TY - JOUR
T1 - Prevalence of germline TP53 mutations in HER2+ breast cancer patients
AU - Rath, Michelle G.
AU - Masciari, Serena
AU - Gelman, Rebecca
AU - Miron, Alexander
AU - Miron, Penelope
AU - Foley, Kathleen
AU - Richardson, Andrea L.
AU - Krop, Ian E.
AU - Verselis, Sigitas J.
AU - Dillon, Deborah A.
AU - Garber, Judy E.
PY - 2013/5/1
Y1 - 2013/5/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Li-Fraumeni syndrome
KW - TP53
UR - http://www.scopus.com/inward/record.url?scp=84877581424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877581424&partnerID=8YFLogxK
U2 - 10.1007/s10549-012-2375-z
DO - 10.1007/s10549-012-2375-z
M3 - Article
C2 - 23580068
AN - SCOPUS:84877581424
VL - 139
SP - 193
EP - 198
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 1
ER -