To re-test or not: Evaluating candidacy for precision therapy in breast cancer.

Abstract

e12599 Background: Breast cancer is one of the most common types of cancer as well as a leading cause of cancer death among women in the United States. Receptor status (estrogen receptor ER, progesterone receptor PR, HER 2) carries both prognostic and predictive value in breast cancer and testing for these findings is essential in order to identify appropriate candidates for endocrine therapy (ET) and/or HER2 directed treatment (HDT), respectively. There have been numerous studies evaluating receptor testing between primary breast and synchronous lymph nodes with varying levels of discordance ranging from 3-50%. Across Tufts Medicine, patients whose primary breast biopsy shows an ER- or PR-negative and/or HER2-negative invasive cancer often have a second specimen (e.g., either axillary node or final breast specimen) re-tested. We report the proportional discordance between primary and secondary samples among people newly diagnosed with de novo non-metastatic breast cancer. Methods: This study involved a retrospective review of patients with a new diagnosis of breast cancer at an academic health system between 2023-2025. All patients had breast biopsy testing available and underwent a second round of testing as part of initial evaluation of breast cancer. We excluded patients with de novo metastatic (stage IV) breast cancer. We compared ER/PR and HER2 testing between serial pathology specimens to determine concordance and how the information was ultimately utilized in individual patient treatment. Results: We identified 74 patients who underwent multiple receptor testing. Age ranged from 25-86 years and the cohort was predominantly female. Patients identified as 61% white, 12% African American, 18% Asian, and 8% Hispanic/Latino. 41.9% of patients had simultaneously performed breast and axillary core biopsies performed while 54% of patients had these done sequentially. The rate of concordance was 94.6% for ER, 84.8% for PR and 94.6% for HER2. Based on initial biopsy, 79.7% and 17.6% of patients were eligible for ET and/or HDT, respectively. Secondary testing increased candidacy to 81.1 (+1.4%) and 23 (+5.4%) for ET and HDT. Of the 19 patients who received neo-adjuvant chemotherapy and had repeat HER2 testing of their surgical specimen, two patients had HER2 negative disease at initial biopsy and HER2 positive disease following neoadjuvant therapy. One patient with HER2 positive disease at diagnosis continued with adjuvant targeted therapy despite repeat negative testing. Conclusions: Re-testing of ER/PR and HER2 in the context of a new diagnosis of breast cancer changes management in very few patients. However, given the predictive value of this information, it may be warranted in select patients, especially when the goal of treatment is cure. Our data suggests that repeat testing for HER2 may prove to be more valuable, given that four patients (5.4%) were deemed candidates for HDT despite negative HER2 results on breast biopsy.