Additional support OCP's reduce ovarian cancer risk
Additional support OCP's reduce ovarian cancer risk
Abstract & Commentary
By Robert L. Coleman, MD, Associate Professor, University of Texas; M.D., Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.
Dr. Coleman is on the speaker's bureau for GlaxoSmithKline, Bristol-Myers Squibb and Ortho Biotech.
Synopsis: Reproductive risk factors for ovarian cancer in carriers of BRCA1 of BRCA2 mutations: a case-control study.
Source: McLaughlin JR, et al. Lancet Oncol. 2007;8:26-34.
Women with pathogenic mutations in BRCA1 or BRCA2 are known to be at substantially higher lifetime risk for ovarian and breast cancer than the general population. The degree to which reproductive factors affect this risk has been estimated but is limited by studies of small sample size or faulty methodology. McLaughlin and colleagues conducted a matched case-control study in women who were known BRCA carriers. Case patients were 799 women with ovarian cancer who were carefully matched (median 3:1) with 2424 control patients without ovarian cancer on the basis of age, BRCA mutation, country of residence, and history of breast cancer. Each completed a questionnaire detailing their reproductive history. The authors identified that use of oral contraceptives reduced the risk of ovarian cancer in BRCA1 (odds ratio: 0.56, 95% CI: 0.45-0.71, p < 0.0001) and BRCA2 (0.39, 0.23-0.66, p = 0.0004) mutation carriers. Breastfeeding reduced the risk of ovarian cancer in BRCA1 mutation carriers but not BRCA2 mutation carriers. Parity was associated with a protective effect on BRCA1 mutation carriers (0.67, 0.46-0.96, p = 0.03) but was detrimental for BRCA2 mutation carriers (2.74, 1.18-6.41, p=0.02). Tubal ligation had no apparent association with ovarian cancer risk. The authors concluded that oral contraceptives could be used as a means to prevent ovarian cancer in carriers of BRCA1 and BRCA2 mutations. The reason for the observed increased risk of ovarian cancer in patients with deleterious BRCA2 mutations is unknown.
Commentary
It has been previously documented that the use of oral contraceptives represents one of the few chemoprevention strategies available for women to alter their risk for ovarian cancer. In unselected populations, investigators have documented that "ever" use was associated with an approximately 50% reduction in lifetime ovarian cancer risk and trending analyses support the contention that the longer the duration of use the better protection. Fortunately, ovarian cancer is rare in the population, therefore recommendations for use of steroidal contraception as a chemoprotective agent was largely focused in "high-risk" settings. However, clear documentation that similar effects could be realized in these women is lacking. In addition, other reproductive factors such as parity, breastfeeding and tubal ligation have had a suggested role in reduction of ovarian cancer risk primarily through factors related to ovulation and ovarian steroidogenesis. However, the degree to which these factors modify risk in patients with substantially higher lifetime risk of cancer is largely unknown.
The investigators of the current report represent one of the few large Study Groups who are gathering data in population-based studies to address these issues in women who carry deleterious mutations in BRCA1 or BRCA2. Limitations of retrospective analyses are widely known and appreciated in the context of making cause and effect statements. However, carefully controlled analytical studies, such as the current report, aid in making valuable inferences into populations being studied. That being said, there are a few important considerations that should be borne in mind in interpreting the results outlined in this excellent report; first, both incident and prevalent cases of ovarian cancer are included. Some of the women included in the risk assessment were diagnosed 10 years or longer following enrollment. The potential bias here is that these women may not represent the general population of ovarian cancer patients. If the risk factors under study are related to overall cancer survival, information from these patients may misrepresent the impact of risk reduction in the general population. To their credit, the authors did repeat the analysis restricting enrollment to those completing the questionnaire within 3 years of diagnosis and similar results (with wider confidence limits) were found. Second, no pathological review was undertaken on the case patients. This means the confidence of diagnosis (including epithelial, borderline and metastatic) is based on patient reporting and natural incidence. However, the "softest" data in the report relates to information regarding duration of use, which is a limitation in retrospective reports. Women in this study were asked to estimate the temporal use of oral contraceptives and the duration of breastfeeding. Trending was seen in use of oral contraceptives and parity but not in breastfeeding. Interestingly, ovarian cancer risk is increased with increasing parity for patients with BRCA2 mutations, but decreased in BRCA1 patients. In fact, when compared to each other there is a significant difference, suggesting the hypothesis that parity affects ovarian cancer risk primarily through ovulation interruption may be faulty and related to other factors.
Overall, the report adds confidence that there may be an effective risk-reducing strategy for ovarian cancer in truly high-risk women. Prospective data are desperately needed to define this effect further.
References
- Cullinane CA, et al. Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers. Int J Cancer. 2005 Dec 20;117(6):988-991.
- Modan B, et al. Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. N Engl J Med. 2001 Jul 26;345(4):235-240.
- Whittemore AS, et al. Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations. Br J Cancer. 2004;91(11):1911-1915.
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