Brinton L A, Daling J R, Liff J M, Schoenberg J B, Malone K E, Stanford J L, Coates R J, Gammon M D, Hanson L, Hoover R N
Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
J Natl Cancer Inst. 1995 Jun 7;87(11):827-35. doi: 10.1093/jnci/87.11.827.
Several studies have suggested a link between oral contraceptive use and breast cancer in younger women, but it is possible that chance or bias, including selective screening of contraceptive users, contributed to the putative association.
Given that oral contraceptives were first marketed in the United States in the early 1960s, we conducted a population-based case-control study to examine the relationship between use of oral contraceptives and breast cancer among women in a recently assembled cohort, focusing on women younger than 45 years of age who had the opportunity for exposure throughout their entire reproductive years.
Breast cancer patients and healthy control subjects were identified, the latter group by random-digit dialing, in Atlanta, Ga., Seattle/Puget Sound, Wash., and central New Jersey. In Seattle and New Jersey, the study was confined to women 20 through 44 years of age; in Atlanta the age range was extended through 54 years. Patients included women with in situ or invasive breast cancer newly diagnosed during the period of May 1, 1990, through December 31, 1992. In-person interviews were completed by 2203 (86.4%) of 2551 eligible patients and 2009 (78.1%) of 2571 eligible control subjects. Analyses focused on women younger than 45 years of age (1648 patients and 1505 control subjects) to maximize opportunities for extended exposure. Logistic regression analyses were used to obtain maximum likelihood estimates of relative risks (RRs) and their 95% confidence intervals (CIs).
Among women younger than 45 years, oral contraceptive use for 6 months or longer was associated with an RR for breast cancer of 1.3 (95% CI = 1.1-1.5). Risks were enhanced for breast cancers occurring prior to age 35 years (RR = 1.7; 95% CI = 1.2-2.6), with the RR rising to 2.2 (95% CI = 1.2-4.1) for users of 10 or more years. The RR for breast cancer for those whose oral contraceptive use began early (before age 18 years) and continued long-term (> 10 years) was even higher (RR = 3.1; 95% CI = 1.4-6.7). The RRs observed for those who used oral contraceptives within 5 years of cancer diagnosis were higher than for those who had not, with the effect most marked for women younger than age 35 years (RR = 2.0; 95% CI = 1.3-3.1). Oral contraceptive associations were also strongest for cancers diagnosed at advanced stages. Evaluation of screening histories and methods of diagnosis failed to support the speculation that associations could be due to selective screening. Among women 45 years of age and older, no associations of risk with use of oral contraceptives were noted.
The relationship between oral contraceptives and breast cancer in young women appears to have a biologic basis rather than to be an artifact or the result of bias.
多项研究表明年轻女性口服避孕药与乳腺癌之间存在联系，但这种假定的关联可能是偶然因素或偏差所致，包括对避孕药使用者的选择性筛查。
鉴于口服避孕药于20世纪60年代初首次在美国上市，我们开展了一项基于人群的病例对照研究，以探讨在一个最近组建的队列中，口服避孕药的使用与乳腺癌之间的关系，重点关注年龄小于45岁、在整个生育期都有机会接触口服避孕药的女性。
在佐治亚州亚特兰大、华盛顿州西雅图/普吉特海湾和新泽西州中部确定了乳腺癌患者和健康对照者，后者通过随机数字拨号选取。在西雅图和新泽西州，研究仅限于20至44岁的女性；在亚特兰大，年龄范围扩大到54岁。患者包括1990年5月1日至1992年12月31日期间新诊断出原位或浸润性乳腺癌的女性。2551名符合条件的患者中有2203名（86.4%）和2571名符合条件的对照者中有2009名（78.1%）完成了面对面访谈。分析集中在年龄小于45岁的女性（1648名患者和1505名对照者），以最大限度地增加长期接触的机会。采用逻辑回归分析获得相对风险（RR）及其95%置信区间（CI）的最大似然估计值。
在年龄小于45岁的女性中，口服避孕药6个月或更长时间与乳腺癌的RR为1.3（95%CI=1.1-1.5）。35岁之前发生的乳腺癌风险增加（RR=1.7；95%CI=1.2-2.6），使用10年或更长时间的使用者RR升至2.2（95%CI=1.2-4.1）。口服避孕药使用开始早（18岁之前）且长期使用（>10年）的女性患乳腺癌的RR甚至更高（RR=3.1；95%CI=1.4-6.7）。在癌症诊断前5年内使用口服避孕药的女性的RR高于未使用者，这种影响在年龄小于35岁的女性中最为明显（RR=2.0；95%CI=1.3-3.1）。口服避孕药与晚期诊断出的癌症之间的关联也最强。对筛查史和诊断方法的评估未能支持这种关联可能是由于选择性筛查的推测。在45岁及以上的女性中，未发现口服避孕药使用与风险之间的关联。
年轻女性口服避孕药与乳腺癌之间的关系似乎有生物学基础，而非人为因素或偏差的结果。
