Capecitabine or Trastuzumab Emtansine with Radiation Therapy for the Treatment of High-Risk Stage I-IIIB Breast Cancer

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 or older
• Diagnosis of stage I-IIIB breast cancer
• Received neoadjuvant chemotherapy (minimum of 3 cycles) and surgical resection (lumpectomy and/or mastectomy)
• Discovered to have residual disease at least ypT1aNx or at least ypTxN1mic at surgical resection
• Candidate for adjuvant chemoradiation
• Planned initiation of radiation within 12 weeks of their final oncologic surgery
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Adequate cardiac function, with left ventricular ejection fraction (LVEF) greater or equal to 45% within 3 months before start of radiation treatment (only for patients who will receive T-DM1 therapy)
• Absolute neutrophil count >= 1.5 k/uL (within 21 days before the start of treatment)
• Platelets >= 100 k/uL (within 21 days before the start of treatment)
• Hemoglobin >= 10 g/dL (within 21 days before the start of treatment)
• Serum creatinine =< 1.5 x upper limit of normal (ULN) (within 21 days before the start of treatment)
• Bilirubin =< 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 4 x ULN is allowed) (within 21 days before the start of treatment)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (within 21 days before the start of treatment)
• Alkaline phosphatase =< 2.5 x ULN (within 21 days before the start of treatment)
• For females and males of reproductive potential: agreement to use adequate contraception during study participation and for an additional 6 months after the end of chemoradiation administration or until advised by their medical oncologist
• Agreement to adhere to lifestyle considerations throughout study duration
• Subjects taking warfarin and plan to receive capecitabine will need their anticoagulant management assessed before starting treatment

Exclusion Criteria

• Had a mastectomy with expander placement or immediate implant based reconstructions. Subjects receiving autologous reconstructions (i.e. traverse rectus abdominal muscle [TRAM] flaps, deep inferior epigastric artery perforator [DIEP] flaps, gluteal flaps, etc.) are eligible
• Diagnosed with systemic lupus
• Diagnosed with scleroderma
• Diagnosed with a genetic mutation associated with increased sensitivity to radiation (e.g. ataxia-telangectasias [AT]). AT heterozygotes without known radiation sensitivity may be included
• Acute bacterial or fungal infection requiring intravenous antibiotics at time of registration
• Pathologic evidence of metastatic disease, or strong clinical/radiological evidence of metastatic disease, at the investigator’s judgment
• Pregnancy or lactation
• Incarceration
• Presence of cardiac pacemaker on side of the body that is being treated unless the pacemaker can be moved prior to treatment
• Anthracycline exposure exceeding a cumulative doxorubicin dose of 264 mg/m^2 (240 mg/m^2 plus a 10% threshold)
• Known allergic reactions to components of capecitabine or T-DM1
• Known dihydropyrimidine dehydrogenase (DPD) deficiency for patients prescribed capecitabine
• Febrile illness within a week of starting treatment
• Incomplete healing of chest wall or breast in the treatment field within 12 weeks from surgery
• Known human immunodeficiency virus (HIV) or active hepatitis
• Unwilling to discontinue endocrine therapy during chemoradiation therapy, if currently taking endocrine therapy