{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:25:23Z","timestamp":1787117123317,"version":"build-2736575974"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      This retrospective cohort study included 178 HR+\/HER2-negative breast cancer patients who received NACT followed by surgery at Yichang Central People\u2019s Hospital between January 2020 and December 2024. Patients were categorized into HER2-low (immunohistochemistry [IHC] 1+ or 2+\/\n                      <jats:italic>in situ<\/jats:italic>\n                      hybridization [ISH]-, n=102) and HER2-zero (IHC 0, n=76) groups. Clinicopathological characteristics, pCR rates, residual cancer burden (RCB), Ki-67 changes, and treatment responses were compared. The primary outcome was total pathological complete response (tpCR, ypT0\/is ypN0). Multivariable logistic regression and subgroup analyses were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The HER2-low group exhibited significantly higher proportions of Ki-67 index \u226520% (57.8% vs. 38.2%, P\u00a0=\u00a00.01) and grade III histology (45.1% vs. 28.9%, P\u00a0=\u00a00.03) 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\u00a0=\u00a00.02). 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\u00a0=\u00a00.02). The HER2-low group showed significantly smaller median Ki-67 reduction (-14.5% vs. -23.8%, P\u00a0=\u00a00.02). Subgroup analyses revealed that the negative impact of HER2-low status on pCR was more pronounced in patients with Ki-67 \u226520% (interaction P\u00a0=\u00a00.03) and grade III disease (interaction P\u00a0=\u00a00.04).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u00a0=\u00a00.40, 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1862110","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:40:43Z","timestamp":1787114443000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinicopathological characteristics and response to neoadjuvant chemotherapy in HER2-low hormone receptor-positive breast cancer: a retrospective cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Wanyan","family":"Wu","sequence":"first","affiliation":[{"name":"Oncology Department, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People\u2019s Hospital","place":["Yichang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuetao","family":"Li","sequence":"additional","affiliation":[{"name":"Oncology Department, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People\u2019s Hospital","place":["Yichang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Wei","sequence":"additional","affiliation":[{"name":"Oncology Department, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People\u2019s Hospital","place":["Yichang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Liu","sequence":"additional","affiliation":[{"name":"Oncology Department, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People\u2019s Hospital","place":["Yichang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Yang","sequence":"additional","affiliation":[{"name":"Oncology Department, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People\u2019s Hospital","place":["Yichang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Liu","sequence":"additional","affiliation":[{"name":"Oncology Department, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People\u2019s Hospital","place":["Yichang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2203690","article-title":"Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer","volume":"387","author":"Modi","year":"2022","journal-title":"N Engl J 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