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Genetic testing in a cohort of young patients with HER2-amplified breast cancer

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单位: [1]Univ Southampton, Fac Med & Canc Sci, Southampton, Hants, England [2]Peter MacCallum Canc Ctr, Canc Genet Lab, East Melbourne, Australia [3]Huazhong Univ Sci & Technol,Tongji Hosp,Canc Biol Res Ctr,Wuhan 430074,Peoples R China [4]Queen Mary Univ London, Barts Canc Inst CRUK, London, England [5]Queen Mary Univ London, Ctr Tumour Biol, London, England [6]Univ Manchester, Genom Med Inst Human Dev, Manchester, Lancs, England [7]St Marys Hosp, Manchester M13 0JH, Lancs, England [8]Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
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关键词: HER2 positive breast cancer young onset genetic testing gene panel

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Young age at diagnosis for breast cancer raises the question of genetic susceptibility. We explored breast cancer susceptibility genes testing on a parts per thousand currency sign40-year-old patients with HER2-amplified invasive breast cancer. Patients were selected from a large UK cohort study. The inclusion criterion was age a parts per thousand currency sign40 at diagnosis with confirmed HER2-amplified breast cancer. The probability of finding a BRCA gene mutation was calculated based on family history. Genetic testing used was either clinical testing for BRCA1 and BRCA2, with a subset also tested for TP53 mutations, or research-based testing using a typical panel comprising 17 breast cancer susceptibility genes (CSGs) including BRCA1, BRCA2 and TP53. Of the 591 eligible patients, clinical testing results were available for 133 cases and an additional 263 cases had panel testing results. BRCA testing across 396 cases found 8 BRCA2 (2%) and 6 BRCA1 (2%) pathogenic mutations. Of the 304 patients tested for TP53 mutations, overall 9 (3%) had deleterious TP53 mutations. Of the 396 patients, 101 (26%) met clinical criteria for BRCA testing (a parts per thousand yen10% probability), among whom 11% had pathogenic BRCA mutations (6 BRCA2, 5 BRCA1). Where the probability was calculated to be < 10%, only 4 of 295 (1%) patients had BRCA mutations. Among the 59 patients who had TP53 testing meeting the 10% threshold, 7 had mutations (12%). Likely functionally deleterious mutations in 14 lower penetrance CSGs were present in 12 of 263 (5%) panel-tested patients. Patients aged < 41 at diagnosis with HER2+ breast cancer and no family history of breast cancer can be reassured that they have a low chance of being a high-risk gene carrier. If there is a strong family history, not only BRCA but also TP53 gene testing should be considered. The clinical utility of testing lower penetrance CSGs remains unclear.

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出版当年[2015]版:
大类 | 1 区 医学
小类 | 2 区 肿瘤学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
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出版当年[2014]版:
Q1 ONCOLOGY
最新[2023]版:
Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2014版] 出版当年五年平均 出版前一年[2013版] 出版后一年[2015版]

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第一作者单位: [1]Univ Southampton, Fac Med & Canc Sci, Southampton, Hants, England [*1]Univ Southampton, Southampton Gen Hosp, Canc Sci, Somers Canc Res Bldg,Tremona Rd, Southampton SO16 6YA, Hants, England
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通讯机构: [1]Univ Southampton, Fac Med & Canc Sci, Southampton, Hants, England [*1]Univ Southampton, Southampton Gen Hosp, Canc Sci, Somers Canc Res Bldg,Tremona Rd, Southampton SO16 6YA, Hants, England
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