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 germlineTP53 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.