A study of more than 3,000 families including women with breast cancer showed that close relatives of women who carry mutations in a BRCA gene – but who themselves do not have such genetic mutations  carry lesser risks of developing breast cancer compared to relatives of women with breast cancer who do not have such mutations.
While these results support most previous evidence regarding risks for non-carriers of BRCA mutations, they run counter to a 2007 study that indicated first-degree relatives (mothers, sisters and daughters) of women with BRCA gene mutations are several times more likely than the general population to develop breast cancer – despite not having the mutation themselves.
The new findings suggest that women who test negative for the mutation may not need extra cancer screening and other increased preventive measures.
“This new study gives reassurance to non-carriers that they do not have an increased risk due to the familial mutation, and should be regarded the same as other non-carriers with first-degree relatives who have had breast cancer.“- Allison Kurian MD assistant professor Stanford University School of Medicine
“One strength of the current study is the control women it used as a yardstick for comparing the breast cancer incidence in non-carriers of family-specific mutations. The control women were also relatives of breast cancer patients, but of patients without mutations. This is a more appropriate yardstick than average risk in the general population, since close relatives of all breast cancer patients have somewhat higher than average risks.”
Women who inherit a mutation in the BRCA1 or BRCA2 gene carry a 5- to 20-fold higher risk of developing breast or ovarian cancers. First-degree relatives who have not inherited the same familial BRCA mutation have been considered to have a considerably lower risk for breast cancer.
In 2007, a study of women who tested negative for a specific familial BRCA mutation showed they had a 2- to 5-fold increased risk of developing breast cancer; which could be considered comparable to the risk of having a BRCA mutation.
According to Dr. Kurian, the results raised concerns that non-carriers might require similar screening and preventive measures as their mutation-carrying relatives, such as annual breast MRI and prophylactic surgery, and cast some doubt on the meaning of a negative BRCA test.
Kurian said that the studies had looked at women who were in cancer family clinics and compared their breast cancer risk to that of women in the general population. Women from cancer family clinics were more likely to have intensive screening, and breast cancer risks tend to be higher among close relatives of breast cancer patients than those in the general population.
The investigators also found that a small percentage of women – 3.4 percent of women in the general populations of Australia, Canada and the U.S. – who are at highest risk for unexplained reasons (reasons other than a BRCA mutation) account for approximately 32 percent of all breast cancer cases, reflecting the wide range of factors that could play a role in breast cancer development.
“Earlier reports of higher risk among non-carriers of family-specific BRCA mutations compared to risks in the general population may reflect a comparison of women with and without a family history of breast cancer.” – Alice Whittemore PhD professor Stanford University School of Medicine.
The Journal of Clinical Oncology is the tri-monthly peer-reviewed journal of the American Society of Clinical Oncology (ASCO), the world’s leading professional society representing physicians who treat people with cancer.
