Poor response of HER2-positive mucinous carcinomas of breast to neoadjuvant HER2-targeted therapy: A study of four cases

Background: Breast mucinous carcinoma (MC) is typically positive for estrogen receptor (ER) and progesterone receptor (PR) expressions and negative for human epidermal growth factor receptor (HER2) overexpression. HER2 positive MC is a rare entity; its response to neoadjuvant HER2-targeted therapy remains unclear. Methods: Four cases of HER2 positive MC and seven cases of HER2 positive invasive ductal carcinoma with mucinous features (MCF) were identified. Clinicopathologic features were collected. Patients' germline data was gathered if available. Tumor's response to HER2-directed treatment were recorded and compared. Results: Two HER2 positive MCs were treated with neoadjuvant HER2-directed treatment and showed no response in the subsequent surgical resection specimens including one positive lymph node showing no treatment effect. One patient had upfront surgery. The fourth patient presented with advanced stage and showed progression on HER2-directed treatment. Six HER2 positive MCFs received neoadjuvant HER2-directed therapy; two cases showed complete pathologic response and four had only minimal residual carcinomas in the breast. Two cases with positive lymph nodes had complete response in the lymph nodes. The seventh patient presented at an advanced stage and was stable on HER2-directed treatment. Conclusions: Our findings suggest that HER2 positive MCs may be resistant to HER2-directed treatment. This is in contrast with the excellent treatment response observed in HER2 positive MCFs. It is important to report mucinous carcinoma percentage in biopsies on HER2 positive tumors as it may be related to treatment response. Further investigation of the underlying mechanisms may help optimize clinical management in this patient population.