Clinical characteristics and prognostic implications in patients with HER2-low breast cancer undergoing neoadjuvant chemotherapy: a retrospective cohort study

Abstract

Background

HER2-low breast cancer represents a distinct biological subtype, and its clinical characteristics and prognostic outcomes require further exploration. This study aimed to investigate disparities in short- and long-term outcomes between HER2-0 and HER2-low breast cancer patients undergoing neoadjuvant chemotherapy (NAC) in a Chinese cohort.

Methods

This retrospective multicenter cohort study included 711 breast cancer patients diagnosed between 2016 and 2020 in four tertiary hospitals in China. Participants were categorised into HER2-0 and HER2-low subgroups based on immunohistochemical analysis. Logistic and Cox regression analyses, incorporating propensity score-based inverse probability of treatment weighting (IPTW), were used to evaluate treatment outcomes, including real-world overall survival (rwOS), breast pathological complete response (bpCR), and objective response rate (ORR) at 24 weeks.

Findings

Out of 303 patients included in the final analysis, 213 were classified as HER2-low and 90 as HER2-0. The majority were hormone receptor (HR)-positive, with varying TNM stages, Ki-67 expression levels, and menopausal status. Inclusion criteria were based on neoadjuvant chemotherapy treatment and immunohistochemistry results. The overall rwOS rate for all patients was 86.1% (HER2-low: 87.3% vs. HER2-0: 83.3%). Kaplan-Meier survival curves showed no significant difference in rwOS between the HER2-low and HER2-0 groups before or after applying the IPTW method (log-rank P = 0.17, IPTW-weighted log-rank P = 0.45). Multivariate Cox regression analysis confirmed no significant difference in rwOS between the groups (IPTW-adjusted hazard ratio [HR]: 1.60; 95% confidence interval [CI]: 0.78–3.31). For breast pathological complete response (bpCR), 45 patients (21.1%) in the HER2-low group achieved bpCR compared to 16 patients (17.8%) in the HER2-0 group (adjusted odds ratio [OR]: 1.26; 95% CI: 0.6–2.75). Similarly, no significant difference was observed in the odds of bpCR between the groups when adjusted using IPTW (OR: 1.08; 95% CI: 0.72–1.64). Objective response rates (ORR) at 24 weeks were also comparable, with 137 patients (57.4%) in the HER2-low group and 61 patients (67.8%) in the HER2-0 group achieving a response. The IPTW-adjusted OR for ORR was 1.1 (95% CI: 0.77–1.57). Subgroup analysis revealed that in HR-negative patients, the HER2-low group exhibited significantly better outcomes compared to the HER2-0 group, with an rwOS HR of 0.42 (95% CI: 0.23–0.77; P < 0.001) and bpCR odds of 2.6 (95% CI: 1.14–6.29; P = 0.027). Conversely, among HR-positive patients, HER2-0 patients had a better rwOS than HER2-low patients (P < 0.001).

Interpretation

HER2-low breast cancer should be considered a distinct subtype with differing outcomes based on hormone receptor (HR) status. HR-negative patients with HER2-low tumors showed better overall survival and response rates compared to HER2-0 patients, suggesting enhanced chemotherapy sensitivity. Conversely, HR-positive HER2-0 patients had better survival, indicating potential treatment resistance in HER2-low HR-positive cases. These findings highlight the need for tailored treatment strategies for HER2-low breast cancer, especially for HR-positive patients, and suggest potential benefits from novel therapies like antibody-drug conjugates (ADCs).