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
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 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
Patients must have either:* Estrogen receptor (ER) negative/progesterone receptor (PR) negative (< 10% by immunohistochemistry [IHC] staining) and HER-2 negative breast cancer OR* ER negative/PR negative (< 10% by IHC staining) and HER-2 positive tumors* HER2 status will be determined per the 2013 American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines:** 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** 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* For patients enrolling after neoadjuvant therapy, the ER, PR, and HER2 markers are based on assessment prior to initiating neoadjuvant treatment
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
Patients with HER2-positive tumors must have received neoadjuvant anti-HER2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen), unless medically contraindicated
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* Note: If HER2 status has not been clearly determined (i.e. equivocal/indeterminate), then patients should not be enrolled
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: * 0 or 1+ by immunohistochemistry (IHC) and in situ hybridization (ISH) not done* 0 or 1+ by IHC or ISH ratio (HER2 gene copy/chromosome 17) < 2* 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
Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that is one of the two following phenotypes:* TNBC defined as:** ER and PgR negative defined as immunohistochemistry (IHC) nuclear staining < 1%** HER2 negative (not eligible for anti-HER2 therapy) defined as:*** IHC 0, 1+ without in situ hybridization (ISH) OR *** IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells OR *** ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells (without IHC)* ER and/or PgR positive, HER2 negative breast cancer defined as:** ER and/or PgR positive defined as IHC nuclear staining >= 1%; AND** HER2 negative (not eligible for anti-HER2 therapy) defined as:*** IHC 0, 1+ without ISH OR*** IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells OR*** ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells (without IHC)
Patients with multifocal or multicentric invasive disease are eligible as long as all the lesions for which HER2 characterization is available are HER2 negative
Patients with synchronous bilateral invasive disease are eligible as long as all the lesions assessed for HER2 on both sides are negative
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)
Known estrogen, progesterone, and HER2 status of either primary tumor or metastasis; * Note: estrogen, progesterone and HER2 status of metastasis preferred for stratification
Female and male patients must have histologically confirmed invasive breast cancer that meets the following criteria:* 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* ER- and PR- should meet one of the following criteria:** =< 10% cells stain positive, with weak intensity score (equivalent to Allred score =< 3)** =< 1% cells stain positive, with weak or intermediate intensity score (equivalent to Allred score =< 3)* HER2 negative (not eligible for anti-HER2 therapy) will be defined as:** Immunohistochemistry (IHC) 0, 1+ without in situ hybridization (ISH) HER2/neu chromosome 17 ratio OR** 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** 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** 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** 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)
The tumor must have been determined to be human epidermal growth factor receptor 2 (HER2)-negative as follows:* Immunohistochemistry (IHC) 0-1+; or* 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* ISH non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells
Patient must NOT have human epidermal growth factor-2 positive (HER2+) metastatic disease
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
Primary and/or metastatic breast tumor must be negative for human epidermal growth factor receptor (HER-2/neu) over-expression based on 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)
Patients must have metastatic and/or recurrent (distant or locoregionally recurrent) breast cancer and be HER2 non-over expressing per 2013 American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) HER testing guidelines (0 or 1+ by immunohistochemistry [IHC]; and/or HER2 ratio < 2.0 and HER2 copy number < 4 signals/cell by in-situ hybridization [ISH])* Local Regional Recurrence** In the breast (after preserving therapy)** In the chest wall (after mastectomy)** In the ipsilateral/parasternal/infra-or supraclavicular lymph nodes** In the skin of the chest wall (not breast)** In the reconstructed breast
Her-2 negative, defined as:* In-situ hybridization (ISH) ratio of < 2.0 (if performed)* Immunohistochemistry (IHC) staining of 0-2 positive (+) (if performed) * Deemed to not be a candidate for Her-2 directed therapy
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
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* NOTE: Immunohistochemistry (IHC)-positive isolated tumor cells in the lymph node (N0 [i+]) are not considered node-positive and these patients also must have >= 1 cm residual invasive cancer in the breast in order to be eligible
Patients 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 with HER2-positive tumors must have received neoadjuvant anti-HER2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen), unless medically contraindicated