P2-13-04: Testing Women with Invasive Lobular Breast Cancer for BRCA Mutations.

Abstract

Abstract Background: Infiltrating lobular carcinoma (ILC) is the second most common type of invasive breast cancer behind infiltrating ductal carcinoma (IDC). ILC makes up approximately eight percent of all invasive lesions. In addition, the mixed ductal and lobular carcinoma histology makes up approximately seven percent of all invasive diagnoses. There are several biologic differences that are demonstrated by ILC compared to other common pathologies. They are more frequently bilateral and multicentric. They tend to be seen in women slightly older than the average age of diagnosis and are usually ER positive. It is also known that individuals with a genetic predisposition have an increased risk to develop breast cancers. Women with a mutation in their CDH1 gene have up to a 39% chance to develop ILC. The majority of hereditary breast cancer is caused by germ line mutations in the BRCA1 and BRCA2 genes. Women with a mutation in their BRCA1 or BRCA2 gene have up to an 87% risk to develop an invasive breast cancer, however, the presence of ILC in this population has not been well defined. Therefore, the aim of this study is to evaluate the rate of germline BRCA mutations in a cohort of patients both with pure ILC, as well as mixed ILC/IDC. Methods: A retrospective chart review revealed one hundred and sixty nine women with ILC and mixed ILC/IDC who underwent genetic testing for mutations in the BRCA1 and BRCA2 genes through the Clinical Cancer Genetics Program at M. D. Anderson Cancer Center. Women are referred for genetic testing using referral guidelines based on the NCCN guidelines, this usually involves a personal history of early onset breast cancer and/or a family history of breast and/or ovarian cancer. Results: Out of the 169 patients, 19 (11.24%) were found to have a germline mutation in their BRCA1 or BRCA2 gene. A significant majority (73.7%) of these patients were BRCA2 positive. Five women tested for a variant of uncertain significance. The average age of diagnosis for the cohort was 55.6 years (range 30–87); while the average age of diagnosis for a positive patient was 49.4 years (range 30–72). Of the 62 women with pure ILC, 5 (8.06%) were positive for a BRCA gene mutation. Historically, out of all the patients with breast cancer referred and tested through the Clinical Cancer Genetics Program, approximately 15% test positive, and research shows that in the general population, 7–10% of breast cancer patients will test positive. Conclusions: while the positivity rates between the cohorts are not statistically significant, we have shown that patients with a BRCA mutation can develop ILC in addition to the more commonly seen IDC. We suggest that patients continue to be referred for genetic counseling according to the NCCN guidelines, regardless of the pathology of their tumor. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-04.