Early onset HER2‐positive breast cancer is associated with germline TP53 mutations
Open Access
- 14 July 2011
- Vol. 118 (4), 908-913
- https://doi.org/10.1002/cncr.26377
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 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. Cancer 2012;. © 2011 American Cancer Society.Keywords
This publication has 25 references indexed in Scilit:
- p53 status influences response to tamoxifen but not to fulvestrant in breast cancer cell linesInternational Journal of Cancer, 2011
- Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndromeRadiation Oncology, 2010
- Understanding wild-type and mutant p53 activities in human cancer: new landmarks on the way to targeted therapiesCancer Gene Therapy, 2010
- A novel HER2-positive breast cancer phenotype arising from germline TP53 mutationsJournal of Medical Genetics, 2010
- Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in humanCancer Gene Therapy, 2010
- TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypesJournal of Medical Genetics, 2010
- Breast Magnetic Resonance Imaging: An Overview for NonradiologistsMount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine, 2009
- TP53mutation status and gene expression profiles are powerful prognostic markers of breast cancerBreast Cancer Research, 2007
- Impact of mutant p53 functional properties onTP53mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 databaseHuman Mutation, 2007
- Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implicationsProceedings of the National Academy of Sciences, 2001