BRCA Family History Not Always A Greater Risk Factor For Breast Cancer

US researchers on Monday revealed that women do not automatically have a greater risk of developing breast cancer just because someone in their family tested positive for breast cancer genes.

The findings are based on analysis of more than 3,000 families including women with breast cancer. Researchers found that close relatives of women who carry mutations in a BRCA gene — but do not have the mutation themselves — do not have an increased risk of developing breast cancer compared to relatives of women with breast cancer who do not have the mutations.

The results support most previous evidence regarding risks for non-carriers of BRCA mutations, however, they do contradict a 2007 study that showed that first-degree relatives 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 finding suggests that women who test negative for the BRCA gene mutation may not need extra cancer screening and other preventative treatments.

“The results are encouraging and reassuring,” said Dr. Allison Kurian of Stanford University School of Medicine, whose study appears in the Journal of Clinical Oncology.

Women in the United States have, on average, a 12 to 13 percent chance of developing breast cancer in their lifetime. About 5 to 10 percent of breast cancers are genetic, and most of those cases are caused by abnormalities in the BRCA1 and BRCA2 genes. Women with these mutations have a 5 to 20 times greater risk of developing breast or ovarian cancer, and must take necessary precautions to reduce their risk of developing cancer. Many elect to have their breasts or ovaries removed to prevent cancer development.

Once these mutations show up in a woman, it is important for other female family members to be screened as well.

In the past, women who test negative have traditionally been told they have the same risk as women in the general population. But the 2007 study contradicted those beliefs, causing mass hysteria among physicians and patients alike. Kurian believed those study findings to be false-positives, and wanted to ease women´s minds.

For the study, Kurian and colleagues studies women with breast cancer in 3,047 families in three population-based cancer registries in Northern California (1,214), Australia (799) and Canada (1,034) through a consortium called the Breast Cancer Family Registry. They found 292 families in which a woman had a BRCA mutation.

They compared the risk of breast cancer among first-degree relatives (mothers, sisters, daughters) of breast cancer patients who did and did not carry a BRCA mutation and found no significant difference, meaning that non-carriers of a familial BRCA mutation did not have a markedly elevated risk of developing breast cancer.

They also found that a small percentage (3.4%) of women in the general populations of Australia, Canada and the US who are at highest risk for reasons other than BRCA mutations account for nearly 32 percent of all breast cancer cases. That finding reflects the wide range of factors that can 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,” noted study co-author Alice Whittemore, PhD, professor of epidemiology and biostatistics at Stanford University School of Medicine. “The control group we used – relatives of breast cancer patients in families without a BRCA mutation – was important.“

“The results suggest that women who test negative for their family´s BRCA mutation have no greater breast cancer risk than a woman who also has relatives with breast cancer but no family-specific mutation,” said Whittemore.

“First-degree relatives of breast cancer patients are themselves at higher risk than women in the general population. So some reports of higher risk among non-carriers, as compared to risk in the general population, may have been an inappropriate comparison of apples and oranges,” Whittemore added.

“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,” noted the researchers.

The findings should quell questions about risk based on a familial BRCA mutation. But, “it´s important for patients and clinicians to remember this doesn´t rule out other risk factors, which might increase a non-carrier´s probability of getting breast cancer,” Kurian concluded. 

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