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Background Tobacco smoke contains carcinogens, which may increase the risk of breast cancer (BC). Conversely, cigarette smoking also has antiestrogenic effects, which may reduce the risk of BC. The association between smoking and BC remains controversial. Methods Prospective cohort study of 111 140 participants of the Nurses' Health Study from 1976 to 2006 for active smoking and 36 017 women from 1982 to 2006 for passive smoking. Results During 3 005 863 person-years of follow-up, 8772 incident cases of invasive BC were reported. After adjustment for potential confounders, the hazard ratio (HR) of BC was 1.06% (95% confidence interval [CI], 1.01%-1.10%) for ever smokers relative to never smokers. Breast cancer incidence was associated with a higher quantity of current ( P for trend = .02) and past ( P for trend = .003) smoking, younger age at smoking initiation ( P for trend = .01), longer duration of smoking ( P for trend = .01), and more pack-years of smoking ( P for trend = .005). Premenopausal smoking was associated with a slightly higher incidence of BC (HR, 1.11; 95% CI, 1.07-1.15 for every increase of 20 pack-years), especially smoking before first birth (1.18; 1.10-1.27 for every increase of 20 pack-years). Conversely, the direction of the association between postmenopausal smoking and BC was inverse (0.93; 0.85-1.02 for every increase of 20 pack-years). Passive smoking in childhood or adulthood was not associated with BC risk. Conclusion Active smoking, especially smoking before the first birth, may be associated with a modest increase in the risk of BC.

Background Induced abortion has been inconsistently associated with breast cancer risk in case-control studies. Retrospective cohort studies using registry information in Scandinavia have not suggested an increase in the incidence of breast cancer, although data on individual reproductive factors were not accounted for. Methods We examined the association between induced and spontaneous abortion and the incidence of breast cancer in a prospective cohort of young women, the Nurses' Health Study II. The study included 105 716 women 29 to 46 years old at the start of follow-up in 1993. Information on induced or spontaneous abortions was collected in 1993 and updated biennially. During 973 437 person-years of follow-up between 1993 and 2003, 1458 newly diagnosed cases of invasive breast cancer were ascertained. Results A total of 16 118 participants (15%) reported a history of induced abortion, and 21 753 (21%) reported a history of spontaneous abortions. The hazard ratio for breast cancer among women who had 1 or more induced abortions was 1.01 (95% confidence interval, 0.88-1.17) after adjustment for established breast cancer risk factors; among women with 1 or more spontaneous abortions, the covariate-adjusted hazard ratio was 0.89 (95% confidence interval, 0.78-1.01). The relation between induced abortion and the incidence of breast cancer did not differ materially by number of abortions ( P for trend = .98), age at abortion ( P for trend = .68), parity ( P for interaction = .54), or timing of abortion with respect to a full-term pregnancy ( P for interaction = .10). Conclusion Among this predominantly premenopausal population, neither induced nor spontaneous abortion was associated with the incidence of breast cancer.

A high body mass index (BMI) has been related to a reduced risk of breast cancer in premenopausal women. The mechanisms underlying this association have not been elucidated.We explored whether factors affecting ovulation may explain the inverse association between BMI (calculated as weight in kilograms divided by the square of height in meters) and breast cancer in 113,130 premenopausal participants in the Nurses' Health Study II. During 1,225,520 person-years of prospective follow-up between 1989 and 2003, 1398 incident cases of invasive breast cancer were diagnosed. Weight, height, ovulatory infertility, menstrual cycle patterns, and a multitude of covariates were assessed throughout follow-up. Cox proportional hazards regression was used to compute hazard ratios and 95% confidence intervals (CIs).We observed a significant linear inverse trend between current BMI and breast cancer incidence (P.001) that was not explained by menstrual cycle characteristics or infertility due to an ovulatory disorder (covariate-adjusted hazard ratio for breast cancer in women with a BMIor =30 vs 20.0-22.4, 0.81; 95% CI, 0.68-0.96). We found BMI at age 18 years to be the strongest predictor of breast cancer incidence (covariate-adjusted hazard ratio for breast cancer in women with a BMI at age 18 yearsor =27.5 vs 20.0-22.4, 0.57; 95% CI, 0.41-0.81).Body size during the early phases of adult life seems to be particularly important in the development of premenopausal breast cancer. Factors other than anovulation are likely to mediate the protection conferred by a high BMI.

Background Hyperthyroidism caused by Graves’ disease is common in women, yet little is known about risk factors for the disease. We sought to determine whether lifestyle factors, including smoking, alcohol consumption, physical activity level, and body mass index, are risk factors for Graves’ hyperthyroidism. Methods This analysis was conducted using data from the Nurses’ Health Study II, among 115109 women aged 25 to 42 at entry. Incident reports of women with Graves’ hyperthyroidism, confirmed to have the disorder, were included. Results During 1 328 270 person-years of follow-up, incident diagnoses of Graves’ hyperthyroidism were confirmed in 543 women; the 12-year incidence was 4.6 per 1000 women. Cigarette smoking was a predictor of Graves’ hyperthyroidism. The hazard ratio among current smokers was 1.93 (95% confidence interval [CI], 1.54-2.43), and among past smokers it was 1.27 (95% CI, 1.03-1.56), after adjusting for recent pregnancy, parity, and other variables. Among current smokers, the hazard ratio increased with the intensity of smoking and was 2.63 (95% CI, 1.71-4.04) among women who smoked 25 or more cigarettes daily. Obesity was associated with a decreased risk of Graves’ hyperthyroidism. The hazard ratio for the disorder among women with a body mass index of 30 kg/m 2 or higher was 0.68 (95% CI, 0.49-0.92). Alcohol intake and physical activity level were not associated with risk of Graves’ hyperthyroidism. Conclusions Smoking is a risk factor for Graves’ hyperthyroidism in women. Obesity may be associated with a reduced risk, although weight loss as the first manifestation of hyperthyroidism cannot be excluded.

Background Findings from observational studies suggest an inverse association between lactation and premenopausal breast cancer risk, but results are inconsistent, and data from large prospective cohort studies are lacking. Methods We used information from 60 075 parous women participating in the prospective cohort study of the Nurses' Health Study II from 1997 to 2005. Our primary outcome was incident premenopausal breast cancer. Results We ascertained 608 incident cases of premenopausal breast cancer during 357 556 person-years of follow-up. Women who had ever breastfed had a covariate-adjusted hazard ratio (HR) of 0.75 (95% confidence interval [CI], 0.56-1.00) for premenopausal breast cancer compared with women who had never breastfed. No linear trend was found with duration of total lactation ( P = .95), exclusive lactation ( P = .74), or lactation amenorrhea ( P = .88). The association between lactation and premenopausal breast cancer was modified by family history of breast cancer ( P value for interaction = .03). Among women with a first-degree relative with breast cancer, those who had ever breastfed had a covariate-adjusted HR of 0.41 (95% CI, 0.22-0.75) for premenopausal breast cancer compared with women who had never breastfed, whereas no association was observed among women without a family history of breast cancer. Conclusion In this large, prospective cohort study of parous premenopausal women, having ever breastfed was inversely associated with incidence of breast cancer among women with a family history of breast cancer.

Background Anovulation has been hypothesized to decrease the risk of breast cancer. Therefore, infertility attributed to ovulatory disorders and ovulation-induction therapy may influence breast cancer risk. Methods We analyzed prospectively collected data from the Nurses' Health Study II, a cohort of 116 671 female registered nurses aged 25 to 42 years at baseline. Information on infertility was assessed every 2 years starting in 1989, ovulation induction was assessed every 2 years from 1993 to 1997, and incident cases of breast cancer were included through 2001. Results During 1 275 566 person-years of follow-up (1989-2001), 1357 incident cases of invasive breast cancer were diagnosed. Overall, women who reported infertility due to ovulatory disorder had a significantly lower incidence of breast cancer than women who did not report problems conceiving during a 12-month period (covariate-adjusted hazard ratio, 0.75; 95% confidence interval, 0.59-0.96). The incidence of breast cancer was lowest among women with infertility due to ovulatory disorder who received ovulation-induction therapy (covariate-adjusted hazard ratio, 0.60; 95% confidence interval, 0.42-0.85). Conclusions Among women who participated in the Nurses' Health Study II, we observed an inverse association between infertility due to ovulatory disorder and breast cancer incidence. We observed the greatest reduction in the incidence of breast cancer for women who reported ovulatory disorder and use of ovulation-induction therapy, but these results should be interpreted with caution because these women may be the most infertile.