Biomarker Profiling in Determining Radiation Therapy Omission in Patients with Favorable-Risk Breast Cancer Who Have Undergone Breast-Conserving Surgery

Inclusion Criteria

• Histologically confirmed invasive breast cancer
• The primary tumor must be excised via breast conserving surgery (“lumpectomy”) with negative margins (no ink on tumor) in the final specimen
• The tumor must be =< 2 cm (T1) in the largest dimension
• Immunohistochemical studies must demonstrate the invasive component of the tumor to be estrogen receptor positive (ER+) (>= 10%) or progesterone receptor positive (PR+), human epidermal growth factor receptor 2 negative (HER2-) and grade 1 or 2
• The patient must have undergone either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) demonstrating pathologic node-negativity (pN0); however, patients with immunohistochemical evidence of isolated tumor cells in a lymph node [pN0(i+)] are eligible if no deposit > 0.2 mm is identified; if the patient is 70 years of age or older and are clinically node negative, a SLNB or ALND is not required
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%); however, if a patient has an ECOG performance status >= 3 due to mobility limitations and the physician deems capable of study participation, the patient is eligible
• Life expectancy of > 5 years per the clinical impression of the treating physician(s)
• Eligible for and willing to undergo a course of adjuvant endocrine therapy
• Women of child-bearing potential must attest to not being pregnant; pregnancy testing will be at the discretion of the treating physician

Exclusion Criteria

• At the time of enrollment, subjects may not have received any systemic therapy for the current breast cancer (including chemotherapy, targeted biologic therapy or hormonal therapy) prior to the core biopsy or prior to the primary breast excision; up to 3 months of hormonal therapy prior to enrollment is permitted, provided the treatment is entirely after both the core biopsy and the primary breast excision; chemotherapy or targeted biologic therapy must not be part of the adjuvant postoperative treatment plan
• Clinical, radiographic or pathologic evidence of multicentric disease
• Evidence of T4 disease (e.g., involvement of the chest wall, skin, dermal lymphatics, or inflammatory breast cancer)
• The invasive component of the tumor has a grade 3 histology
• Tumors in which the invasive component is present only as micro-invasion
• Multicentric invasive or in situ carcinoma
• Bilateral breast malignancy
• Inability or unwillingness to tolerate endocrine therapy
• Documented mutation of tumor protein 53 (TP53), breast cancer (BRCA)1, BRCA2, or other hereditary cancer syndromes
• Significant comorbidity associated with an estimation of < 5 remaining life years
• Another diagnosis of malignancy within the 5 years preceding enrollment (excluding non-melanoma skin cancers or in situ cervical lesions, which are permitted)
• Inability to understand or provide informed consent
• Current addictive or psychiatric disorder which may preclude protocol adherence
• Prior breast or chest radiotherapy for any indication
• Pregnant or lactating