defined as less than 3% PR staining by IHC)
Newly diagnosed triple negative breast cancer (TNBC) clinical stage Ic, II, or III\r\n* Estrogen receptor (ER) and progesterone receptor (PR) < 10%\r\n* HER2 negative based on one of the following:\r\n** Immunohistochemistry (IHC) 0 or 1+\r\n** IHC 2+ and fluorescence in situ hybridization (FISH) negative\r\n** IHC 2+ and FISH equivocal and no indication for HER2 targeted therapy based on the treating investigators discretion (i.e., HER2: CEP17 ratio < 2.0 or HER2 total copy number < 6)
The following disease subtypes are eligible:\r\n* Triple negative disease (defined as estrogen receptor [ER] < 10%, progesterone receptor [PR] < 10%, HER2 negative)\r\n* Hormone receptor positive, HER2 negative disease with evidence of progression on at least two prior lines of hormone therapy\r\n* HER2 positive disease with evidence of disease progression on trastuzumab, pertuzumab, T-DM1 and oral tyrosine kinase inhibitor unless contraindicated with no other HER2 targeted therapy options available (patients in this category will be classified by ER status)\r\n** Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) methodology using standard criteria.\r\n** Cardiac function must be determined within 4 weeks of study entry to be >= institutional lower limit of normal (LLN) using echo or multigated acquisition scan (MUGA)
SAFETY RUN-IN: Hormone receptor status (ER and PR) both =< 5% by immunohistochemistry, and HER2 status confirmed by means of immunohistochemistry (with 0 or 1+ indicating negative status) or fluorescence in situ hybridization (with amplification ratio < 2.0 indicating negative status)
RANDOMIZED PHASE II CLINICAL TRIAL: Hormone receptor status (ER and PR) both =< 5% by immunohistochemistry, and HER2 status confirmed by means of immunohistochemistry (with 0 or 1+ indicating negative status) or fluorescence in situ hybridization (with amplification ratio < 2.0 indicating negative status)
Histologically confirmed triple negative breast cancer (estrogen receptor [ER] < 10%, progesterone receptor [PR] < 10%, Her2neu immunohistochemistry [IHC] 0 or 1 or fluorescence in situ hybridization [FISH]/in situ hybridization [ISH] negative)
Either the primary tumor and/or metastatic tumor must be triple-negative as defined below:\r\n* Hormone receptor status: the invasive tumor must be estrogen receptor (ER)- and progesterone receptor (PR)-negative, or staining present in < 1% by immunohistochemistry (IHC)\r\n* HER2 status: the invasive tumor must be human epidermal growth factor receptor 2 negative (HER2-negative) by the American Society of Clinical Oncology College of American Pathologists (ASCO CAP) guidelines\r\n* Note: In cases where both primary tumor and metastatic sample(s) have been tested for ER, PR, and HER2, the triple-negative status of the most recent sample should be used
<1% staining by immunohistochemistry (IHC) for estrogen (ER) and progesterone (PR) receptors, 0 or 1+ IHC for human epidermal growth factor receptor 2 (HER2), OR
Either the primary invasive tumor and/or the metastasis must be triple-negative, defined as:\r\n* Hormone-receptor poor, estrogen receptor (ER)- and progesterone receptor (PR)-negative, or staining present in < 1% by immunohistochemistry (IHC)\r\n* HER2-negative: 0 or 1+ by IHC, or fluorescence in situ hybridization (FISH) < 2.0
All patients must have one of the following pathologically documented recurrent tumor types with FRalpha positivity by the Ventana immunohistochemistry (IHC):\r\n* Ovarian, primary peritoneal, fallopian tube (with exclusion of low grade, clear cell or sarcomatoid histologies for ovarian cancer) >= 25% of tumor staining >= 2+ intensity\r\n* Endometrial >= 25% of tumor staining >= 2+ intensity\r\n* TNBC confirmed by medical history of HER2-negative (confirmed by IHC 0, 1+ regardless of fluorescence in situ hybridization [FISH] ratio; IHC 2+ with FISH ratio < 2.0 or HER2 gene copy < 6.0; FISH ratio of 0, indicating gene deletion; when positive and negative in situ hybridization controls are present); estrogen receptor (ER) negative (confirmed as ER expression =< 1% positive tumor nuclei); progesterone receptor (PR) negative (confirmed as PR expression =< 1% positive tumor nuclei): >= 25% of tumor staining >= 1+ intensity
Triple-negative breast cancer (defined as estrogen receptor [ER] and progesterone receptor [PR] < 10% positive; HER2 0-1+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] ratio < 2.0)
Clinical stage IV invasive mammary carcinoma or unresectable locoregional recurrence of invasive mammary carcinoma that is:\r\n* ER/progesterone receptor (PR)-positive (> 1% cells) by immunohistochemistry (IHC) and HER2 negative per American Society of Clinical Oncology (ASCO) guidelines (by IHC or fluorescence in situ hybridization [FISH])\r\n* Previously exposed to an aromatase inhibitor (AI) or a selective estrogen-receptor modulator/ downregulator (SERM; SERD) + a CDK4/6 inhibitor\r\n* Appropriate candidates for chemotherapy\r\n* Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria that has not been previously irradiated and which can be followed by computed tomography (CT) or magnetic resonance imaging (MRI).\r\n* Amenable to biopsy at the time of study entry.
Core biopsy proven estrogen negative (< 1%), progesterone negative (< 1%), and HER2-neu negative (+1 by immunohistochemistry and/or fluorescence in situ hybridization [FISH] ratio < 2.0) invasive breast cancer
Either the primary tumor and/or metastatic tumor must be triple-negative as defined below:\r\n* Hormone receptor status: the invasive tumor must be estrogen receptor (ER)- and progesterone receptor (PR) negative, or staining present in < 1% by immunohistochemistry (IHC)\r\n* HER2 status: the invasive tumor must be human epidermal growth factor receptor 2 negative (HER2-negative) by the American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines\r\n* In cases where both primary tumor and metastatic sample(s) have been tested for ER, PR, and HER2, then the triple-negative status of the tumor should be determined from the most recent sample available
Confirmed invasive triple-negative breast cancer defined as estrogen receptor (ER) < 10%; progesterone receptor (PR) < 10% by immunohistochemistry (IHC) and HER2 0-1+ by IHC or 2+, fluorescence in situ hybridization (FISH) < 2, gene copy number < 4
Patients must have histologically confirmed, metastatic or unresectable malignancy of the following types: (a) non-small cell lung cancer (NSCLC), (b) triple-negative breast cancer (TNBC; defined by estrogen receptor [ER] < 1%, progesterone receptor [PR] < 1% and HER2 1+ or less by immunohistochemistry [IHC]; if HER-2 expression is 2+, a negative fluorescence in situ hybridization [FISH] testing is required) (c) pancreatic adenocarcinoma (PDAC), or (d) small cell lung cancer (SCLC)
Histological confirmation of triple negative breast cancer defined as:\r\n* Her2/neu by fluorescence in situ hybridization (FISH) (ratio =< 1.8) or immunohistochemistry (IHC) (0 or 1+)\r\n* Estrogen receptor (ER) and progesterone receptor (PR) expression < 10%
Histologically proven invasive breast carcinoma with triple negative receptor status (estrogen receptor, progesterone receptor and HER2 negative by immunohistochemistry [IHC] and/or fluorescence in situ hybridization [FISH]); patients who are weekly positive for the estrogen or progesterone receptor (i.e. =< 10%) are eligible
HER2 positive (immunohistochemistry [IHC] 3+ and or fluorescence in situ hybridization [FISH] amplified) or triple receptor negative (triple negative [TN], estrogen receptor [ER]/progesterone receptor [PR] < 10% HER2 negative [IHC 1+ or 2+ FISH non-amplified]) receiving any standard routine clinical NST regimen
New diagnosis of invasive cyclin D1 +, estrogen receptor (ER)+, progesterone receptor (PR) +/-, Her2- breast cancer\r\n* Cyclin D1 positive as defined as a total immunohistochemical score of 5 or greater\r\n* Hormone receptor positive as defined as >= 10% positive stained cells\r\n* HER2-normal (immunohistochemistry [IHC] score 0-1 or fluorescence in situ hybridization [FISH] negative [in-situ hybridization (ISH) ratio =< 2.0 status])
Patients must have histologically or cytologically confirmed clinical stage T2-3 N0-2 triple negative (estrogen receptor/progesterone receptor < 1% HER2 0-1 by immunohistochemistry [IHC] or unamplified by fluorescence in situ hybridization [FISH]) invasive ductal carcinoma
Patients must have histologically or cytologically confirmed stage I-III triple negative breast cancer\r\n* Estrogen receptor (ER) and progesterone receptor (PR) must be < 10% by standard assay methods\r\n* Human epidermal growth factor receptor 2 (HER2) must be either 0, 1+ by immunohistochemistry (if 2+, in situ hybridization method used to define HER2) OR have HER2: 17 centromere signal of < 2.0 using a standard in situ hybridization method
INCLUSION CRITERIA FOR TNBC: Histologically confirmed diagnosis of metastatic TNBC; i.e. breast cancer that is estrogen receptor (ER) negative (=< 10%), progesterone receptor (PR) negative (=< 10%), and human epidermal growth factor receptor 2 (HER2) negative (0 or 1+ by immunohistochemistry or negative for gene amplification by fluorescence in situ hybridization [FISH])
Patients must have triple-negative breast cancer defined as estrogen receptor (ER) < 10%; progesterone receptor (PR) < 10% by immunohistochemistry (IHC) and human epidermal growth factor receptor 2 (HER2) 0-1+ by IHC or 2+, fluorescence in situ hybridization (FISH) non-amplified
Clinical stage IV invasive mammary carcinoma that is estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) negative (triple negative) previously documented by conventional methods (immunohistochemistry [ISH], fluorescence in situ hybridization [FISH]); ER negative is defined as expression of ER in =< 5% cells, PR negative is defined as expression of PR in =< 5% cells, HER2 negative (acceptable methods of HER2 analysis include IHC [0, 1+], fluorescence in situ hybridization [FISH] with HER2/chromosome 17 centromere [CEN-17] ratio < 2, and/or chromogenic in situ hybridization [CISH] with HER2/CEN-17 ratio < 2), as previously documented by histological analysis
Triple-negative breast cancer defined as estrogen receptor (ER) < 10%; progesterone receptor (PR) < 10% by immunohistochemistry (IHC) and human epidermal growth factor receptor 2 (HER2) 0-1 positive (+) by IHC or 2+, fluorescence in situ hybridization (FISH) < 2, gene copy number < 4
Patients must have a histologically documented (either primary or metastatic site) diagnosis of breast cancer that is HER2 non-overexpressing by immunohistochemistry, namely 0 or 1; if they have an equivocal immunohistochemistry, 2, the tumor must be non-gene amplified by fluorescence in situ hybridization (FISH) performed upon the primary tumor or metastatic lesion (ratio < 2 and HER2 copy number < 4); estrogen receptor (ER) positivity is defined as 1% or greater; progesterone receptor (PR) positivity will be defined as a result of greater than 10%; documentation of ER and PR status should be available at registration; the expansion cohort will only include HER2-negative, ER and PR-negative patients
Stage 1, 2 or 3 invasive breast cancer which is triple negative; triple negative breast cancer is defined as estrogen receptor (ER) < 1%, progesterone receptor (PR) < 1% and HER2 0 or 1+ or fluorescence in situ hybridization (FISH) not amplified if IHC 2+
Confirmed invasive triple-negative breast cancer defined as estrogen receptor (ER) < 10%; progesterone receptor (PR) < 10% by immunohistochemistry (IHC) and human epidermal growth factor receptor 2 (HER2) 0-1+ (by IHC), or 2+ (fluorescence in situ hybridization [FISH] < 2, gene copy number < 4)
Estrogen receptor negative - defined as less than or equal to 5% staining by immunohistochemistry (IHC)
Progesterone receptor negative - defined as less than or equal to 5% staining by IHC
Histologically documented metastatic or locally advanced unresectable breast cancer that is estrogen receptor (ER) and progesterone receptor (PR) < 10% expression and does not over-express HER2 protein (immunohistochemistry [IHC] 0, 1+, or 2+ and fluorescence in situ hybridization [FISH] < 2.0)
Must have histologically or cytologically confirmed triple negative (estrogen receptor [ER]-/progesterone receptor [PR]-/HER2-) or estrogen poor invasive breast cancer\r\n* NOTE: ER and PR negative or estrogen poor is defined as any one of the following:\r\n** Local pathology report classifies them as negative\r\n** Allred score of 2 or below for ER and PR\r\n** < 5% weakly positive staining for ER and PR\r\n* NOTE: HER2- is defined as follows: \r\n** HER2 will be considered negative if scored 0 or 1+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of < 2.0 or < 6 copies per cell
Estrogen receptor negative – defined as less than 1% staining by immunohistochemistry (IHC)
TNBC defined as ER and PR negative (<1%) and HER-2 negative (FISH negative or IHC 0-1+)
Patients must have known estrogen receptor (ER), progesterone receptor (PR), and HER2 status defined as triple-negative breast cancer (TNBC), defined as:\r\n* ER and PR =< 10% by immunohistochemistry, and HER2-negative (as per American Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] guidelines, defined as immunohistochemistry [IHC] 0 or 1+, or fluorescence in situ hybridization [FISH] ratio < 2.0 or HER2 copy number < 6.0)
Clinical stage operable I, II or III invasive mammary carcinoma, which is estrogen receptor (ER)-positive by immunohistochemistry (IHC) and human epidermal growth factor receptor 2 (Her2)-negative by Hercep test (0 or 1+) or not overexpressed by fluorescent in situ hybridization (FISH)
Estrogen receptor (ER) and progesterone receptor (PR) negative; defined as ER =< 10% and PR =< 10% staining by immunohistochemistry (IHC)
PSTAT3 SCREENING: Patients must have known estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status defined as either:\r\n* Triple-negative breast cancer, defined as: ER and PR < 10% by immunohistochemistry, and HER2-negative (defined as IHC 0 or 1+, or fluorescent in situ hybridization [FISH] ratio < 2.0) (Note, in patients who have ER, PR, HER2 results available on both primary and metastatic biopsy, results of the metastatic biopsy should take precedence in defining tumor phenotype)\r\n* Or, inflammatory breast cancer with any ER, PR, HER2 status
Histologically proven HER-2 negative breast cancer (HER-2 negative defined as HER immunohistochemistry [IHC] 0 or 1+ and/or HER-2 fluorescence in situ hybridization [FISH] negative); HER-2 negative breast cancer includes hormone positive (estrogen receptor [ER] and/or progesterone receptor [PR] positive) breast cancer and triple negative breast cancer (TNBC)
Have histologically confirmed invasive breast cancer that is estrogen receptor (ER) negative (=< 10%), progesterone receptor (PR) negative (=< 10%) and human epidermal growth factor receptor 2 (HER2) normal (=< 10% of cells) by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
Tumor must be human epidermal growth factor receptor 2 (HER-2-neu) negative (defined as 0 or 1+ staining by immunohistochemistry or gene amplification ratio =< 2.0, by fluorescent in situ hybridization [FISH]), estrogen and progesterone receptors negative (< 1%); patients with BRCA 1 or 2 mutations will NOT be included
Patients must have histologically-confirmed unresectable, locally advanced or metastatic breast cancer that meets one of the following:\r\n* Triple negative, defined as estrogen receptor (ER) negative, progesterone receptor (PR) negative, human epidermal growth factor receptor 2 (HER2) negative; HER2 negative defined as immunohistochemistry (IHC) 0 or 1+ or fluorescence in situ hybridization (FISH) negative\r\n* Her2- negative hormone-refractory breast cancer which denotes progression on one or more endocrine therapies (e.g., tamoxifen, aromatase inhibitors, fulvestrant) unless contraindicated
Subject must have histologically confirmed stage IV TNBC (estrogen receptor [ER]-, progesterone receptor [PR]-, HER2-negative) and have received at least 1 prior line of systemic therapy\r\n* ER- and PR-negative: defined as < 1% staining by immunohistochemistry (IHC)\r\n* HER2-negative disease, defined as IHC 0-1+ or fluorescence in situ hybridization (FISH) ratio < 2.0
Histologically or cytologically-confirmed triple-negative breast cancer (TNBC) (defined as estrogen receptor [ER] < 1%, progesterone receptor [PR] < 1%, human epidermal growth factor receptor 2 [her-2]-neu 0-1+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH]-negative or as per doctor of medicine [MD] discretion) at each enrolling institution
PHASE II: Patients must have known estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status defined as triple-negative breast cancer (TNBC), defined as:\r\n* ER and PR =< 10% by immunohistochemistry, and HER2-negative (defined as immunohistochemistry [IHC] 0 or 1+, or fluorescent in situ hybridization [FISH] ratio < 2.0)
Non-metastatic, histologically or cytologically-confirmed triple negative breast cancer (TNBC) (defined as estrogen receptor [ER] <1%, progesterone receptor [PR] <1%, her-2-neu 0-1+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH]-negative or as per doctor of medicine [MD] discretion).
Patients may have hormone receptor positive or hormone receptor negative HER2-negative disease; hormone receptor positivity (estrogen receptor [ER] and/or progesterone receptor [PR]) is defined by at least 1% of positive tumor cells in the sample by immunohistochemistry (IHC); “triple negative” is defined by the lack of estrogen and progesterone receptor and by HER2-negative status; HER2-negative disease can be determined by fluorescent in situ hybridization (FISH) or IHC; negativity by IHC is defined as scores of 0 or 1+; borderline IHC results (i.e., 2+) should undergo FISH testing; subjects with an HER2 FISH ratio =< 2.0 are eligible
Histologically confirmed adenocarcinoma of the breast with the following markers: estrogen receptor negative (< 1%), progesterone receptor negative (< 1%), and human epidermal growth factor receptor (Her)-2/neu negative (Her-2/neu 0-1+ immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] ratio < 1.8 or average HER2 gene copy number of < four signal/nucleus for test systems without internal control probe) or breast adenocarcinoma identified as basal-like subtype on molecular testing
Clinical stage IV invasive mammary carcinoma, estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive by immunohistochemistry (IHC); patients with HER2 fluorescence in-situ hybridization (FISH) ratio < 2 (IHC 3+ is acceptable) will be enrolled in the ER+ / HER2-non-amplified cohort of patients; patients with HER2 FISH ratio >= 2 will be enrolled in the ER+ / HER2-amplified cohort of patients; patients may have either measurable or non-measurable disease, both are allowed
Patients enrolling on the phase II portion of this trial must have estrogen receptor (ER), progesterone receptor (PR) and HER2 negative disease defined as less than 10% staining for ER and PR, and HER2 0-1+ by immunohistochemistry (IHC), or 2+ by IHC and no evidence of amplification by fluorescence in situ hybridization (FISH) using local laboratory testing
For TNBC Subjects: Have histologically or cytologically confirmed diagnosis of metastatic (Stage IV) TNBC, and irrespective of PD-L1 status. TNBC is defined as negative immunohistochemistry (IHC) assays for Estrogen Receptor (ER), and Progesterone Receptor (PR), and HER2 negative (IHC 0 or 1+, or 2+ by IHC confirmed negative by FISH)
TNBC confirmed by medical history as: human epidermal growth factor receptor 2 [HER2]-negative (confirmed by IHC 0, 1+ regardless of fluorescence in situ hybridization [FISH] ratio; IHC 2+ with FISH ratio lower than 2.0 or HER2 gene copy less than 6.0; FISH ratio of 0, indicating gene deletion, when positive and negative in situ hybridization [ISH] controls are present); estrogen receptor (ER) negative (confirmed as ER expression less than or equal to 1% positive tumor nuclei); progesterone receptor negative (confirmed as progesterone receptor expression less than or equal to 1% positive tumor nuclei)
Patients with 1) stage IV metastatic triple negative breast cancer (triple negative is defined as estrogen receptor [ER] and progesterone receptor [PgR] status is < 1% of tumor cell nuclei are immunoreactive for ER or PgR, and HER2 status is fluorescence in situ hybridization [FISH] negative or immunohistochemistry [IHC] 0 or 1+), or 2) stage IV HR+ HER2- (HR+) breast cancer (defined as ER or PgR > 1% of tumor cell nuclei are immunoreactive for ER or PgR and HER2 status is FISH negative or IHC 0 or 1+)
Patients with histologically confirmed invasive breast cancer that is: triple negative (estrogen receptor [ER] < 10%, progesterone receptor [PR] < 10%, and human epidermal growth factor receptor 2 (HER2) 0/1+ or 2+/fluorescence in situ hybridization [FISH] not amplified)
Estrogen receptor (ER) and progesterone receptor negative (a tumor is ER and/or progesterone receptor positive if at least 1 percent (%) of the cells examined have estrogen and/or progesterone receptors) and human epidermal growth factor receptor 2 (HER2) negative (defined as immunohistochemistry [IHC] less than (<) 2+ or fluorescence in situ hybridization [FISH] negative).
Patients with stage II-III breast cancer that is HER2-negative by immunohistochemistry (IHC) (0-2+) or fluorescence in situ hybridization (FISH) (HER2/chromosome enumeration probe [CEP]17 amplification ratio < 2.0) who have completed “third generation” neoadjuvant chemoT and planned local treatment (surgery and radiation if indicated); estrogen receptor (ER) or progesterone receptor (PR) status can be ER negative (=< 10% by IHC) or PR negative (=< 10% by IHC)
Histological confirmation of triple negative breast cancer (TNBC) on outside or Duke University Health System (DUHS) biopsy report based on diagnostic biopsy and defined as:\r\n* Estrogen receptor negative (ER-) and progesterone receptor (PR)-negative: < 10% staining by immunohistochemistry (IHC)\r\n* HER2-negative disease, defined as IHC 0-1+ or non-amplified fluorescence in situ hybridization (FISH < 2.0)
Histologically confirmed adenocarcinoma of the breast, with sufficient tissue available for estrogen receptor (ER), progesterone receptor (PR), and HER 2 testing\r\n* HER2 must be positive by immunohistochemistry (IHC) or in situ hybridization (ISH) testing by laboratory standard.
Invasive breast cancer must be estrogen receptor (ER)/progesterone receptor (PR)-negative (defined as less than 10% positivity by immunohistochemistry [IHC]), and human epidermal growth factor 2 (Her2)-negative; if breast cancer is Her2 2+ by IHC, then fluorescence in situ hybridization (FISH) must be negative for Her2 gene amplification
Pre-treatment biopsy with the following characteristics:\r\n* Hormone receptor-positive cancer as defined as estrogen receptor (ER) and/or progesterone receptor (PR)-positive by standard immunohistochemistry (IHC)\r\n* Human epidermal growth factor receptor 2 (HER2)-negative (HER2 =< 2 by IHC; if HER2 2+ by IHC must be fluorescence in situ hybridization [FISH] non-amplified)\r\n* Recurrence score >= 25 using Oncotype DX 21-gene assay
Patients must have histologically confirmed operable triple negative breast cancer\r\n* Estrogen receptor (ER) and progesterone receptor (PR) expression must be < 1%\r\n* HER2 must negative as shown be either 0 or 1+ by immunohistochemistry (if 2+, in situ hybridization method used to define HER2) OR by a HER2: 17 centromere signal of < 2.0 using a standard in situ hybridization method
Primary tumor must be triple negative breast cancer (i.e., the invasive tumor must be estrogen receptor [ER]-negative and progesterone receptor [PR]-negative, or stain < 10% by immunohistochemistry [IHC]; the invasive tumor must be HER2-negative, defined as 0 or 1+ by IHC or fluorescent in situ hybridization [FISH] < 2.0)
The patient has proven TNBC, defined by standard pathologic assays as negative for estrogen receptor (ER) and progesterone receptor (PR) (< 10% tumor staining) and negative for human epidermal growth factor 2 (HER2) (immunohistochemistry [IHC] score < 3, gene copy number not amplified)
Histologically-confirmed invasive triple negative breast cancer (estrogen receptor [ER] < 1%, progesterone receptor [PR] < 1%, human epidermal growth factor receptor 2 [her-2-neu] 0-1+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH]-negative) or as determined by Doctor of Medicine (MD) discretion
Histologically confirmed TNBC (i.e., estrogen receptor [ER] negative, progesterone receptor [PR] negative (each < 10% staining by immunohistochemistry) and human epidermal growth factor receptor 2 (Her2) negative (0-1+ or fluorescent in situ hybridization [FISH] nonamplified; by clinical assay on primary tumor)
Patients must have estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) non-expressing breast cancer defined as:\r\n* < 1% of tumor nuclei that are immunoreactive for ER and PR\r\n* Fluorescence in situ hybridization (FISH) ratio of less than 2.0 or immunohistochemistry (IHC) staining of 0 or 1+