Suitable for breast conserving surgery and radiotherapy All women who undergo breast conserving therapy must receive concomitant radiotherapy; radiation after mastectomy is to be administered according to pre-specified institutional guidelines; radiation must be completed at least 21 days prior to registration Patients must have completed either breast-conserving surgery or total mastectomy, with negative margins and appropriate axillary staging; a negative margin is defined as no evidence of tumor or ductal carcinoma in situ (DCIS) at the line of resection; additional operative procedures may be performed to obtain clear margins\r\n* Patients who had breast-conserving surgery must have completed whole breast radiation; use of regional nodal basin radiation will be at the discretion of the investigator according to institutional guidelines\r\n* Patients with >= 4 positive lymph nodes must have completed breast/chest wall and nodal basin radiation therapy according to standard of care guidelines before randomization; omission of radiation therapy is not allowed in this high-risk population of patients\r\n* Patients must be registered at least 21 days after completion of radiation therapy and must have recovered (=< grade 1) from any of the effects of radiation Cancer patients with stage 0-III breast cancer (BrCA) treated with breast conserving surgery or mastectomy and clear margins will be recruited to the study Patient has elected breast-conserving surgery (BCS) as surgical treatment for early-stage breast cancer No contraindication to breast conserving surgery, sentinel lymph node biopsy, or radiation therapy Operable DCIS, suitable for breast conserving surgery Appropriate candidate for breast-conserving surgery based on multi-disciplinary assessment Subjects are not a candidate for breast conserving surgery Patient desires breast conserving therapy Patients must have undergone breast-conserving surgery The tumor has been excised with a breast-conserving resection and there is no tumor seen at any of the margins of the resection The primary tumor must be excised via breast conserving surgery (“lumpectomy”) with negative margins (no ink on tumor) in the final specimen Participant agreement to undergo mastectomy or breast-conserving surgery after neoadjuvant therapy Whole breast radiotherapy is required for patients who underwent breast conserving therapy, including lumpectomy or partial mastectomy. Patients receiving adjuvant radiation therapy must have completed radiotherapy at least 14 days prior to registration for protocol therapy. Planning to undergo breast-conserving surgery Preference for mastectomy instead of breast-conserving surgery Patients must not have had prior ipsilateral breast-conserving surgery or total mastectomy and be eligible for neoadjuvant treatment Adequately excised: participants must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy Whole breast radiotherapy is required for participants who underwent breast-conserving therapy, including lumpectomy or partial mastectomy. Participants must have completed radiotherapy at least 14 days prior (but no more than 84 days prior) to study registration. Definitive surgical treatment with breast-conserving surgery or mastectomy and axillary lymph node evaluation. Treatment with breast conserving surgery Patients must be enrolled on the trial within 12 weeks of the later of two dates: the final breast conserving surgical procedure or administration of the last cycle of cytotoxic chemotherapy Systemic chemotherapy prior to final breast conserving surgery Patients must have been treated by breast conserving surgery (BCS) or mastectomy Will be two weeks post-breast conserving surgery or three weeks post-breast conserving surgery with sentinel lymph node biopsy or four weeks post-mastectomy at the start of participation Women who have undergone a total mastectomy or breast-conserving surgery for primary breast cancer +/- chemotherapy, +/- radiotherapy The patient must be deemed an appropriate candidate for breast conserving therapy (i.e. not pregnant, never had radiation to the treated breast, breast size would allow adequate cosmesis after volume loss from partial mastectomy) Patients eligible for the study will be newly-diagnosed female breast cancer patients with stage I-ll invasive breast cancer who are eligible for and considering either mastectomy or breast-conserving surgery (BCS) with radiation, and who may be eligible for adjuvant systemic treatment Breast conserving surgery and indications for whole breast radiotherapy Patients must be undergoing breast conserving therapy No patients scheduled to receive partial breast irradiation following breast conserving surgery Participants must be candidates for definitive local therapy with breast conserving therapy or deemed as potential candidates following NAT (this takes into account tumor to breast size ratio appropriate for breast cancer therapy [BCT], and the ability to undergo standard radiation therapy post-operatively) Participants must be candidates for definitive local therapy with breast conserving therapy (this takes into account tumor to breast size ratio appropriate for breast-conserving surgery [BCS], and the ability to undergo standard radiation therapy post-operatively) Eligible for breast conserving surgery, lumpectomy and radiation Patient desire to undergo breast conserving surgery