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Early onset HER2‐positive breast cancer is associated with germline TP53 mutations
Author(s) -
MelhemBertrandt Amal,
Bojadzieva Jasmina,
Ready Kaylene J.,
Obeid Elias,
Liu Diane D.,
GutierrezBarrera Angelica M.,
Litton Jennifer K.,
Olopade Olufunmilayo I.,
Hortobagyi Gabriel N.,
Strong Louise C.,
Arun Banu K.
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26377
Subject(s) - medicine , breast cancer , odds ratio , germline mutation , oncology , germline , genetic testing , cancer , confidence interval , estrogen receptor , gynecology , mutation , genetics , biology , gene
Abstract BACKGROUND: Germline TP53 mutations predispose to early onset breast cancer in women and are associated with Li‐Fraumeni syndrome. Published data on the pathological characteristics of breast cancer among women with TP53 mutations is limited. METHODS: We retrospectively reviewed the clinical records of women who underwent genetic testing for suspected germline TP53 mutations and who were diagnosed with breast cancer between 2000 and 2011. The pathological characteristics of the breast tumors from patients testing positive for a mutation (cases) were compared with those testing negative (controls). RESULTS: Patients who tested positive for germline TP53 mutations (n = 30) were compared with controls (n = 79). Human epidermal growth factor receptor 2 (HER2) amplification and/or overexpression was found in 67% of the tumors from the cases, compared with 25% for the controls ( P = .0001). Among patients with a mutation, 70% had estrogen receptor‐ and/or progesterone receptor‐positive tumors, compared with 68% in the control group ( P = .87). After adjusting for age at breast cancer diagnosis, having a HER2‐positive tumor increased the odds of testing positive for a germline TP53 mutation (odds ratio, 6.9; 95% confidence interval, 2.6‐18.2). For each yearly increment in age at breast cancer diagnosis, there was decreased likelihood of having a TP53 mutation of 5% (odds ratio, 0.95; 95% confidence interval0.91‐0.99). CONCLUSIONS: This study suggests an association between germline TP53 mutations and early onset HER2‐positive breast cancer. If confirmed in a larger cohort, these results could guide genetic testing strategies, lead to chemoprevention trials incorporating HER2‐targeted therapies, and elucidate some of the molecular pathways involved in breast cancer. Cancer 2012;. © 2011 American Cancer Society.