Receptor status change from primary to residual breast cancer after neoadjuvant chemotherapy (NCT) and analysis of survival outcome.

Abstract

48 Background: Treatment and prognosis of breast cancer is determined by tumor subtype. Tumor heterogeneity and lack of stability in ER, PR and HER2 has been described. We evaluated the changes receptor status between primary and residual disease after NCT and its association with outcome. Methods: 398 women with known ER, PR and HER2 status in primary and residual disease were identified. Patients were classified as no receptor change vs. any receptor change. For ER and PR we explored absolute percent changes. Descriptive statistics were used. Kaplan-Meier method was used to estimate overall (OS) and recurrence-free (RFS) survival. Cox proportional models were fit to determine the association of receptor status changes with outcomes after adjustment for patient and disease characteristics. Results: From the 398 patients, 162 (40.7%) had a change in at least one biomarker. Twenty-three (10.9%) of the 211 ER-positive tumors changed to ER-negative and 39 (20.8%) of the 187 ER-negative tumors changed to ER-positive. Fifty-seven (35.2%) of the 162 PR-positive tumors changed to PR-negative and 28 (11.9%) of the 235 PR-negative tumors changed to PR-positive. Lastly, 29 (40%) of the 72 HER2-positive tumors changed to HER2-negative and among the 35 trastuzumab-treated patients, 16 (45.7%) had HER2 status changed. At a median follow up of 40 months, 128 women (32%) had died, and 167 (41.8%) had experienced a recurrence. Five-year OS estimates were 73% and 63% for patients with or without any receptor change, (P=0.07); 5-year RFS estimates were 63% and 48% for patients with or without any receptor change, (P=0.003). Among patients with baseline ER-positive tumors, 5-year OS estimates was 73% and 87% (P=0.03), and the 5-year RFS estimates was 59% and 71% (P=0.03) for those whose absolute ER percent decrease was less than 20% or more than 20%, respectively. A change in any receptor was associated with better RFS (HR: 0.63, 95% CI 0.44-0.9) but not with OS, (HR: 0.79, 95% CI 0.53-1.18). Conclusions: Changes in ER, PR and HER2 status between the primary and the residual disease after neoadjuvant chemotherapy are frequent. In this study, a change in biomarker status was associated with significant improved RFS.