Abstract P3-12-01: Increased Rate of HER2-Positive Breast Cancers among Women with Germline TP53 Mutations
Authors: Melhem-Bertrandt A , Ready KJ , Gutierrez-Barrera AM , Litton J , Strong LC , Olopade OI , Hortobagyi GN , Arun BK. 
Published: April 2011

Abstract
Background: Germline TP53 mutations are the primary cause of Li Fraumeni syndrome (LFS), which is a cancer predisposition syndrome primarily associated with breast cancer, sarcomas, brain tumors, and adrenocortical carcinoma. The risk of cancer is higher for women than men and is mostly the result of the increased frequency of breast cancer among women with LFS. Published data on the specific clinical and pathological characteristics among women with breast cancer and germline TP53 mutations is limited.
Methods: To better describe the genotype-phenotype characteristics of women with breast cancer and LFS, we performed a retrospective chart review of all women with a known history of breast cancer that have undergone genetic testing for suspected germline TP53 mutations at M. D. Anderson Cancer Center between 2001 to present date. All women had documented breast pathology and most met the NCCN consortium guidelines for TP53 mutational analysis testing based on their personal and/or family history of cancer. The pathological characteristics of the women testing positive for TP53 mutation were then compared to the women testing negative, with a focus on specific histological features, Estrogen Receptor (ER) and HER2 status (as assessed by FISH ratio &gt; 2.2 or IHC 3).
Results: We identified 45 women with breast cancer who underwent testing for germline TP53 mutations because of a personal and family history suggestive of LFS. A total of 15 out of 45 women tested positive as identified by TP53 mutational analysis. Average age of breast cancer diagnosis for women testing positive was 30 years (range 20-45) and for women testing negative 32 years (range 21-58). Of the 15 women with LFS, 2 had DCIS, one had a spindle cell cancer of the breast, and one had incomplete pathologic assessment (HER2 unknown). These were excluded from the analysis. Of the 30 women testing negative for LFS, only 25 had complete pathological assessment available and were includedfor the comparison. The remainder of the patients all had Invasive Ductal Carcinoma of the breast. Among the LFS patients who had documented pathological grade, all had high grade. 73% of the LFS patients tested positive for ER expression as compared to 60% in the non-LFS group (p=0.71). 63% of the LFS patient had evidence of Her-2/neu amplification and/or overexpression compared to 24% in the non-LFS group (p=0.03). Conclusion: These data suggest an association between early onset HER2 positive breast cancer and LFS. If confirmed in a larger cohort of patients, these results could guide genetic testing strategies or open the door for future chemoprevention trials incorporating HER2 targeted therapies and vaccine trials in women with LFS. This association could also shed some light on the potential interaction between TP53 and Her2-neu both major molecular markers in breast cancer.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-01.