Role of Radiotherapy After Breast-Conserving Surgery in T1-2N0M0 Luminal (HR+/HER2-) Breast Cancer Stratified by Tumor Quadrant Location.

BACKGROUND The survival association of adjuvant radiotherapy (RT) in early-stage node-negative luminal (HR+/HER2-) breast cancer remains under evaluation, and whether this association is modified by tumor quadrant location is unknown. MATERIAL AND METHODS We identified 5831 patients with T1-2N0M0 luminal breast cancer treated with breast-conserving surgery from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2017), stratified by RT receipt. Breast cancer-specific survival (BCSS) was analyzed using Kaplan-Meier, Cox regression, and Fine-Gray competing-risk models, with a prespecified RT-by-quadrant interaction test. RESULTS RT was independently associated with a lower hazard of breast cancer-specific death (hazard ratio=0.623, 95% confidence interval: 0.512-0.792, P<0.001) in the Cox regression analysis. In the competing-risk Fine-Gray model, the subdistribution hazard ratio was 0.661 (95% confidence interval: 0.530-0.825, P<0.001). A significant interaction was observed between RT and tumor quadrant (P=0.019). Quadrant-stratified analyses showed a significant adjusted association between RT and a lower hazard of breast cancer-specific death for upper-inner and lower-outer quadrant tumors; estimates for upper-outer and lower-inner quadrant tumors were in the same direction but did not display statistical significance. Sensitivity analyses using the Fine-Gray model and E-value calculations were consistent with the primary findings. CONCLUSIONS In this observational study of T1-2N0M0 luminal breast cancer, a significant statistical interaction was observed between postoperative RT and tumor quadrant location, generating the hypothesis that the association between RT and BCSS varies according to primary tumor quadrant. These findings require prospective validation before informing individualized treatment decisions.