Pathologic Response to Neoadjuvant Sequential Chemoradiation Therapy in Locally Advanced Breast Cancer: Preliminary, Translational Results from the French Neo-APBI-01 Trial

SIMPLE SUMMARY: Combined radiation therapy sequentially to neoadjuvant chemotherapy has been progressively assessed in breast cancer. The prediction of response to this innovative sequence is mandatory for treatment personalization. We conducted a translational study of the randomized phase 2 Neo-APBI-01 trial comparing standard neoadjuvant chemotherapy and neoadjuvant sequential chemoradiotherapy in locally advanced breast cancer of triple-negative and luminal B subtypes. Several potential immune-related biomarkers have been identified to be associated with pathologic complete response after chemoradiation therapy. The results of this study will constitute reflection support for the design of future trials evaluating the role of intact tumor-directed radiation therapy in breast cancers. ABSTRACT: Background: Radiation therapy (RT), a novel approach to boost the anticancer immune response, has been progressively evaluated in the neoadjuvant setting in breast cancer (BC). Purpose: We aimed to evaluate immunity-related indicators of response to neoadjuvant chemoradiation therapy (NACRT) in BC for better treatment personalization. Patients and Methods: We analyzed data of the first 42 patients included in the randomized phase 2 Neo-APBI-01 trial comparing standard neoadjuvant chemotherapy (NACT) and NACRT regimen in locally advanced triple-negative (TN) and luminal B (LB) subtype BC. Clinicopathological parameters, blood counts and the derived parameters, total tumor-infiltrating lymphocytes (TILs) and their subpopulation, as well as TP53 mutation status, were assessed as predictors of response. Results: Twenty-one patients were equally assigned to each group. The pathologic complete response (pCR) was 33% and 38% in the NACT and NACRT groups, respectively, with a dose-response effect. Only one LB tumor reached pCR after NACRT. Numerous parameters associated with response were identified, which differed according to the assigned treatment. In the NACRT group, baseline hemoglobin of ≥13 g/dL and body mass index of <26 were strongly associated with pCR. Higher baseline neutrophils-to-lymphocytes ratio, total TILs, and T-effector cell counts were favorable for pCR. Conclusion: This preliminary analysis identified LB and low-TIL tumors as poor responders to the NACRT protocol, which delivered RT after several cycles of chemotherapy. These findings will allow for amending the selection of patients for the trial and help better design future trials of NACRT in BC.