Pathologic complete response to neoadjuvant chemotherapy in early-stage male breast cancer across molecular subtypes and racial/ethnic groups.

Abstract

550 Background: Male breast cancer (mBC) accounts for ~1.0% of all breast cancers in the U.S. Neoadjuvant chemotherapy (NACT) is often used to downsize locally advanced tumors and/or allow for lumpectomy in early-stage breast cancer. However, data on pathologic complete response (pCR) after NACT in mBC is scarce. This study aimed to explore how pCR in male patients with early-stage breast cancer differed by molecular subtype and by race/ethnicity. Methods: This retrospective study analyzed data from the 2004-2021 U.S. National Cancer Database registry. Patients were eligible if they were male sex, aged ≥18 years, diagnosed with stage I-III disease, and underwent NACT. pCR (achieved/did not achieve) was defined as ypT0/TisypN0. Molecular subtypes included HR+/HER2–, HR+/HER2+, HR–/HER2+, and TNBC. Racial/ethnic groups included Asian or Pacific Islander, Black, Hispanic, White, and Other. We performed multivariable logistic regression, adjusting for age, race/ethnicity, molecular subtype, clinical T/N, and tumor grade. Results: Of 1428 patients, the mean age was 58.5 years (SD=12.8); 69.3% identified as White, followed by 18.8% as Black, 6.2% as Hispanic, 3.4% as Asian or Pacific Islander, and 2.4% as Other. Most (87.2%) patients had invasive ductal carcinoma. 51.3% were HR+/HER2–, 31.9% were HR+/HER2+, 11.7% were TNBC, and 5.1% were HR–/HER2+. Overall, the rate of pCR was 10.9%. Patients with HR–/HER2+ tumors achieved the highest pCR rate (37.3%) compared to 33.8% with TNBC, 14.9% with HR+/HER+, and only 3.7% with HR+/HER2– tumors ( p <.001). The pCR rate trended higher in Asian or Pacific Islander (14.6%) or Hispanic (13.6%) patients than in Black (11.2%), White (10.4%), or Other (8.8%) patients, though not statistically significant ( p =.728). On multivariable regression analysis, patients with HR+/HER2+ (adjusted odds ratio [aOR] 3.89, 95% CI: 2.24-6.76; p <.001), TNBC (aOR 8.80, 95% CI: 4.76-16.28; p <.001), or HR–/HER2+ (aOR 13.45, 95% CI: 6.40-28.28; p <.001) tumors had greater odds of having achieved pCR than those with HR+/HER2– tumors. No significant differences in odds of pCR by race/ethnicity were found. Additionally, older age (aOR 0.84 [per 10-year increase], 95% CI: 0.72-0.98; p =.026) and grade 1/2 ( vs grade 3) tumors (aOR 0.39, 95% CI: 0.25-0.60; p <.001) were associated with lower odds of pCR. Conclusions: In early-stage mBC, the post-NACT pCR rate varied significantly across molecular subtypes, with the lowest rate in HR+/HER2– tumors, mirroring patterns observed in female breast cancer in the neoadjuvant setting. pCR rates were similar by race/ethnicity but lower among patients who were older or had low-grade tumors. These data suggest pCR dependence on tumor biology and could help neoadjuvant treatment selection to achieve optimal outcomes for early-stage mBC. Future research could investigate survival outcomes by pCR in this mBC population.