Receptor Conversion in Invasive Breast Carcinoma Following Neoadjuvant Chemotherapy and Its Prognostic Significance

Testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is carried out on pre-neoadjuvant chemotherapy (NAC) core biopsies of invasive breast carcinoma (IBC). Yet, these assays are not standard practice on post-NAC IBC specimens that harbor residual malignancy. This research contributes to understanding how shifts in ER, PR, and HER2 expression between pre- and post-NAC IBC with persistent disease correlate with prognostic endpoints, namely disease-free survival (DFS) and overall survival (OS). The investigation followed a cohort framework, integrating both prospective and retrospective arms. Consequently, newly identified IBC patients who received surgical resection after NAC, whose pre-NAC biopsy material was accessible, and who had residual tumor within the breast, were recruited between January 2017 and January 2020 (n = 174) and observed longitudinally until July 2022. The analysis encompassed 174 subjects. Out of these 174, 77 (44%) cases initially classified as ER-positive switched to negative, 10 ER-positive cases retained positivity, and 87 (50%) cases originally ER-negative remained so. For PR, 48 (27%) PR-positive cases became negative, 10 PR-positive cases stayed positive, and 116 (67%) cases persisted as negative. Concerning HER2, 64 (36%) HER2-positive cases converted to negative, 4 (2%) HER2-positive cases maintained their positive status, and 103 (59%) cases remained negative. Individuals who transitioned from ER/HER2-positive to negative status achieved significantly longer DFS and OS. Discordance in hormone receptor (HR) and HER2 status occurs in IBC with residual disease following NAC, and subjects with post-NAC receptor profile changes have more favorable OS and DFS than those with stable receptor expression.