Adjuvant Chemoradiation and Biomarkers of Response in High-risk 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 ypTxN1mic at surgical resection
• Candidate for adjuvant chemoradiation as part of standard clinical care
• Planned initiation of radiation within 12 weeks of their final oncologic surgery
• ECOG performance status ≤2
• Adequate cardiac function, with LVEF greater or equal to 45% (only for patients who will receive TDM-1 therapy)
• Adequate organ function per the following criteria within 21 days before the start of treatment. If a laboratory value required for study eligibility does not meet the below requirements, the value may be retested.
• Absolute neutrophil count ≥1.5 k/uL
• Platelets ≥100 k/uL
• Hemoglobin ≥ 10 g/dL
• Serum Creatinine ≤ 1.5 x ULN
• Bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 4x ULN is allowed).
• AST and ALT ≤ 2.5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN
• 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 reconstructions
• 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/m2 (240 mg/m2 plus a 10% threshold)
• Known allergic reactions to components of capecitabine or T-DM1
• Known 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 HIV or active hepatitis.
• Unwilling to discontinue endocrine therapy if currently taking endocrine therapy.