Prospective comparison of switches in biomarker status between primary and recurrent breast cancer: the Breast Recurrence In Tissues Study (BRITS)

TLDR

Immunohistochemistry of primary breast cancer is routinely used to guide therapy at relapse, yet retrospective studies suggest that estrogen, progesterone, and HER2 receptor status may differ between primary tumors and recurrences. The Breast Recurrence In Tissues Study (BRITS) prospectively examined changes in ER, PR, and HER2 status by collecting matched primary and recurrent tissue samples from 205 women across 20 institutions. Central laboratory analysis employed Allred and Quickscore IHC for ER and PR and FISH confirmation for HER2 2+ on core biopsies and tissue microarrays, yielding 137 analyzable paired samples. Receptor status switched in 10.2% of patients for ER, 24.8% for PR, and 2.9% for HER2, with such changes prompting altered treatment plans in 17.5% of cases, confirming that confirmatory sampling is essential for relapsed breast cancer management.

Abstract

Immunohistochemistry of primary breast cancer is routinely used to guide changes in therapy at the time of relapse. Retrospective reviews suggest that the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2) receptor may differ between the primary and loco-regional recurrence or distant metastases. The Breast Recurrence In Tissues Study (BRITS) was a large, multicentre, prospective study to examine changes in ER, PR and HER2.Matched primary and recurrent breast cancer tissue samples were prospectively collected from 205 women attending 20 institutions. Central laboratory immunohistochemical analysis of core biopsies and tissue microarrays of ER and PR using the Allred and Quickscore methods and HER2 (confirmed by fluorescence in situ hybridisation (FISH) for HER2 2+) were performed.From 205 consenting women, 18 (8.8%) did not have recurrent disease on biopsy, 35 were ineligible, 13 had insufficient paired tissue and 2 were excluded for safety reasons. Paired samples from 137 women, mean age 62.6 years (range 27-87 years), 83/137 (60.6%) postmenopausal with a median 92.2 months (range 5-327 months) from primary to recurrence and 88 (64.2%) as locoregional recurrence were successfully analysed. A switch in receptor status, in either direction, by Allred score, was identified for ER in 14 patients (10.2%; P = 0.983 Wilcoxon sign rank test), PR in 34 (24.8%; P = 0.003 Wilcoxon sign rank test) and HER2 in 4 (2.9%; P = 0.074 Wilcoxon sign rank test). There was no difference between locoregional or distant recurrence in the proportion who switched. The switch in receptor status led to a change in the subsequent treatment plan for 24 patients (17.5%).This prospective study confirms retrospective evidence that the management of relapsed breast cancer should include confirmatory tissue sampling and identify switches of ER, PR or HER2 which change therapeutic management for one in six patients.