{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:58:22Z","timestamp":1786121902534,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA129639"],"award-info":[{"award-number":["CA129639"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA083178"],"award-info":[{"award-number":["CA083178"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA097397"],"award-info":[{"award-number":["CA097397"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA234752"],"award-info":[{"award-number":["CA234752"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA206464"],"award-info":[{"award-number":["CA206464"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA008748"],"award-info":[{"award-number":["P30CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Women with estrogen receptor negative (ER\u2010) contralateral breast cancer (CBC) are 50% more likely to die of CBC compared to women with estrogen receptor positive (ER+) CBC. We comprehensively investigated risk factors for ER subtype\u2010specific CBC using the Women's Environmental Cancer and Radiation Epidemiology Study, a population\u2010based, case\u2013control study of 1521 CBC cases under age 55\u2009years and 2212 individually matched unilateral breast cancer controls. Information about breast cancer risk factors and ER status was obtained by interview and medical record abstraction and common genetic variants with GWAS. Multivariable rate ratios and 95% confidence intervals were estimated using conditional logistic regression models, adjusting for known and suspected risk factors. Among 2800 women where the matched case had known ER CBC status, chemotherapy, hormone therapy, and increasing number of full\u2010term pregnancies were associated with decreased ER+ CBC risk. Drinking, smoking, first breast cancer lobular histology, first\u2010degree breast cancer family history, a polygenic risk score (PRS) of 313 common variants, and an ER+ subtype\u2010specific PRS were associated with increased ER+ CBC risk. More than 2\u2009years of breastfeeding was associated with decreased ER\u2212 CBC risk. While none of the PRSs were associated with ER\u2212 CBC risk, first\u2010 and second\u2010degree family history of breast cancer and second\u2010degree family history of ovarian cancer were associated with increased ER\u2212 CBC risk. We identified differential risk factors for ER subtype\u2010specific CBC which can inform individualized risk prediction models for future clinical impact. There remains an unexplained genetic component of ER\u2212 CBC.<\/jats:p>","DOI":"10.1002\/ijc.70683","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T07:40:03Z","timestamp":1786088403000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Risk Factors for Estrogen Receptor Subtype\u2010Specific Contralateral Breast Cancer in Women Under Age 55\u2009Years"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1258-6112","authenticated-orcid":false,"given":"Anne S.","family":"Reiner","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen E.","family":"Malone","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F.","family":"Lynch","sequence":"additional","affiliation":[{"name":"University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9222-6215","authenticated-orcid":false,"given":"Lene","family":"Mellemkj\u00e6r","sequence":"additional","affiliation":[{"name":"Danish Cancer Institute  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7610-7635","authenticated-orcid":false,"given":"Julia A.","family":"Knight","sequence":"additional","affiliation":[{"name":"University of Toronto, Dalla Lana School of Public Health  Toronto Canada"},{"name":"Lunenfeld\u2010Tanenbaum Research Institute, Sinai Health  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3259-8003","authenticated-orcid":false,"given":"Esther M.","family":"John","sequence":"additional","affiliation":[{"name":"Stanford School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Liang","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Woods","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The WECARE Study Collaborative Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonine L.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"issue":"4","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s41416-021-01417-7","article-title":"The Risk of Contralateral Breast Cancer: A SEER\u2010Based Analysis","volume":"125","author":"Giannakeas V.","year":"2021","journal-title":"British Journal of Cancer"},{"issue":"16","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1016\/j.ejca.2015.07.016","article-title":"Prognosis, Stage and Oestrogen Receptor Status of Contralateral Breast Cancer in Relation to Characteristics of the First Tumour, Prior Endocrine Treatment and Radiotherapy","volume":"51","author":"Alkner S.","year":"2015","journal-title":"European Journal of Cancer"},{"issue":"1","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13058-017-0874-x","article-title":"Hormone Receptor Status of a First Primary Breast Cancer Predicts Contralateral Breast Cancer Risk in the WECARE Study Population","volume":"19","author":"Reiner A. S.","year":"2017","journal-title":"Breast Cancer Research"},{"issue":"12","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.52158","article-title":"Breast Cancer Susceptibility Gene Sequence Variations and Development of Contralateral Breast Cancer","volume":"7","author":"Reiner A. S.","year":"2024","journal-title":"JAMA Network Open"},{"issue":"1","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13058-016-0726-0","article-title":"Systemic Therapy for Breast Cancer and Risk of Subsequent Contralateral Breast Cancer in the WECARE Study","volume":"18","author":"Langballe R.","year":"2016","journal-title":"Breast Cancer Research"},{"issue":"7","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/jnci\/djz010","article-title":"The Influence of Adjuvant Systemic Regimens on Contralateral Breast Cancer Risk and Receptor Subtype","volume":"111","author":"Kramer I.","year":"2019","journal-title":"Journal of the National Cancer Institute"},{"issue":"2","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s10552-024-01900-5","article-title":"Adjuvant Endocrine Therapy and Risk of Contralateral Breast Cancer: A Systematic Review and Meta\u2010Analysis of Observational Studies","volume":"36","author":"Ghosh R.","year":"2025","journal-title":"Cancer Causes & Control"},{"issue":"3","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/ijc.70089","article-title":"Reproductive Factors and Risk of Contralateral Breast Cancer by Age and Hormone Receptor Status: The California Breast Cancer Survivorship Consortium","volume":"158","author":"John E. M.","year":"2026","journal-title":"International Journal of Cancer"},{"issue":"6","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1093\/aje\/kwk054","article-title":"Alcohol Consumption and Breast Cancer Risk in the Women's Health Study","volume":"165","author":"Zhang S. M.","year":"2007","journal-title":"American Journal of Epidemiology"},{"issue":"3","key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1093\/jnci\/djae254","article-title":"Risk Factors for Second Primary Breast Cancer by Laterality, Age, and Race and Ethnicity","volume":"117","author":"John E. M.","year":"2025","journal-title":"Journal of the National Cancer Institute"},{"issue":"9","key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1093\/jnci\/djab053","article-title":"Body Mass Index and Risk of Second Cancer Among Women With Breast Cancer","volume":"113","author":"Feigelson H. S.","year":"2021","journal-title":"Journal of the National Cancer Institute"},{"issue":"2","key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41416-025-03240-w","article-title":"Contralateral Breast Cancer After Radiotherapy and Hormone Therapy in Two Cohorts of US Breast Cancer Survivors","volume":"134","author":"Veiga L. H. S.","year":"2026","journal-title":"British Journal of Cancer"},{"issue":"5","key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/ijc.30791","article-title":"Alcohol Consumption and Cigarette Smoking in Combination: A Predictor of Contralateral Breast Cancer Risk in the WECARE Study","volume":"141","author":"Knight J. A.","year":"2017","journal-title":"International Journal of Cancer"},{"issue":"15","key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1200\/JCO.2017.77.3424","article-title":"Breast Cancer Family History and Contralateral Breast Cancer Risk in Young Women: An Update From the Women's Environmental Cancer and Radiation Epidemiology Study","volume":"36","author":"Reiner A. S.","year":"2018","journal-title":"Journal of Clinical Oncology"},{"issue":"15","key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1158\/0008-5472.CAN-23-3854","article-title":"Case\u2010Case Genome\u2010Wide Analyses Identify Subtype\u2010Informative Variants That Confer Risk for Breast Cancer","volume":"84","author":"Sun X.","year":"2024","journal-title":"Cancer Research"},{"issue":"1","key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/jnci\/djm267","article-title":"Effect of Systemic Adjuvant Treatment on Risk for Contralateral Breast Cancer in the Women's Environment, Cancer and Radiation Epidemiology Study","volume":"100","author":"Bertelsen L.","year":"2008","journal-title":"Journal of the National Cancer Institute"},{"issue":"4","key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.ijrobp.2008.02.040","article-title":"Dose to the Contralateral Breast From Radiotherapy and Risk of Second Primary Breast Cancer in the WECARE Study","volume":"72","author":"Stovall M.","year":"2008","journal-title":"International Journal of Radiation Oncology, Biology, Physics"},{"issue":"1","key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ajhg.2018.11.002","article-title":"Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes","volume":"104","author":"Mavaddat N.","year":"2019","journal-title":"American Journal of Human Genetics"},{"issue":"3","key":"e_1_2_12_20_1","doi-asserted-by":"crossref","first-page":"R199","DOI":"10.1186\/bcr771","article-title":"Study Design: Evaluating Gene\u2010Environment Interactions in the Etiology of Breast Cancer \u2013 The WECARE Study","volume":"6","author":"Bernstein J. L.","year":"2004","journal-title":"Breast Cancer Research"},{"issue":"12","key":"e_1_2_12_21_1","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1093\/oxfordjournals.aje.a009966","article-title":"Application of the Missing\u2010Indicator Method in Matched Case\u2010Control Studies With Incomplete Data","volume":"150","author":"Huberman M.","year":"1999","journal-title":"American Journal of Epidemiology"},{"issue":"1","key":"e_1_2_12_22_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.7326\/M18-1323","article-title":"Breast Cancer Risk After Recent Childbirth: A Pooled Analysis of 15 Prospective Studies","volume":"170","author":"Nichols H. B.","year":"2018","journal-title":"Annals of Internal Medicine"},{"issue":"12","key":"e_1_2_12_23_1","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1093\/annonc\/mdv379","article-title":"Breastfeeding and Breast Cancer Risk by Receptor Status\u2014A Systematic Review and Meta\u2010Analysis","volume":"26","author":"Islami F.","year":"2015","journal-title":"Annals of Oncology"},{"issue":"1","key":"e_1_2_12_24_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s10911-012-9269-x","article-title":"Smoking and Breast Cancer","volume":"18","author":"Reynolds P.","year":"2013","journal-title":"Journal of Mammary Gland Biology and Neoplasia"},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","DOI":"10.18332\/tid\/174132","article-title":"Smoking History and Breast Cancer Risk by Pathological Subtype: MCC\u2010Spain Study","volume":"21","author":"Pe\u00f1alver\u2010Arg\u00fceso B.","year":"2023","journal-title":"Tobacco Induced Diseases"},{"issue":"1","key":"e_1_2_12_26_1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1097\/01.GME.0000079740.18541.DB","article-title":"An Update on the Antiestrogenic Effect of Smoking: A Literature Review With Implications for Researchers and Practitioners","volume":"11","author":"Tank\u00f3 L. B.","year":"2004","journal-title":"Menopause"},{"issue":"2","key":"e_1_2_12_27_1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/0002-9378(90)90420-C","article-title":"The Antiestrogenic Effect of Cigarette Smoking in Women","volume":"162","author":"Baron J. A.","year":"1990","journal-title":"American Journal of Obstetrics and Gynecology"},{"issue":"4","key":"e_1_2_12_28_1","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/S0015-0282(16)58219-3","article-title":"Influence of Smoking on Fertility in Women Attending an In\u00a0Vitro Fertilization Program","volume":"65","author":"Sterzik K.","year":"1996","journal-title":"Fertility and Sterility"},{"issue":"4","key":"e_1_2_12_29_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/oxfordjournals.aje.a008939","article-title":"Predictors of Ovarian Steroid Secretion in Reproductive\u2010Age Women","volume":"144","author":"Westhoff C.","year":"1996","journal-title":"American Journal of Epidemiology"},{"issue":"3","key":"e_1_2_12_30_1","first-page":"881","article-title":"Pooled Analysis of Active Cigarette Smoking and Invasive Breast Cancer Risk in 14 Cohort Studies","volume":"46","author":"Gaudet M. M.","year":"2017","journal-title":"International Journal of Epidemiology"},{"issue":"32","key":"e_1_2_12_31_1","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.1200\/JCO.2009.23.1597","article-title":"Relationship Between Potentially Modifiable Lifestyle Factors and Risk of Second Primary Contralateral Breast Cancer Among Women Diagnosed With Estrogen Receptor\u2010Positive Invasive Breast Cancer","volume":"27","author":"Li C. I.","year":"2009","journal-title":"Journal of Clinical Oncology"},{"issue":"3","key":"e_1_2_12_32_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1158\/1055-9965.EPI-17-0837","article-title":"Family History and Risk of Second Primary Breast Cancer After In\u00a0Situ Breast Carcinoma","volume":"27","author":"Baglia M. L.","year":"2019","journal-title":"Cancer Epidemiology, Biomarkers & Prevention"},{"issue":"1","key":"e_1_2_12_33_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s10549-010-1137-z","article-title":"Risk of Second Breast Cancer According to Estrogen Receptor Status and Family History","volume":"127","author":"Bouchardy C.","year":"2011","journal-title":"Breast Cancer Research and Treatment"},{"issue":"5","key":"e_1_2_12_34_1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.ajhg.2020.09.001","article-title":"Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk","volume":"107","author":"Kramer I.","year":"2020","journal-title":"American Journal of Human Genetics"},{"issue":"8","key":"e_1_2_12_35_1","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1158\/1055-9965.EPI-09-0301","article-title":"Breast Cancer Receptor Status: Do Results From a Centralized Pathology Laboratory Agree With SEER Registry Reports?","volume":"18","author":"Ma H.","year":"2009","journal-title":"Cancer Epidemiology, Biomarkers & Prevention"},{"issue":"7","key":"e_1_2_12_36_1","doi-asserted-by":"crossref","first-page":"e48","DOI":"10.5858\/134.7.e48","article-title":"American Society of Clinical Oncology\/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer (Unabridged Version)","volume":"134","author":"Hammond M. E. H.","year":"2010","journal-title":"Archives of Pathology & Laboratory Medicine"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70683","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70683","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70683","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T07:40:08Z","timestamp":1786088408000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":35,"alternative-id":["10.1002\/ijc.70683"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70683","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"assertion":[{"value":"2026-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ijc.70683"}}