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Abstract：
The relationship between reproductive factors and breast cancer (BC) risk has been investigated in previous studies. Considering the discrepancies in the results, the aim of this study was to estimate the causal effect of reproductive factors on BC risk in a case-control study using the double robust approach of targeted maximum likelihood estimation.
This is a causal reanalysis of a case-control study done between 2005 and 2008 in Shiraz, Iran, in which 787 confirmed BC cases and 928 controls were enrolled. Targeted maximum likelihood estimation along with super Learner were used to analyze the data, and risk ratio (RR), risk difference (RD), andpopulation attributable fraction (PAF) were reported.
Our findings did not support parity and age at the first pregnancy as risk factors for BC. The risk of BC was higher among postmenopausal women (RR = 3.3, 95% confidence interval (CI) = (2.3, 4.6)), women with the age at first marriage ≥20 years (RR = 1.6, 95% CI = (1.3, 2.1)), and the history of oral contraceptive (OC) use (RR = 1.6, 95% CI = (1.3, 2.1)) or breastfeeding duration ≤60 months (RR = 1.8, 95% CI = (1.3, 2.5)). The PAF for menopause status, breastfeeding duration, and OC use were 40.3% (95% CI = 39.5, 40.6), 27.3% (95% CI = 23.1, 30.8) and 24.4% (95% CI = 10.5, 35.5), respectively.
Postmenopausal women, and women with a higher age at first marriage, shorter duration of breastfeeding, and history of OC use are at the higher risk of BC.
This is a causal reanalysis of a case-control study done between 2005 and 2008 in Shiraz, Iran, in which 787 confirmed BC cases and 928 controls were enrolled. Targeted maximum likelihood estimation along with super Learner were used to analyze the data, and risk ratio (RR), risk difference (RD), andpopulation attributable fraction (PAF) were reported.
Our findings did not support parity and age at the first pregnancy as risk factors for BC. The risk of BC was higher among postmenopausal women (RR = 3.3, 95% confidence interval (CI) = (2.3, 4.6)), women with the age at first marriage ≥20 years (RR = 1.6, 95% CI = (1.3, 2.1)), and the history of oral contraceptive (OC) use (RR = 1.6, 95% CI = (1.3, 2.1)) or breastfeeding duration ≤60 months (RR = 1.8, 95% CI = (1.3, 2.5)). The PAF for menopause status, breastfeeding duration, and OC use were 40.3% (95% CI = 39.5, 40.6), 27.3% (95% CI = 23.1, 30.8) and 24.4% (95% CI = 10.5, 35.5), respectively.
Postmenopausal women, and women with a higher age at first marriage, shorter duration of breastfeeding, and history of OC use are at the higher risk of BC.
摘要：
先前的研究已经研究了生殖因素与乳腺癌（BC）风险之间的关系。考虑到结果的差异，本研究的目的是在一项病例对照研究中,使用有针对性的最大似然估计的双重稳健方法,估计生殖因素对BC风险的因果影响.
这是对2005年至2008年在设拉子进行的病例对照研究的因果再分析，伊朗,纳入787例确诊BC病例和928例对照.使用目标最大似然估计和超级学习者来分析数据，和风险比(RR)，风险差异(RD)，报告了人口归因分数（PAF）。
我们的研究结果不支持首次妊娠时的胎次和年龄是BC的危险因素。绝经后妇女的BC风险较高（RR=3.3，95％置信区间（CI）=（2.3，4.6）），初婚年龄≥20岁的女性（RR=1.6，95%CI=（1.3，2.1）），和口服避孕药（OC）使用史（RR=1.6，95％CI=（1.3，2.1））或母乳喂养时间≤60个月（RR=1.8，95％CI=（1.3，2.5））。更年期状态的PAF，母乳喂养持续时间，OC使用率为40.3%(95%CI=39.5，40.6)，27.3%（95%CI=23.1，30.8）和24.4%（95%CI=10.5，35.5），分别。
绝经后妇女,和初婚年龄较高的女性，母乳喂养持续时间较短，和OC使用史的BC风险较高。
这是对2005年至2008年在设拉子进行的病例对照研究的因果再分析，伊朗,纳入787例确诊BC病例和928例对照.使用目标最大似然估计和超级学习者来分析数据，和风险比(RR)，风险差异(RD)，报告了人口归因分数（PAF）。
我们的研究结果不支持首次妊娠时的胎次和年龄是BC的危险因素。绝经后妇女的BC风险较高（RR=3.3，95％置信区间（CI）=（2.3，4.6）），初婚年龄≥20岁的女性（RR=1.6，95%CI=（1.3，2.1）），和口服避孕药（OC）使用史（RR=1.6，95％CI=（1.3，2.1））或母乳喂养时间≤60个月（RR=1.8，95％CI=（1.3，2.5））。更年期状态的PAF，母乳喂养持续时间，OC使用率为40.3%(95%CI=39.5，40.6)，27.3%（95%CI=23.1，30.8）和24.4%（95%CI=10.5，35.5），分别。
绝经后妇女,和初婚年龄较高的女性，母乳喂养持续时间较短，和OC使用史的BC风险较高。
