Invasive breast cancer is one of the most common and lethal malignant cancers affecting women worldwide. The majority of invasive breast cancers develop over a long period of time from premalignant breast lesions. At present, these premalignant lesions can only be diagnosed using histopathological features. It is known from a number of epidemiological studies that certain of these premalignant lesions contain an elevated risk of eventually developing into invasive disease. Unfortunately, there are no current genetic tests to determine which of these lesions will develop into cancer.

The developers have identified a mutation in the estrogen receptor alpha gene that is a somatic gain-of-function mutation, an A908G mutation (K303R), occurring in the breast of women with premalignant hyperplasias. Approximately 34% of the premalignant lesions studied contain the mutation. More importantly, the mutation was found in roughly 50% of invasive breast cancers. There was a significant difference in the presence of the mutation as stratified by clinical variables. The mutation was more frequent in women > 50 years of age, those with metastasis to the lymph node and larger tumor size. In a study of 267 untreated breast cancer patients, the mutation was significantly associated with shorter time to recurrence; 10-year recurrence-free survival (RFS) was 46% compared to a RFS of 70% for wild-type ER alpha patients. A group at the University of North Carolina recently published a paper discussing that in 653 breast tumors evaluated in the Carolina Breast Cancer Study, 37 had the mutation and 616 did not have the mutation. The mutation was significantly associated with first-degree family history of breast cancer and long-term use of oral contraceptives (10+ years).

File Number: BLG 01-050 

Web site: http://www.bcm.edu/blg/showned.cfm?01-050

Disease: Cancer