A female today who has a BRCA gene mutation is being diagnosed with breast and ovarian cancer about eight years earlier than their mothers or aunts were, researchers from the University of Texas MD Anderson Cancer Center reported in the journal Cancer. The authors say their findings could impact on how females at very high risk of breast cancer are counseled or screened in years to come.

Jennifer Litton, M.D., assistant professor in MD Anderson’s Department of Breast Medical Oncology, said:

“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. 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.”

Between 5% and 10% of breast cancers are linked to either the BRCA1 or BRCA1 mutation – which are associated with a higher risk of developing breast and ovarian cancers.

A woman with this type of mutation has a 60% lifetime risk of developing breast cancer, compared to other women at an estimated risk of 12%.

Women whose mothers and aunts have/had the mutation start breast screening when they are 25 years old.

The American Cancer Society added MRI (magnetic resonance imaging) scans to the surveillance of women with the genetic mutations in their guidelines. MRIs can identify smaller tumors better and earlier on than other scanning devices. Litton said that prophylactic mastectomies – surgical breast removal as a preventive measure – are considered during their surveillance, Litton added.

Litton said:

“Currently, BRCA positive women are counseled to start screening by 25 years, or five to ten 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.”

The scientists in this retrospective study identified 132 women the BRCA 1 or 2 genes who had breast cancer; they had taken part in a high-risk protocol through MD Anderson’s Clinical Cancer Genetics Program between 2003 and 2009.

106 of the 132 women had a female mother or aunt who also had a BRCA-related breast or ovarian cancer. The investigators recorded the ages at diagnosis of the women in Generation 1 (older ones) and Generation 2 (younger ones).

The median age of diagnosis in Generation 2 was 42 years, and 48 years in Generation 1. The difference was six years when they compared generations within a family. They used novel mathematical novels to evaluate for anticipation, and came up with a 7.9 years age difference between generations.

Litton said:

“These findings are certainly concerning and could have implications on the screening and genetic counseling of these women. 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.”

This research stresses that females with BRCA mutations should be screened according to the ACS guidelines – which includes mammography, MRI and the consideration of prophylactic mastectomy. The authors add that doctors should perhaps start at an even earlier age. Litton believes that the extra MRI screening may account for some of the diagnosis change observed in this study.

As this study did not involve many women, further larger ones are required. Litton and team plan to investigate a biological basis for potential earlier diagnosis.

Christian Nordqvist