title: Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens.
abstract: The aim of this study is to delineate more clearly the prevalence of HER2+ breast cancer in women with germline BRCA1/2 mutations. For this purpose, we analysed primary mutation screens on women with breast cancer with unequivocal HER2 amplification and assessed the proportion of BRCA1 and BRCA2 breast cancers that were HER2+ comparing this with the existing literature. The results are that 1063 primary BRCA screens had confirmed tumour HER2 status. If HER2+ only 2.5 % (4/156) and 3.2 % (5/156) of women had a BRCA1 or BRCA2 mutation identified respectively; compared to 27.7 % (115/415) and 8.2 % (34/415) with triple negative tumours. Only 2.1 % (4/195) women with BRCA1-related breast cancer had HER2 amplified breast cancers rising to 6.8 % (n = 12, p = 0.04) in BRCA2. These rates are in keeping with most of the existing literature except a recent large multicenter report which documented higher rates but with no control group. The study concluded that true HER2-amplified breast cancers are rare amongst BRCA1 mutation carriers and are less common in BRCA2 than background rates.
authors.affiliation: Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre (MAHSC), Institute of Human Development, University of Manchester, Manchester, M13 9WL, UK. gareth.evans@cmft.nhs.uk.|Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Trust, Wythenshawe, Manchester, M23 9LT, UK. gareth.evans@cmft.nhs.uk.|Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK. gareth.evans@cmft.nhs.uk.|Manchester Breast Centre, The Christie, Manchester, M20 4BX, UK. gareth.evans@cmft.nhs.uk.
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
authors.affiliation: Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK.
authors.forename: F
authors.initials: F
authors.lastname: Lalloo
authors.affiliation: Manchester Breast Centre, The Christie, Manchester, M20 4BX, UK.|Department of Medical Oncology, The Christie, Manchester, M20 4BX, UK.
authors.forename: S
authors.initials: S
authors.lastname: Howell
authors.affiliation: Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK.
authors.forename: S
authors.initials: S
authors.lastname: Verhoef
authors.affiliation: Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre (MAHSC), Institute of Human Development, University of Manchester, Manchester, M13 9WL, UK.|Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK.
authors.forename: E R
authors.initials: ER
authors.lastname: Woodward
authors.affiliation: Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Trust, Wythenshawe, Manchester, M23 9LT, UK.|Manchester Breast Centre, The Christie, Manchester, M20 4BX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Howell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; C506487:ESR1 protein, human; C508053:ERBB2 protein, human
keywords: BRCA1; BRCA2; HER2; Triple negative