Treatment of HER2+ breast cancer: a retrospective of disease prognosis with loss of HER2 amplification on residual disease after neoadjuvant treatment in a community hospital setting.

Neoadjuvant chemotherapy (NAC) with Anti-Human Epidermal Growth Factor Receptor 2 (Anti-HER2) agents increase rates of pathologic complete response (pCR) in stage II-III, HER2+ breast cancer (BC). Several retrospective studies show HER2 amplification discordance from biopsy to post-NAC residual disease (RD). This phenomenon has unclear prognostic significance. This data was obtained from patients with HER2+ BC treated with NAC between 2018-2021 at our institution. Patients with biopsy and surgical specimens at our institution were analyzed. PCR was defined as ypT0/is N0, and HER2 status on RD was evaluated. 2018 HER2 ASCO/CAP definitions were used. In total, 71 patients were identified. 34/71 patients had pCR and were not included in further analysis. 37/71 patients had RD and HER2 was analyzed. 17/37 had HER2 loss and 20/37 remained HER2 positive. Mean follow-up time for HER2 loss was 43 months and 27 months for patients remaining HER2 positive, but neither group met 5-year Overall Survival as follow-up is ongoing. Recurrence Free Survival (RFS) was 35 months for HER2+ and 43 months for HER2 loss (P = 0.007). However, short follow-up time since diagnosis likely contributed to the underrepresentation of the true RFS of both groups. Therefore, at our institution, retained HER2 positivity on RD after NAC was associated with a statistically worse RFS. Although limited by sample size and follow-up time, further prospective investigation into the significance of HER2 discordance on RD assessed by 2018 definitions could clarify true RFS and if next-generation tumor profiling on RD will yield changes in tailored management.