Patients must have a histologically confirmed diagnosis of invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2, for whom standard adjuvant endocrine therapy is planned; estrogen and progesterone receptor positivity must be assessed according to American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guidelines as either estrogen receptor (ER) or progesterone receptor (PR) >= 1% positive nuclear staining; HER-2 test result negativity must be assessed as per ASCO/CAP 2013 guidelines using immunohistochemistry (IHC), in situ hybridization (ISH) or both; HER-2 is negative if a single test (or all tests) performed in a tumor specimen show: a) IHC negative (0 or 1+) or b) ISH negative using single probe or dual probe (average HER-2 copy number < 4.0 signals per cell by single probe or HER-2/chromosome enumeration probe [CEP] ratio < 2.0 with an average copy number < 4.0 signals per cell by dual probe); if HER-2 IHC is 2+, evaluation for gene amplification (ISH) must be performed and the ISH must be negative; ISH is not required if IHC is 0 or 1+; HER-2 equivocal is not eligible
The tumor must have been determined to be human epidermal growth factor receptor 2 (HER2)-negative as follows:\r\n* Immunohistochemistry (IHC) 0-1+; or\r\n* IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to centromere enumerator probe 17 (CEP17) < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells; or\r\n* ISH non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells
Female and male patients must have histologically confirmed invasive breast cancer that meets the following criteria:\r\n* Clinical stage II-III (American Joint Committee on Cancer [AJCC] 7th edition) at diagnosis, based on initial evaluation by clinical examination and/or breast imaging; no metastatic disease allowed\r\n* ER- and PR- should meet one of the following criteria:\r\n** =< 10% cells stain positive, with weak intensity score (equivalent to Allred score =< 3)\r\n** =< 1% cells stain positive, with weak or intermediate intensity score (equivalent to Allred score =< 3)\r\n* HER2 negative (not eligible for anti-HER2 therapy) will be defined as:\r\n** Immunohistochemistry (IHC) 0, 1+ without in situ hybridization (ISH) HER2/neu chromosome 17 ratio OR\r\n** IHC 2+ and ISH HER2/neu chromosome 17 ratio non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells OR\r\n** ISH HER2/neu chromosome 17 ratio non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells without IHC\r\n** NOTE: patients that originally present with synchronous bilateral tumors are eligible provided both tumors are TNBC, and at least one of them fulfills the remainder eligibility criteria of the protocol; multifocal or multicentric breast cancers are eligible as long as all tumors fulfill eligibility criteria\r\n** NOTE: patients that have a discrepancy in ER/PR/HER2 status between original diagnosis and surgical specimen (only applicable if ER/PR/HER2 status were repeated; repeating it is not mandatory) are not eligible for study participation (i.e. ER/PR/HER2 has to fulfill above criteria in both scenarios)
Invasive breast cancer is human epidermal growth factor receptor 2 (HER2) negative; a patient is considered to have HER2 negative breast cancer if one of the following if one of the following applies: \r\n* 0 or 1+ by immunohistochemistry (IHC) and in situ hybridization (ISH) not done\r\n* 0 or 1+ by IHC or ISH ratio (HER2 gene copy/chromosome 17) < 2\r\n* 2+ by IHC and ISH ratio (HER2 gene copy/chromosome 17) < 2
Patients whose tumors have HER2 immunohistochemistry (IHC) 3+, in situ hybridization (ISH) >= 2.0, or average HER2 copy number >= 6.0 signals per cell are not eligible; receptor status may be based on any time during treatment prior to study randomization, and from any site (i.e. primary, recurrent, or metastatic)
Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that is one of the two following phenotypes:\r\n* TNBC defined as:\r\n** ER and PgR negative defined as immunohistochemistry (IHC) nuclear staining < 1%\r\n** HER2 negative (not eligible for anti-HER2 therapy) defined as:\r\n*** IHC 0, 1+ without in situ hybridization (ISH) OR \r\n*** IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells OR \r\n*** ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells (without IHC)\r\n* ER and/or PgR positive, HER2 negative breast cancer defined as:\r\n** ER and/or PgR positive defined as IHC nuclear staining >= 1%; AND\r\n** HER2 negative (not eligible for anti-HER2 therapy) defined as:\r\n*** IHC 0, 1+ without ISH OR\r\n*** IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells OR\r\n*** ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells (without IHC)
Primary tumors and/or metastatic lesions must demonstrate HER2-neu overexpression by immunohistochemistry (IHC 3+) or amplification by in situ hybridization based on the following:\r\n* Single-probe average HER2 copy number >= 6.0 signals/cell\r\n* Dual-probe HER2/chromosome enumeration probe 17 (CEP17) ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell\r\n* Dual-probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell\r\n* Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number > 6.0 signals/cell\r\nPatients may be estrogen and/or progesterone positive (>= 1%) or negative (< 1%); hormone receptor status will be a stratification factor
Evidence of HER2 positive metastatic breast cancer in either a primary or metastatic site, if 3+ by an immunohistochemistry (IHC) method defined as uniform membrane staining for HER2 in 10% or more of tumor cells or demonstrate HER2 gene amplification by an in situ hybridization (ISH) method (single probe, average HER2 copy number >= 6.0 signals/cell; dual probe HER2/chromosome enumeration probe [CEP] 17 ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell; dual probe HER2/CEP 17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell; and HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell) or amplified by fluorescence in situ hybridization (FISH) > 2.0; high average copy number of HER2 (>= 6.0 signals/cell) is considered positive regardless of the HER2/CEP17 ratio
Participants must NOT have HER2 positive status based on American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines defined as:\r\n* Immunohistochemistry (IHC) 3+ based on circumferential membrane staining that is complete, intense -AND/OR – \r\n* Fluorescence in situ hybridization (FISH) positive based on one of the three following criteria:\r\n** Single-probe average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/CEP17 ratio >= 2.0
Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0) from toxicities related to any prior treatments, unless adverse event(s) (AE[s]) are clinically nonsignificant and/or stable on supportive therapy:\r\n* Cohort 1: HER2-positive, defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines: \r\n** IHC 3+ based on circumferential membrane staining that is complete, intense OR\r\n** FISH positive based on one of the three following criteria:\r\n*** Single-probe average HER2 copy number >= 6.0 signals/cell; OR\r\n*** Dual-probe HER2/chromosome 17 centromere (CEP17) ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell; OR\r\n*** Dual-probe HER2/CEP17 ratio >= 2.0\r\n* Cohort 2: Hormone receptor positive (estrogen receptor [ER]-positive and/or progesterone receptor [PR]-positive, defined as >= 1% staining by immunohistochemistry) and HER2-negative\r\n* Cohort 3: Triple negative (ER-negative, PR-negative, HER2-negative)
Pathologically confirmed HER2-positive MBC by local laboratory with the following requirements: HER2 overexpressed or amplified (immunohistochemistry of 3+ or HER2 gene amplification by in situ hybridization with a ratio of HER2-gene signals to centromere 17 signals ? 2.0 or average HER2 copy number ? 6.0 signals/cells)
Single-probe average HER2 copy number < 4.0 signals/cell
Dual-probe HER2/CEP17 ratio < 2 with an average HER2 copy number < 4.0 signals/cell.
Metastatic triple negative breast cancer (TNBC), as defined by: \r\n* Estrogen receptor (ER) and progesterone receptor (PR) negative as defined as ER < 10% and PR < 10% by immunohistochemistry according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing\r\n* Human epidermal growth factor receptor 2 (HER2) non-amplified per ASCO/CAP guidelines, defined as: \r\n** immunohistochemistry (IHC) score 0/1+\r\n** IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells; or\r\n** ISH non-amplified with a ratio of HER2 to chromosome enumeration probe 17 (CEP17) < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells
Has confirmed HR+ and HER2 negative breast cancer with known metastatic disease. HR defined as positive if expression greater than 10% by immunohistochemistry (IHC). HER2 negative or non-amplified is determined by the current American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) criteria which are as follows: HER2 testing by IHC as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be performed. HER2 is positive if: i. IHC 3+ based on circumferential membrane staining that is a. complete, intense ii. ISH positive based on: a. single-probe average HER2 copy number >= 6.0 signals/cell. b. Dual-probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell c. Dual-probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell d. Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell.
COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: Patients must have histologically confirmed persistent or recurrent invasive metastatic hormone receptor positive, HER2 normal breast cancer for which standard curative measures do not exist or are no longer effective; hormone receptor positive is defined as estrogen receptor (ER) positive >= 10% by immunohistochemistry (IHC) and/or progesterone receptor (PR) positive >= 10% by IHC; HER2 will be considered negative per American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines (HER2 test result as negative if a single test (or both tests) performed show: 1) IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within >10% of the invasive tumor cells; 2) IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =< 10% of the invasive tumor cells; or 3) in situ hybridization (ISH) negative based on: a) single-probe average HER2 copy number < 4.0 signals/cell or b) dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell)and HER2 testing must have been performed in a laboratory accredited by the College of American Pathologists (CAP) or another accrediting entity
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Patients must have histologically or cytologically confirmed persistent or recurrent invasive, metastatic triple negative breast cancer (TNBC) for which standard curative measures do not exist or are no longer effective; TNBC, defined as ER negative (ER < 10%), PR negative (PR < 10%); HER2 will be considered negative per ASCO-CAP guidelines (HER2 test result as negative if a single test (or both tests) performed show: 1) IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of the invasive tumor cells; 2) IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =< 10% of the invasive tumor cells; or 3) ISH negative based on: a) single-probe average HER2 copy number < 4.0 signals/cell or b) dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell) and HER2 testing must have been performed in a laboratory accredited by the College of American Pathologists (CAP) or another accrediting entity
Hormone receptor positive (defined as estrogen receptor [ER] and/or progesterone receptor [PR] positive), HER2 negative breast cancer that is clinically staged II-III with no known metastatic disease. ER and/or PR defined as positive if expression > 10% by immunohistochemistry (IHC). HER2 negative or non-amplified as determined by the current American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) criteria which are as follows: HER2 testing by immunohistochemistry (IHC) as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be performed. HER2 is positive if: IHC 3+ based on circumferential membrane staining that is complete, intense ISH positive based on: 1) Single-probe average HER2 copy number >= 6.0 signals/cell, 2) Dual-probe HER2/CEP17 ratio >= 2.0; c,e with an average HER2 copy number >= 4.0 signals/cell, 3) Dual-probe HER2/CEP17 ratio >= 2.0; c,e with an average HER2 copy number < 4.0 signals/cell, 4) Dual-probe HER2/CEP17 ratio < 2.0; c,e with an average HER2 copy number >= 6.0 signals/cell
HER2 status confirmed positive by means of immunohistochemistry (IHC) or in situ hybridization (ISH) according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2013 guidelines; it is considered positive if scored as 3+ by an IHC method defined as uniform membrane staining for HER2 in 10% or more of tumor cells or demonstrate HER2 gene amplification by an ISH method (single probe, average HER2 copy number >= 6.0 signals/cell; dual probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell; dual probe HER2/chromosome enumeration probe (CEP)17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell; HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell)
Cohort 1: Phase 1b: subject must have HER2 + (regardless of hormonal receptor status) primary metastatic or locally advanced breast cancer (IBC or Non-IBC); HER2 positive status is defined as strongly positive (3+) staining score by immunohistochemistry (IHC), or gene amplification using fluorescence in situ hybridization (FISH), if performed; if IHC is equivocal (2+), assays using FISH require gene amplification based on recent American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guideline: dual-probe HER2/CEP17 ratio is >= 2.0 and/or an average HER2 copy number >= 6.0 signals/cell; IBC is determined by using international consensus criteria: onset: rapid onset of breast erythema, edema and/or peau d’orange, and/or warm breast, with/without an underlying breast mass; duration: history of such findings no more than 6 months; extent erythema occupying at least 1/3 of whole breast; pathology: pathologic confirmation of invasive carcinoma
Cohort 2 patient must have HER2-/HR+ stage III IBC; HER2 negative status, which determined by assays using IHC require negative (0 or 1+) staining score; if IHC is equivocal (2+) staining score, assays using FISH require the absence of gene amplification: dual-probe HER2/CEP17 ratio is < 2.0 and an average HER2 copy number < 4.0 signals/cell; if HER2 testing result is confirmed at M D Anderson Cancer Center (MDACC), it does not require centralized repeat testing; hormone receptor (HR) positivity is determined by estrogen receptor (ER) >= 10% and /or progesterone receptor (PR) >= 10% by IHC staining
Breast cancer determined to be HER2-negative per current American Society of Clinical Oncologists/College of American Pathologists (ASCO/CAP) HER2 guidelines (if immunohistochemistry [IHC] was performed, IHC 0 or 1+; if fluorescence in situ hybridization [FISH] or other in situ hybridization test, dual probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell)
Estrogen receptor (ER) and progesterone receptor (PR) expression both < 10% by immunohistochemistry (IHC) and human epidermal growth factor receptor 2 (HER2) negative or non-amplified as determined by the current American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) criteria which are as follows: HER2 testing by IHC as 0 or 1+; if HER2 is 2+, ISH (in situ hybridization) must be performed; HER2 is positive for gene amplification if: - IHC 3+ based on circumferential membrane staining that is complete, intense - ISH positive based on: \r\n* Single-probe average HER2 copy number >= 6.0 signals/cell\r\n* Dual-probe HER2/chromosome enumeration probe (CEP)17 ratio >= 2.0; with an average HER2 copy number >= 4.0 signals/cell\r\n* Dual-probe HER2/CEP17 ratio >= 2.0; with an average HER2 copy number < 4.0 signals/cell\r\n* Dual-probe HER2/CEP17 ratio < 2.0; with an average HER2 copy number >= 6.0 signals/cell
Hormone receptor positive and HER2 negative breast cancer; patients with HER2/neu positive tumors irrespective of their hormone receptor status will be excluded; at least 10% of tumor cell nuclei should be immunoreactive for hormone receptors (ER and/or PR) to be deemed eligible for the study; Her2/neu negative is defined as:\r\n* Immunohistochemistry (IHC) score of 0 (no staining is observed or membrane staining that is incomplete and is faint/barely perceptible and within =< 10% of tumor cells) OR\r\n* IHC score of 1 (incomplete membrane staining that is faint/barely perceptible and within < 10% of tumor cells) OR\r\n* Fluorescence in situ hybridization (FISH) HER2/chromosome enumeration probe 17 (CEP17) ratio of < 1.8 or average HER2 gene copy number of < 4 signals/nucleus for test systems without an internal control probe\r\n* Equivocal results for HER2/neu (defined as: IHC 2+ or FISH HER2/CEP17 ratio of 1.8-2.2 or average HER2 gene copy number 4-6 HER2 signals/nucleus for test systems without an internal control probe) should prompt reflex test (same specimen using an alternative method) or order a new test (new specimen if available, using IHC or FISH)
The tumor specimen obtained at the time of diagnosis of locally recurrent or metastatic disease must have been demonstrated to be HER2-positive based on central testing; HER2-positive is defined as HER2/chromosome enumeration probe 17 (CEP17) ratio >= 2.0 or >= 6 average HER2 copy number per cell by in situ hybridization (ISH) or IHC 3+ by current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines; sites must send biopsy specimens for central testing which have been determined to be HER2-positive or HER2-equivocal on local testing
HER2 negative in the primary or metastatic tumor tissue defined as:\r\n* Immunohistochemistry (IHC) grade 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =< 10% of the invasive tumor cell; OR\r\n* IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of the invasive tumor cell; OR\r\n* IHC grade 2+ staining intensity by means of IHC analysis with no gene amplification below; OR\r\n* No gene amplification on in situ hybridization (ISH) based on:\r\n** Single-probe average HER2 copy number < 4.0 signals/cell OR\r\n** Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell
The tumor must have been determined to be HER2-postive as follows:\r\n* Immunohistochemistry (IHC) 3+ or\r\n* In situ hybridization (ISH)-positive (defined by ratio of HER2 to circulating endothelial progenitors [CEP]17 >= 2.0 or HER2 gene copy number >= 6 per nucleus)
Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes) invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2 status; estrogen and progesterone receptor positivity must be assessed according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as either estrogen receptor (ER) or progesterone receptor (PR) >= 1% positive nuclear staining; HER-2 test result negativity must be assessed as per ASCO/CAP 2013 guidelines using immunohistochemistry (IHC), in situ hybridization (ISH) or both; HER-2 is negative if a single test (or all tests) performed in a tumor specimen show: a) IHC negative (0 or 1+) or b) ISH negative using single probe or dual probe (average HER-2 copy number < 4.0 signals per cell by single probe or HER-2/CEP ration < 2.0 with an average copy number < 4.0 signals per cell by dual probe); if HER-2 IHC is 2+, evaluation for gene amplification (ISH) must be performed and the ISH must be negative; ISH is not required if IHC is 0 or 1+; HER-2 equivocal is not eligible
HER-2 positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines, confirmed by central testing confirmed by central testing (NeoGenomics Laboratories): \r\n* Immunohistochemistry (IHC) 3+ based on circumferential membrane staining that is complete, intense AND/OR\r\n* FISH positive based on one of the three following criteria:\r\n** Single-probe average HER2 copy number >= 6.0 signals/cell OR\r\n** Dual-probe HER2/chromosome 17 centromere (CEP17) ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell OR\r\n** Dual-probe HER2/CEP17 ratio >= 2.0\r\n* NOTE: HER-2 status must be confirmed to be positive by central review prior to patient starting protocol therapy; patients previously having had HER2 testing at NeoGenomics Laboratories, Inc. (formerly Clarient Laboratories) do not need to undergo retesting for central confirmation of HER2 status; ductal carcinoma in situ (DCIS) components should not be counted in the determination of HER2 status
Documented HER2-negative tumor based on local testing on most recent tumor biopsy (immunohistochemistry score 0/1+ or negative by in situ hybridization HER2/CP17 ratio < 2 or for single probe assessment HER2 copy number < 4)
Invasive breast cancer must be HER2 negative; HER2 negative is defined as a single test or both tests used to determine HER2 status (in situ hybridization [ISH] and immunohistochemistry [IHC]) show:\r\n* IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of the invasive tumor cells\r\n* IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =< 10% of the invasive tumor cells\r\n* ISH single-probe average HER2 copy number < 4.0 signals/cell\r\n* ISH dual-probe HER2/chromosome 17 centromere probe (CEP17) ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell
HER2 negative, defined as 0-1+ by immunohistochemistry or fluorescence in situ hybridization (FISH)-negative (HER2 copy number < 6 and HER2/chromosome enumeration probe [CEP]17 ratio < 2.0); central confirmation is not required
HER2 positive breast cancer (3+ by immunohistochemistry or Her2 gene amplification by in situ hybridization with a ratio of HER2 gene signals to centromere 17 signals > 2.0 or average HER2 copy number > 6.0 signals/cell)
Participants must have invasive primary tumor or metastatic tissue confirmation of HER2-positive status, defined as presence of one or more of the following criteria: HER2-positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines\r\n* Immunohistochemistry (IHC) 3+ based on circumferential membrane staining that is complete, intense OR\r\n* Fluorescent in situ hybridization (FISH) positive based on one of the three following criteria:\r\n** Single-probe average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/chromosome 17 centromere (CEP17) ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/CEP17 ratio >= 2.0\r\n* Note: participants with a negative or equivocal overall result (FISH ratio of < 2.0 or =< 6.0 HER2 gene copies per nucleus) and IHC staining scores of 0, 1+, 2+ are not eligible for enrollment
HER-2 positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines, confirmed by central testing (Clarient laboratories [labs]):\r\n* IHC 3+ based on circumferential membrane staining that is complete, intense OR\r\n* Fluorescence in situ hybridization (FISH) positive based on one of the three following criteria:\r\n** Single-probe average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/chromosome 17 centromere (CEP17) ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell; OR\r\n** Dual-probe HER2/CEP17 ratio >= 2.0\r\n* NOTE: ductal carcinoma in situ (DCIS) components should not be counted in the determination of HER2 status\r\n* NOTE: HER-2 status must be confirmed to be positive by central review prior to patient starting protocol therapy; patients previously having had HER2 testing at Clarient Laboratories do not need to undergo retesting for central confirmation of HER2 status; a pathology report documenting testing at Clarient should be provided at time of patient registration
HER2-positive breast cancer, defined as by American Society of Clinical Oncology College of American Pathologists (ASCO CAP) 2013 guidelines\r\n* Immunohistochemistry (IHC) 3+ based on circumferential membrane staining that is complete, intense AND/OR\r\n* Fluorescence in situ hybridization (FISH) positive based on one of the following three criteria: \r\n** Single-probe average HER2 copy number >= 6.0 signals/cell OR\r\n** Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0signals/cell; OR \r\n** Dual-probe HER2/CEP17 ratio >= 2.0
Histologically proven diagnosis HER2-positive breast cancer; Her2-positive is defined as follows:\r\n* Validated immunohistochemistry (IHC) assay score of 3+ (defined as uniform, intense staining of > 30% of invasive tumor cells)\r\n* Average HER2 gene copy number of > 6\r\n* Gene amplified (HER2:D17Z1 ratio > 2.20)
Patients must have either:\r\n* Estrogen receptor (ER) negative/progesterone receptor (PR) negative (< 10% by immunohistochemistry [IHC] staining) and HER-2 negative breast cancer OR\r\n* ER negative/PR negative (< 10% by IHC staining) and HER-2 positive tumors\r\n* HER2 status will be determined per the 2013 American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines:\r\n** HER2 is considered positive if a) there is IHC 3+ staining or b) positive using either single probe in situ hybridization (ISH) or dual probe ISH\r\n** HER2 is considered negative if a) there is IHC 0 or 1+ staining or b) ISH negative using either single probe ISH or dual probe ISH\r\n* For patients enrolling after neoadjuvant therapy, the ER, PR, and HER2 markers are based on assessment prior to initiating neoadjuvant treatment
Clinical stage IV ER, PR, HER2 negative invasive mammary carcinoma, previously documented by histological analysis and that meets the following criteria:\r\n* HER2 negativity is defined as any of the following by local laboratory assessment: in-situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell), or IHC 0 or IHC 1+ (if more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the protocol chair to establish eligibility of the patient)\r\n* ER and PR negativity are defined as =< 10% of cells expressing hormonal receptors via IHC analysis
or c-MET amplification; FISH c-MET to chromosome 7 (CEP 7) ratio ? 2.2; NGS copy number variation ? 4
c-MET amplification; FISH c-MET to chromosome 7 (CEP 7) ratio ? 2.2; NGS copy number variation ? 4