Stage: clinical T1 >= 1.0 cm, T2 or T3, N0-3, M0; participants with multicentric or bilateral disease are eligible if at least one lesion meets stage eligibility criteria for the study (i.e., >= 1.0 cm operable breast cancer) and no tumor is human epidermal growth factor receptor 2 (HER2)-positive (3+ by immunohistochemistry [IHC] or in situ hybridization [ISH] amplified >= 2.0); in this circumstance, the investigator must determine which will represent the target lesion to be assessed for response; this should remain consistent throughout the study; the target lesion should be selected on the basis of its size (lesion with the longest diameter) and suitability for accurate repetitive measurements
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
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
ER(+) and/or PR(+) by IHC (? 10% staining or Allred score ? 4)
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
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
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
Histologic documentation of women or men with node positive, HER2 negative, anatomic stage II or III breast carcinoma and high risk node negative (defined as estrogen receptor [ER] and progesterone receptor [PR] negative and tumor size > 2 cm) within one year of diagnosis and free of recurrence; patients with pN1mic are eligible; if neoadjuvant therapy was received, either initial clinical stage (determined by physical and or radiologic examination) or post-operative pathologic stage can be used for eligibility purposes, with the higher stage determining eligibility; histologic documentation of node positivity is required; bilateral breast cancers are allowed, as long as both cancers are HER2 negative and at least one of the cancers meets eligibility
Any ER/progesterone receptor (PgR) status allowed
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
The tumor must have estrogen receptor (ER)-and progesterone receptor (PgR)-status assessed using current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines; patients are eligible if the tumor staining meets one of the following criteria:\r\n* ER-negative and PgR- negative by ASCO/CAP guidelines, OR\r\n* ER or PgR stains are positive in 1-9% of cells and neither is positive in >= 10% of cells
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
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)
Patients must also meet at least one of the following criteria:\r\n* Triple negative: histologically confirmed primary and/or metastatic site that is estrogen receptor (ER)-negative (=< 1%), progesterone receptor (PR)-negative (=< 1%), and HER2–negative\r\n* BRCA mutation: previously confirmed deleterious breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) germline mutation or suspected deleterious BRCA1 or BRCA2 germline mutation if the classification being used is the 5-tier classification; documentation of germline test results are required
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
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
Tumor ER Allred score between 0-5 or HER2 positive by IHC (3+) or amplified by FISH > 2.0
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)
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)
Patients must have had estrogen receptor (ER) analysis performed on the primary breast tumor before neoadjuvant therapy according to current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing; if negative for ER, assessment of progesterone receptor (PgR) must also be performed according to current ASCO/CAP guideline recommendations for hormone receptor testing
Patients must have had HER2 testing performed on the primary breast tumor before neoadjuvant chemotherapy according to the current ASCO/CAP guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer; patients who have a primary tumor that is either HER2-positive or HER2-negative are eligible
* 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
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)
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
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)
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)
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
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
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
Oestrogen receptor, progesterone receptor and HER2 negative advanced adenocarcinoma of breast. Parts A, B or D1 (solid malignancies) - Consented provision of formalin fixed paraffin embedded blocks/ slides from most recent tissue sample. Part C (all patients):
No prior anti-epidermal growth factor (EGF) or anti-human epidermal growth factor receptor 2 (HER2) therapy
Known positivity for HER2 (as defined by a positive IHC test of 3+ or IHC of 2_ with fluorescent in situ hybridization [FISH])
Estrogen receptor positive (ER+) breast cancer patients must have received and progressed on fulvestrant and be post-menopausal
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
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
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Hormone receptor (HR)-positive, HER2-negative metastatic breast cancer according to ASCO CAP guidelines
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Hormone receptor (HR)-positive, HER2-negative metastatic breast cancer according to ASCO CAP guidelines
Only for the 1L Cohort: human epidermal growth factor receptor 2 (HER2)-negative tumors;
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
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)
Either the primary tumor and/or the metastasis must have been tested for estrogen receptor (ER), progesterone receptor (PR) and HER2; patient must have HER2+ breast cancer per American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines 2013
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
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])
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)
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: Women diagnosed with pathologically confirmed triple negative invasive breast cancer, metastatic (locally confirmed immunophenotype negative for all three receptors ER, PR, HER2)
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)
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)
Participants must have histologically confirmed invasive breast cancer, with locally advanced or metastatic disease; patients without pathologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation; for subjects in Cohort C, the tumor must also be hormone receptor positive, defined as demonstrating at least 1% tumor cell nuclei staining positive for either ER or progesterone receptor (PR)
The primary tumor, and/or metastasis must have been tested for ER, PR and HER 2, and be HER2 positive as defined by the 2013 American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines
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
Breast cancer must be estrogen receptor (ER)-negative, and HER-2 negative according to College of American Pathologists (CAP)/American Society of Clinical Oncology (ASCO) biomarkers testing guidelines; tumors may be progesterone receptor (PgR) positive with an Allred score of less than 5
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)
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
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
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)
Histologically or cytologically confirmed invasive breast cancer of the following subtype:\r\n* TRIPLE NEGATIVE (estrogen receptor [ER]-negative, progesterone receptor [PR]-negative, and HER2-negative disease); triple-negative patients will be defined per American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines\r\n* HER2-POSITIVE: HER2-positive patients will be defined per ASCO-CAP guidelines\r\n* HORMONE REFRACTORY: patients with ER/PR-positive disease according to ASCO-CAP guidelines above may be considered if they have disease progression after two lines of hormonal therapy (administered in the adjuvant or metastatic setting), or are deemed clinically hormone-resistant taking into consideration the rate of progression of disease or a short interval of time on first line hormonal therapy before progression; clinically hormone resistant patients MUST also be discussed with the Study Chair, Study co-Chair (Roisin Connolly, MBBCh), or designee in advance for approval\r\n** NOTE: ASCO-CAP guidelines state that ER and PR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls; HER2-positive is defined as HER2 immunohistochemistry (IHC) 3+, in situ hybridization (ISH) >= 2.0, or average HER2 copy number >= 6.0 signals\r\n** NOTE: a patient who has a change in receptor status (e.g. PR negative to positive) may be stratified as triple negative or hormone positive, contrary to the most recent receptor testing, for the purposes of the study, based upon the clinical course at the discretion of the Study Chair, Study co-Chair (Roisin Connolly, MBBCh), or designee in advance for approval
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)
Hormone receptor (HR) status of the invasive component must be documented before trial enrollment; the tumor must be HR-positive; HR will be considered positive if staining is 1% or greater for ER and/or PR; this will be determined at the enrolling institution for purposes of study participation and enrollment onto the trial; subsequently, HR status will be confirmed by central pathology review, but this central review will not be required prior to enrolling the patient; HER2 status will be determined locally only, based upon current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
Estrogen receptor positive, progesterone receptor positive, HER2 negative
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
Have a diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer for Parts A to E, G, and I.
Have a diagnosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer for Parts F and H.
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
Have a diagnosis of Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) breast cancer • Prior combined CDK 4/6 inhibitor and endocrine therapy and 1 or 2 prior lines of chemotherapy
Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (triple-negative breast cancer; TNBC);
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
Histopathological diagnosis of metastatic or inoperable locally advanced triple negative breast cancer (TNBC) that meets the following criteria:\r\n* Triple negative is generally defined as estrogen receptor (ER) < 1%, progesterone receptor (PR) < 1%, and HER2 negative according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines by local testing according to institutional standards\r\n** Note: for tumors with equivocal interpretation of receptor status (e.g., ER/PR >= 1% “weak” or “faint” staining), the principal investigator will have final determination of triple-negative status; for tumors with discrepant receptor results between 2 or more biopsies (including metastatic and/or early stage biopsies), the principal investigator will have final determination of triple negative status, but in general the most recent biopsy can be used for eligibility purposes; if receptor testing is not available on a metastatic biopsy, the primary tumor test result is acceptable\r\n* Metastatic or inoperable locally advanced disease is defined as either: histologically confirmed metastatic breast cancer by biopsy; or locally advanced breast cancer that, in the opinion of the treating physician, is not amenable to curative intent surgical resection; or, radiological or clinical evidence suggestive and supportive of metastatic disease without a documented metastatic biopsy, provided the patient has a prior diagnosis of TNBC that otherwise meets the eligibility criteria\r\n* Ductal, lobular, mixed, or metaplastic histology
<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
Negative for HER2 amplification by in situ hybridization (ISH) for 2+ IHC disease.
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.
Participant has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor (ER) positive breast cancer by local laboratory.
Participant has human epidermal growth factor receptor 2 (HER2) negative breast cancer as defined by American Society of Clinical Oncology (ASCO)-College of American Pathologists guidelines.
Histologically documented TNBC (negative human epidermal growth factor receptor 2 [HER2], estrogen receptor [ER], and progesterone receptor [PgR] status)
Invasive disease must have been tested for estrogen receptor (ER), progesterone receptor (PR) and HER2; participants must have hormone-receptor positive, HER2-negative breast cancer defined as:\r\n* ER > 1% or PR > 1%\r\n* HER2-negative per American Society of Clinical Oncology (ASCO) College of American Pathologist (CAP) guidelines, 2013
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
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
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
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
Invasive disease must have been tested for estrogen receptor (ER), progesterone receptor (PR), and HER2 and participants must have hormone receptor-positive, HER2-negative breast cancer (ER > 1% or PR > 1%, AND HER2-negative per American Society of Clinical Oncology [ASCO] College of American Pathologists [CAP] guidelines, 2013)
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
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:
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
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
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)
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
Known HER2-, ER-positive, or PR-positive breast cancer by local laboratory assessment
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
Phase II: Patients must have histologically or cytologically confirmed adenocarcinoma of the breast associated with the following clinical stage: IIB, IIIA, IIIB, or IIIC (see AJCC staging criteria, 7th edition); the tumor must be human epidermal growth factor receptor 2 (Her2)/neu negative (by DAKO HercepTest, fluorescence based in situ hybridization [FISH], or other approved assay)
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
Histologically confirmed metastatic triple negative breast cancer with measurable disease by RECIST 1.1 criteria hormone receptor (HR) defined as positive for the purposes of this study, if expression of estrogen receptor (ER) and/or progesterone receptor (PR) expression is greater than 10% by immunohistochemistry (IHC) and 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.
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.
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.
Locally tested, Human Epidermal Growth Factor Receptor 2 (HER2)-expressing BC
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)
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
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)
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
For triple-negative breast cancer, a minimum of 1 prior cytotoxic chemotherapy regimen must have been administered for the indication of metastatic disease.Depending on receptor status, 1 or 2 prior cytotoxic regimens are required prior to enrollment in this trial; hormonal and/or human epidermal growth factor receptor 2 (HER2) -targeted agents may be required.
Documentation of estrogen receptor positive ((ER+), human epidermal growth factor receptor 2 (HER2 negative (HER2-)) tumor.
Must have a confirmed Epidermal growth factor receptor amplification in tumor tissue
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.
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™)
Tumor must be estrogen receptor and/or progesterone receptor positive (i.e hormone receptor positive [HR+] and HER-2 negative as defined by the American Society of Clinical Oncology/College of American Pathologists [ASCO-CAP] guidelines: HR+ is defined as expression of ER and/progesterone receptor [PR] in >= 1% of cells, or HR+ by local laboratory or regional definition; HER2? is defined as a HER2 immunohistochemistry [IHC] score of 0 or 1+, or an IHC score of 2+ accompanied by a negative fluorescence, chromogenic, or silver in situ hybridization test indicating the absence of HER2 gene amplification, or a HER2/CEP17 ratio of < 2.0, or local clinical guidelines
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
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).
HER2 positive and ER and PR negative tumors: must have failed at least 2 regimens containing at least two anti-HER2 agents (e.g. trastuzumab and pertuzumab).
Estrogen-receptor and progesterone-receptor expression both < 10% by immunohistochemistry (IHC) and HER2 negative by IHC or non-amplified as determined by the current American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) criteria; if patient has more than one histological result, the most recent one has to be considered for inclusion
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
Clinical stage IV or inoperable locoregional recurrent invasive mammary carcinoma that is:\r\n* ER+ and/or progesterone receptor (PgR)+ (>= 1% positive stained cells) by immunohistochemistry (IHC)\r\n* HER2-negative (by IHC or fluorescence in situ hybridization [FISH], per American Society of Clinical Oncology [ASCO] guidelines)\r\n* FGFR1, FGFR2, FGF3 or FGF4 amplified (may be determined by local assessment through either targeted capture next generation sequencing [NGS], plasma cell-free tumor [cf] DNA or FISH [in the case of FGFR1 amplifications]* in 50% of the patients participating in the expansion cohort of the trial [not necessary in the escalation cohort])\r\n** Cases will be considered as FGFR1-positive (‘amplified’) under one of the following conditions:\r\n*** The FGFR1/CEN8 ratio is >= 2.0\r\n*** The average number of FGFR1 signals per tumor cell nucleus is >= 6\r\n* Evaluable (may have either measurable or non-measurable disease)
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
Have diagnosis of triple negative breast cancer (defined as estrogen receptor [ER] < 1% by immunohistochemistry [IHC], progesterone receptor [PR] < 1% by IHC, Her 2 negative by  American Society of Clinical Oncology [ASCO] College of American Pathologists [CAP] guidelines)
COHORT 2 (HORMONE RECEPTOR POSITIVE [HR+])
Have a diagnosis of ER+ breast cancer (defined as ER > 1% by IHC)
Positive for HPV by p16 immunohistochemistry (IHC) or in situ hybridization (ISH).
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
Patients must have either:\r\n*Hormone receptor (HR) negative and HER-2 negative (TNBC) metastatic breast cancer and have not received prior chemotherapy for metastatic disease and should have been exposed to anthracyclines and taxane in neoadjuvant and adjuvant settings (first-line); demonstrated HER-2 negative MBC (0 or 1+ by immunohistochemistry [IHC] or non-amplified by fluorescence in situ hybridization [FISH]) according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPA) guidelines; Or\r\n* Histologically or cytologically confirmed estrogen receptor (ER) positive and HER-2 negative metastatic breast cancer are eligible if they have progressed on single agent or combination endocrine therapy (e.g. AI/palbociclib or everolimus) indicating an endocrine-refractory disease
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
HER2 negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
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
Subjects must be estrogen receptor (ER) positive
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])
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
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
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
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)
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
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
Patients can have hormone receptor (HR)+ or HR-negative disease
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)
Qualifying risk status, at diagnosis utilizing receptor testing by American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, meeting one of the following:\r\n* Histologically positive axillary lymph nodes\r\n* Primary tumor that is estrogen receptor (ER)/progesterone receptor (PR)/Her2 negative\r\n* Primary tumor that is ER+/Her2 negative/lymph node negative with Breast Cancer Recurrence Score of >= 25 per the Genomic Health Oncotype diagnosis (DX) breast cancer test\r\n* Evidence of residual disease in the breast on pathological assessment after neoadjuvant chemotherapy
Patients must have histologically confirmed hormone receptor positive (ER and/or progesterone receptor [PR]), human epidermal growth factor receptor 2 (HER2) negative, early invasive breast cancer; ER, PR and HER2 measurements should be performed according to institutional guidelines, in a Clinical Laboratory Improvement Amendments (CLIA)-approved setting in the United States (US) or certified laboratories for non-US regions; cut-off values for positive/negative staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines; central confirmation is not required for ER, PR, or HER statuses
Most recent tumor biopsy or surgical resection specimen must be either estrogen receptor (ER) positive, progesterone receptor (PgR) positive, or both, as defined by immunohistochemistry (IHC) >= 1% (as per the American Society of Clinical Oncology-College of American Pathologists [ASCO-CAP] guidelines)
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)
Prior selective estrogen receptor downregulator use (SERD), including fulvestrant
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
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.
Has positive estrogen receptor (ER) or progesterone receptor (PR) status. ER or PR >= 10%.
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)
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
Estrogen receptor (ER)+ Her2- breast cancer
Estrogen receptor (ER)+ Her2- breast cancer
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
Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
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.
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])
Estrogen receptor negative invasive breast carcinoma as defined as less than 10% stained cells
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
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%
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
The current cancer must over express HER2 as determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
Express at least 1 of the hormone receptors [HR; estrogen receptor (ER) or progesterone receptor (PR)] by immunohistochemistry (IHC) to fulfill the requirement for HR+ disease on the primary tumor or metastatic lesion of the breast cancer. ER and PR assays are considered positive if there is at least 1% positive tumor nuclei in their sample as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) or local guidelines.
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.
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
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
Have histologically confirmed adenocarcinoma of the breast that is either TNBC or HR positive/HER-2 negative; TNBC is defined as: estrogen receptor (ER)/progesterone receptor (PR) < 1% and HER-2 negative disease (Immunohistochemistry [IHC] 0-1+ or 2+ with HER2/17 ratio on Fluorescence In Situ Hybridization [FISH] =< 1.8) according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines; HR positive is defined as: ER/PR >= 1% and HER-2 negative as per ASCO/CAP guidelines
Documentation of the following receptors based on local testing from most recent assessment:\r\n* ER-positive and/or PR-positive tumor (>= 1% positive stained cells)\r\n* HER2-negative tumor; NOTE: HER2-negative is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH) defined as a HER2/CEP17 ratio < 2, for single probe assessment a HER2 copy number < 6 or per current American Society Clinical Oncologists (ASCO)-College of American Pathologists (CAP) or National Comprehensive Cancer Network (NCCN) guidelines
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
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
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])
Estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive tumor (? 1% positive stained cells) based on local laboratory results
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
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
Known androgen receptor (AR) positive breast cancer (AR staining > 10% by immunohistochemistry is considered positive); if the AR status is unknown, the patient can go on study
Minimum number of prior treatments required given standard nab-paclitaxel dosing:\r\n* If HER2 negative: none; Note: Subjects with hormone-receptor positive tumors (estrogen receptor positive [ER+] and/or progesterone receptor positive [PR+]) must have failed available appropriate lines of hormonal therapy (eg, ovarian suppression or ablation, selective estrogen receptor modulators, aromatase inhibitors, estrogen receptor antagonists, etc), unless intolerant to hormonal therapy or hormonal therapy is not considered to be clinically appropriate\r\n* If HER2 positive: two prior regimens containing HER2 targeted therapies in the inoperable locally advanced and/or metastatic setting; prior therapy for inoperable locally advanced/metastatic disease should include trastuzumab plus pertuzumab as well as ado-trastuzumab; pertuzumab and ado-trastuzumab must have been previously used, unless for reasons that include, but are not limited, to the following: intolerance to pertuzumab and/or ado-trastuzumab, medical contraindication, regimen declined by patient, treating investigator discretion, or medical insurance coverage issues which prevented administration of pertuzumab or ado-trastuzumab; these reasons must be reviewed with the study chairs and documented in the medical record and care report form; patients who relapse within 12 months of completing neoadjuvant/adjuvant pertuzumab or ado-trastuzumab would be considered as having progressed on that regimen\r\n* There is no maximum number of prior treatments allowed in the metastatic setting
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
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
The invasive cancer must be estrogen receptor alpha (ER)-positive, defined as having ER staining by IHC in >= 10% of malignant tumor cells
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
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
Estrogen Receptor-positive pathology
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
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.
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)
HER2/neu positive or estrogen and progesterone receptor negative breast cancer; patients with triple negative breast cancer are also excluded
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
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
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+
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)
ER+ status
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
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 (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
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
Histologically confirmed metastatic or recurrent triple-negative (i.e. estrogen receptor =< 5%, progesterone receptor =< 5%, HER2-negative via immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH] per American Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] guidelines 2013) breast cancer
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
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
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
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
Human epidermal receptor 2 (HER2) negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
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
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.)
Breast cancer must be determined by local testing to be human epidermal growth factor receptor 2 (HER2)-positive prior to study entry using American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) HER2 test guidelines.
Clinical T2-T4c, any N, M0 invasive estrogen receptor positive (ER+) (Allred Score of 6-8) and human epidermal growth factor receptor 2 negative (HER2-) (0 or 1+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] negative for amplification) breast cancer by American Joint Committee on Cancer (AJCC) 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node; patients with T1c tumors are eligible if they are considered candidates for neoadjuvant endocrine therapy
COHORT II: Core biopsy demonstrating breast cancer and receptors that are estrogen receptor (ER) or progesterone receptor (PR) positive
COHORT II: Core tissue must have human epidermal growth factor receptor 2 (HER 2) testing
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
Human epidermal growth factor receptor 2 (HER2) negative by fluorescent in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
Estrogen receptor (ER) less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor
Clinically node negative, hormone receptor positive (+). HER2 negative (-), with <25% intraductal component in the aggregate.
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
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
Estrogen and/or progesterone receptor positive
Human epidermal growth factor receptor 2 (HER2)-neu positive
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)
Must have ER positive disease with ER/PR report available.
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)
HER2-negative and hormone receptor-positive status (common breast cancer classification tests)
Have either human epidermal growth factor receptor 2 positive (HER2+) (Study Part A) or HER2- (Study Part B) breast cancer.
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
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
Documented HER3-positive disease measured by immunohistochemistry (IHC)
Has documented hormone (estrogen and/or progesterone) receptor (HR)-positive disease
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
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
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
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
A diagnosis of invasive breast cancer, with or without an in situ component, that is: \r\n* Originally identified by screening mammography \r\n* Characterized by standard diagnostic mammography +/- breast ultrasound\r\n* Clinically node negative \r\n* Confirmed by breast magnetic resonance imaging (MRI) in a facility that maintains active American College of Radiology (ACR) accreditation to be of low clinical stage (=< 2 cm, node negative, unifocal invasive)\r\n* Estrogen receptor (ER) and progesterone receptor (PR) Allred scored, each > 5/8\r\n* Her2 negative using American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines\r\n* ki?67 proliferation scored, < 20%\r\n* Clinical Nottingham grade 1 or 2\r\n* Scored on the MammaPrint 70-gene breast cancer recurrence assay as low risk
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])
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
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 -).
Estrogen receptor negative – defined as less than 1% staining by immunohistochemistry (IHC)
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
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)
TNBC defined as ER and PR negative (<1%) and HER-2 negative (FISH negative or IHC 0-1+)
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
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)
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
Newly diagnosed histologically confirmed stage I-III, estrogen receptor (ER), progesterone receptor (PR) and HER2 negative invasive breast cancer as defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines for whom systemic chemotherapy would be indicated based on physician judgment following standard National Comprehensive Cancer Network (NCCN) practice guidelines (Theriault et al, 2013)
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
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
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)
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
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
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
The subject must have histologically or cytologically confirmed metastatic estrogen-receptor positive (ER+) and/or progesterone-receptor positive (PR+) and human epidermal growth factor receptor 2 (HER2) negative breast cancer; (stains may be performed on either primary or metastatic tumor samples, ER and PR assays will be considered positive if there are at least 1% positive tumor nuclei in the sample as per American Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] guidelines, HER2 negative as per ASCO/CAP guidelines)
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
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
Estrogen receptor positive tumor and/or progesterone receptor positive tumor
Estrogen receptor negative and progesterone receptor negative tumor
Histologically and/or cytologically confirmed diagnosis of ER+ and/or progesterone receptor positive (PR+) breast cancer by local laboratory
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
Histologically confirmed TNBC, defined as negative immunohistochemical staining for estrogen and progesterone receptors (=< 5% of nuclei positive by immunohistochemistry [IHC]) and human epidermal growth factor receptor 2 (HER2) negative (IHC 0-1+ or HER2-neu negative according to American Society of Clinical Oncology and the College of American Pathologists [ASCO-CAP] guideline)
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)
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)
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
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)
The tumor must have been determined to be estrogen receptor (ER) and/or progesterone (PgR) positive assessed by current American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline recommendations for hormone receptor testing; patients with >= 1% ER or PgR staining by IHC are considered positive
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)
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
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
Patients have positive HER2 expression by immunohistochemistry (IHC) (3+) or fluorescence in situ hybridization (FISH) testing (> 2.0 ratio)
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
HER2 positive breast cancer (immunohistochemistry [IHC] 3+ or fluorescent in situ hybridization [FISH] ratio of >= 2.0)
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)
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)
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
Documented HER2 overexpression or gene-amplified tumor (immunohistochemistry [IHC] 3+ or IHC 2+ with confirmatory fluorescence in situ hybridization [FISH]+).
Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast cancer
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
Estrogen receptor (ER) and progesterone receptor (PgR) negative.
Human epidermal growth factor receptor 2 (HER2) negative as per American Society of Clinical Oncology/College of American Pathologists guidelines.
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.
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
Subjects must meet at least one of the following two criteria:\r\n* Histologically proven TNBC defined as estrogen receptor (ER) immunohistochemistry (IHC) =< 10%, progesterone receptor (PgR) IHC =< 10% and human epidermal growth factor receptor (HER)-2 negative disease per 2013 American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) HER testing guidelines (0 or 1+ by IHC; and/or HER2 ratio < 2.0 and HER2 copy number < 4 signals/cell by fluorescence in situ hybridization [FISH])\r\n* Confirmed germline BRCA1 or BRCA2 mutation associated breast cancer regardless of the subtype of breast cancer
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
Estrogen-receptor and progesterone-receptor expression both =< 1% by immunohistochemistry (IHC), and HER2-negative status as determined by the current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines; if a patient has more than one histological result, the most recent sample will be considered for inclusion
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.
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)
Tumors must stain positive for estrogen receptor (>= 10%) by immunohistochemistry (IHC)
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
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 positive disease is defined as > 10% nuclear staining
HER2 negative disease as per 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, one of the following must apply:\r\n* 0 or 1+ by immunohistochemistry (IHC) and not amplified by in situ hybridization (ISH)\r\n* 0 or 1+ by IHC and ISH not done\r\n* 2+ by IHC and not amplified by ISH or\r\n* IHC not done and not amplified by ISH
Documentation of histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative adenocarcinoma of the breast must be available.
Human Epidermal Growth Factor Receptor 2 (HER2)-positive gastric cancer
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)
Estrogen Receptor (ER)-, Progesterone Receptor (PR)-, and Human Epidermal Growth Factor Receptor (HER)2-negative (triple-negative) cancer of the breast.
HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
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
Triple-negative breast cancer (TNBC) defined as histologically confirmed diagnosis of breast cancer and must have received at least 1 chemotherapy-containing regimen for advanced disease (recurrent or metastatic). Tumour must be triple-negative, defined as minimal or no expression of estrogen and progesterone receptors [<10% of cells positive by immunohistochemistry (IHC)], and minimal or no expression of HER2 (IHC staining 0 or 1+ or FISH-).
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.
If IHC HER2 2+, a negative FISH test is required
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.
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
Patients that are estrogen receptor positive (ER+) will take anti-estrogen therapy for treatment of their DCIS during vaccinations
Participants with human epidermal growth factor receptor 2 (HER2)-positive status.
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+
Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer
Have a diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer
Known Human Epidermal Growth Factor Receptor 2 (HER2) positive, erythrocyte receptor (ER) positive, or progesterone receptor (PR) positive breast cancer
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
HER2 negative breast cancer. Central testing (required for all subjects) must demonstrate that the tumor is HER2 negative by FISH or Immunohistochemistry (IHC).
ER positive breast cancer. Central testing (required for all subjects) must demonstrate that the tumor is ER+ with low expression (H-score [1-159]).
Invasive ductal, lobular, medullary, papillary, colloid (mucinous), tubular histologies, or mixed histologies (lesions =< 2 cm) that are estrogen or progesterone receptor positive and do not exhibit human epidermal growth factor receptor 2 (HER2)/neu gene amplification OR ductal carcinoma in situ (lesions =< 2 cm)
All positive or negative ER (estrogen receptor), PR (progesterone receptor), and HER-2 subjects are eligible for this study.
Known hormone receptor status (estrogen receptor and progesterone receptor)
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
Histologically proven diagnosis of TNBC per current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline;\r\n* Estrogen receptor (ER) negative (ER expression =< 1% positive tumor nuclei), progesterone receptor (PR) negative (PR expression =< 1% positive tumor nuclei) and HER2 negative breast cancer by IHC and /or fluorescence in situ hybridization (FISH)
Documentation of ER-positive and/or progesterone receptor (PR)-positive tumor.
Documentation of human epidermal growth factor receptor 2 (HER2)-negative tumor.
The patient must have a pathologically confirmed (by histology, cytology, or immunohistology) diagnosis of TNBC (a cancer that does not meaningfully express the estrogen or progesterone hormone receptors or overexpress the human epidermal growth factor receptor 2 tyrosine kinase), which is currently advanced/metastatic disease.
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
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
Estrogen receptor and/or progesterone receptor positive disease
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
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
Estrogen receptor (ER)+ (ER- DCIS meeting other eligibility criteria are eligible)
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
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
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
ER/PR determination assays performed by IHC methods according to the local institution standard protocol
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.
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)
Operable ER-positive/HER2- negative, invasive early breast cancer, suitable for neoadjuvant AI treatment. HER2-negative as determined by American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines.
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
Patients must have a histologically confirmed diagnosis of hormone receptor positive, HER2 negative invasive breast carcinoma
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
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
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
Human epidermal growth factor receptor 2 (HER-2) positive esophagogastric cancer; patients with unknown HER2 status are permitted
Any histologically confirmed locally advanced recurrent endometrial adenocarcinoma (except for carcinosarcoma), recurrent high-grade serous ovarian/primary peritoneal/fallopian tube carcinoma, or deleterious BRCA mutant recurrent ovarian/primary peritoneal/fallopian tube cancer for whom no curative option is available will be eligible; any patient proven to have metastatic triple negative breast cancer, defined from standard pathologic assays as negative for estrogen receptor (ER) and progesterone receptor (PR) (< 10% tumor staining) will be eligible
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
Postmenopausal, Hormone receptor positive (HR+), HER2 negative breast cancer
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
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)
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
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)
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
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
Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
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.
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
HER2 overexpression and/or amplification as determined by immunohistochemistry (3+) or fluorescence in situ hybridization (FISH) (>= 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).
Documented HER2 overexpression (immunohistochemistry [IHC] 3+ or gene-amplified tumor with fluorescence in situ hybridization [FISH] ratio of >= 2.0)
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
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)
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
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
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
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
ER/progesterone receptor (PR) determination is required; ER- and PR-assays should be performed by immunohistochemical methods according to the local institution standard protocol
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 negative (IHC 0,1 or FISH HER2:CEP17 ratio < 2.0)
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
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 or cytologically confirmed estrogen/progesterone receptors (ER/PR) +/-; human epidermal growth factor receptor 2 (HER2)-, metastatic breast cancer.
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
Histological or cytological confirmation of estrogen-receptor positive (ER+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer
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
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
Estrogen and/or progesterone receptor positive breast cancer, as determined by pathology from either primary or metastatic site(s); central confirmation is not required
HER2 negative, defined as 0-1+ by immunohistochemistry or FISH-negative (ratio < 2.2); central confirmation is not required
Hormone-receptor positive defined as estrogen receptor-positive and/or progesterone receptor-positive
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
Tumors are positive for ER, PgR, or both
Tumors must be negative for HER2 (by FISH, CISH or IHC)
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
Her-2 normal as determined by fluorescence in situ hybridization (FISH) or 0 or 1+ by immunohistochemistry (IHC) staining.
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
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 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%)
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)
Participants must have histologically confirmed hormone receptor positive (HR+) HER2 negative metastatic or locally recurrent unresectable invasive breast cancer; both measurable and non-measurable disease are allowed; ER, progesterone receptor (PR) and HER2 measurements should be performed according to institutional guidelines, in a Clinical Laboratory Improvement Act (CLIA)-approved setting; cut-off values for positive/negative staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines
For invasive cancers, the tumor must be estrogen receptor positive (defined as 10% or greater expression of estrogen receptor)
Subjects must have a histologically confirmed diagnosis of hormone receptor (HR)+/HER2+ positive locally advanced unresectable or metastatic breast cancer; estrogen or progesterone receptor positivity is defined by immunohistochemistry (IHC) according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines 2010; HER2 positivity is defined by standard of care fluorescence in situ hybridization (FISH) and/or 3+ staining by IHC according to ASCO/CAP guidelines 2014
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)
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
HER2-positive breast carcinoma (IHC staining more than 3+ or HER2 gene amplification by fluorescent in situ hybridization [FISH])
Invasive carcinoma should be ER alpha receptor positive
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)
Documented pathological evaluation of the breast cancer for hormone receptor (estrogen receptor [ER] and progesterone receptor [PR]) status and HER-2 status
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
Tumors must be HER-2/neu expression negative, as determined by local hospital laboratory (immunohistochemistry [IHC] =< 2+ or fluorescence in situ hybridization [FISH] negative)
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
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)
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)
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
Human epidermal growth factor receptor 2 (HER2)/neu negative on the core biopsy analysis defined as 0 or 1+ by immunohistochemistry or not amplified by fluorescent in situ hybridization analysis
Estrogen receptor and progesterone receptor negative tumor with clinical size > 1 cm
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
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
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+)
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
Human epidermal growth factor receptor 2 (HER2) normal (immunohistochemistry [ICH] 0-1; fluorescence in situ hybridization [FISH] < 2.0)
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)
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% )
Tumors must express ER positivity by immunohistochemistry (ER expression >10% by immunohistochemistry).
Patient has estrogen-receptor and/or progesterone positive breast cancer as per local laboratory testing
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
Known human epidermal growth factor 2 (HER2)-positive, estrogen receptor (ER)-positive, or progesterone receptor (PgR)-positive breast cancer
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)
Estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer
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
Inoperable estrogen receptor positive and HER2 negative breast cancer.
HER2 positive by 2013 American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines (immunohistochemistry [IHC] 3+ and/or fluorescence in situ hybridization [FISH] positive; IHC 2+ HER2 patients are eligible with reflex FISH positive testing with the ratio >= 2.0) breast cancer patients with untreated asymptomatic or minimally symptomatic brain metastasis by MRI; there is no upper or lower limit to the size or number of brain metastases
Local histologic or cytologic confirmation of HER2+ solid tumors by fluorescent in situ hybridization (FISH) amplification or immunohistochemistry (IHC) (3+)
Subjects with a primary tumor that is hormone (estrogen, progesterone, or both) receptor-positive or receptor-negative are eligible.
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
Group 2: Post-menopausal women with advanced stage estrogen receptor positive breast cancer who are candidates for exemestane or fulvestrant
There should be a minimum of 4 weeks from any prior chemotherapy, immunotherapy and/or radiation, with the exception of hormonal therapy for prostate and breast cancers, human epidermal growth factor receptor (HER)2-directed therapy for HER2+ breast cancer (3+ immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH]+), and erlotinib in epidermal growth factor receptor (EGFR)-mutated lung cancer in the expansion cohort; there should be a minimum of 6 weeks from any prior antibody therapies, (such as ipilimumab or anti-programmed cell death [PD]1/programmed death-ligand [PDL]1)
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 are required to have HER2+ breast cancer defined as a fluorescent in situ hybridization (FISH)- ratio of >= 2.0 or immunohistochemistry (IHC) 3+
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
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.
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
Patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer are also excluded from this portion of the study
ER and/or PR-positive disease. Tumors must be HER-2/neu negative or equivocal.
Presence of tissue sample for IHC assay of MET receptor and HER2 status
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.
Patients must be ER >= 1% and HER2 negative on local testing
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)
HER2 negative disease, and a known positive hormone receptor status (common breast cancer classification tests)
For Stage 2: Participants with human epidermal growth factor receptor 2 (HER2) negative, estrogen-receptor (ER) negative, and progesterone-receptor (PR) negative breast cancer
Met diagnostic-positive status tested by immunohistochemistry (IHC)
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
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
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)
HER2/neu-negative breast cancer by standard criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH]-negative if IHC 3+) at primary diagnosis
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
Human epidermal growth factor receptor 2 (HER-2)/neu negative (phase II)
Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast cancer
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 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
Participants must have HR positive, HER2-negative breast cancer (estrogen receptor [ER] > 1% and/or, progesterone receptor [PR] > 1%, HER2-negative per American Society of Clinical Oncology [ASCO] College of American Pathologists [CAP] guidelines, 2013 resulted on the primary tumor and/or a metastatic lesion)
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)
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
Low grade disease positive for estrogen and progesterone receptors
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)
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)
HER2 expression as defined by ISH positive and/or 3+ by immunohistochemistry (IHC)
Dose expansion: patients must have histologically or cytologically confirmed invasive adenocarcinoma of the breast (human epidermal growth factor receptor 2 [HER2]-negative) that is locally advanced/metastatic and has progressed despite standard therapy; at least 1 prior chemotherapy regimen in the metastatic setting, and two lines of hormonal therapy (administered in the adjuvant or metastatic setting) for patients with hormone receptor-positive disease; NOTE: HER2-negativity will be defined per American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines; 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
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)
Human epidermal growth factor receptor- 2 (HER- 2) negativity will be based on the current American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines for HER testing
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 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
Have histologic diagnosis of human epidermal growth factor receptor 2 (HER2) positive (+) breast carcinoma
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
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
Patients will be included in the study based on the following criteria:\n\n          -  Women 18 years or older\n\n          -  Node-positive breast cancer (AJCC N1, N2, or N3)\n\n          -  Node-negative breast cancer if negative for both estrogen (ER) and progesterone (PR)\n             receptors and have received chemotherapy as standard of care\n\n          -  Clinically cancer-free (no evidence of disease) after standard of care therapy\n             (surgery, chemotherapy, radiation therapy as directed by NCCN guidelines). Hormonal\n             therapy will continue per standard of care. Neoadjuvant chemotherapy is allowed.\n\n          -  Recovery from any toxicity(ies) associated with prior adjuvant therapy.\n\n          -  HER2 expression of 1+ or 2+ by IHC. FISH or Dual-ISH testing must be performed on IHC\n             2+ tumors and shown to be non-amplified by FISH (?2.0) or by Dual-ISH (?2.0).\n\n          -  HLA-A2, A3, A24, or A26 positive\n\n          -  LVEF >50%, or an LVEF within the normal limits of the institution's specific testing\n             (MUGA or Echo)\n\n          -  ECOG 0,1\n\n          -  Signed informed consent\n\n          -  Adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral\n             tubal ligation, oral contraception, IUD, or use of condoms or diaphragms)\n\n          -  Must start study treatment (receive first Herceptin infusion) 15between 3-12 weeks\n             from completion of standard of care therapy.\n\n        4.1.3 Exclusion Criteria\n\n        Patients will be excluded from the study based on the following criteria:\n\n          -  Node-negative breast cancer (AJCC N0 or N0(i+)) unless negative for both estrogen (ER)\n             and progesterone (PR) receptors and has received chemotherapy as standard of care\n\n          -  Clinical or radiographic evidence of distant or residual breast cancer\n\n          -  HER2 negative (IHC 0) or HER2 3+ or FISHDual-ISH amplified (FISH >2.0); Dual-ISH >2.0\n\n          -  HLA-A2, A3, A24, A26 negative\n\n          -  History of prior Herceptin therapy\n\n          -  NYHA stage 3 or 4 cardiac disease\n\n          -  LVEF <50%, or less than the normal limits of the institution's specific testing (MUGA\n             or Echo)\n\n          -  Immune deficiency disease or HIV, HBV, HCV\n\n          -  Receiving immunosuppressive therapy including chemotherapy, chronic steroids,\n             methotrexate, or other known immunosuppressive agents\n\n          -  ECOG ?2\n\n          -  Tbili >1.8, creatinine>2, hemoglobin<10, platelets<50,000, WBC<2,000\n\n          -  Pregnancy (assessed by urine HCG)\n\n          -  Breast feeding\n\n          -  Any active autoimmune disease requiring treatment, with the exception of vitiligo\n\n          -  Active pulmonary disease requiring medication to include multiple inhalers\n\n          -  Involved in other experimental protocols (except with permission of the other study\n             PI)
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
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)
Documentation of histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative adenocarcinoma of the breast must be available.
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
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)
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.
Participants must have biopsy proven localized estrogen receptor (ER) positive (+) (>= 10%), HER2 negative, any grade, invasive breast adenocarcinoma, with pathological stage (including post-neoadjuvant therapy) T1c-T4c, any N, M0, by American Joint Committee on Cancer (AJCC) seventh (7th) edition staging; invasive breast cancer must be ER+ in >= 10% of the cells and HER2 negative (immunohistochemistry [IHC] 0 or 1+ and/or fluorescence in situ hybridization [FISH] negative with a ratio < 2) by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines; for IHC 2+, the tumor must be FISH negative with a ratio < 2; progesterone receptor (PR) status must be performed; ER, PR and HER2 measurements should be performed according to institutional (local) guidelines, in a Clinical Laboratory Improvement Act (CLIA)-approved setting; evaluation for metastatic disease is not required in the absence of symptoms; patients must have completed definitive surgery for breast cancer
Estrogen receptor- or progesterone receptor-negative disease
HER2/neu-expressing tumor (immunohistochemistry [IHC] 3+ and/or amplified fluorescence in situ hybridization [FISH] >2.2, or N0 (i+))
HER2/neu-negative breast cancers (IHC 0)
Histological or cytological confirmation of hormone-receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer
HER2 negative (HER2 1+ by IHC or HER2 2+ by IHC/FISH)
Patients must have had ER analysis performed on the primary breast tumor collected prior to neoadjuvant therapy according to current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing; if negative for ER, assessment of progesterone receptor (PgR) must also be performed according to current ASCO/CAP Guideline Recommendations for hormone receptor testing
Patients must have had HER2 testing performed on the primary breast tumor collected prior to neoadjuvant chemotherapy according to the current ASCO/CAP guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer; patients who have a primary tumor that is HER2-positive, HER2-equivocal, or HER2-negative are eligible
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
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
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
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
Known Folate Receptor-negative lung nodules
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.
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
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 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)
Adult patients with a history of pathologically confirmed estrogen receptor positive (ER+) breast cancer
Patients with histologic/immunochemical proof of estrogen receptor (ER)+ primary or metastatic malignancy (positive staining in >= 1% of cells by immunohistochemistry)
Two patients must be HER2 3+ by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) positive
Histologically proven infiltrating carcinoma of the breast on core needle biopsy that is:\r\n* ER/progesterone receptor (PR) =< 10% staining by immunohistochemistry (IHC)\r\n* HER2 positive – IHC 3+, in situ hybridization (ISH) >= 2.0, or average HER2 copy number >= 6.0 signals per cell or per current ASCO-CAP (American Society of Clinical Oncology – College of American Pathologists) or NCCN (National Comprehensive Cancer Network) guidelines\r\n* Note: All histological diagnostic material should be reviewed at enrolling institution as required per local standards
Histologic diagnosis of triple negative or human epidermal growth factor receptor 2 (HER2) amplified breast cancer, clinical stage T1-4, N0-3, M0/1 receiving preoperative systemic therapy and planned surgery
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
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
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
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)
Estrogen receptor positive breast cancer
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
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+
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.
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.
Patients must have estrogen receptor (ER) positive, HER2 negative metastatic breast\n             cancer (MBC) with at least one non-irradiated distant site of metastasis.
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).
Histologically proven diagnosis of breast cancer with evidence of metastatic disease or locoregional recurrence. 3. Histological confirmation and documentation of estrogen receptor (ER)-positive status (?1% positive stained cells). 4. Histological or cytological confirmation and documentation of human epidermal growth factor receptor-2 (HER2)-negative status by local laboratory testing using criteria in the American Society of Oncology (ASCO)/College of American Pathologists (CAP) Clinical Practice Guideline update.