Correspondence to: William D. Foulkes, MB, PhD, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, 546 Pine Ave. West, Montreal, Quebec H2W 1S6, Canada (e-mail: william.foulkes{at}mcgill.ca).
The commentary by Klaren et al. (1) is a thoughtful piece of work. I would like to comment on the issue of the effect of parity on breast and ovarian cancer risk. In the context of BRCA1/2 mutation carriers, it is incorrect to state that parity is "an established factor that decreases breast and ovarian cancer risk" and thus not accounting for parity would "result in an overestimation of the efficacy of prophylactic surgery" (1). Although parity does decrease risk of breast and ovarian cancer in the general population, data suggest that this is not the case for breast cancer occurring in either BRCA1 (2) or BRCA2 (2,3) mutation carriers. Parous women are more likely than non-parous women to be genetically tested and to subsequently choose preventive surgery (4). Excluding parity from a proportional hazards model would therefore result in underestimation, not overestimation of the benefit of prophylactic mastectomy. By contrast, parity does seem to decrease the risk of BRCA1/2-related ovarian cancer (5). Studies of prophylactic mastectomy will need to consider the effect of parity differently from when the intervention is prophylactic oophorectomy. When both forms of preventive surgery are used, it may be difficult to fully disentangle the subtle relationships among parity, ascertainment, and cancer risk. This example illustrates the peculiar difficulty of estimating the true benefits of preventive surgery in BRCA1/2 mutation carriers.
REFERENCES
1 Klaren HM, vant Veer LJ, van Leeuwen FE, Rookus MA. Potential for bias in studies on efficacy of prophylactic surgery for BRCA1 and BRCA2 mutation. J Natl Cancer Inst 2003;95:9417.
2 Jernström H, Lerman C, Ghadirian P, Lynch HT, Weber B, Garber J, et al. Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2. Lancet 1999;354:184650.[CrossRef][ISI][Medline]
3 Tryggvadottir L, Olafsdottir EJ, Gudlaugsdottir S, Thorlacius S, Jonasson JG, Tulinius H, et al. BRCA2 mutation carriers, reproductive factors and breast cancer risk. Breast Cancer Res 2003;5:R1218. Available at: http://breastcancer-research.com/content/5/5/R121. [Last accessed: August 12, 2003.]
4 Meijers-Heijboer EJ, Verhoog LC, Brekelmans CT, Seynaeve C, Tilanus-Linthorst MM, Wagner A, et al. Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation. Lancet 2000;355:201520.[CrossRef][ISI][Medline]
5 Modan B, Hartge P, Hirsh-Yechezkel G, Chetrit A, Lubin F, Beller U, 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;345:23540.
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |