Chemotherapy With or Without Trastuzumab After Surgery in Treating Women With Invasive Breast Cancer

Inclusion Criteria

• Patients should have a life expectancy of at least 10 years, excluding their diagnosis of breast cancer; (comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer)
• Women of reproductive potential must agree to use an effective non-hormonal method of contraception (for example condoms, some intrauterine devices, diaphragms, tubal ligation, vasectomized partner, or abstinence) during therapy and for at least 6 months (Arm 1 patients) and for at least 7 months (Arm 2 patients) after the last dose of study therapy (chemotherapy or trastuzumab)
• Submission of tumor samples from the breast surgery is required for all patients; therefore, the local pathology department policy regarding release of tumor samples must be considered in the screening process; patients whose tumor samples are located in a pathology department that by policy will not submit any samples for research purposes should not be approached for participation in the B-47 trial
• The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
• Eastern Cooperation Oncology Group (ECOG) performance status of 0 or 1
• The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination
• All of the following staging criteria (according to the 7th edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual) must be met:
• By pathologic evaluation, primary tumor must be pT1-3
• By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN2b, pN3a, or pN3b
• If pN0, one of the following criteria must be met:
• pT2 and estrogen receptor (ER) negative and progesterone receptor (PgR) negative; or
• pT2 and ER positive (PgR status may be positive or negative) and either grade 3 histology or Oncotype DX Recurrence Score of >= 25; or
• pT3 regardless of hormone receptor status, histologic grade, and Oncotype DX Recurrence Score
• HER2 status of the primary tumor must be evaluated prior to randomization; all testing performed must indicate that the tumor is HER2-low as defined below
• IHC must be performed and the IHC staining results must indicate a score of 1+ (in situ hybridization [ISH] testing is not required) or 2+ (ISH must also be performed and must indicate that the tumor is HER2-low as described below)
• If ISH testing is performed, test results must be as follows and IHC must be 1+ or 2+: the ratio of HER2 to chromosome enumeration probe 17 (CEP17) must be = 1,200/mm^3
• Platelet count must be >= 100,000/mm^3
• Hemoglobin must be >= 10 g/dL
• Total bilirubin must be = ULN to 1.5 x ULN due to Gilbert disease or similar syndrome involving slow conjugation of bilirubin
• Alkaline phosphatase must be = the ULN
• Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET]-CT, or PET scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the above requirements are met
• Patients with alkaline phosphatase that is > ULN but = = 50% regardless of the cardiac imaging facility's lower limit of normal
• For patients who will receive the AC-->WP chemotherapy regimen, the LVEF must be >= 55% regardless of the cardiac imaging facility's lower limit of normal
• NOTE: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments, it is critical that this baseline study be an accurate assessment; if the baseline LVEF is > 70%, the investigator is encouraged to have the accuracy of the initial LVEF result confirmed and repeat the test if the accuracy is uncertain

Exclusion Criteria

• Primary tumor with any of the following HER2 testing results:
• IHC staining intensity:
• 0 on all evaluations of specimens
• 3+ on evaluation of any specimen
• ISH