Brohet Richard M, Goldgar David E, Easton Douglas F, Antoniou Antonis C, Andrieu Nadine, Chang-Claude Jenny, Peock Susan, Eeles Rosalind A, Cook Margaret, Chu Carol, Noguès Catherine, Lasset Christine, Berthet Pascaline, Meijers-Heijboer Hanne, Gerdes Anne-Marie, Olsson Håkan, Caldes Trinidad, van Leeuwen Flora E, Rookus Matti A
Netherlands Cancer Institute, Department of Epidemiology, Amsterdam, The Netherlands.
J Clin Oncol. 2007 Sep 1;25(25):3831-6. doi: 10.1200/JCO.2007.11.1179. Epub 2007 Jul 16.
PURPOSE Earlier studies have shown that endogenous gonadal hormones play an important role in the etiology of breast cancer among BRCA1/2 mutation carriers. So far, little is known about the safety of exogenous hormonal use in mutation carriers. In this study, we examined the association between oral contraceptive use and risk of breast cancer among BRCA1/2 carriers. PATIENTS AND METHODS In the International BRCA1/2 Carrier Cohort study (IBCCS), a retrospective cohort of 1,593 BRCA1/2 mutation carriers was analyzed with a weighted Cox regression analysis. Results We found an increased risk of breast cancer for BRCA1/2 mutation carriers who ever used oral contraceptives (adjusted hazard ratio [HR] = 1.47; 95% CI, 1.16 to 1.87). HRs did not vary according to time since stopping use, age at start, or calendar year at start. However, a longer duration of use, especially before first full-term pregnancy, was associated with an increased risk of breast cancer for both BRCA1 and BRCA2 mutation carriers (4 or more years of use before first full-term pregnancy: HR = 1.49 [95% CI, 1.05 to 2.11] for BRCA1 carriers and HR = 2.58 [95% CI, 1.21 to 5.49] for BRCA2 carriers). CONCLUSION No evidence was found among BRCA1/2 mutation carriers that current use of oral contraceptives is associated with risk of breast cancer more strongly than is past use, as is found in the general population. However, duration of use, especially before first full-term pregnancy, may be associated with an increasing risk of breast cancer among both BRCA1 and BRCA2 mutation carriers.
目的 早期研究表明，内源性性腺激素在BRCA1/2突变携带者的乳腺癌病因中起重要作用。到目前为止，对于突变携带者使用外源性激素的安全性知之甚少。在本研究中，我们调查了BRCA1/2携带者使用口服避孕药与乳腺癌风险之间的关联。
患者与方法 在国际BRCA1/2携带者队列研究（IBCCS）中，对1593名BRCA1/2突变携带者的回顾性队列进行加权Cox回归分析。
结果 我们发现，曾经使用过口服避孕药的BRCA1/2突变携带者患乳腺癌的风险增加（调整后的风险比[HR]=1.47；95%可信区间，1.16至1.87）。HRs并不因停止使用后的时间、开始使用时的年龄或开始使用时的日历年而有所不同。然而，使用时间越长，尤其是在首次足月妊娠之前使用，与BRCA1和BRCA2突变携带者患乳腺癌的风险增加有关（首次足月妊娠前使用4年或更长时间：BRCA1携带者的HR=1.49[95%可信区间，1.05至2.11]，BRCA2携带者的HR=2.58[95%可信区间，1.21至5.49]）。
结论 在BRCA1/2突变携带者中，没有证据表明目前使用口服避孕药比过去使用与乳腺癌风险的关联更强，这与一般人群中的情况相同。然而，使用时间，尤其是在首次足月妊娠之前的使用时间，可能与BRCA1和BRCA2突变携带者患乳腺癌的风险增加有关。
