Haile Robert W, Thomas Duncan C, McGuire Valerie, Felberg Anna, John Esther M, Milne Roger L, Hopper John L, Jenkins Mark A, Levine A Joan, Daly Mary M, Buys Saundra S, Senie Ruby T, Andrulis Irene L, Knight Julia A, Godwin Andrew K, Southey Melissa, McCredie Margaret R E, Giles Graham G, Andrews Lesley, Tucker Katherine, Miron Alexander, Apicella Carmel, Tesoriero Andrea, Bane Anita, Pike Malcolm C, Whittemore Alice S
Department of Preventive Medicine, University of Southern California-Keck School of Medicine, 1441 Eastlake Avenue, MS 9175, Los Angeles, CA 90089-9175, USA.
Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1863-70. doi: 10.1158/1055-9965.EPI-06-0258. Epub 2006 Oct 4.
Understanding the effect of oral contraceptives on risk of breast cancer in BRCA1 or BRCA2 mutation carriers is important because oral contraceptive use is a common, modifiable practice.
We studied 497 BRCA1 and 307 BRCA2 mutation carriers, of whom 195 and 128, respectively, had been diagnosed with breast cancer. Case-control analyses were conducted using unconditional logistic regression with adjustments for family history and familial relationships and were restricted to subjects with a reference age under 50 years.
For BRCA1 mutation carriers, there was no significant association between risk of breast cancer and use of oral contraceptives for at least 1 year [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.53-1.12] or duration of oral contraceptive use (P(trend) = 0.62). For BRCA2 mutation carriers, there was no association with use of oral contraceptives for at least 1 year (OR, 1.62; 95% CI, 0.90-2.92); however, there was an association of elevated risk with oral contraceptive use for at least 5 years (OR, 2.06; 95% CI, 1.08-3.94) and with duration of use (OR(trend) per year of use, 1.08; P = 0.008). Similar results were obtained when we considered only use of oral contraceptives that first started in 1975 or later.
We found no evidence overall that use of oral contraceptives for at least 1 year is associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers before age 50. For BRCA2 mutation carriers, use of oral contraceptives may be associated with an increased risk of breast cancer among women who use them for at least 5 years. Further studies reporting results separately for BRCA1 and BRCA2 mutation carriers are needed to resolve this important issue.
了解口服避孕药对携带BRCA1或BRCA2基因突变者患乳腺癌风险的影响十分重要，因为口服避孕药的使用是一种常见且可改变的行为。
我们研究了497名携带BRCA1基因突变者和307名携带BRCA2基因突变者，其中分别有195名和128名已被诊断患有乳腺癌。采用无条件逻辑回归进行病例对照分析，并对家族史和家族关系进行了校正，分析仅限于参考年龄在50岁以下的受试者。
对于携带BRCA1基因突变者，患乳腺癌风险与使用口服避孕药至少1年之间无显著关联[比值比（OR）为0.77；95%置信区间（95%CI）为0.53 - 1.12]，与口服避孕药的使用时长也无关联（P趋势 = 0.62）。对于携带BRCA2基因突变者，使用口服避孕药至少1年与之无关联（OR为1.62；95%CI为0.90 - 2.92）；然而，使用口服避孕药至少5年与之存在风险升高的关联（OR为2.06；95%CI为1.08 - 3.94），且与使用时长有关联（每年使用的OR趋势为1.08；P = 0.008）。当我们仅考虑1975年或之后首次开始使用的口服避孕药时，得到了类似结果。
总体而言，我们没有发现证据表明，对于50岁之前的BRCA1和BRCA2基因突变携带者而言，使用口服避孕药至少1年与患乳腺癌风险有关。对于携带BRCA2基因突变者，使用口服避孕药至少5年的女性患乳腺癌风险可能会增加。需要进一步分别报告BRCA1和BRCA2基因突变携带者结果的研究来解决这一重要问题。
