Study Sheds Light on Age-Specific Breast and Ovarian Cancer Risks

Antonis Antoniou, PhD

Antonis Antoniou, PhD

While researchers have yet to determine the degree to which harboring aBRCA1orBRCA2mutation raises a woman’s lifetime risk of developing breast and ovarian cancer, a recent study is now offering more insight in this area by estimating the age at whichBRCA1/2-positive women are most at risk.

In a study published in theJournal of the American Medical Association,researchers from Europe, Australia, and the United States analyzed 6036 BRCA1 and 3820 BRCA2 carriers. Of those, 5046 women did not have cancer, whereas 4810 women had breast, ovarian cancer, or both. 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 withBRCA1andBRCA2mutations has enabled us to obtain the most precise estimates of age-specific breast and ovarian cancer risks to date,” study author Antonis Antoniou, PhD, explained in an interview withTargeted Oncology.“These should provide more confidence in the counselling and clinical management of women with faults in theBRCA1andBRCA2genes.” Antoniou is a research fellow with the Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, at the University of Cambridge.

At a median follow-up of 5 years, 426 women were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer. Researchers found that the cumulative breast cancer risk to age 80 forBRCA1was 72% (95% CI, 65%-79%) and 69% forBRCA2(95% CI, 61%-77%). In addition, researchers reported a rapid increase in breast cancer cases among women with BRCA1 in early adulthood up to the age of 30 to 40 years and until age 40 to 50 years for women harboring the BRCA2 mutation. For women with either mutation, the incidence of breast cancer then remained steady at 20 to 30 cases per 1000 years until age 80.

The number of relatives diagnosed with the disease affected breast cancer risk for women with either mutation. The hazard ratio (HR) for &ge;2 first- or second-degree relatives versus no affected relatives was 1.99 (95% CI, 1.41-2.82;P<.001 for trend) in women with the BRCA1 mutation and for those withBRCA2, (HR, 1.91; 95% CI, 1.08-3.37;P= .02 for trend). Breast cancer risk also varied by whether the mutation was located outside versus within specific positions in theBRCA1andBRCA2genes.

For ovarian cancer, researchers discovered that women withBRCA1had a 44% cumulative risk to age 80 years (95% CI, 36%-53%) and 17% for those withBRCA2(95% CI, 11%-25%).

The cumulative risk of contralateral breast cancer 20 years after a breast cancer diagnosis was 40% forBRCA1carriers (95% CI, 35%-45%) and 26% forBRCA2(95% CI, 20%-33%).

&ldquo;The results show clearly, and for the first time in a prospective study, that the cancer risks for women withBRCA1andBRCA2mutations depend on the extent of the woman&rsquo;s family history of cancer and the position of the specific fault within the gene,&rdquo; Antoniou said. &ldquo;Therefore, the mutation location can now be confidently incorporated in the risk assessment of women withBRCA1andBRCA2mutations.&rdquo;

Although genetic testing for such mutations seems like the logical next step for women who are unsure if they carry the genes, the debate continues over who needs to be tested.

&ldquo;There are ongoing studies that are aiming to assess the benefits and harms of such population-based screening approaches,&rdquo; said Antoniou. &ldquo;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 offeringBRCA1andBRCA2mutation screening to all women.&rdquo;

To further investigate theBRCA-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, pregnancy, and lifestyle factors like alcohol consumption.

&ldquo;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,&rdquo; he said.

Reference:

Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.JAMA.2017;317(23):2402-2416. doi: 10.1001/jama.2017.7112.