{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T12:06:19Z","timestamp":1793966779893,"version":"4.8.0"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T00:00:00Z","timestamp":1578873600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T00:00:00Z","timestamp":1578873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000869","name":"Susan G. Komen for the Cure","doi-asserted-by":"publisher","award":["KG110101"],"award-info":[{"award-number":["KG110101"]}],"id":[{"id":"10.13039\/100000869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003923","name":"Dr. Susan Love Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joseph B. Gould Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res Treat"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>We quantified cytotoxic T cells in nonmalignant breast tissues from women with and without subsequent breast cancer to assess evidence of whether immunosurveillance may be suppressed prior to tumor development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used an age-matched set of breast tissues from women with benign breast disease (BBD) who subsequently developed breast cancer (BBD with later BC), women with BBD who remained cancer free (BBD cancer-free), and normal Komen Tissue Bank (KTB) tissue donors (KTB controls). We evaluated terminal duct lobular units (lobules) for degree of epithelial abnormality and density of dual-positive CD8\/CD103 T cells, as CD103+\u2009cells are thought to be a subset of CD8+\u2009cytotoxic T cells located primarily in the intraepithelial compartment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 10 sets of age-matched women, 256 breast lobules were studied: 85 in BBD women with later BC, 85 in BBD cancer-free women, and 86 in KTB donors. The majority of all lobules were histologically normal (<jats:italic>N<\/jats:italic>\u2009=\u2009143, 56%), with 65 (25%) nonproliferative fibrocystic change, and 48 (19%) proliferative epithelial change (with or without atypia). In BBD women with later BC, median CD8+\/CD103+\u2009cell density was 39.6, 31.7, and 10.5 cells\/mm<jats:sup>2<\/jats:sup>(<jats:italic>p<\/jats:italic>\u2009=\u20090.002) for normal, nonproliferative, and proliferative lobules. In BBD cancer-free women, median CD8+\/CD103+\u2009cell density values were 46.7, 14.3, and 0 cells\/mm<jats:sup>2<\/jats:sup>(<jats:italic>p<\/jats:italic>\u2009=\u20090.004) respectively. In KTB donors, CD8+\/CD103+\u2009cell density was not significantly different across the lobule types (medians 0, 5.8, 10.7,<jats:italic>p<\/jats:italic>\u2009=\u20090.43).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In women with BBD, breast lobules with increasing epithelial abnormality show significant decreases in cytotoxic T cells as measured by CD8\/CD103 staining, suggesting that impaired immunosurveillance may be a component of the earliest stages of breast cancer development.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10549-019-05493-5","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T17:02:43Z","timestamp":1578934963000},"page":"55-61","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cytotoxic T cell depletion with increasing epithelial abnormality in women with benign breast disease"],"prefix":"10.1007","volume":"180","author":[{"given":"Sabina","family":"Adhikary","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya L.","family":"Hoskin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody L.","family":"Stallings-Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Arshad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene H.","family":"Frost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey J.","family":"Winham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine J.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Rakoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori A.","family":"Denison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith L.","family":"Knutson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek C.","family":"Radisky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Visscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2303-4946","authenticated-orcid":false,"given":"Amy C.","family":"Degnim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"5493_CR1","first-page":"247","volume-title":"Beitr\u00e4ge zur experimentellen Pathologie und Chemotherapie","author":"p Ehrlich","year":"1909","unstructured":"Ehrlich P (ed) (1909) Beitr\u00e4ge zur experimentellen Pathologie und Chemotherapie. 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Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of our Mayo Clinic Institutional Review Board (IRB# 11-000932), with evaluation and approval of the use of human samples for this purpose, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}}]}}