Do Oral Contraceptives Put BRCA1 and BRCA2 Mutation Carriers at Increased Risk of Breast Cancer?
Women who inherit the BRCA1 or BRCA2 gene mutation have a 50%-80% lifetime risk of developing ]]>breast cancer]]> . This is in contrast the women in general whose lifetime risk is 10%-12%. Although past research has suggested that long-term use of oral contraceptives slightly increases the risk of early-onset breast cancer in the general population, especially among long-term users, it was not known whether a similar association would be seen in BRCA mutation carriers.
This issue is important, not just because the baseline risk of breast cancer is so high in this subgroup, but because breast cancer in BRCA carriers often appears in premenopausal women. It is also important because some women may consider taking oral contraceptives because they are known to lower the risk of ovarian cancer, which is also increased in women who carry the BRCA gene mutations. A recent study in the December 4, 2002 issue of the Journal of the National Cancer Institute set out to examine whether oral contraceptive use increased the risk of breast cancer among women who carry a BRCA1 or BRCA2 mutation.
About the Study
A collaboration of authors from 53 institutions in 11 countries studied 2622 women who were known carriers of the BRCA1 and BRCA2 mutations to see whether oral contraceptive use was associated with an increase in their breast cancer risk. These women were participants in prior and ongoing research trials at these institutions, and agreed to undergo genetic testing to look for BRCA1 or BRCA2 mutations.
Women were excluded from the study for the following reasons:
- Incomplete oral contraceptive history
- Infrequent use of oral contraceptives
- Missing information regarding gynecologic or reproductive history
- Born before 1920
- Diagnosis of ovarian cancer or history of ]]>oophorectomy]]> (surgical removal of one or both ovaries) before breast cancer diagnosis
Between 1977 and 2001, all women completed a questionnaire that asked about their medical and reproductive histories—including past and present oral contraceptive use—ethnicity, smoking history (ever/never a regular smoker), parity (how many live childbirths), and ages at first and last live births. The 1311 women who were diagnosed with breast cancer were matched to 1311 controls without breast cancer by type of gene mutation (BRCA1 or BRCA2), year of birth (within 2 years), and country of residence. The researchers then compared the two groups of women to see whether there were differences in oral contraceptive use was associated with the prevalence of breast cancer. They also looked at the difference in oral contraception use and breast cancer diagnosis among women with the BRCA1 and BRCA2 mutations.
Oral contraceptives had been used by 69.7% of the women with breast cancer and by 68% of the women in the comparison group. Using oral contraception did not increase breast cancer risk in women with the BRCA2 mutation. In women with the BRCA1 mutation, however, any previous use of oral contraceptives increased the risk of subsequent breast cancer by a statistically significant 20%. When compared with BRCA1 mutation carriers who never used oral contraceptives, BRCA1 mutation carriers who used oral contraceptives for at least 5 years had a 11%-60% increase in their risk of getting breast cancer. Breast cancer risk was also increased in these BRCA1 mutation carriers if they:
- Used oral contraceptives before age 30 (9%-52% increase)
- Were diagnosed with breast cancer before age 40 (11%-72% increase)
- First used oral contraceptives before 1975 when higher levels of estrogen were used than more recent formulas (17%-75% increase)
Though these results are interesting, there are a number of limitations to this study. First, there was a lot of variability among the subjects in terms of their breast cancer risk. This is especially evident when women were evaluated according to their country of origin. For instance, women with the BRCA1 mutation who were from the United States had, on average, a 38% increase in breast cancer risk if they had ever taken oral contraceptives. While women with the BRCA1 mutation in The Netherlands had an 18% reduction in breast cancer risk if they had ever taken oral contraceptives. For this and other reasons, these results cannot be applied to all women with BRCA mutations.
Second, though there was no statistically significant increase in breast cancer risk in the BRCA2 carriers, there were not enough women included in this subgroup to be able to confirm these findings or say that the carriers of this mutation are not at increased risk if they are using oral contraceptives. Further research will need to be done on women with this mutation to confirm the findings this study suggested.
How Does This Affect You?
These findings suggest that women with the BRCA1 mutations should discuss the use of oral contraceptives with their physicians, especially in light of efforts to reduce the risk of breast or ovarian cancer. For example, women who undergo bilateral ]]>mastectomy]]> but keep their ovaries may be good candidates for oral contraceptives, whereas women who opt for frequent screening may not be. Given the results of this preliminary research, women might also wish to discuss with their physicians when to start oral contraceptives and how long to take them.
Although there are no proven methods of preventing breast cancer, randomized trials are currently underway to assess the effectiveness of anti-estrogen medications, such as ]]>tamoxifen]]> , in reducing the risk of breast cancer among high-risk women. While there is yet no conclusive evidence that lifestyle interventions such as weight reduction and ]]>exercise]]> can prevent breast cancer, preliminary evidence does suggests that avoiding ]]>obesity]]> and a sedentary existence may reduce the risk.
American Cancer Society
National Cancer Institute
Narod SA, Dubé MP, Klijn J, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Journal of the National Cancer Institute . 2002;94:1773-1779.
Last reviewed Dec 6, 2002 by ]]>Richard Glickman-Simon, MD]]>
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