Background: Combination of HP with NAC in the neoadjuvant setting leads to an high rate of pathological complete response (pCR) in patients with stage II-III HER2+ breast cancer (BC). The rate of change in HER2-status after NAC reported in literature is between 10-30%, although NAC comprises a various regimens, and the clinical significance of this phenomenon is unclear. Methods: We extracted data on patients with HER2+ BC treated with NAC and HP between September 1, 2013 to November 1, 2019. Only patients with internally verified HER2 status at our center were enrolled. The rate of pCR (ypT0/is ypN0) and the change in HER2 status on residual disease from baseline were evaluated. We used standard definition of HER2 status based on ASCO/CAP guidelines 2018. HER2-low was defined as immunohistochemistry (IHC) 1+ or 2+, FISH non-amplified. Results: Overall, 130 pts were identified. All patients received dose-dense AC-THP, except for 13 patients who received TCHP or other HP-based regimens. The pCR was achieved in 77/130 (59%) of patients and 53/130 (41%) had residual disease. Among 53 patients with residual disease, HER2 status was analyzed in 25 patients and was pending on the remaining patients. In the 25 analyzed patients, 13 had HER2-loss in residual disease. In 4/13 patients, HER2 expression was lost (IHC 0); in 9/13 patients, HER2-low profile was found (IHC 1+ in 6 patients, and IHC 2+, FISH non-amplified in 3). Details on HER2 status change are described in the table below. Conversely, 12/25 had concordant HER2 status after NAC. Conclusions: At single center, the change in HER2 status after NAC with HP appeared frequent. Pathological review of additional cases is ongoing. The clinical significance is still unclear but may open the possibility to investigate tailored approach in post-neoadjuvant setting based on the biological profile of residual disease.

Abbreviations: IHC: immunohistochemistry; FISH: fluorescent in situ hybridization; CN: copy number; ND: not done.