ArticleFrontiers in oncology2026
Clinicopathological characteristics and response to neoadjuvant chemotherapy in HER2-low hormone receptor-positive breast cancer: a retrospective cohort study.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: HER2-low breast cancer constitutes a substantial proportion of hormone receptor-positive (HR+) cases, yet its biological behavior and responsiveness to neoadjuvant chemotherapy (NACT) remain incompletely characterized. This study aimed to compare clinicopathological features and pathological complete response (pCR) rates between HER2-low and HER2-zero expression in HR+ breast cancer patients receiving NACT. Materials and methods: This retrospective cohort study included 178 HR+/HER2-negative breast cancer patients who received NACT followed by surgery at Yichang Central People's Hospital between January 2020 and December 2024. Patients were categorized into HER2-low (immunohistochemistry [IHC] 1+ or 2+/ Results: The HER2-low group exhibited significantly higher proportions of Ki-67 index ≥20% (57.8% vs. 38.2%, P = 0.01) and grade III histology (45.1% vs. 28.9%, P = 0.03) compared to the HER2-zero group. The tpCR rate was significantly lower in the HER2-low group than in the HER2-zero group (11.8% vs. 25.0%, P = 0.02). Multivariable analysis identified HER2-low status as an independent negative predictor of tpCR (odds ratio [OR]=0.40, 95% confidence interval [CI]: 0.18-0.89, P = 0.02). The HER2-low group showed significantly smaller median Ki-67 reduction (-14.5% vs. -23.8%, P = 0.02). Subgroup analyses revealed that the negative impact of HER2-low status on pCR was more pronounced in patients with Ki-67 ≥20% (interaction P = 0.03) and grade III disease (interaction P = 0.04). Conclusions: In this retrospective cohort of HR+ breast cancer patients, HER2-low expression was associated with more aggressive clinicopathological features and a significantly lower pCR rate compared to HER2-zero expression. After multivariable adjustment, HER2-low status remained significantly associated with reduced pCR odds (OR = 0.40, 95% CI: 0.18-0.89). These findings suggest that HER2-low may represent a clinically relevant subgroup within HR+ breast cancer, but the observational design precludes causal interpretation, and these hypothesis-generating results require validation in prospective, adequately powered studies before any clinical treatment recommendations can be made.
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