JAMA Netw Open. 2025 Jun 2;8(6):e2514864. doi: 10.1001/jamanetworkopen.2025.14864.
ABSTRACT
IMPORTANCE: Racial and ethnic disparities in pathologic complete response (pCR) and overall survival (OS) have been reported in patients with triple-negative breast cancer (TNBC). In addition to socioeconomic factors and access to care, differences in tumor biology may affect outcomes. The association of ERBB2-low expression with outcomes in patients with TNBC has been minimally explored, including studies evaluating outcomes based on race and ethnicity.
OBJECTIVE: To investigate whether ERBB2-low expression among patients with TNBC varies by race and ethnicity and is associated with pCR and OS.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used the National Cancer Database, a national hospital-based tumor registry, from 2010 to 2019. Participants included adult female patients with stages I to III TNBC treated with neoadjuvant chemotherapy followed by surgery. Tumors with immunohistochemistry scores of 1+ or 2+, in situ hybridization nonamplified, were classified as ERBB2-low; those with immunohistochemistry scores of 0, as ERBB2-zero. Primary analysis was conducted from September 18 to October 18, 2023.
MAIN OUTCOMES AND MEASURES: Rates of ERBB2-low vs ERBB2-zero TNBC by race and ethnicity and pCR and OS by race and ethnicity and by ERBB2 status.
RESULTS: Overall, 31 888 patients with TNBC were identified (median age, 53 [IQR, 44-61] years). Of those, 1078 patients (3.4%) were Asian; 7642 (24.0%), Black; 2578 (8.1%), Hispanic; 20 264 (63.5%), White; and 326 (1.0%), other. Over half of the study population (16 332 [51.2%]) displayed ERBB2-low expression and 15 556 (48.8%), ERBB2-zero expression. Patients with ERBB2-low expression demonstrated lower rates of pCR than those with ERBB2-zero expression (4675 [28.6%] vs 4787 [30.8%]; P < .001); ERBB2-low expression was associated with lower odds of pCR after adjustment for patient, socioeconomic, and tumor variables (odds ratio, 0.93; 95% CI, 0.88-0.99; P = .01). When patients were stratified by race and ethnicity, Hispanic patients had higher rates of ERBB2-zero expression than ERBB2-low expression (1391 of 2578 [54.0%] vs 1187 of 2578 [46.0%]; P < .001); no differences were noted among other racial and ethnic groups. Hispanic patients also had higher rates of pCR among those with ERBB2-low (Hispanic, 30.7%; Asian, 24.6%; Black, 29.5%; White, 27.1%) and ERBB2-zero (Hispanic, 33.2%; Asian, 32.1%; Black, 27.1%; White, 31.7%) TNBC. Non-Hispanic Asian patients had the highest 60-month OS among both those with ERBB2-zero (79%; 95% CI, 75%-83%) and ERBB2-low expression (84%; 95% CI, 80%-87%). Among Asian and White patients, ERBB2-low expression was associated with prolonged OS compared with ERBB2-zero expression (hazard ratios, 0.69 [95% CI, 0.50-0.95] [P = .02] and 0.85 [95% CI, 0.79-0.92] [P < .001], respectively). Black patients had lower pCR and OS rates regardless of ERBB2 status.
CONCLUSIONS AND RELEVANCE: In this cohort study of patients with TNBC, ERBB2-low expression and its association with clinical outcomes varied across racial and ethnic groups. These findings highlight the need for further research to understand the biological implications of ERBB2-low expression in diverse populations of patients with TNBC.
PMID:40498483 | DOI:10.1001/jamanetworkopen.2025.14864
