HER 2 status: tumors must be HER2 negative defined as HER2 0 or 1+ by immunohistochemical (IHC) assays and/or lack of gene amplification by fluorescence in situ hybridization (FISH) defined as a ratio < 2 on invasive tumor; a tumor is considered HER2+ if 3+ by IHC or ISH amplified >= 2.0
HER2 0, 1+, or 2+ by IHC if HER2 testing is performed
Her-2 negative, defined as:\r\n* In-situ hybridization (ISH) ratio of < 2.0 (if performed)\r\n* Immunohistochemistry (IHC) staining of 0-2 positive (+) (if performed) \r\n* Deemed to not be a candidate for Her-2 directed therapy
Patients must have histologically confirmed mantle cell lymphoma, with cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH) and with proliferation rate determination, using Ki-67 or MIB-1 immunohistochemistry (=< 30% versus > 30% versus “indeterminate” Ki-67 index)
Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization [FISH])
Newly diagnosed de novo ALL (B-ALL or T-ALL) with definitive evidence of BCR-ABL1 fusion by karyotype, fluorescence in situ hybridization (FISH) and/or reverse transcriptase (RT)-PCR
HER2-overexpressing breast cancer (3+ staining by immunohistochemistry or HER2 gene amplification by fluorescent in situ hybridization [FISH] or silver in situ hybridization [SISH] >= 2.0)
Pathologically confirmed mantle cell lymphoma (MCL) which is relapsed or refractory to at least one chemotherapy containing regimen\r\n* Presence of cyclin D1 expression and/or t(11;14) by fluorescence in situ hybridization (FISH) or cytogenetics is required
Participants must have histologically confirmed HER2+ invasive breast cancer (immunohistochemistry [IHC] 3+ and/or fluorescence in situ hybridization [FISH] positive [HER2/chromosome 17 centromere [CEP17] >= 2 and/or > 6 HER2 gene copies per nucleus]); note: central confirmation of HER2 status is not required
Known positivity for HER2 (as defined by a positive IHC test of 3+ or IHC of 2_ with fluorescent in situ hybridization [FISH])
To qualify for Part 1, the participant must be t(11;14) positive as determined by an analytically validated Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
HER2 negative metastatic breast carcinoma defined as 0 or 1+ by IHC or with a FISH ratio (HER2 gene copy/ chromosome 17) < 2 if IHC 2+ by local institution standard protocol
Histologically confirmed HER2-positive metastatic breast cancer (HER-2 3+ by immunohistochemistry); if immunohistochemistry (IHC) score of 2, fluorescence in situ hybridization (FISH) ratio must be greater than 2.0; if FISH less than 2.0, HER2 copy number must be greater than 6; NOTE: Brain lesions are not required to have pathologic confirmation; estrogen receptor (ER)-positive patients are allowed
Patients must harbor a tumor HER2/neu+ based upon IHC staining score of “3+” or 2+ with confirmed gene amplification by fluorescence in situ hybridization (FISH) to be included
Patients may have any of the following:\r\n* Myc-overexpression (> 40%) by immunohistochemistry (IHC)\r\n* Myc-amplification (> 4 copies), as determined by fluorescent in-situ hybridization (FISH)\r\n* MYC-rearrangement, as determined by FISH
The following results must be available or pending at time of registration, though results will not affect enrollment/treatment:\r\n* B-cell lymphoma (BCL)-2 rearrangement by FISH\r\n* BCL-6 rearrangement by FISH\r\nNOTE: although not required, it is encouraged that MYC and BCL-2 be measured by immunohistochemistry (IHC) and clearly documented
Primary and/or metastatic breast tumor must be negative for human epidermal growth factor receptor (HER-2/neu) over-expression based on immunohistochemistry (IHC) (0 or 1+, 2+ if fluorescence in-situ hybridization [FISH] test is negative) or FISH (HER2/copy number of centromere of chromosome 17 [CEP17] ratio < 2.0 or < 4 Her-2/neu signals per nucleus)
HER2 negative in the primary tumor as defined by:\r\n* Grade 0 or 1+ staining intensity (on a scale of 0 to 3) by means of immunohistochemistry (IHC) analysis OR\r\n* Grade 2+ staining intensity by means of IHC analysis with gene amplification on fluorescence in situ hybridization (FISH) < 2.0 OR\r\n* Gene amplification on fluorescence in situ hybridization (FISH) < 2.0
Tumor positive or negative for expression of hormone receptors (< 1% or > 1%) and overexpressing HER2 by immunohistochemistry (IHC) (3+), or, HER2-amplified by fluorescence in situ hybridization (FISH) or by alternative gene testing
Negative for HER2 amplification by in situ hybridization (ISH) for 2+ IHC disease.
Patients must have histologically confirmed, relapsed/refractory ALK+ ALCL (with ALK positivity defined by immunohistochemistry and/or fluorescence in situ hybridization [FISH]/cytogenetics from any prior biopsy), MCL, or BCL6+ DLBCL (with BCL6 positivity defined by immunohistochemistry from any prior biopsy) and meet the following criteria:
Histologically or cytologically confirmed HER2-negative (0 or 1+ by immunohistochemistry [IHC] or non-amplified by fluorescent in situ hybridization [FISH]) breast cancer that is stage IV
IHC 1+ or 0
In situ hybridization negative based on:
Cohort 1: HER2 IHC 2+/FISH negative breast cancer
Cohort 2: HER2 IHC 3+ or HER2 IHC 2+/FISH positive breast cancer
Cohort 3: HER2 IHC 2+/FISH negative gastric/GEJ cancer
Cohort 4: HER2 IHC 3+ or HER2 IHC 2+/FISH positive gastric/GEJ cancer
Cohort 5: Any other HER2 IHC 3+ or FISH positive cancer
HER2 IHC 1+ or IHC2+/FISH- breast cancer patients who have received at least 1 and no more than 3 prior systemic chemotherapy regimens
HER2 IHC 2+ or 3+ FISH+ or FISH- gastric/GEJ cancer patients who have received at least 1 and no more than 3 prior systemic chemotherapy regimens.
For subjects with MCL (confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)
Patients must have a diagnosis of mantle cell lymphoma confirmed at diagnosis by one of the following:\r\n* t(11;14) detected by fluorescence in situ hybridization (FISH), conventional cytogenetics, or other molecular evaluation\r\n* Expression of cyclin D1 confirmed by immunohistochemistry
PART I: Adults with malignant soft tissue and bone tumors and recurrent or progressive, metastatic solid tumors who have progressed on standard therapies with known benefit but for whom anti-HER2 therapy is not clinically indicated:\r\n* Patients with ovarian, cervical, colon, gastric/gastroesophageal junction, non-small cell lung, renal cell, bladder, malignant soft tissue and bone tumor, prostate cancer or other solid tumors that is known to be HER2 1+, 2+ or 3+ by immunohistochemistry (IHC) OR have a Vysis fluorescent in situ hybridization (FISH) result >= 1.8\r\n* Patients with breast cancer that is known to be HER2 1+ or 2+ by IHC or with a Vysis FISH result of 1.8 - < 2.2
Tumor negative for expression of hormone receptors (< 1%) and not over-expressing HER2 by immunohistochemistry (IHC) (0-1), or in case of IHC of 2, negative by fluorescence in situ hybridization (FISH) or by alternative gene testing
INCLUSION - ENROLLMENT: Her-2 3+ or fluorescence in situ hybridization (FISH) ratio of 2.2 or higher, background gene expression with normal copy number
Cohort #2: histologic confirmation of relapsed or relapsed/refractory MCL confirmed by presence of cyclin D1 by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
Human epidermal growth factor receptor 2 (HER2) negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+ according to National Comprehensive Cancer Network (NCCN) guidelines
History of biopsy-proven HER2-overexpressing breast cancer and radiographic evidence of metastatic disease, or locally recurrent unresectable disease; the HER2 status can be determined either by immunohistochemistry (IHC) (IHC score, 3+) or by fluorescence in situ hybridization (FISH) (as defined by HER2/CEP-17 ratio >= 2.0, or HER2 copy number >= 6); patients must have received prior trastuzumab, independent of response to prior trastuzumab, and a taxane (in any disease setting, e.g. neo-adjuvant, adjuvant, metastatic)
Patients must have HER2 status determined by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC); HER2 status of positive or negative are both eligible for the study
Positive for HPV by p16 immunohistochemistry (IHC) or in situ hybridization (ISH).
Histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC) (stage IV, American Joint Committee on Cancer [AJCC] v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA)-approved fluorescence in situ hybridization (FISH) test, using Vysis ALK Break apart FISH Probe, or the Ventana immunohistochemistry (IHC) test; diagnosis using next generation sequencing (NGS) via a local diagnostic test will be accepted for enrollment but will need to be confirmed with either FISH or IHC
HER2 negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
for subjects with MCL (confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)
Histopathologically or cytologically documented TNBC or TN-IBC. Tumors must have been confirmed negative for ER and PR by IHC (<1% positive tumor nuclei, as per ASCO-CAP guideline recommendations) and negative for HER2 by IHC or fluorescent or chromogenic in situ hybridization (FISH or CISH). Patients with equivocal HER2 results by IHC should have their negativity status confirmed by FISH.
Patients must have histologically confirmed HER2-negative breast cancer (defined as immunohistochemistry [IHC] 0 or 1+ and/or fluorescence in situ hybridization [FISH] < 2.0), that is metastatic in stage
Must be negative for Her-2 amplification; (either 1+ on semi-quantitative evaluation of immunostain or negative by fluorescent in-situ hybridization)
Subjects must not have amplification of Her-2 (either 3+ by semi-quantitative immunostain or positive by fluorescent in-situ hybridization [FISH])
MCL cohort: MCL (diagnosis must be confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization [FISH], or PCR) with relapsed or refractory disease after at least 1 prior line of MCL therapy
Human epidermal growth factor receptor 2 (HER2)-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+; if IHC is 2+ (i.e. indeterminate), a negative in situ hybridization (fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], or silver in situ hybridization [SISH]) test is required by local laboratory testing; (as per the ASCO-CAP guidelines)
Patients must have an ongoing complete cytogenetic response (CCyR) on a TKI (imatinib, dasatinib, nilotinib, or bosutinib), defined as follows:\r\n* 0% Ph+ cells in metaphase, in the bone marrow and/or a negative peripheral blood fluorescence in situ hybridization (FISH) analysis for BCR-ABL1 gene fusion
Is HER2 normal, defined as HER2 0 or 1+ by immunohistochemistry (IHC) and negative by fluorescence in situ hybridization (FISH) if performed; or HER2 is 2+ by IHC and negative by FISH; or HER2 negative by FISH if IHC is not performed.
Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
Patients must have a metastatic tumor negative for HER2; the lack of HER2 overexpression by immunohistochemistry (IHC), is defined as 0 or 1+ whereas hyperexpression is defined as 3+; if equivocal IHC, 2+, the tumor must be non-gene amplified by fluorescence in situ hybridization (FISH) performed upon the primary tumor or metastatic lesion (ratio < 2 and HER2 copy number < 4)
Patients must have negative HER2 expression on immunohistochemistry (IHC) (defined as 0 or 1+) or fluorescence in situ hybridization (FISH) analysis; if HER2 is 2+, negative HER2 expression must be confirmed by FISH (HER2/cep17 ration < 2, and/or copy number less than 6); ER and PgR expression should be less than 10%
The current cancer must over express HER2 as determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
Histologically confirmed adenocarcinoma of the breast that is Her2 negative (by DAKO Herceptest, fluorescence in situ hybridization [FISH], or other approved assay)
To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization (ISH) as defined in the relevant ASCO/CAP or local guidelines.
HER2-negative breast cancer based on local laboratory results (test to be used as per local practice); HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (fluorescence in situ hybridization [FISH]/chromogenic in situ hybridization [CISH]/silver-enhanced in situ hybridization [SISH]) defined as a HER2/CEP17 ratio < 2 or for single probe assessment a HER2 copy number < 4
The invasive cancer must be HER2-low, defined as immunohistochemistry (IHC) 0-1+, or with a fluorescence in situ hybridization (FISH) ratio of < 1.8 if IHC is 2+ or if IHC has not been performed
Histologically or cytologically confirmed diagnosis of lung adenocarcinoma that demonstrates ALK rearrangement as detected by the approved fluorescence in situ hybridization (FISH) test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); or the Ventana immunohistochemistry (IHC) test; evidence of rearrangement by gene sequencing tests such as FoundationOne or Caris will also be seen as evidence of ALK abnormality and meeting eligibility requirement
Documented human epidermal growth factor receptor 2 (HER2)-negative tumor based on local testing on most recent tumor biopsy: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (fluorescence in situ hybridization [FISH]/chromogenic in situ hybridization [CISH]/silver in situ hybridization [SISH]) defined as a HER2/centromeric probe for chromosome 17 (CEP17) ratio < 2 or for single probe assessment a HER2 copy number < 4
For Cohort 2 (subjects with relapsed/refractory synovial sarcoma only), the following tests must be available by local laboratory: Morphology consistent with synovial sarcomas, and cytogenetics or fluorescence in situ hybridization (FISH) and/or molecular confirmation (e.g., DNA sequencing) of SS18 rearrangement t(X;18)(p11;q11)
For phase II: ER negative (defined as expression of ER in =< 1% cells), PR negative (defined as expression of PR in =< 1% cells), HER2 negative (acceptable methods of HER2 analysis include IHC [0, 1+], fluorescence in situ hybridization [FISH] with HER2/centromere on chromosome 17 [CEN17] ratio < 2, and/or chromogenic in situ hybridization [CISH] with HER2/CEN-17 ratio < 2), as previously documented by histological analysis
Human epidermal growth factor receptor 2 (HER2) negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
Is HER2 normal, defined as HER2 0 or 1+ by immunohistochemistry (IHC) and negative by fluorescence in situ hybridization (FISH) if performed; or HER2 is 2+ by IHC and negative by FISH; or HER2 negative by FISH if IHC is not performed
The invasive cancer must have been confirmed to be human epidermal growth factor receptor 2 (HER2)-negative at some point in a given patient’s disease history (can be from any tumor specimen from a given patient, including archived primary, recurrent, or metastatic tumor), defined as immunohistochemistry (IHC) 0-1+, or with a fluorescent in situ hybridization (FISH) ratio of < 1.8 if IHC is 2+ or if IHC has not been performed
Human epidermal growth factor receptor (HER) 2 negative defined as 0 or 1+ using IHC or a ratio of less than 2.0 on fluorescence in situ hybridization (FISH) testing; HER 2 of 2+ on IHC should have a ratio of less than 2.0 on FISH testing to be considered HER2 negative
Human epidermal receptor 2 (HER2) negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
Human epidermal growth factor receptor 2 (HER2) negative by fluorescent in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+
HER2 positive breast cancer, defined by immunohistochemical staining for HER2 protein of 3+ intensity and/or amplification of the HER2 gene on fluorescence in situ hybridization (FISH) >= 2.0 on breast specimen or biopsy of a metastatic site
HER2 overexpression of tumor by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH); tumors tested by IHC must be 3+ positive; tumors tested by FISH must have a ratio of HER2:CEP17 > 2.0; when both tests are performed, the FISH result must be positive
Diagnosis of multiple myeloma (MM) with deletion 17p (del17p) or monosomy 17 by fluorescence in situ hybridization (FISH) who have received at least one line of therapy
Bone marrow analysis demonstrating normal cytogenetics, and no more than 5% of cells with a single clonal abnormality by fluorescence in situ hybridization (FISH) for myelodysplastic syndrome (MDS) panel within 3 months of stem cell collection
Multiple myeloma (MM): patients who\r\n* Have received induction therapy for a minimum of 4 cycles\r\n* In addition, patients must meet at least one of the following criteria I-IX (I-VII at time of diagnosis or pre-autograft): \r\n** Any abnormal karyotype by metaphase analysis except for isolated t(11,14),\r\n** Fluorescent in situ hybridization (FISH) translocation 4:14,\r\n** FISH translocation 14:16,\r\n** FISH deletion 17p,\r\n** Beta2 (B2)-microglobulin > 5.5 mg/ml,\r\n** Cytogenetic hypodiploidy\r\n** Plasmablastic morphology (>= 2%)\r\n** Recurrent or non-responsive (less than partial remission [PR]) MM after at least two different lines of conventional chemotherapy\r\n** Progressive MM after a previous autograft (provided stored autologous cluster of differentiation [CD]34 cells are available)
Patients with histologically confirmed adenocarcinoma of the breast that does not over-express HER-2/neu; this is defined as fluorescent in situ hybridization (FISH) negative, or 0, 1+ or 2+ by immunohistochemistry (IHC); IHC 2+ tumors must be FISH negative with an amplification ratio of less than 2.0; patients must not be eligible for therapy of known curative potential for metastatic breast cancer if it is identified during the course of the study
Breast adenocarcinoma that is amplified for HER-2/neu gene expression by 2-fold or more by FISH analysis, or that is IHC 3+
Expansion cohort only: Plasma cell fluorescence in situ hybridization (FISH) test demonstrating presence of t(11;14)
Documented HER3-positive disease measured by immunohistochemistry (IHC)
HER2 overexpression by immunohistocytochemistry (IHC) of 2+ or 3+, in the primary tumor or metastasis; if overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by fluorescence in situ hybridization (FISH)
Subjects with diagnosis of HER2-negative breast cancer that was confirmed by IHC or in situ hybridization (ISH) assessment of tumor samples
Histologically or cytologically confirmed ER+ HER2- breast cancer; ER-positivity is to follow local guidelines; if immunohistochemistry (IHC) HER2 is 2+, a negative fluorescence in situ hybridization (FISH) test is required
Progesterone receptor negative – defined as less than 1% staining by IHC\r\n* HER2 negative defined as 0 or 1+ using IHC or a ratio of less than 2.0 on fluorescence in situ hybridization (FISH) testing; HER2 of 2+ on IHC should have a ratio of less than 2.0 on FISH testing to be considered HER2 negative
Documentation of HER2 negative breast cancer at the time of protocol registration; (Note: HER2 negativity is defined as 0 or 1+ by immunohistochemistry OR nonamplified or equivocal by fluorescence in situ hybridization [FISH]; status may be defined on the basis of historic results on the breast primary or a metastatic site, whichever is most recent; repeat biopsies are not required for participation in this protocol)
Participants with mature B-cell (Burkitt’s) ALL are excluded from study; mature B-cell is defined by the presence of surface immunoglobulin and/or the t(8;14)(q24;q32), t(8;22), or t(2;8) translocation and/or c-myc-gene rearrangement by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR); (FISH/PCR testing for c-myc rearrangements is not required prior to study entry, but it is suggested for patients with surface immunoglobulin expression or L3 morphology)
Completely resected unilateral or bilateral primary carcinoma of the breast without clinical evidence of disease, negative for estrogen receptor (ER) and progesterone receptor (PR) (cut-off for positivity is > 1% positive tumor cells with nuclear staining), and negative for HER2 as defined by one of the four situations delineated below: \r\n* HER2 immunohistochemistry (IHC) expression of 0 or 1+ and in-situ hybridization non-amplified\r\n* HER2 IHC expression of 0 or 1+ and in-situ hybridization not done\r\n* HER2 IHC expression of 2+ and in-situ hybridization non-amplified\r\n* IHC not done and in-situ hybridization non-amplified\r\n* Note: central review is not required
HER2+ as 3+ by IHC or in-situ hybridation (ISH) amplified.
Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing >= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
Note: patients with mature B-cell (Burkitt's) ALL are excluded from study; mature B-cell is defined by the presence of surface immunoglobulin and/or the t(8;14)(q24;q32), t(8;22), or t(2;8) translocation and/or c-myc-gene rearrangement by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)
Tumors must be HER2 negative defined as HER2 0 or 1+ by immunohistochemistry (IHC) assays and/or lack of gene amplification by fluorescence in situ hybridization (FISH) defined as a ratio < 2 on invasive tumor by local review
HER2-negative breast cancer defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+ or 2+; if IHC is 2+, a negative in situ hybridization (fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], or silver in situ hybridization [SISH]) test is required by local laboratory testing
Cytogenetics, fluorescence in situ hybridization (FISH) or mutational analysis confirming adverse risk features must have been done within 90 days prior to enrollment
Human epidermal growth factor receptor 2 (HER2)/neu-negative breast cancer by standard criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH] negative if IHC 2+) at primary diagnosis
HER2 positive disease as defined by 3+ IHC or positive FISH (both in primary and metastatic sites)
Patients with histologically confirmed, metastatic HER2+ (by immunohistochemistry [IHC] 3+ or fluorescence in situ hybridization [FISH] ratio >= 2.0) breast cancer
Patients with HER2+ (immunohistochemistry [IHC] 3+ or fluorescence in situ hybridization [FISH]+ R/G > 2.0 or silver-enhanced in situ hybridization [SISH]+ HER2/chromosome 17 centromere [CEP17] > 2.0) breast cancer with documented central nervous system (CNS) recurrence or progression (potential participants with newly diagnosed brain metastasis who have not received prior treatment for their lesions in the brain are eligible)
Patients have positive HER2 expression by immunohistochemistry (IHC) (3+) or fluorescence in situ hybridization (FISH) testing (> 2.0 ratio)
HER2 positive breast cancer (immunohistochemistry [IHC] 3+ or fluorescent in situ hybridization [FISH] ratio of >= 2.0)
Patients must harbor a tumor HER2/neu+ based upon IHC staining score of “3+” or 2+ with confirmed gene amplification by FISH to be included
Has sufficient tumor tissue (slides or blocks) available for central confirmatory testing of immunohistochemistry and/or cytogenetics/fluorescence in situ hybridization (FISH) and/or deoxyribonucleic acid mutation analysis (required for study entry but enrollment based on local results) For Dose Escalation Only:
Documented HER2 overexpression or gene-amplified tumor (immunohistochemistry [IHC] 3+ or IHC 2+ with confirmatory fluorescence in situ hybridization [FISH]+).
Histologically-confirmed metastatic adenocarcinoma of the breast with either invasive primary tumor or metastatic tissue confirmation of HER2+ status as defined by immunohistochemistry (IHC) with score of 3+, or, if 2+ with confirmatory fluorescence in situ hybridization (FISH) ratio of >= 2.0
Patients must have stage IV gastric or GEJ adenocarcinoma with HER2 overexpression and/or amplification as determined by next generation sequencing assay, (immunohistochemistry [IHC] 3+) or fluorescent in situ hybridization (FISH+ is defined as HER2:chromosome 17 centromere probe [CEP17] ratio >= 2.0); MSKCC confirmation of HER2 status is not mandatory prior to enrollment and treatment on study; for patients with outside HER2 testing, if sufficient tissue is available HER2 testing will be repeated at MSKCC for purpose of analysis and will not impact the patient's eligibility
Documented HER2+ breast cancer defined as: 3+ by immunohistochemistry (IHC) or with amplification by in situ hybridization with ratio >= 2.0; results from the local lab are acceptable; eligibility will not be affected by hormone receptor status
Human epidermal growth factor receptor 2 (HER2)-negative tumor by local laboratory testing (immunohistochemistry [IHC] 0, 1+ regardless of fluorescence in situ hybridization [FISH] ratio; IHC 2+ with FISH ratio lower than 2.0 or HER2 gene copy less than 6.0; FISH ratio of 0, indicating gene deletion, when positive and negative in situ hybridization [ISH] controls are present)
International Prognostic Index score ? 2 or DLBCL with double-positive for BCL2 and c-MYC by IHC (immunohistochemistry) or FISH (fluorescent in situ hybridization) based on local pathology lab assessment.
HER2-positive disease by local laboratory testing (immunohistochemistry 3 positive [IHC 3+] staining or in situ hybridization positive)
Must have evidence of MET expression by fluorescence in situ hybridization (FISH), MET immunohistochemistry (IHC) score of 2-3+, reverse-transcriptase polymerase chain reaction (RT-PCR) or a mutation
HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
Patients must have histological documented or cytological confirmed mantle cell lymphoma; cyclin D1 must be present as evidenced by either fluorescence in situ hybridization (FISH) or immunohistochemical staining
If IHC HER2 2+, a negative FISH test is required
Negative human epidermal growth factor receptor 2 (HER-2)/neu- disease defined as patients with fluorescence in situ hybridization (FISH) ratio < 2.0 or < 6.0 HER2 gene copies per nucleus, and IHC staining scores of 0, 1+, or 2+
HER2 negative breast cancer. Central testing (required for all subjects) must demonstrate that the tumor is HER2 negative by FISH or Immunohistochemistry (IHC).
Histologically confirmed untreated mantle cell lymphoma, with documented cyclin D1 (BCL1) by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescent in situ hybridization (FISH)
Documentation of amplified PDGFR by fluorescent in-situ hybridization (FISH), colorimetric in-situ hybridization (CISH), or quantitative polymerase chain reaction (PCR) from tumor tissue (>= 3 copy number), or over expression by immunohistochemistry (IHC)
HER2+ patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
Participants' primary and/or metastatic tumor is human epidermal growth factor receptor 2 (HER2)-negative by fluorescence in-situ hybridization (FISH) or chromogenic in-situ hybridization (CISH) or 0, 1+ overexpression by immunohistochemistry (IHC)
Molecular testing result from Clinical Laboratory Improvement Act (CLIA)-certified laboratory confirming that the tumor tissue has at least one of the following:\r\n* HER2 overexpression (3+ immunohistochemistry [IHC]); Note: HER2 2+ IHC is eligible if the tumor is amplified by fluorescence in situ hybridization (FISH)\r\n* HER2 amplification by in situ hybridization assay (FISH or chromogenic in situ hybridization [CISH] signal ratio >= 2.0 or gene copy number > 6)\r\n* HER2 amplification by CLIA-certified next generation sequencing (NGS) sequencing assay
Detection of one of the following must be present:\r\n* t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics\r\n* Breakpoint cluster region (BCR)-Abelson (ABL) positive status by molecular analysis with qualitative polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH)
Histologically confirmed mantle cell lymphoma with documented expression of cyclin D1 (BCL1) by immunohistochemical stains and/or t (11; 14) by cytogenetics or fluorescence in situ hybridization (FISH)
Histologically or cytologically confirmed invasive breast cancer that is HER2-positive (3+ by immunohistochemistry [IHC] and/or > 2.0 by fluorescence in situ hybridization [FISH]) if concurrent HER2-directed therapy is planned
Confirmed HER2-positive disease by local pathology, defined as immunohistochemistry (IHC) 3+ or amplification by fluorescent in situ hybridization (FISH) (HER2/chromosome 17 centromere [CEP17] ratio >= 2 or an average of >= 6 HER2 gene copies per nucleus) AND confirmed by Central Pathology Review (Mayo Clinic Rochester) prior to patient being registered to begin protocol therapy\r\n* NOTE: ductal carcinoma in situ (DCIS) components should not be counted in the determination of HER2 status
Subject has human epidermal growth factor receptor 2 negative (HER2-) breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
Histologically documented HER2 (+) breast cancer as defined as immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) amplification of >= 2.0 of primary or metastatic site; results from the local lab are acceptable
Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0-1+ by immunohistochemistry (IHC) or non-amplified fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH); if HER2 IHC is 2+, FISH/CISH must be performed and must not be positive (must be a ratio of < 2), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by institutional standards
Documented results of cytogenetics/ fluorescence in situ hybridization (FISH) obtained at any time before transplant, and International Staging System (ISS) staging at the time of diagnosis available.
Patients must have histologically or cytologically confirmed mantle cell lymphoma as defined by the World Health Organization; all patients must have either t(11;14) by karyotype or fluorescent in-situ hybridization (FISH) or positive immunohistochemistry for cyclin D1
Patients must have histologically-confirmed HER2-positive breast cancer that is locally advanced or metastatic; HER2-positive disease must be documented by one of the following results using Food and Drug Administration (FDA)-approved testing methods: \r\n* Fluorescence in situ hybridization (FISH)-positive (with an amplification ratio >= 2.0 indicating positive status) and/or \r\n* Immunohistochemistry (IHC) 3 + by local laboratory assessment
A cytogenetics or fluorescence in situ hybridization (FISH) analysis of the leukemic cells within 24 months of randomization is required to document the presence or absence of del(17p). Note: if a sample from within 24 months is not available, it should be evaluated as part of the screening laboratory evaluation to inform stratification
Human growth factor receptor 2 (HER2) positive tumors as defined by Food and Drug Administration (FDA) guidelines (3+ immunohistochemical staining, defined as uniform, intense membrane staining of more than 10% of invasive tumor cells, and for cases with 2+ staining showing gene amplification by fluorescence in situ hybridization [FISH], expressed as a ratio of more than 2 when comparing HER-2 gene and chromosome 17 fluorescent signals)
Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
HER2 overexpression and/or amplification as determined by immunohistochemistry (3+) or fluorescence in situ hybridization (FISH) (>= 2.0)
Documented HER2 overexpression (immunohistochemistry [IHC] 3+ or gene-amplified tumor with fluorescence in situ hybridization [FISH] ratio of >= 2.0)
Patients have HER2-positive breast carcinoma (IHC staining more than 3+ or HER2 gene amplification by fluorescent in situ hybridization [FISH])
HER2 overexpression by immunohistochemistry (IHC) of 2+ or 3+ in the primary tumor or metastasis; or documented gene amplification by fluorescent in situ hybridization (FISH) analysis; IHC =< 2+ must have HER2 gene amplification documented by FISH
Patients with histologically confirmed stage I-III, HER2-positive invasive breast cancer for which adjuvant/neoadjuvant chemotherapy is indicated based on physician judgment following National Comprehensive Cancer Network (NCCN) practice guidelines\r\n* HER2 overexpression or amplification will be based on local test results and is defined as either:\r\n** Immunohistochemistry (IHC) staining of 3+ (uniform, intense membrane staining) in >= 10% of invasive tumor cells or\r\n** Fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or\r\n** FISH ratio (HER2 gene signals to chromosome 17 signals) of >= 2.0
HER2 negative (IHC 0,1 or FISH HER2:CEP17 ratio < 2.0)
PRE-REGISTRATION INCLUSION CRITERIA: Histologically confirmed HER2-negative primary invasive ductal or invasive lobular breast carcinoma; for patients enrolling for neoadjuvant treatment, diagnosis must be clinical stage II or III; for patients enrolling for adjuvant treatment, diagnosis must be pathologic stage IIA to IIIC\r\n* Standard HER2 testing will be performed in the surgical specimen at Washington University according to the standard of care in the department of pathology; a HER2-negative primary breast cancer sample from a patient eligible for randomization should have a HER2 immunohistochemistry (IHC) score of 0 or 1+; those patients with IHC score of 2+ should be HER2 fluorescent in situ hybridization (FISH)-negative in standard testing\r\n* Patient will have undergone staging studies including a computed tomography (CT) of the chest/abdomen/pelvis and bone scan and/or positron emission tomography (PET) scan either prior to the initiation of treatment or prior to entry into the trial\r\n* In addition, patients with non-metastatic, HER2-negative, recurrent tumors who need chemotherapy are eligible
Expanded cohort only: Cohort 1: patients with predominant metastatic bone disease; Cohort 2: patients with primary squamous head and neck cancers; Cohort 3: patients presenting any molecular abnormality of interest, which can include an ALK translocation, ALK amplification, ALK mutation and overexpression as determined by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR), quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), array Comparative Genomic Hybridization or direct sequencing (aCGH); a c-MET abnormality, either c-MET amplification by FISH, overexpression by IHC or c-MET mutation; BRAF, DDR2 and CDKN2A mutations; and, finally, TRIM 16 expression and CCN2 expression
An adverse risk karyotype defined by:\r\n* Complex karyotype by cytogenetics, or\r\n* Deletion of all or part of chromosome 5, 7, 12, or 17 defined by fluorescence in situ hybridization (FISH) or cytogenetics, or\r\n* Somatic TP53 mutation
HER2 negative, defined as 0-1+ by immunohistochemistry or FISH-negative (ratio < 2.2); central confirmation is not required
Enrollment will be restricted to patients demonstrating NAD(P)H dehydrogenase, quinone 1 (NQO1) immunohistochemistry (IHC) overexpression; demonstration of NQO1 overexpression by IHC should be confirmed prior to conducting other study procedures (e.g., laboratory and imaging studies)
Note: patients with a negative or equivocal overall result (FISH ratio of < 2.0 or =< 6.0 HER2 gene copies per nucleus) and IHC staining scores of 0, 1+, 2+ are not eligible for enrollment
Tumors must be negative for HER2 (by FISH, CISH or IHC)
Previously untreated patients with a morphologic diagnosis of APL, confirmed by demonstration of t(15;17) using conventional cytogenetics OR fluorescence in situ hybridization (FISH), OR a positive reverse transcriptase (RT)-polymerase chain reaction (PCR) assay for promyelocytic leukemia (PML)-retinoic acid receptor, alpha (RAR-alpha) at the subject's local institution
Participants must have a diagnosis of chronic myelogenous leukemia as confirmed by fluorescent in situ hybridization (FISH) for BCR/ABL translocation and/or standard cytogenetics analysis
Her-2 normal as determined by fluorescence in situ hybridization (FISH) or 0 or 1+ by immunohistochemistry (IHC) staining.
Confirmed pathologic diagnosis of breast cancer which is metastatic and for which capecitabine is a reasonable treatment option\r\n*ARMS C & D: Histologically confirmed human epidermal growth factor receptor 2 (HER2) positive (+) breast cancer: immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) amplified; by clinical assay on either primary or metastatic tumor
Patients must have esophageal, gastric or gastroesophageal adenocarcinoma with HER2 overexpression and/or amplification as determined by next generation sequencing assay, immunohistochemistry (IHC 3+) or fluorescent in situ hybridization (FISH+ is defined as HER2:CEP17 ratio >= 2.0); MSKCC or enrolling institution confirmation of HER2 status is not mandatory prior to enrollment and treatment on study; for patients with outside HER2 testing, if sufficient tissue is available HER2 testing will be repeated at MSKCC or the enrolling institution for purpose of analysis and will not impact the patient's eligibility
For patients with evidence of minimal residual disease prior to vaccination, assessment of minimal residual disease status by cytogenetics or fluorescence in situ hybridization (FISH) will be followed post vaccination
HER2-positive breast carcinoma (IHC staining more than 3+ or HER2 gene amplification by fluorescent in situ hybridization [FISH])
Patients who have already received an allogeneic hematopoietic cell transplant and have either a documented relapse of leukemia or MDS or have recurrent persistent minimal residual disease as documented by at least 2 sequential testings, separated by 1 week, demonstrating molecular evidence of leukemia or MDS by fluorescence in situ hybridization (FISH), cytogenetics or fluorescent immunocytometry
Patients must have HER2-positive (fluorescence in situ hybridization [FISH]+ or immunohistochemistry [ICH] 3+) metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma to be eligible for trastuzumab; for the purposes of this protocol, FISH+ is defined as HER2:centromeric probe for chromosome 17 (CEP17) ratio >= 2.0; biopsy samples with cohesive IHC3+ or FISH+ clones are considered HER2 positive irrespective of size, i.e. < 10%; FISH+ defined as > 2 HER2:CEP17; Note: samples will be processed locally in the laboratory of investigational sites; the results of local laboratory HER2 analysis will be required and sufficient to start the study treatment; the Memorial Sloan-Kettering (MSK) laboratory will be used for subsequent confirmation of HER2 status; MSK pathology review will not be required to begin therapy on the protocol; samples provided to the MSK laboratory must either be HER2 IHC slides, or if FISH confirmation is necessary, a paraffin block(s) of adequate size to allow if possible for at least 5 slides with cuts that are 5-microns thick or if a paraffin block is not available, then if possible at least 5 slides with cuts that are 5-microns thick will be acceptable; archived or fresh tumor samples may be used
Documentation of complete cytogenetic response (CCR) by conventional cytogenetics or fluorescent in situ hybridization (FISH) analysis on a frontline TKI with stable dosing
Myc positive lymphoma is defined by:\r\n* Positive for Myc gene rearrangement by fluorescence in-situ hybridization (FISH) involving various breakpoints (e.g. 8-14, 8-22 and 2-8) AND concurrent gene rearrangements in bcl-2 and/or bcl-6 by FISH OR\r\n* Myc and Bcl-2 overexpression defined by >= 40% Myc and > 50% Bcl-2 expression by immunohistochemistry (IHC); patients may enroll in the study based on the local laboratory evaluation, but these should be confirmed by the University of North Carolina (UNC) Hematopathology Laboratory retrospectively
Patients meeting the above pathologic criteria will be eligible for therapy irrespective of their HER2/neu over expression status; immunohistochemical staining will be not be required for protocol entry but fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) studies for HER2/neu are preferred
Have negative HER2 expression by immunohistochemistry (IHC) (defined as 0 or 1+), or fluorescence in situ hybridization (FISH); if HER2 is 2+, negative HER2 expression must be confirmed by FISH
Tumor must be HER2 positive 3+ by immunohistochemistry or positive by fluorescence in situ hybridization (FISH) analysis if 2+ by immunohistochemistry
Double hit lymphoma is defined as B-cell lymphoma with genetic abnormalities involving A) and in addition, B) and/or C): A) v-myc myelocytomatosis viral oncogene homolog (avian) (C-MYC) arrangement or amplification by fluorescence in situ hybridization (FISH) study; B) B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL2) rearrangement or amplification by FISH study; C) BCL6 rearrangement or amplification by FISH study
Tumors must be HER-2/neu expression negative, as determined by local hospital laboratory (immunohistochemistry [IHC] =< 2+ or fluorescence in situ hybridization [FISH] negative)
c-MET positive (defined by c-MET IHC intensity score +2 in ? 50% of tumor cells and MET gene copy number ? 5 by FISH or IHC intensity score +3 in ? 50% of tumor cells) and K/NRAS WT status for mCRC patients only
Females with histologically or cytologically confirmed HER2-positive breast cancer. HER2-positive is defined as 3+ staining by immunohistochemistry or HER2 gene amplification by fluorescent in situ hybridization or silver in situ hybridization with HER2/CEP17 ratio ? 2.0
Presence of 17p deletion in CLL cells as demonstrated by fluorescence in-situ hybridization (FISH) testing
The invasive cancer must be HER2-negative (IHC 0-1+, or with a fluorescence based in situ hybridization [FISH] ratio of < 1.8 if IHC is 2+ or if IHC has not been done)
Any Her 2+ breast cancer (immunohistochemistry 3+; or amplified by fluorescence in situ hybridization [FISH])
Invasive breast cancer must be Her2-negative; if breast cancer is Her2 2+ by immunohistochemistry (IHC), then fluorescence in situ hybridization (FISH) must be negative for Her2 gene amplification
Tumor determined to be HER2-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (HER2/CEP17 amplification ratio >= 2.0); tumors determined to be ER or PR positive by immunohistochemistry (> 10% )
Patient has HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0 or 1+ as per local laboratory testing
HER2 positive as determined by score of 3 on immunohistochemistry (IHC) staining or gene amplification by fluorescence in situ hybridization (FISH).
3+ by IHC and/or
Local histologic or cytologic confirmation of HER2+ solid tumors by fluorescent in situ hybridization (FISH) amplification or immunohistochemistry (IHC) (3+)
HER2 Positive disease documented as FISH-positive and/or 3+ by IHC on previously collected tumor tissue.
Patients are required to have HER2+ breast cancer defined as a fluorescent in situ hybridization (FISH)- ratio of >= 2.0 or immunohistochemistry (IHC) 3+
For participants with lung cancer, centrally confirmed high expression of a sodium-dependent phosphate transporter (NaPi2b) by immunohistochemistry (IHC) is required (i.e., IHC 2+ or 3+).
Tumor negative for HER2 expression (0 or 1+ by immunohistochemistry [IHC]) or negative fluorescent in situ hybridization (FISH) testing
HER2-positive disease documented as in situ hybridization (ISH)-positive and/or 3+ by immunohistochemistry (IHC) on previously collected tumor tissue
Met diagnostic-positive status tested by immunohistochemistry (IHC)
HER2/neu-negative breast cancer by standard criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH]-negative if IHC 3+) at primary diagnosis
Progressive HER2 positive solid tumours (immunohistochemistry [IHC] positive or equivocal) with no available standard or curative treatment.
Currently on fish oil or has been on fish oil within the last 10 days
HER2 expression as defined by ISH positive and/or 3+ by immunohistochemistry (IHC)
Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer by local laboratory testing (immunohistochemistry [IHC] 3+ staining or fluorescent in situ hybridization [FISH] positive)
Patients with non-metastatic, node positive, HER2 negative breast cancer, confirmed by pathology report, who are in remission and defined as having no evidence of disease (NED); HER2 negative is defined as\r\n* 0-1+ HER2 expression by immunohistochemistry (IHC) OR\r\n* Fluorescence in situ hybridization (FISH) negative OR\r\n* HER2 2+ and FISH negative
Subjects with invasive breast cancer at least stage IIIA >= N2 (> 4 positive nodes) or have recurrent metastatic breast cancer rendered no evidence of disease (NED) by any means that are classic HER-2 3+ 10%, 2+ immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) positive or HER-2 2+ FISH negative that have completed chemotherapy and/or trastuzumab and have no evidence of disease
HER2/neu-expressing tumor (immunohistochemistry [IHC] 3+ and/or amplified fluorescence in situ hybridization [FISH] >2.2, or N0 (i+))
HER2/neu-expressing tumor (IHC 1-3+ and or positive FISH >1.2)
HER2 negative (HER2 1+ by IHC or HER2 2+ by IHC/FISH)
HER2 immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH) ordered on core biopsy, if biopsy indicates invasive cancer; Oncotype DX or other deoxyribonucleic acid (DNA) testing performed on core biopsy or not requested
History of HER2/neu positive cancer (IHC 3+ and/or fluorescence in situ hybridization [FISH] positive) as assessed by medical record review at screening
Pathologically or cytologically confirmed metastatic or primary esophagogastric cancer; HER2 positive status by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) as currently being implemented for patients with esophagogastric cancer; HER2 overexpression and/or amplification as determined by IHC (3+) or FISH (>= 2.0)
Two patients must be HER2 3+ by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) positive
The cancer must over express HER2 as determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH)
Cohort 1: Her2-positive (defined as 3+) or fluorescence in situ hybridization (FISH) HER2:Chromosome 17 centromere (CEP17) ratio > 2 biopsy-proven breast cancer
Cohort 2: Her2-positive (defined as 3+) or FISH HER2:CEP17 ratio > 2 OR HER2-negative (0 or 1+, 2+ and FISH negative) biopsy-proven breast cancer
Histologically confirmed HER2+ breast cancer: immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) amplified; by clinical assay on either primary or metastatic tumor
For patients with evidence of minimal residual disease prior to vaccination, assessment of minimal residual disease status by cytogenetics or fluorescence in situ hybridization (FISH) will be followed post vaccination
Histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC) (stage IV, American Joint Committee on Cancer [AJCC] v7.0) that carries (a) an ALK rearrangement, as determined by fluorescence in-situ hybridization (FISH), immunohistochemistry, or next generation sequencing (NGS) of either tissue or plasma, or (b) a ROS1 rearrangement as determined by FISH or reverse transcriptase-polymerase chain reaction (RT-PCR) or NGS via a local diagnostic test (LDT) or plasma analysis
Tumor HER2/neu expression must be determined (as part of standard clinical care) prior to study enrollment; HER2 may be tested by any Food and Drug Administration (FDA) approved HER2 testing method; if determination is intermediate by immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) or another alternate HER2 test must be performed
HER2/neu positive by IHC and/or another FDA approved HER2 testing method
The patient is receiving preoperative chemotherapy other than adriamyacin, cyclophosphamide, and a taxane (ACT) in standard or dose-dense fashion; herceptin may be added to the neoadjuvant chemotherapy regimen in cases where the tumor is Human Epidermal growth factor Receptor 2 (Her-2)/neu positive by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and must not be positive (HER2/CEP17 ratio must be < 2, and HER2 copy number < 6 signals/cell), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by institutional standards.