Statement: A patient who had a breast-conserving surgery in the year prior to study entry would be excluded from both the primary trial and the secondary trial.
Primary_evidence: Inclusion Criteria:   Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1   Non-metastatic histologically confirmed primary invasive breast carcinoma that was operable   HER2-positive breast cancer   Known hormone receptor status of the primary tumor Adequately excised: participants must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy   Pathological tumor-node-metastasis staging (Union for International Cancer Control-American Joint Committee on Cancer [UICC/AJCC] 7th edition): eligible participants must have either:   Node-positive disease (pN more than or equal to [>/=] 1), any tumor size except T0, and any hormonal receptor status; or Node-negative disease (pN0) with pathologic tumor size >2.0 centimeters by standard local assessment and negative for estrogen receptor (ER) and progesterone receptor (PR) determined by a central pathology laboratory   Participants with synchronous bilateral invasive disease are eligible only if both lesions are HER2-positive   No more than 9 weeks (63 days) may elapse between definitive breast surgery (or the last surgery if additional resection required for breast cancer) and randomization   Baseline left ventricular ejection fraction (LVEF) >/=55% measured by echocardiogram (ECHO; preferred) or multiple-gated acquisition (MUGA) scans   Documentation on hepatitis B virus (HBV) and hepatitis C virus (HCV) serology is required   Female participants of childbearing potential must be willing to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception. For male participants with partners of childbearing potential, one highly effective form of contraception or two effective forms of contraception must be used. Contraception must continue for the duration of study treatment and for 6 months after the last dose of study treatment Exclusion Criteria:   History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma   History of non-breast malignancies within the 5 years prior to randomization, except for carcinoma in situ (CIS) of the cervix, CIS of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin   Any clinical T4 tumor as defined by tumor-node-metastasis classification in UICC/AJCC 7th edition, including inflammatory breast cancer   For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment (for example, neoadjuvant or adjuvant), including but not limited to, chemotherapy, anti-HER2 therapy (for example, trastuzumab, trastuzumab emtansine, pertuzumab, lapatinib, neratinib, or other tyrosine kinase inhibitors), hormonal therapy, OR anti-cancer radiation therapy (RT) (intra-operative radiotherapy as a boost at the time of primary surgery is acceptable)   Previous therapy with anthracyclines, taxanes, or HER2-targeted therapy for any malignancy   History of DCIS and/or lobular CIS (LCIS) that was treated with any form of systemic chemotherapy, hormonal therapy, or RT to the ipsilateral breast where invasive cancer subsequently developed. Participants who had their DCIS/LCIS treated with surgery only and/or contralateral DCIS treated with radiation are allowed to enter the study   Participants with contraindication to RT while adjuvant RT is clinically indicated   Concurrent anti-cancer treatment in another investigational trial   Cardiopulmonary dysfunction as defined by protocol: angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease, significant symptoms (Grade >/=2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia, myocardial infarction within 12 months prior to randomization, uncontrolled hypertension, evidence of transmural infarction on electrocardiogram (ECG), requirement for oxygen therapy   Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes, or known infection with HIV   Any known active liver disease. For participants who are known carriers of HBV/HCV, active hepatitis B/C infection must be ruled out per local guidelines   Inadequate hematologic, renal or liver function   Pregnant or lactating women   Hypersensitivity to any of the study medications or any of the ingredients or excipients of these medications, including hypersensitivity to benzyl alcohol   Chronic immunosuppressive therapies, including systemic corticosteroids
Secondary_evidence: Inclusion Criteria:   female   subject is 25-100 years of age   subjects has at least one breast imaging finding on mammography and/or ultrasound which is assessed as highly suggestive of malignancy and recommended to biopsy   subject is able to provide informed consent Exclusion Criteria:   subject is pregnant   subject is actively lactating or discontinued breastfeeding less than 2 months ago   subject has breast implants   subject is scheduled for sentinel node procedure using radioactive Tc-99m within 24 hours of the PEM study   subject has contraindications for core biopsy and other invasive procedures   subject has Type I diabetes mellitus or poorly controlled Type II diabetes mellitus   subject has had surgery or radiation therapy on the study breast or has had chemotherapy within the past 12 months   subject has not fasted for 4-6 hours prior to the procedure and/or have a fasting blood glucose level greater than 140 mg/dl on day of PEM imaging