Omission of Adjuvant Radiotherapy in Low-Risk Elderly Males with Breast Cancer

Abstract

Randomized clinical trials demonstrate that lumpectomy + hormone therapy (HT) without radiation therapy (RT) yields equivalent survival and acceptable local-regional outcomes in elderly women with early-stage, node-negative (T1-2N0) hormone-receptor positive (HR+) breast cancer. Whether these data apply to men with the same inclusion criteria remains unknown. We hypothesized that outcomes in males would be comparable to those seen in females, with RT not conferring an overall survival (OS) benefit over HT alone. We conducted a retrospective matched-cohort study using the National Cancer Database for males ≥65 years with pathologic T1-2N0 (≤3 cm) HR+ breast cancer treated with breast conserving surgery with negative margins from 2004-2019. Patients who received chemotherapy, had nodal or distant metastases, or unknown follow-up were excluded. Adjuvant treatment was classified as HT alone, RT alone, or HT+RT. Due to limitations of survival analysis on retrospective data, male patients were matched with female patients to determine comparable outcomes based on age (± 3 years), Charlson Deyo comorbidity score, T-stage, and adjuvant treatment. Survival analysis was performed using Cox regression and Kaplan-Meier analysis. To adjust for confounding, inverse probability of treatment weighting (IPTW) was used. A total of 523 patients met inclusion criteria, with 24.4% receiving HT, 16.3% receiving RT, and 59.2% receiving HT+RT. Median follow-up was 6.9 years (IQR: 5.0-9.4 years). Unadjusted 5-yr OS rates in the HT, RT, and HT+RT cohorts were 79.2% (95% CI 70.7-85.5%), 80.9% (95% CI 70.3-88.0%), and 93.3% (95% CI 89.7-95.7%), respectively. Adjusted 10-yr OS rates in the HT, RT, and HT+RT cohorts were 82.3% (95% CI 78.6-85.5%), 83.6% (95% CI 80.0-86.7%), and 92.8% (95% CI 90.1-94.8%), respectively. On unadjusted multivariable Cox regression analysis (MVA), relative to HT, receipt of HT+RT was associated with improvements in OS (HR: 0.603; 95% CI: 0.410-0.888; p = 0.01). RT alone was not associated with improved OS (HR: 1.116; 95% CI: 0.710-1.755; p = 0.633). On adjusted MVA, relative to HT, receipt of HT+RT was associated with improvements in OS (HR: 0.551; 95% CI: 0.370-0.820; p = 0.003). Again, RT alone was not associated with improved OS (HR: 0.991; 95% CI: 0.613-1.604; p = 0.972). Other factors associated with OS included age, Charlson Deyo score, T stage, and grade. Overall, in the matched women, the same trends were found as in the men, the best survival was in HT+RT, but no difference in OS between HT vs. RT. Among men ≥65 years old with T1-2N0 HR+ breast cancer, RT alone did not confer an OS benefit over HT alone. Combined RT+HT did yield improvements in OS, though there are likely significant unmeasured confounders contributing to these outcomes in patients treated with the most aggressive approach. Our findings support that RT omission may be a reasonable option in elderly men with T1-2N0 HR+ breast cancer treated with lumpectomy + HT.