Pathologic complete response and survival in HER2-low and HER2-zero early breast cancer treated with neoadjuvant chemotherapy

BACKGROUND: Breast cancers without HER2 amplification but still expressing this membrane protein constitute a new entity called HER2-low tumors. It is important to characterize them in terms of sensitivity to treatment and prognosis. PATIENTS AND METHODS: To investigate chemosensitivity and long-term prognosis of HER2-low early breast cancer (eBC), compared to HER2-0 tumors, we retrospectively retrieved clinicopathological characteristics, response to treatment, and survival data from 511 patients treated for eBC with neoadjuvant chemotherapy (NAC) in a French cancer center between 2007 and 2018. Factors associated with the achievement of pathologic complete response (pCR) and survival were studied among hormone receptor positive (HR+) and negative (HR–) eBC. RESULTS: A total of 280 HR+ (61% HER2-low), and 231 HR– (28% HER2-low) eBC were included. We found classical clinicopathological factors usually associated with chemosensitivity and prognosis, in both HR+ and HR– eBC. By uni- and multivariable analysis, HER2 status (low vs 0) was not independently associated with pCR, either in HR+ or HR– eBC. Relapse free (RFS) and overall survival (OS) were not significantly different between HER2-low and HER2-0 among HR+ tumors. In contrast, among HR– negative tumors, RFS and OS were slightly better in HER2-0 eBC by univariable but not by multivariable analysis. CONCLUSIONS: In eBC patients treated with NAC, taking into account HR expression subtype and other current clinicopathological features, HER2-low tumors did not appear to have different chemosensitivity or prognosis, compared to their HER2-0 counterparts. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12282-023-01490-1.