{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:05:54Z","timestamp":1785240354222,"version":"3.55.0"},"reference-count":28,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Zhejiang Provincial Medical and Health Science and Technology Project","award":["2023KY617"],"award-info":[{"award-number":["2023KY617"]}]},{"name":"Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project","award":["2023ZL292"],"award-info":[{"award-number":["2023ZL292"]}]},{"name":"Key Project of the Zhejiang Provincial Health Major Science and Technology Plan","award":["WKJZJ2417"],"award-info":[{"award-number":["WKJZJ2417"]}]},{"DOI":"10.13039\/100022963","name":"key research and development program of zhejiang province","doi-asserted-by":"publisher","award":["2019C04001"],"award-info":[{"award-number":["2019C04001"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022963","name":"key research and development program of zhejiang province","doi-asserted-by":"publisher","award":["2025C02066"],"award-info":[{"award-number":["2025C02066"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Hormone receptor-positive\/human epidermal growth factor receptor 2-negative (HR+\/HER2\u2212) breast cancer represents the most prevalent molecular subtype but demonstrates pronounced biological and clinical heterogeneity. Homologous recombination deficiency (HRD) and tumor-infiltrating lymphocytes (TILs) have recently emerged as key determinants of prognosis and immune activity, but their interplay in this subtype remains understudied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To assess the relationship between HRD, TILs, and clinical outcomes in HR+\/HER2\u2212 breast cancer and validate the prognostic value of HRD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Retrospective multicenter cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A total of 365 patients (332 with available TILs data) from three institutions were enrolled. HRD was quantified using Shallow HRD algorithm on low-depth whole-genome sequencing (threshold: score \u2a7e6). TILs were evaluated by the MD Anderson system (\u2a7e10% classified as high). Spearman correlation, Kaplan\u2013Meier survival analysis, and multivariable Cox regression were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      HRD scores were inversely correlated with TILs (Spearman rho\u2009=\u2009\u22120.13,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.031). HRD-high patients had significantly inferior 10-year survival (invasive disease-free survival (IDFS): 31.0% vs 57.9%, hazard ratio (HR)\u2009=\u20092.36; distant recurrence-free survival (DRFS): 34.1% vs 61.1%, HR\u2009=\u20092.48; overall survival (OS): 48.7% vs 79.0%, HR\u2009=\u20092.79;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). HRD was confirmed as an independent prognostic predictor (IDFS HR\u2009=\u20092.03, DRFS HR\u2009=\u20092.16, OS HR\u2009=\u20092.15;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.01). No significant survival benefit from anthracycline-based chemotherapy was observed in HRD-high tumors (HR\u2009=\u20091.32,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.451). High TILs showed no significant association with survival outcomes in this cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>HRD represents a reliable independent prognostic biomarker in HR+\/HER2\u2212 breast cancer in this cohort, with an inverse association with TILs suggesting immune evasion. Its potential impact on prognosis and treatment requires further validation in prospective clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359261456794","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:00:57Z","timestamp":1781863257000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Homologous recombination deficiency correlates with tumor-infiltrating lymphocytes and predicts patient outcomes in hormone receptor-positive\/HER2-negative breast cancer"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9234-9327","authenticated-orcid":false,"given":"Shu-Jie","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China"},{"name":"Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Fei","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine (Jinhua Municipal Central Hospital), Jinhua, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui-Cui","family":"Li","sequence":"additional","affiliation":[{"name":"Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, China"},{"name":"Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Wang","sequence":"additional","affiliation":[{"name":"Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, China"},{"name":"Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, China"},{"name":"Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, China"},{"name":"Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Liang","family":"Qian","sequence":"additional","affiliation":[{"name":"Hongyuan Biotech, Biobay, Suzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Yong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Feng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Affiliated Hospital of Jiaxing University (First Hospital of Jiaxing), Jiaxing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Breast Disease, Affiliated Hospital of Jiaxing University (First Hospital of Jiaxing), Jiaxing 314001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5644-3156","authenticated-orcid":false,"given":"Wen-Ming","family":"Cao","sequence":"additional","affiliation":[{"name":"Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou 310022, China"},{"name":"Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0111-2"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01507-7"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-024-01560-3"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2105215"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010207"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-024-01936-y"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08377-x"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.2217\/bmm-2022-0044"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.06.013"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03415-7"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03414-8"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.09.440"},{"key":"e_1_3_5_14_2","article-title":"Homologous recombination deficiency across subtypes of primary breast cancer","volume":"7","author":"Yndestad S","year":"2023","unstructured":"Yndestad S, Engebrethsen C, Herencia-Ropero A, et al. Homologous recombination deficiency across subtypes of primary breast cancer. JCO Precis Oncol 2023; 7: e2300338.","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-022-06529-z"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39335.541782.AD"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa261"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-023-02839-8"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.01.009"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-020-05771-7"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells13181526"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1218"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03282-3"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.08.2064"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-3328"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/1179554921996288"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-48300-4"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.10.003"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.4627"}],"container-title":["Therapeutic Advances in Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17588359261456794","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17588359261456794","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17588359261456794","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:57:17Z","timestamp":1785239837000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17588359261456794"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":28,"alternative-id":["10.1177\/17588359261456794"],"URL":"https:\/\/doi.org\/10.1177\/17588359261456794","relation":{},"ISSN":["1758-8359","1758-8359"],"issn-type":[{"value":"1758-8359","type":"print"},{"value":"1758-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"article-number":"17588359261456794"}}