{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:18:39Z","timestamp":1783703919453,"version":"3.55.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003483","name":"Hebrew University of Jerusalem","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003483","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Familial Cancer"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Germline pathogenic variants (PVs) in\n                    <jats:italic>POT1<\/jats:italic>\n                    , one of the shelterin complex genes, correlate with tumor predisposition, primarily with melanoma, hematologic malignancies, sarcoma, papillary thyroid carcinoma and glioma. Breast cancer (BC) risk has not been shown to be elevated. We analyzed BC occurrence and features in a cohort of 29 female PV heterozygotes, of whom 13\/29 (45%) were diagnosed with BC. Data regarding genetic, clinical, pathologic, treatment, and outcome characteristics were extracted. Patients in our cohort harbored three different POT1 PVs; The c.233T\u2009&gt;\u2009C Ashkenazi founder PV occurred in 11\/13 (84.6%). Median age at first BC diagnosis was 54 years (range 44\u201372); no patient was diagnosed before the age of 40. Pathological subtypes varied; invasive ductal carcinoma was the most common. All primary tumors were estrogen receptor positive; one was HER2-enriched; no triple-negative cancers were observed. Stage at diagnosis varied: 6 of 10 tumors with known staging were stage 0 or I, and one patient presented with metastatic disease. Treatment approaches were diverse as clinically appropriate. After a median follow-up of 110 months, three second BC events occurred, with no BC-related mortality. Personal and family history of other malignancies were frequent. This is the first dedicated report describing BC phenotypes in\n                    <jats:italic>POT1<\/jats:italic>\n                    PV heterozygotes. Our findings suggest that enhanced BC surveillance may be warranted in this population. Larger cohorts are needed to further characterize the clinicopathological features of BC in\n                    <jats:italic>POT1<\/jats:italic>\n                    carriers, to define lifetime BC risk and determine whether BC-specific screening recommendations should be established for this group.\n                  <\/jats:p>","DOI":"10.1007\/s10689-026-00589-6","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:07:31Z","timestamp":1783660051000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Breast cancer phenotypes in carriers of pathogenic POT1 variants"],"prefix":"10.1007","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6787-3285","authenticated-orcid":false,"given":"Tal","family":"Hadar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aasem","family":"Abu Shtaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinat","family":"Bernstein-Molho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Eskin-Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbal","family":"Kedar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Peretz-Yablonsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiri","family":"Shkedi-Rafid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinat","family":"Yerushalmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviad","family":"Zick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gili","family":"Reznick-Levi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanir","family":"Allweis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"issue":"9","key":"589_CR1","doi-asserted-by":"publisher","first-page":"e44308","DOI":"10.1371\/journal.pone.0044308","volume":"7","author":"J Shen","year":"2012","unstructured":"Shen J, Terry MB, Liao Y, Gurvich I, Wang Q, Senie RT et al (2012) Genetic variation in telomere maintenance genes, telomere length and breast cancer risk. PLoS ONE 7(9):e44308","journal-title":"PLoS ONE"},{"issue":"2","key":"589_CR2","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.yexcr.2012.09.005","volume":"319","author":"W Lu","year":"2013","unstructured":"Lu W, Zhang Y, Liu D, Songyang Z, Wan M (2013) Telomeres-structure, function, and regulation. Exp Cell Res 319(2):133\u2013141","journal-title":"Exp Cell Res"},{"issue":"6","key":"589_CR3","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1002\/jcp.31034","volume":"238","author":"NH Zade","year":"2023","unstructured":"Zade NH, Khattar E (2023) POT1 mutations cause differential effects on telomere length leading to opposing disease phenotypes. J Cell Physiol 238(6):1237\u20131255","journal-title":"J Cell Physiol"},{"issue":"5","key":"589_CR4","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1001\/jamadermatol.2018.3662","volume":"155","author":"K Wong","year":"2019","unstructured":"Wong K, Robles-Espinoza CD, Rodriguez D, Rudat SS, Puig S, Potrony M et al (2019) Association of the POT1 Germline Missense Variant p.I78T With Familial Melanoma. JAMA Dermatol 155(5):604\u2013609","journal-title":"JAMA Dermatol"},{"key":"589_CR5","unstructured":"Accardo ML, Osborne J, Else T (1993) POT1 Tumor Predisposition. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A (eds) GeneReviews(\u00ae). Seattle (WA): University of Washington, Seattle Copyright \u00a9 1993\u20132025, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved."},{"issue":"11","key":"589_CR6","doi-asserted-by":"publisher","first-page":"100937","DOI":"10.1016\/j.gim.2023.100937","volume":"25","author":"J Herrera-Mullar","year":"2023","unstructured":"Herrera-Mullar J, Fulk K, Brannan T, Yussuf A, Polfus L, Richardson ME et al (2023) Characterization of POT1 tumor predisposition syndrome: Tumor prevalence in a clinically diverse hereditary cancer cohort. Genet Med 25(11):100937","journal-title":"Genet Med"},{"issue":"26","key":"589_CR7","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1056\/NEJMoa2300503","volume":"388","author":"EA DeBoy","year":"2023","unstructured":"DeBoy EA, Tassia MG, Schratz KE, Yan SM, Cosner ZL, McNally EJ et al (2023) Familial clonal hematopoiesis in a long telomere syndrome. 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