Clinical outcomes and prognostic biomarkers among pregnant, post-partum and nulliparous women with breast cancer: a prospective cohort study.

Abstract

To compare clinical-pathologic characteristics and outcomes of pregnancy-associated, post-partum (PP) and nulliparous (NP) breast cancer (BC) patients and explore mediators of the poor prognosis associated with post-partum BC. A prospective database of 233 women ≤ 40years of age diagnosed with BC between February 2008 and January 2015 was analysed. Clinical-pathologic characteristics and outcomes among pregnant, PP and NP patients were compared using chi-square or Kruskal-Wallis tests. The Kaplan-Meier method was used to estimate disease-free survival (DFS), distant DFS and overall survival (OS). Survival curves were compared using the log-rank test. Univariable Cox proportional hazards regression models were used to evaluate factors that were potentially prognostic for the clinical outcomes of interest; a multivariable Cox model was constructed using a forward stepwise selection process. Androgen receptor (AR), GATA3, PDL1 status and the presence/absence of tumour-infiltrating lymphocytes (TILs) were assessed when possible. Pre-treatment neutrophil and lymphocyte counts were abstracted retrospectively. Statistical significance was defined as a p value ≤ 0.05. Women ≤ 2years PP had a numerically higher incidence of lymph node-positive and high-grade disease and were significantly more likely to have estrogen receptor-negative BC compared to NP controls. With a median follow-up of 7.2years, increasingly poor outcomes were observed among NP (longest OS), > 2years PP, ≤ 2years PP and pregnant (shortest OS) patients, but these differences were not statistically significant. The ≤ 2years PP group had significantly lower AR expression, a strong trend toward higher PDL1 expression and a higher expression of stromal TILs compared to NP women. PPBC patients had numerically lower DFS and OS compared to NP controls. Higher PDL1 and stromal TILs in PPBC suggest that adjuvant immunotherapy may be effective in the post-partum BC subgroup.