Abstract
Although keeping a healthy weight and being physically active are among the few modifiable risk factors for post-menopausal breast cancer, the possible interaction between these two risk factors remains to be established. We analyzed prospectively a cohort of 19,196 women who provided detailed self-report on anthropometric measures, physical activity and possible confounders at enrollment in 1997. We achieved complete follow-up through 2010 and ascertained 609 incident cases of post-menopausal invasive breast cancer. We calculated metabolic energy turnover (MET h/day) per day and fitted Cox proportional hazards models to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs). The incidence of post-menopausal breast cancer among obese women (BMI ≥ 30 kg/m2) was 58 % higher (HR 1.58, CI 1.16–2.16) than in women of normal weight (18.5 ≤ BMI < 25). Women in the lowest tertile of total physical activity (< 31.2 MET h/day) had 40 % higher incidence of post-menopausal breast cancer (HR 1.40, CI 1.11–1.75) than those in the highest tertile (≥ 38.2 MET h/day). The excess incidence linked to these two factors seemed to combine in an approximately additive manner; the incidence among the most obese and sedentary women was doubled (HR 2.07, CI 1.31–3.25) compared with the most physically active women with normal weight. No heterogeneity of the physical activity-linked risk ratios across strata of BMI was detected (p value for interaction = 0.98). This prospective study revealed dose-dependent, homogenous inverse associations between post-menopausal breast cancer incidence and physical activity across all strata of BMI, and between post-menopausal breast cancer incidence and BMI across all strata of physical activity, with no evidence of additive or multiplicative interaction between the two, suggesting independent effects.
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Acknowledgments
We would like to thank Statistics Sweden for scanning the questionnaires. Furthermore, we would like to express sincere gratitude to the Swedish Cancer Society and volunteers who worked with the National March. This work was supported by ICA AB; Telefonaktiebolaget LM Ericsson; the Swedish Cancer Society [CAN 2012/591 to H–O.A.]; Karolinska Institutet Distinguished Professor Award [2368/10-221 to H–O.A.]; and the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet [to Y.T.L.].
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Rino Bellocco and Gaetano Marrone have contributed equally to this work.
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Supplementary figure 1a-c
Adjusted Hazard Ratios (HR) of post-menopausal breast cancer in the Swedish National March Cohort according to total physical activity (MET h/day) and stratified by category of body mass index (BMI, the weight in kilograms divided by the square of height in meters), a) normal weight (18.5≤BMI<25), b) overweight (25≤BMI<30), c) obesity (BMI≥30 kg/m2). The solid lines indicate hazard ratios, and dashed lines indicate 95% confidence intervals derived from restricted cubic spline regression, with knots placed at the 5th, 25th, 75th, and 95th percentiles of the physical activity distribution. The reference points correspond to the 25th percentile. The graph is truncated and ranges around 90% of the distribution. The hazard ratios are plotted on a logarithmic scale and adjusted for age at enrollment, cigarette smoking status, alcohol drinking, use of vitamin and mineral supplements, education level, contraceptive pill use, hormonal replacement therapy, age at menarche, number of children, age at first full-term pregnancy and childlessness. (DOCX 118 kb)
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Bellocco, R., Marrone, G., Ye, W. et al. A prospective cohort study of the combined effects of physical activity and anthropometric measures on the risk of post-menopausal breast cancer. Eur J Epidemiol 31, 395–404 (2016). https://doi.org/10.1007/s10654-015-0064-z
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DOI: https://doi.org/10.1007/s10654-015-0064-z