The purpose of this study to test an alternative treatment approach that involves giving participants radiotherapy before their mastectomy (preoperative radiotherapy) and performing immediate reconstruction surgery at the time of mastectomy. The immediate reconstruction surgery is called an immediate autologous reconstruction (IR) and is different than the standard reconstruction surgery people with T4 breast cancer have. IR is a surgical procedure where immediately following your mastectomy, the surgeon takes tissue from another part of your body and uses it to re-create your breast. The standard reconstruction surgery occurs later and can be done with an implant or tissue from your body.

The main purpose of this study to find out if the alternative treatment approach shown above is feasible. The study will see how safe this alternative treatment approach is compared with the standard treatment approach.

Inclusion Criteria:

• Female sex, aged ≥18 years, with biopsy-proven invasive breast cancer
• cT3-4 cN0-3 tumor
• Partial or complete response to NAC on imaging and clinical examination using the Response Evaluation Criteria in Solid Tumors (RECISTv1.1) definition.
• Desire to undergo autologous reconstruction and assessed to be an appropriate candidate by a plastic and reconstructive surgeon
• Able to read and understand English

Exclusion Criteria:

• Prior ipsilateral breast cancer
• Bilateral breast cancer
• Pregnant
• Stage IV disease at presentation
• Stable disease or progressive disease after NAC
• Surgically unresectable breast disease
• BMI >40
• Prior history of thoracic radiotherapy

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.