Together: Transforming and Translating Discovery to Improve Health

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Abstract: Breast cancer outcomes for Black women are inferior to their white non-Hispanic counterparts. In addition, the University of Florida obtained data from four national cooperative group trials demonstrating that for patients with breast cancer who receive neoadjuvant chemotherapy, womenwho have residual breast disease (ypT+) have significantly inferior overall survival and worsedistant recurrence, even with a pathologic complete response in the axilla (apCR). Level I evidencedemonstrates regional nodal irradiation (RNI) improves distant metastasis-free survival and overallsurvival for women with high risk node negative disease and clinical node-positive disease. However,neoadjuvant chemotherapy has obfuscated the clear indications for RNI and level I evidence with thattreatment strategy ispending; in the absence of level I data, many use apCR to guide decisions. To thatend, our proposal consists of a three-aimed strategy to determine retrospectively (Aim 1) and prospectively (Aim 2) if RNI improves overall survival in patients with ypT+ breast cancer and (Aim3) determine if and how longitudinal changes in circulating tumor DNA (ctDNA) across trimodality breastcancer curative treatment associate with cancer outcome. For Aims 2 and 3,specific sub-aimsare to evaluate comparative outcomes between Black women and non-Hispanic white counterparts.We will realize these goals through retrospective analysis of national cooperative group data, aninterventional single-arm phase II trial of RNI for women with ypT+ disease, and a prospective cohortstudy of women receiving curative breast cancer treatment beginning with neoadjuvant chemotherapy.Aims 2 and 3 are complementary such that women can enroll in one or both trials, allowing forheterogeneity in the second aim to better explore how different treatments may affect ctDNA.Aim 1: Evaluate the benefit of radiotherapy in women treated with neoadjuvant therapy on NSABP trials B-40 and B-41. Aim 2: Evaluate the benefit of regional nodal irradiation in women withresidual breast disease after neoadjuvant chemotherapy. Sub-Aim 2: Determine if the benefit of RNIin women with residual breast disease after neoadjuvant chemotherapy differs between Black womenand non-Hispanic white women. Aim 3: Measure the change in circulating tumor DNA longitudinallyfor women with PIK3CA mutated invasive breast cancer completing all three modalities of treatment inthe course of neoadjuvant chemotherapy -> surgery -> regional nodal irradiation. Sub-Aim 3: Measurein women with invasive PIK3CA mutated breast cancer receiving triple modality care if circulating tumorDNA their change differ between Black women and non-Hispanic whitewomen. 17