Association of Chemotherapy with Survival for Patients with Small, Node-Negative, Triple Negative Breast Cancer

Abstract

Clinical outcome in breast cancer is in part driven by molecular subtypes, and triple negative breast cancer is associated with a high rate of recurrence. Yet, in the setting of small, node-negative breast cancer, de-escalating adjuvant treatments may be considered due to their associated toxicity and relatively smaller benefits. Prospective literature on adjuvant chemotherapy for pT1a-bN0 triple negative breast cancer is limited. To address this knowledge gap, we sought to investigate the outcome of adjuvant chemotherapy in such cohort. The National Cancer Database (NCDB) was queried for patients diagnosed with triple negative, pT1a-bN0 breast cancer treated with or without adjuvant chemotherapy (2010-2015). Primary endpoint was overall survival (OS). Kaplan-Meier method, Cox multivariable analysis (MVA), interaction term, and subgroup analyses were performed for survival outcomes. Propensity score matching in a 1:1 ratio without any replacement was also performed to address selection bias. A total of 16180 patients were identified, including 9498 and 6682 patients with and without chemotherapy, respectively. The median follow-up was 41.6 months (IQR 24.3-62.0). On multivariable analysis, chemotherapy was not associated with improved OS (HR 0.99, p = 0.92). Interaction analysis showed that the use of chemotherapy had interaction with tumor size (p<0.001) and age (p<0.001). On subgroup analysis, chemotherapy was associated with worse mortality among pT1a (HR 1.46, p<0.001) but improved survival among pT1b (HR 0.74, p<0.001), and worse mortality among young patients compared to older patients (age <50: HR 1.77, p = 0.035; age 50-75: HR 0.91, p = 0.21; age >75: HR 0.83, p = 0.28). Similar findings were observed in matched pairs of 1674 (pT1a: HR 1.43, p = 0.016), 1969 (pT1b: HR 0.61, p<0.001), 434 (age <50: HR 1.89, p = 0.047), and 2851 patients (age 50: HR 0.82, p = 0.052), respectively. For patients with pT1bN0 triple negative breast cancer, the addition of adjuvant chemotherapy was associated with improved survival outcomes. For young patients (age <50) with long life expectancy or those with pT1a breast cancer, chemotherapy was not associated with survival benefits.