Pathological complete response and prognosis after neoadjuvant chemotherapy in patients with HER2-low breast cancer

The development of novel human epidermal growth factor receptor 2 (HER2) antibody drug conjugates brings encouraging opportunities for the treatment of HER2-low breast cancer. In this study, we investigated the clinical factors and prognosis of HER2-low breast cancer after neoadjuvant chemotherapy (NAC). Data from patients diagnosed with HER2-zero or HER2-low breast cancer at a single center between January 2017 and December 2021 who underwent NAC followed by surgery were retrospectively reviewed. HER2 status was detected by immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH), and classified as HER2-zero (IHC 0), HER2-low (IHC 1+ or IHC 2+ and FISH–), and HER2-positive (IHC 3+ or IHC 2+ and FISH+). Baseline characteristics were analyzed and compared between the HER2-low and HER2-zero groups. Survival outcomes were analyzed using the Kaplan–Meier method with the log-rank test and Cox proportional-hazards regression analysis. The sample comprised 132 patients with HER2-zero [n = 62 (47.0 %)] and HER2-low [n = 70 (53.0 %)] breast cancer. Relative to the HER2-zero group, the HER2-low group contained larger proportions of patients with hormone receptor (HR) positivity (37.1 % vs. 75.7 %, P < 0.001) and low nuclear grades and Ki-67 indices (both P < 0.05). The pathological complete response (pCR) rate was significantly lower in the HER2-low group than in the HER2-zero group (20.0 % vs. 37.1 %, P = 0.03). At the final follow-up [median 20 (range 4–66) months], patients with HER2-low status had significantly favorable disease-free survival (DFS) and overall survival (OS) outcomes relative to those with HER2-zero status (87.1 % vs. 71.0 %, P = 0.02 and 94.3 % vs. 82.3 %, P = 0.02, respectively). HER2-low status and pCR were independent prognostic factors for DFS [hazard ratio (HR) = 0.31, 95 % confidence interval (CI) 0.13–0.75, P = 0.009 and HR = 0.08, 95 % CI 0.01–0.67, P = 0.02, respectively]. This analysis revealed that HER2-low status is associated significantly with HR positivity and low nuclear grades, Ki-67 indices, and pCR rate. It is also associated with favorable DFS and OS outcomes after NAC. HER2-low status and pCR are independent prognostic factors for DFS.