Elsevier

European Journal of Cancer

Volume 52, January 2016, Pages 138-154
European Journal of Cancer

Original Research
Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies

https://doi.org/10.1016/j.ejca.2015.10.063Get rights and content

Highlights

  • Increasing physical activity is associated with meaningful reductions in the risk of breast cancer.

  • Risk reductions associated with physical activity are independent from adiposity and menopausal status.

  • Risk reductions seem more pronounced for cancers that are oestrogen–progesterone receptor negative.

  • The preventative effect of physical activity seems to be cancelled out in women who ever used hormone replacement therapy.

Abstract

Background

Lower risk of breast cancer has been reported among physically active women, but the risk in women using hormone replacement therapy (HRT) appears to be higher. We quantified the association between physical activity and breast cancer, and we examined the influence that HRT use and other risk factors had on this association.

Methods

After a systematic literature search, prospective studies were meta-analysed using random-effect models applied on highest versus lowest level of physical activity. Dose–response analyses were conducted with studies reporting physical activity either in hours per week or in hours of metabolic equivalent per week (MET-h/week).

Results

The literature search identified 38 independent prospective studies published between 1987 and 2014 that included 116,304 breast cancer cases. Compared to the lowest level of physical activity, the highest level was associated with a summary relative risk (SRR) of 0.88 (95% confidence interval [CI] 0.85, 0.90) for all breast cancer, 0.89 (95% CI 0.83, 0.95) for ER+/PR+ breast cancer and 0.80 (95% CI 0.69, 0.92) for ER−/PR− breast cancer. Risk reductions were not influenced by the type of physical activity (occupational or non-occupational), adiposity, and menopausal status. Risk reductions increased with increasing amounts of physical activity without threshold effect. In six studies, the SRR was 0.78 (95% CI 0.70, 0.87) in women who never used HRT and 0.97 (95% CI 0.88, 1.07) in women who ever used HRT, without heterogeneity in results. Findings indicate that a physically inactive women engaging in at least 150 min per week of vigorous physical activity would reduce their lifetime risk of breast cancer by 9%, a reduction that might be two times greater in women who never used HRT.

Conclusion

Increasing physical activity is associated with meaningful reductions in the risk of breast cancer, but in women who ever used HRT, the preventative effect of physical activity seems to be cancelled out.

Introduction

Breast cancer is the commonest incident form of cancer in women worldwide which is responsible for approximately 1.7 million new cases in 2012 [1]. The ageing of the world's population, the notable increase in life expectancy, the sharp tendency towards adoption of a westernized lifestyle including lower fertility and sedentary, shorter duration of breastfeeding, and the raising prevalence of obese and diabetic subjects represent an accumulation of factors known to be associated with breast cancer that will contribute to the continual increase in the global burden of this cancer [2]. A public health priority is the identification of environmental or lifestyle factors whose modification could lead to reductions in breast cancer occurrence. Adiposity, alcohol consumption, and physical inactivity are modifiable risk factors that would contribute to 25% of breast cancer cases in France, 33% in United States of America (USA), 38% in the United Kingdom, 22% in Brazil and 11% in China [3], [4]. The preventive potential of physical activity was unveiled by a small study on 69 breast cancers that found a 44% (95% confidence interval [CI] 0, 77) reduced rate of breast cancer among female college athletes [5]. Since then, epidemiological studies have generally corroborated the inverse association between physical activity and breast cancer [6], [7]. However, the magnitude of the reduction in breast cancer risk associated with physical activity remains imprecise because of the variability in the way epidemiological studies measured physical activity, analysed data and reported results.

Higher levels of circulating oestrogen and androgen are related to higher breast cancer risk [8], [9], [10], and studies among post-menopausal women consistently showed that physical activity can reduce serum levels of these hormones [11], [12]. Use of hormone replacement therapy (HRT) increases levels of circulating sex hormones and the risk of breast cancer [13], [14]. A question is, thus, whether HRT use could influence the preventative effect of physical activity.

In this study, we quantified the association between physical activity and breast cancer risk in prospective studies, exploring in more depth the influence that exposure assessment and breast cancer risk factors, especially HRT use, could have on this association. Risk reductions associated with measurable amounts of physical activity were also evaluated.

Section snippets

Literature search and study selection

A systematic literature search and quantitative analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines [15]. This search was restricted to articles published in English language up to November 2014 and available in the following database: Ovid MEDLINE database, ISI Web of Science, Science Citation Index Expanded, and PUBMED. A combination of key words and MesH index terms was used including ‘breast neoplasm’ or ‘breast cancer’,

Study selection and description

The literature search identified 928 potentially relevant studies, of which 60 met the inclusion criteria (Fig. 1). Among the eligible studies, 22 were further excluded as they were duplicates of main or most recent articles (Table S2) leaving 38 studies in the final analysis. However, nine duplicate studies were included in stratified analyses as they provided results that were not reported in main or most recent articles. Selected and duplicate articles with relevant data are summarised in

Discussion

This meta-analysis demonstrates three important findings. Firstly, increased levels of physical activity lead to reductions in the risk of breast cancer irrespective of the type of physical activity, place of residence, adiposity, menopausal status, and the hormone receptor status of tumours. Secondly, breast cancer risk seems to decline with increasing physical activity, without a threshold effect. Thirdly, women who ever used HRT had no reduction of breast cancer risk associated with physical

Conflict of interest statement

None declared.

Funding

This work was supported internally by the International Prevention Research Institute. There was no external funding for this study.

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