Women with a harmful gene mutation are diagnosed with breast cancer almost eight years earlier than relatives of the previous generation who also had the disease or ovarian cancer, according to new research from The University of Texas MD Anderson Cancer Center.

The findings, published online in Cancer and updated since first presented at the 2009 Breast Cancer Symposium, could have an impact on how women at highest risk for the disease are counseled and even screened in the future, says Jennifer Litton, assistant professor in MD Anderson's Department of Breast Medical Oncology.

"In our practice, we've noticed that women with a known deleterious BRCA gene mutation are being diagnosed earlier with the disease than their moms or aunts," says Litton, the study's first author. "With this study, we looked at women who had been both treated and had their BRCA testing at MD Anderson to determine if what we were seeing anecdotally was consistent scientifically, a phenomenon known as anticipation."

It's estimated that 5 to 10 percent of all breast cancers are associated with either the BRCA1 or 2 mutation, both of which are associated with an increased risk for breast and ovarian cancers. According to the American Cancer Society, women with BRCA1 or 2 have a 60 percent lifetime risk of developing breast cancer, compared with a 12 percent risk for women in the general population.

Given their greater risk, women with known BRCA mutations whose mothers or aunts from either side of the family have the mutation are screened beginning at age 25. In 2007, as a complement to mammography, ACS added to its guidelines magnetic resonance imaging in the surveillance of these women at highest risk, as MRI is thought to catch smaller tumors even earlier. Consideration of preventive mastectomies is also a component of their surveillance, Litton says.

"Currently, BRCA positive women are counseled to start screening by 25 years, or five to 10 years earlier than their youngest affected family member. However, our findings show that we may need to continue to follow these trends with future generations, and make changes accordingly in order to best advise and care for women at greatest risk," Litton says.

For the retrospective study, the researchers identified 132 BRCA positive women with breast cancer who participated in a high-risk protocol through MD Anderson's Clinical Cancer Genetics Program between 2003 and 2009. Reviewing each woman's pedigree, 106 were found to have a female family member in the previous generation who also had a BRCA-related cancer, either breast or ovarian. Age at diagnosis, location of mutation, and birth year were recorded in both the older and younger women.

The study found that in younger women, the median age of diagnosis was 42, compared with age 48 in the previous generation. In comparing generations within a family, the median difference was six years. By using new mathematical models to evaluate for anticipation, the difference in age between generations was 7.9 years.

"These findings are certainly concerning and could have implications on the screening and genetic counseling of these women," Litton says. "In BRCA positive women with breast cancer, we actually might be seeing true anticipation—the phenotype or cancer coming out earlier per generation. This suggests more than the mutation could be involved; perhaps lifestyle and environmental factors are also coming into play."

The research reconfirms that women with BRCA mutations should continue to be screened as suggested for the guidelines—mammography, MRI and consideration of preventive surgeries. Perhaps, those screenings should be performed with increased suspicion and even at an earlier age, says Litton, who notes that the addition of MRI screening may account for some of the change in diagnosis seen in the study.

Further analysis is needed given the relatively small number of women in the cohort and the possibility of recall bias, as the younger women were providing their family histories, Litton says. As follow-up study, Litton plans to look into biological basis for potential earlier diagnosis.

The study was funded by the Nellie B. Connally Breast Cancer Research Fund.