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However, the predictive value of triple-negative breast cancer, when taken in the context of personal and family cancer characteristics, is unknown. The aim of this study was to determine whether TNBC is a predictor of germline <jats:italic>BRCA1<\/jats:italic> mutations, in the context of multiple predictive factors.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Germline mutations in <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> were analyzed by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA) analysis in 431 women from the Malaysian Breast Cancer Genetic Study, including 110 women with TNBC. Logistic regression was used to identify and to estimate the predictive strength of major determinants. Estrogen receptor (ER) and phosphatase and tensin homologue (PTEN) status were assessed and included in a modified Manchester scoring method.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Our study in an Asian series of TNBC patients demonstrated that 27 (24.5%) of 110 patients have germline mutations in <jats:italic>BRCA1<\/jats:italic> (23 of 110) and <jats:italic>BRCA2<\/jats:italic> (four of 110). We found that among women diagnosed with breast cancer aged 36 to 50 years but with no family history of breast or ovarian cancer, the prevalence of <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> mutations was similar in TNBC (8.5%) and non-TNBC patients (6.7%). By contrast, in women diagnosed with breast cancer, younger than 35 years, with no family history of these cancers, and in women with a family history of breast cancer, the prevalence of mutations was higher in TNBC compared with non-TNBC (28.0% and 9.9%; P = 0.045; and 42.1% and 14.2%; P &lt; 0.0001, respectively]. Finally, we found that incorporation of estrogen-receptor and TNBC status improves the sensitivity of the Manchester Scoring method (42.9% to 64.3%), and furthermore, incorporation of <jats:italic>PTEN<\/jats:italic> status further improves sensitivity (42.9% to 85.7%).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>We found that TNBC is an important criterion for highlighting women who may benefit from genetic testing, but that this may be most useful for women with early-onset breast cancer (35 years or younger) or with a family history of cancers. Furthermore, addition of TNBC and PTEN status improves the sensitivity of the Manchester scoring method and may be particularly important in the Asian context, where risk-assessment models underestimate the number of mutation carriers.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr3347","type":"journal-article","created":{"date-parts":[[2012,11,2]],"date-time":"2012-11-02T01:17:15Z","timestamp":1351819035000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Triple-negative breast cancer and PTEN (phosphatase and tensin homologue)loss are predictors of BRCA1 germline mutations in women with early-onset and familial breast cancer, but not in women with isolated late-onset breast cancer"],"prefix":"10.1186","volume":"14","author":[{"given":"Sze-Yee","family":"Phuah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai-Meng","family":"Looi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norhashimah","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Rhodes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Dean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Aishah Mohd","family":"Taib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Har","family":"Yip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Hwang","family":"Teo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,11,2]]},"reference":[{"key":"3162_CR1","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1038\/nrclinonc.2010.172","volume":"7","author":"FL Rehman","year":"2010","unstructured":"Rehman FL, Lord CJ, Ashworth A: Synthetic lethal approaches to breast cancer therapy. 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