A high number of births may reduce the risk of breast cancer in women who carry a BRCA1 gene mutation, while increasing risk among women who carry a BRCA2 gene mutation, according to a study published in the International Journal of Cancer .
Inherited mutations in two genes-BRCA1 and BRCA2-have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Alterations in these genes can be passed down through either the mother’s or the father’s side of the family. While it’s important to note that BRCA1 and BRCA2 alterations account for only a small proportion of all breast and ovarian cancers, some families may benefit from genetic testing.
Because not all women with a BRCA1 or BRCA2 mutation develop cancer, there is interest in identifying factors that increase or decrease the likelihood of breast cancer. Reproductive factors may play a role since they have been found to affect breast cancer risk in the general population. Younger age at first birth and a greater number of births, for example, appear to decrease the risk of breast cancer among women in general.
In order to determine the influence number of births has on breast cancer risk in women with a BRCA1 or BRCA2 mutation, researchers conducted a study among women from North America, Europe, and Israel. All study participants had a known BRCA1 or BRCA2 mutation. Women with breast cancer were matched to women without breast cancer by age, country, and mutation (BRCA1 or BRCA2). The reproductive histories of the matched pairs were compared. Birth was defined as a pregnancy that resulted in either a live birth or a stillborn child. The study enrolled a total of 1260 pairs of women-934 with BRCA1 mutations and 326 with BRCA2 mutations.
Among women with a BRCA1 mutation, there was no overall difference in breast cancer risk between those who had or had not given birth. Women with several births (four or more), however, appeared to be at decreased risk of breast cancer compared to women with no births. Risk of breast cancer was 38% lower among women with four or more births.
The conclusions for women with a BRCA2 mutation were different: Among these women, an increasing number of births appeared to increase the risk of breast cancer. Women with a BRCA2 mutation and two or more births had a roughly 50% increased risk of breast cancer compared to women with a BRCA2 mutation and no births. The increased risk was only observed for women under the age of 50 and was particularly elevated during the two years that followed each birth.
The researchers conclude that the effect of pregnancy on breast cancer risk among women with a BRCA1 or BRCA2 mutation varies by type of mutation. A large number of births appears to decrease risk of breast cancer among women with a BRCA1 mutation, while increasing the risk of breast cancer in a subset of women with a BRCA2 mutation.
Reference: Cullinane CA, Lubinski J, Neuhausen SL et al. Effect of Pregnancy as a Risk Factor for Breast Cancer in BRCA1/BRCA2 mutation carriers. International Journal of Cancer. 2005;117:988-991.