Are All Prognostic Stage IB Breast Cancers Equivalent?

Abstract

The 8th edition of the American Joint Committee on Cancer (AJCC) has recognized the prognostic influence of histologic grade and biomarker status for breast cancer (BC). Contemporary BC staging includes both anatomic tumor extent and prognostic stage. However, prognostic stage IB remains heterogeneous and includes patients with locally advanced anatomic pathologic stage IIIA-B (pT3N1 or pT1-3N2, G1-2) hormone-receptor positive/HER2-negative BC (LA-HR+/HER2-) as well as patients with early-stage anatomic clinical/pathologic stage IA (T1cN0, G2-3) triple-negative BC (ES-TNBC). We hypothesized that although both are classified as prognostic stage IB BC, overall survival (OS) is worse for LA-HR+/HER2- compared to ES-TNBC. We used the National Cancer Database to identify patients with surgically-resected LA-HR+/HER2- BC (pT3N1 or pT1-3N2, grade 1-2) and those with ES-TNBC (T1N0, grade 2-3) from 2004-2017. Patients were excluded if receptor status, tumor grade, and/or TNM staging data were unknown. HR+/HER2- patients treated with neoadjuvant therapy were also excluded. The primary endpoint was OS. Multivariable Cox regression analysis was used to evaluate differences in OS between LA-HR+/HER2- BC and ES-TNBC (adjusting for baseline patient demographic characteristics) in the entire cohort and in the subset of patients that received appropriate treatment based on anatomic stage: radiation (RT), chemotherapy (CT) and hormone therapy for LA-HR+/HER2- BC and CT or CT+RT for ES-TNBC treated with mastectomy or lumpectomy, respectively. We report hazard ratios (HR) with 95% confidence intervals (CI) with p<0.05 considered statistically significant. A total of 45,818 patients met inclusion criteria (N = 17,359 with LA-HR+/HER2- BC and N = 28,459 with ES-TNBC). Over 75% of the LA-HR+/HER2- BC patients have anatomic pathologic stage IIIB disease (pT1-3N2, G1-2). With a median follow-up of 56 months, the 6-year OS rates were 86.1% (LA-HR+/HER2-) vs. 90.4%patients (ES-TNBC) which corresponded to a 63% relative increased risk of death in LA-HR+/HER2- patients compared to ES-TNBC patients (HR = 1.63, 95% CI 1.53-1.73, p<0.0001) after adjusting for all covariates. Approximately 66% (N = 11,533) LA-HR+/HER2- and 69% (N = 19,512) ES-TNBC received appropriate therapy. The 6-year OS was 91.8% (LA-HR+/HER2-) vs. 93.3% (ES-TNBC) which corresponded to a 35% increased risk of death in the LA-HR+/HER2- patients compared to ES-TNBC (adjusted HR = 1.35, 95% 1.24-1.48, p<0.0001). Other covariates associated with OS were age, income, insurance status, facility type, and ethnicity/race. We found that LA-HR+/HER2- BC has significantly worse OS compared to ES-TNBC despite both being classified as prognostic stage IB, even when accounting for treatments delivered. The categorization of pT3N1 or pT1-3N2, G1-2 HR+/HER2- BC as prognostic stage IB needs to be reconsidered in order to provide patients with more accurate information regarding expected OS.