The ovaries of women with the BRCA1 mutation appear to have fewer eggs.
BRCA1 and BRCA2 gene mutations are associated with an elevated risk of cancer in the breast, ovaries, fallopian tubes and peritoneum. The risk increases with age, and it tends to be higher for those with BRCA1.
In the general population, the prevalence of BRCA1 is around 0.1%, and for BRCA2, it is 0.2%, but some groups are more susceptible, for example, Ashkenazi Jews.
According to the National Cancer Institute, around 12% of all women develop breast cancer at some time. However, 55-65% of those with a BRCA1 mutation and 45% of those with a BRCA2 mutation will develop it by the age of 70 years.
Since the cancers are difficult to detect in the earlier, treatable stages, women who have the mutation are sometimes advised to have children at an earlier age and then undergo surgery to remove their ovaries and fallopian tubes when they reach their early 40s.
However, there is little quality evidence regarding the effects of the BRCA1 and BRCA2 mutations on conditions that are not related to cancer, such as fertility.
AMH levels 25% lower in women with BRCA1 mutation
An international group of researchers, including first author Prof. Kelly-Anne Phillips, a consultant medical oncologist at the Peter MacCallum Cancer Centre in East Melbourne, Australia, looked at the anti-Müllerian hormone (AMH) levels of 693 women, with an average age of 35 years, who had no personal history of cancer.
AMH is known to be a reliable indicator of the number of eggs in a woman's ovaries.
The women, aged 25-45 years, were participants in a 1997-2012 study by the Australian and New Zealand Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab).
- Around 1.3% of women will develop ovarian cancer
- 39% of women with a BRCA1 mutation will develop ovarian cancer by the age of 70 years
- 11-17% of those with a BRCA2 mutation will develop ovarian cancer by age 70.
Among the women with a family history of the BRCA1 mutation, 172 were carriers and 216 were not.
There were also 147 carriers and 158 non-carriers from families with the BRCA2 mutation.
The scientists carried out blood tests on the women while they were neither pregnant nor breastfeeding. All the participants had both ovaries. The team adjusted for age, use of oral contraceptives, body mass index (BMI) and smoking.
Results showed an average concentration of AMH that was 25% lower in women who carried the BRCA1 mutation than in non-carriers. When the women were divided into four groups according to AMH levels, the women with the BRCA1 mutation were in the lowest quartile.
The same was not true among carriers of the BRCA2 mutation.
The team believes that the results could relate to the role of BRCA1 and BRCA2 in repairing breaks in both strands of the DNA helix. Previous studies have shown that inefficient DNA repair can lead to increased aging in a woman's eggs.
Prof. Philips explains that the role of BRCA2 in double-strand DNA break repair is less significant than that of BRCA1. Carriers of BRCA2 also develop fewer cancers and at a later age.
Therefore, she says, it seems plausible that BRCA1 would have a greater impact on ovarian reserve.
She adds that a BRCA2 mutation may also affect the eggs to a lesser extent, but the current study was not sensitive enough to detect it.
Women with BRCA1 should consider having children earlier
According to Prof. Philips, "Women in their mid-30s, who carry the BRCA1 mutation have, on average, ovarian reserves similar to those of non-carriers who are 2 years older."
She adds that, although AMH reliably reflects the number of eggs, it is only one indicator of a woman's potential fertility.
Other factors to consider include the quality of the eggs and the presence of blockages in the fallopian tubes, which AMH levels do not reflect.
Some women with low AMH levels may yet conceive, while others with higher levels may be unable to do so.
However, based the current findings, Prof. Philips suggests:
"Women carrying the BRCA1 mutation should try to avoid delaying pregnancy until their late 30s or 40s when fertility is reduced anyway because of their age. For women trying to conceive in their 20s, any difference in ovarian reserve between BRCA1 mutation carriers and non-carriers is unlikely to be of clinical significance."
On the basis of these findings, the authors speculate that women with the BRCA1 mutation who undergo cancer therapy may have a higher risk of chemotherapy-induced menopause, since they have fewer eggs at the time of starting the treatment.
However, they emphasize that further research is needed to confirm this hypothesis.
Medical News Today reported last year on suggestions that screening for the BRCA gene is not cost-effective, due to its low prevalence in the general population.