Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.
Cancer Med. 2021 Mar;10(6):2153-2163. doi: 10.1002/cam4.3752. Epub 2021 Mar 1.
Prior studies reported the association of reproductive factors with breast cancer (BC), but the evidence is inconsistent. We conducted a pooled analysis of nine cohort studies in Japan to evaluate the impact of six reproductive factors (age at menarche/age at first birth/number of births/age at menopause/use of female hormones/breastfeeding) on BC incidence. We conducted analyses according to menopausal status at the baseline or at the diagnosis. Hazard ratio (HR) and 95% confidence interval (CI) were estimated by applying Cox proportional-hazards model in each study. These hazard ratios were integrated using a random-effects model. Among 187,999 women (premenopausal: 61,113, postmenopausal: 126,886), we observed 873 premenopausal and 1,456 postmenopausal cases. Among premenopausal women, use of female hormones significantly increased BC incidence (HR: 1.53 [1.04-2.25]). Although P value for trend was not significant for age at first birth and number of births (P for trend: 0.15 and 0.30, respectively), women giving first birth at ages ≥36 experienced significantly higher BC incidence than at ages 21-25 years, and women who had ≥2 births experienced significantly lower BC incidence than nulliparous women. Among postmenopausal women, more births significantly decreased BC incidence (P for trend: 0.03). Although P value for trend was not significant for age at first birth and age at menopause (P for trend: 0.30 and 0.37, respectively), women giving first birth at ages 26-35 years experienced significantly higher BC incidence than at ages 21-25 years, and women with age at menopause: ≥50 years experienced significantly higher BC incidence than age at menopause: ≤44 years. BC incidence was similar according to age at menarche or breastfeeding history among both premenopausal and postmenopausal women. In conclusion, among Japanese women, use of female hormones increased BC incidence in premenopausal women, and more births decreased BC incidence in postmenopausal women.
先前的研究报告了生殖因素与乳腺癌（BC）之间的关联，但证据并不一致。我们对日本的九项队列研究进行了荟萃分析，以评估六种生殖因素（初潮年龄/初产年龄/生育次数/绝经年龄/女性激素使用/母乳喂养）对 BC 发病率的影响。我们根据基线或诊断时的绝经状态进行了分析。应用 Cox 比例风险模型在每项研究中估计风险比（HR）和 95%置信区间（CI）。这些风险比通过随机效应模型进行整合。在 187999 名女性中（绝经前：61113 名，绝经后：126886 名），我们观察到 873 例绝经前和 1456 例绝经后病例。在绝经前妇女中，使用女性激素显著增加 BC 发病率（HR：1.53 [1.04-2.25]）。虽然初产年龄和生育次数的趋势检验 P 值无统计学意义（趋势检验 P 值分别为 0.15 和 0.30），但初产年龄≥36 岁的女性 BC 发病率显著高于 21-25 岁，生育次数≥2 次的女性 BC 发病率显著低于未生育的女性。在绝经后妇女中，生育次数越多，BC 发病率越低（趋势检验 P 值：0.03）。虽然初产年龄和绝经年龄的趋势检验 P 值无统计学意义（趋势检验 P 值分别为 0.30 和 0.37），但 26-35 岁初产的女性 BC 发病率显著高于 21-25 岁，绝经年龄≥50 岁的女性 BC 发病率显著高于绝经年龄≤44 岁。绝经前和绝经后妇女的初潮年龄或母乳喂养史与 BC 发病率无关。总之，在日本女性中，使用女性激素会增加绝经前妇女的 BC 发病率，而生育次数越多，绝经后妇女的 BC 发病率越低。
