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Alterations of DNA damage repair mechanisms are associated with invasive breast cancer (BC). This study aims to assess the role of base excision repair (BER) DNA Polymerase Beta (POL\u03b2) in DCIS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A cohort of DCIS comprising pure DCIS (<jats:italic>n<\/jats:italic>\u2009=\u2009776) and DCIS coexisting with invasive BC (<jats:italic>n<\/jats:italic>\u2009=\u2009239) were prepared as tissue microarrays. POL\u03b2 protein expression was assessed using immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Preclinically, we investigated the impact of POL\u03b2 depletion on stem cell markers in representative DCIS cell line models.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Reduced POL\u03b2 expression was associated with aggressive DCIS features including high nuclear grade, comedo necrosis, larger tumour size, hormonal receptor negativity, HER2 overexpression and high Ki67 index. Combined low nuclear\/low cytoplasmic POL\u03b2 expression showed the strongest association with the features\u2019 characteristics of aggressive behaviour. There was a gradual reduction in the POL\u03b2 expression from normal breast tissue, to DCIS, with the lowest expression observed in the invasive BC. Low POL\u03b2 expression was an independent predictor of recurrence in DCIS patients treated with breast conserving surgery (BCS). <jats:italic>POL\u03b2<\/jats:italic> knockdown was associated with a significant increase in cell stemness markers including SOX2, NANOG and OCT4 levels in MCF10-DCIS cell lines.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Loss of POL\u03b2 in DCIS is associated with aggressive behaviour and it can predict recurrence. POL\u03b2 expression in DCIS provides an additional feature for patients\u2019 risk stratification for personalised therapy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10549-021-06357-7","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T05:11:32Z","timestamp":1629263492000},"page":"39-51","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The frequency and clinical significance of DNA polymerase beta (POL\u03b2) expression in breast ductal carcinoma in situ (DCIS)"],"prefix":"10.1007","volume":"190","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-2424","authenticated-orcid":false,"given":"Abdulbaqi","family":"Al-Kawaz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem","family":"Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Toss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Islam M.","family":"Miligy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar J.","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew R.","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivasan","family":"Madhusudan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emad A.","family":"Rakha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"issue":"2","key":"6357_CR1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.gendis.2018.05.001","volume":"5","author":"Y Feng","year":"2018","unstructured":"Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L, Ji X, Liu W, Huang B, Luo W, Liu B, Lei Y, Du S, Vuppalapati A, Luu HH, Haydon RC, He TC, Ren G (2018) Breast cancer development and progression: risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. 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