Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, 1295 N. Martin Ave, Tucson, AZ, 85724, USA.
University of Arizona Cancer Center, University of Arizona, Tucson, USA.
Breast Cancer Res Treat. 2023 May;199(1):185-193. doi: 10.1007/s10549-023-06907-1. Epub 2023 Mar 16.
Research on infertility and risk of breast cancer has been conflicting, potentially because many well-established breast cancer risk factors, such as pregnancy history, are strongly correlated with infertility.
We followed participants in the Nurses' Health Study II from 1989 to 2015 (n = 103,080) for the development of invasive breast cancer and calculated Hazard Ratios (HR) and 95% confidence intervals (CI) using Cox regression. Participants with a self-reported history of infertility (12 months of trying without conception) were compared to gravid women with no history of infertility. We classified breast cancer by menopausal status and investigated mediation by reproductive factors.
Over 26 years of follow-up, 26,208 (25.4%) women reported a history of infertility, and 3,201 women were newly diagnosed with invasive breast cancer. We observed no association between infertility history and risk of overall breast cancer (HR: 1.05, 95% CI: 0.97-1.14) or premenopausal breast cancer (RR: 0.93, 95% CI: 0.83-1.03). However, we observed a modest association between history of infertility and risk of postmenopausal breast cancer (HR: 1.13, 95% CI: 1.00-1.28), approximately 50% of which could be attributed to lower total parity and later age at first birth (95% CI: 8.2%-91.0%).
Women with a history of infertility were at increased risk of postmenopausal breast cancer. Older age at first birth and lower total parity explained approximately half of the association between infertility and risk of postmenopausal breast cancer.
不孕与乳腺癌风险之间的研究结果相互矛盾，这可能是因为许多已确立的乳腺癌风险因素（如妊娠史）与不孕密切相关。
我们对护士健康研究 II 中的参与者进行了随访，从 1989 年到 2015 年（n=103080），观察浸润性乳腺癌的发生，并使用 Cox 回归计算风险比（HR）和 95%置信区间（CI）。将有不孕史（12 个月尝试怀孕但未成功）的参与者与无不孕史的孕妇进行比较。我们根据绝经状态对乳腺癌进行分类，并研究了生殖因素的中介作用。
在 26 年的随访期间，26208 名（25.4%）女性报告有不孕史，3201 名女性被新诊断为浸润性乳腺癌。我们没有观察到不孕史与总体乳腺癌风险（HR：1.05，95%CI：0.97-1.14）或绝经前乳腺癌风险（RR：0.93，95%CI：0.83-1.03）之间存在关联。然而，我们观察到不孕史与绝经后乳腺癌风险之间存在适度关联（HR：1.13，95%CI：1.00-1.28），其中约 50%可归因于总产次较低和首次分娩年龄较大（95%CI：8.2%-91.0%）。
有不孕史的女性绝经后乳腺癌风险增加。首次生育年龄较大和总产次较低解释了不孕与绝经后乳腺癌风险之间关联的约一半。
