Examining Age-Specific Breast and Ovarian Cancer Risk Among BRCA Carriers

A recent study examined how age plays a factor in cancer risk for women with the BRCA1 or BRCA2 genetic mutation.
BY Katie Kosko
PUBLISHED June 23, 2017
Having a BRCA1 or BRCA2 genetic mutation increases a woman's lifetime risk of developing breast and ovarian cancer. Now a recent study, published in the Journal of the American Medical Association, has examined this even further by estimating the age at which these women are most at risk.

Researchers from Europe, Australia and the United States analyzed 6,036 BRCA1 and 3,820 BRCA2 carriers. Of those, 5,046 women did not have cancer, while 4,810 women had breast or ovarian cancer, or both. The women were recruited from 1997 through 2011 from the United Kingdom, the Netherlands and France, and followed through December 2013.

“This large prospective cohort of women with BRCA1 and BRCA2 mutations has enabled us to obtain the most precise estimates of age-specific breast and ovarian cancer risks to date,” Antonis Antoniou, Ph.D., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, said in an interview with CURE. “These should provide more confidence in the counselling and clinical management of women with faults in the BRCA1 and BRCA2 genes.”

During a median follow-up of 5 years, 426 women were diagnosed with breast cancer, 109 with ovarian cancer and 245 with contralateral breast cancer, which is cancer in the breast opposite the one where there was cancer previously.

Researchers found that the cumulative breast cancer risk to age 80 for BRCA1 was 72 percent versus 69 percent for BRCA2. In addition, there was an increase of breast cancer cases in women with BRCA1 in early adulthood until ages 30 to 40 compared with ages 40 to 50 for BRCA2.

The odds of developing breast cancer increased for women with both BRCA1 and BRCA2 mutations depending on the number of first- and second-degree relatives diagnosed with the disease. Breast cancer risk also varied by mutation location within the BRCA1 and BRCA2 gene.

When it came to ovarian cancer, researchers discovered that women with BRCA1 were at 44 percent cumulative risk to age 80 versus 17 percent for those with BRCA2.

For contralateral breast cancer, the cumulative risk 20 years after a breast cancer diagnosis was 40 percent for BRCA1 and 26 percent for BRCA2.

“The results show clearly, and for the first time, in a prospective study, that the cancer risks for women with BRCA1 and BRCA2 mutations depend on the extent of the woman’s family history of cancer and the position of the specific fault within the gene,” he said. “Therefore, the mutation location can now be confidently incorporated in the risk assessment of women with BRCA1 and BRCA2 mutations.”

Although genetic testing for such mutations seems like the logical next step for women who are unsure if they carry the genes, there has been debate among researchers and others in the medical field over who needs to be tested.

“There are ongoing studies that are aiming to assess the benefits and harms of such population-based screening approaches,” said Antoniou. “The cancer risk estimates from our study will provide critical information for these studies. For example, our results show that women without family history of cancer are likely to be at lower breast cancer risk than women with strong cancer family history. These differences would need to be factored in when considering offering BRCA1 and BRCA2 mutation screening to all women.”

He added that women of high risk, who have a family history, should have testing aligned with national guidelines available in the country in which they live.
To further investigate the BRCA-related cancer risk, Antoniou and his colleagues will be examining how other factors play a role, such as use of oral contraceptive pills, hormone replacement therapy, pregnancies and lifestyle factors like alcohol consumption.

“We will then be able to combine all the findings to provide more personalized information on the age-specific cancer risks, and help women decide on the timing and on the options to use to reduce their risk of cancer,” he said.
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