title: Prevalence of germline TP53 mutations in HER2+ breast cancer patients.
abstract: Breast cancer is the most frequent tumor in Li-Fraumeni syndrome (LFS), a rare inherited cancer syndrome associated with germline mutations in the TP53 gene. Recent data show that breast cancer in germline TP53 mutation carriers is commonly HER2+ (63-83 %). We assessed the prevalence of germline TP53 mutations in a cohort of women with HER2+ breast cancer diagnosed age ≤50 years. We identified blood specimens from 213 women with primary invasive HER2+ breast cancer age ≤50 years from a single center. Exon grouping analysis sequencing and multiplex ligation-dependent probe amplification techniques were used to screen for germline TP53 mutations. Among 213 women with HER2+ breast cancer age ≤50 years, 3 (ages at diagnosis 23, 32, 44 years) were found to carry a TP53 mutation (1.4 %, 95 % CI 0.3-4.1 %). ER/PR status was not uniform. Two TP53 carriers met Chompret criteria for LFS; none met classic LFS criteria. Although two-thirds of breast cancers in women with TP53 mutations are HER2+, we observed a low prevalence of germline TP53 mutations among unselected young women with HER2+ breast cancer. Given the potential clinical impact, consideration of germline TP53 testing should be given to young women with HER2+ breast cancer, especially if family cancer history is notable.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Michelle G
authors.initials: MG
authors.lastname: Rath
authors.forename: Serena
authors.initials: S
authors.lastname: Masciari
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gelman
authors.forename: Alexander
authors.initials: A
authors.lastname: Miron
authors.forename: Penelope
authors.initials: P
authors.lastname: Miron
authors.forename: Kathleen
authors.initials: K
authors.lastname: Foley
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Richardson
authors.forename: Ian E
authors.initials: IE
authors.lastname: Krop
authors.forename: Sigitas J
authors.initials: SJ
authors.lastname: Verselis
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Dillon
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000453:epidemiology / Q000235:genetics; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D015995:Prevalence; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53