Effect of HER2-low-positive status on neoadjuvant chemotherapy and survival outcome of breast cancer: a 10-year dual-center retrospective study.

Various novel HER2-targeted antibody-conjugated drugs (ADCs) have shown satisfactory antitumor activity in HER2-low-positive breast cancer (BC). It is urgent to clarify whether HER2-low-positive tumors have unique biological behavior and should be considered a new molecular subtype. We screened eligible BC patients and collected relevant information at the First Hospital of Jilin University and the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2020. A total of 1027 patients were included in our study cohort, and 66.0% (678/1027) had HER2-low-positive tumors. Compared to HER2-zero patients, HER2-low-positive patients tended to have more lymph node metastasis, a larger proportion of hormone receptor (HR)-positive tumors, and a lower proliferation rate (Ki-67). The pathologic complete response (pCR) rate of HER2-low-positive patients was lower than that of HER2-zero patients (19.3% vs 26.1%), especially in the HR-positive subgroup (12.00% vs 20.29%). However, multivariate logistic regression analysis showed that HER2 status was not an independent factor for predicting pCR. HER2-low-positive patients had a higher overall survival (OS) rate in the HR-positive subgroup. The Cox regression model analysis suggested that HER2-low-positive status did not statistically significantly affect the survival outcomes, regardless of disease-free survival (DFS) (P=0.308) or OS (P=0.066). In conclusion, HER2-low-positive tumors have unique clinical and pathological characteristics, with a lower pCR rate in the HR-positive subgroup and better survival in the HR-negative subgroup compared to HER2-zero tumors. However, the effect of HER2-low-positive status on pCR or survival outcomes was not statistically significant.