AbstractPurpose: Estrogen receptor-positive (ER+), progesterone receptor-negative (PR-) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) often developed resistance to endocrine treatment (ET). We aimed to explore (1) the different clinicopathological features between ER+/PR+/HER2- and ER+/PR-/HER2- BC, and (2) whether ER+/PR-/HER2- early BC patients could benefit from adjuvant ET.

摘要目的：雌激素受体阳性（ER+），孕激素受体阴性（PR-）和人表皮生长因子受体2阴性（HER2-）乳腺癌（BC）常对内分泌治疗（ET）产生耐药性。我们旨在探讨（1）ER+/PR+/HER2-和ER+/PR-/HER2-BC之间的不同临床病理特征，以及（2）ER+/PR-/HER2-早期BC患者是否可以从辅助ET中受益。

Methods: All patients treated for ER+/HER2- early BC who underwent surgery between 2010 and 2021 from a BC database in China were retrospectively examined. The cases followed up for less than six months were excluded. Results: The records of ER+/PR+/HER2- (n = 10843) and ER+/PR-/HER2- BC (n = 1193) cases were reviewed, with median follow-up times of 35.8 and 47.0 months, respectively.

方法：回顾性分析2010年至2021年间从中国BC数据库接受ER+/HER2早期BC治疗的所有患者。随访不到6个月的病例被排除在外。结果：回顾了ER+/PR+/HER2-（n=10843）和ER+/PR-/HER2-BC（n=1193）病例的记录，中位随访时间分别为35.8和47.0个月。

Compared with ER+/PR+/HER2- cases, ER+/PR-/HER2- BC occurred more in postmenopausal women (73.1% vs. 52.9%, p = 0.000) and were more likely to be T > 2 cm (40.6% vs. 37.6%, p = 0.048) and Ki67 > 20%+ (48.1% vs. 36.9%, p = 0.000). However, ER+/PR-/HER2- cases had fewer nodal involvement (32.9% vs. 36.9%, p = 0.000).

与ER+/PR+/HER2病例相比，绝经后妇女ER+/PR-/HER2-BC发生率更高（73.1%比52.9%，p=0.000），更可能是T>2 cm（40.6%比37.6%，p=0.048）和Ki67>20%+（48.1%比36.9%，p=0.000）。然而，ER+/PR-/HER2病例的淋巴结受累较少（32.9%比36.9%，p=0.000）。

Approximately 82.2% (981/1193) of ER+/PR-/HER2- patients received ET, while approximately 17.8% (212/1193) did not. Compared to patients did not receive adjuvant ET, the ET group had similar disease-free survival (DFS) (HR = 1.33, 95% confidence interval (CI): 0.68–2.59, p = 0.444) and overall survival (OS) (HR = 1.17, 95%CI: 0.37–3.68, p = 0.799).

大约82.2%（981/1193）的ER+/PR-/HER2患者接受ET，而大约17.8%（212/1193）没有。。

65.7% of recurrent ER+/PR-/HER2- patients experienced distant relapse (65.7% vs. 48.2% (for ER+/PR + cases), p = 0.011). By comparison, recurrent ER+/PR+/HER2- patients were more likely to experience only local relapse (31.6% vs. 14.9% (for ER+/PR- cases), p = 0.007). Conclusions: ER+/PR-/HER2- BC was a special subtype with ag.

65.7%的复发性ER+/PR-/HER2患者出现远处复发（65.7%比48.2%（ER+/PR+）病例），p=0.011）。相比之下，复发性ER+/PR+/HER2患者更可能仅出现局部复发（31.6%比14.9%（ER+/PR病例），p=0.007）。结论：ER+/PR-/HER2-BC是ag的一种特殊亚型。

IntroductionEstrogen receptor-positive (ER+)/ progesterone receptor-negative (PR-) breast cancer (BC) is a special subtype but not rare. According to different studies, it accounts for approximately 6.9–15% of all BC patients1,2,3,4,5. PR is a downstream gene upregulated by ER. Conversely, PR can also modulate the function of ER through the redirection of ERα chromatin binding.

。根据不同的研究，它约占所有BC患者的6.9-15%1,2,3,4,5。PR是ER上调的下游基因。相反，PR还可以通过ERα染色质结合的重定向来调节ER的功能。

The increased expression of gene signature stimulated by PR is associated with better prognosis6. PR loss may be a marker of nonfunctional ER. Hyper-methylation of the PR promoter and genetic loss of PR gene are common in ER+/PR- BC7. Growth factor signaling pathways activate more in this special subtype and may downregulate PR expression7,8,9.

PR刺激的基因特征表达增加与更好的预后相关6。PR缺失可能是无功能ER的标志。ER+/PR-BC7中PR启动子的高甲基化和PR基因的遗传缺失很常见。生长因子信号通路在这种特殊亚型中激活更多，并可能下调PR表达7,8,9。

Consequently, PR is usually inversely correlated to human epidermal growth factor receptor 2 (HER2) status10. ER+/PR- BC has a higher tumor mutational burden (TMB) than ER+/PR + BC, and exhibits more mutations in TP53 and ERBB25. PR negativity is significantly correlated with worse disease-free survival (DFS) and overall survival (OS) in ER+/HER2- BC11,12,13,14.

因此，PR通常与人表皮生长因子受体2（HER2）状态呈负相关10。ER+/PR-BC比ER+/PR++BC具有更高的肿瘤突变负荷（TMB），并且在TP53和ERBB25中表现出更多的突变。PR阴性与ER+/HER2-BC11,12,13,14中较差的无病生存期（DFS）和总生存期（OS）显着相关。

Although ER+/PR-BC has a higher pathological complete response (pCR) rate, the prognosis is still worse after neoadjuvant treatment15. In HER2- inflammatory BC, ER+/PR- subtype exhibits more aggressive biological features and worse breast cancer-specific survival (BCSS) and OS16. Regardless of HER2 status, ER+/PR- BC is also has a significantly worse prognosis1,3,17,18,19,20.The role of endocrine treatment (ET) in ER+/PR- BC is still controversial.

虽然ER+/PR-BC具有较高的病理完全缓解（pCR）率，但新辅助治疗后预后仍然较差15。在HER2炎症性BC中，ER+/PR亚型表现出更具侵袭性的生物学特征和更差的乳腺癌特异性存活（BCSS）和OS16。。

The ER+/PR- BC with epidermal growth factor receptor (HER1) expression or HER2 overexpression is more likely to resist to tamoxifen in adjuvant treatment10,21. Analysis of data from National Cancer Database (NCDB) demonstrates that hormone blocking thera.

具有表皮生长因子受体（HER1）表达或HER2过表达的ER+/PR-BC在辅助治疗中更可能抵抗他莫昔芬10,21。对国家癌症数据库（NCDB）数据的分析表明，激素阻断了thera。

Data availability

数据可用性

The data supporting the conclusions of this article are available from the corresponding author on reasonable request.

支持本文结论的数据可根据合理要求从通讯作者处获得。

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Download referencesFundingThis study was supported by the Public Welfare Technology Application Research Project of Zhejiang Province under Grant No. LGF21H160030, and Medical and Health Science and Technology Project of Zhejiang Province (No.2023KY046 and 2023KY543).Author informationAuthor notes These authors contributed equally: Miaochun Zhong and Xiaoqiu Ren.Authors and AffiliationsGeneral Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, ChinaMiaochun Zhong, Wenjie Xia, Yangyang Qian, Kewang Sun & Jun WuCenter of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaXiaoqiu RenAuthorsMiaochun ZhongView author publicationsYou can also search for this author in.

下载参考文献资助本研究得到了浙江省公益技术应用研究项目（批准号：LGF21H160030）和浙江省医疗卫生科技项目（批准号：2023KY046和2023KY543）的支持。作者信息作者注意到，这些作者做出了同样的贡献：钟妙春和任晓秋。作者和附属机构浙江省人民医院（附属人民医院）乳腺外科肿瘤中心普通外科，杭州医学院，浙江杭州，中国钟妙春，夏文杰，钱杨阳，孙克旺和吴军浙江大学医学院第二附属医院临床药理学中心，浙江杭州，中国小丘人作者钟妙春作者出版物您也可以在中搜索作者。

PubMed Google ScholarXiaoqiu RenView author publicationsYou can also search for this author in

PubMed Google ScholarXiaoqiu RenView作者出版物您也可以在

PubMed Google ScholarWenjie XiaView author publicationsYou can also search for this author in

PubMed谷歌学者Wenjie XiaView作者出版物您也可以在

PubMed Google ScholarYangyang QianView author publicationsYou can also search for this author in

PubMed Google ScholarYangyang QianView作者出版物您也可以在

PubMed Google ScholarKewang SunView author publicationsYou can also search for this author in

PubMed Google ScholarKewang SunView作者出版物您也可以在

PubMed Google ScholarJun WuView author publicationsYou can also search for this author in

PubMed Google ScholarJun WuView作者出版物您也可以在

PubMed Google ScholarContributionsAll authors contributed to the study conception and design. Data collection and analysis were performed by Miaochun Zhong, Xiaoqiu Ren, Wenjie Xia and Yangyang Qian; The first draft of the manuscript was written by Jun Wu and all authors commented on previous versions of the manuscript.

PubMed谷歌学术贡献所有作者都为研究概念和设计做出了贡献。数据收集和分析由钟妙春，任晓秋，夏文杰和钱阳阳进行；手稿的初稿由吴军撰写，所有作者都对手稿的先前版本进行了评论。

All authors read and approved the final manuscript.Corresponding authorCorrespondence to.

所有作者都阅读并批准了最终手稿。对应作者对应。

Jun Wu.Ethics declarations

吴军。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Additional informationPublisher’s noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Electronic supplementary materialBelow is the link to the electronic supplementary material.Supplementary Material 1Rights and permissions

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Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

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You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

根据本许可证，您无权共享源自本文或其部分的改编材料。本文中的图像或其他第三方材料包含在文章的知识共享许可证中，除非该材料的信用额度中另有说明。。

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要查看此许可证的副本，请访问http://creativecommons.org/licenses/by-nc-nd/4.0/..

Reprints and permissionsAbout this articleCite this articleZhong, M., Ren, X., Xia, W. et al. The role of adjuvant endocrine treatment in ER+, PR−, HER2− early breast cancer: a retrospective study of real-world data.

转载和许可本文引用本文Zhong，M.，Ren，X.，Xia，W。等人。辅助内分泌治疗在ER+，PR-，HER2-早期乳腺癌中的作用：对现实世界数据的回顾性研究。

Sci Rep 14, 26377 (2024). https://doi.org/10.1038/s41598-024-78341-2Download citationReceived: 03 July 2024Accepted: 30 October 2024Published: 02 November 2024DOI: https://doi.org/10.1038/s41598-024-78341-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Sci Rep 1426377（2024）。https://doi.org/10.1038/s41598-024-78341-2Download引文接收日期：2024年7月3日接受日期：2024年10月30日发布日期：2024年11月2日OI：https://doi.org/10.1038/s41598-024-78341-2Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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KeywordsBreast cancerEndocrine therapy resistanceHormone receptor-positive breast cancerOutcomes research

关键词乳腺癌内分泌治疗抵抗激素受体阳性乳腺癌结局研究