Clinical behavior of recurrent hormone receptor-positive breast cancer by adjuvant endocrine therapy: A Breast International Group (BIG) 1-98 sub-analyses

538 Background: Endocrine therapy resistance is a major cause of distant recurrence (DR) in HR+ breast cancer. Currently, no data exists evaluating differences in clinical behavior after DR between patients (pts) treated in the adjuvant setting with different endocrine therapy regimens. The aim of this study was to analyze post-DR survival of pts treated on BIG 1-98. Methods: BIG 1-98 compared 5 years of adjuvant treatment between 4 arms: tamoxifen (T), letrozole (L), T followed by L (TL) and L followed by T (LT). After 8.1 years median follow-up (follow-up through 2010), 911 (T n = 302, L n = 285, TL n = 170, LT n = 154) of 8010 pts had DR as site of first recurrence. Univariate and multivariable Cox analyses were performed to determine features associated with post-DR survival. With 661 total observed deaths, statistical power was 0.8 to detect a hazard ratio (HaR) > 1.24 at the 2-sided 0.05 level of significance. Results: Median follow up time after DR was 59 months (IQR: 29-88). Among all pts with DR, 38.1% were ≥ 65 years at study enrollment, 61.9% had tumor size > 2 cm, 69.7% were node positive. Neo/adjuvant chemotherapy was administered to 35.6% of pts. There was no difference in post-DR survival by treatment arm (median survival: T 20.8, L 17.9, TL 17.3, LT 20.8 months; p = 0.21). In multivariable analysis, older pts (HaR 1.36; p = 0.0002), tumors > 2cm (HaR 1.2; p = 0.04), ≥ 4 positive nodes (HaR 1.32; p = 0.05) and PR- tumors (HaR 1.28; p = 0.001) had significantly worse post-DR survival. Endocrine treatment arm, type of surgery, radiotherapy and neo/adjuvant chemotherapy were not associated with post-DR survival in the multivariate model. Conclusions: Treatment with adjuvant T, L or their sequence were not associated with differences in survival after DR. We observed significant differences in survival by primary tumor size, nodal and PR status, which suggest that traditional high-risk features remain prognostic in the metastatic setting. Clinical trial information: NCT00004205.