IntroductionExposure to high levels of endogenous estrogens is a main risk factor for breast cancer in women, and in observational studies was found to be inversely associated with physical activity. The objective of the present study is to determine the effect of physical activity interventions on sex hormone levels in healthy women.MethodsElectronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2014, and reference lists of relevant reviews and clinical trials were searched, with no language restrictions applied. Randomized controlled trials (RCTs) were included if they compared any type of exercise intervention to no intervention or other interventions, and assessed the effects on estrogens, androgens or the sex hormone binding globulin (SHBG) in cancer-free women. Following the method described in the Cochrane Handbook for Systematic Reviews of Interventions, data on populations, interventions, and outcomes were extracted, and combined using the inverse-variance method and a random-effects model. A pre-established protocol was drawn up, in which the primary outcome was the difference in circulating estradiol concentrations between the physical activity (experimental) and the control groups after intervention. Pre-specified subgroup analyses and sensitivity analysis according to the risk of bias were conducted.ResultsData suitable for quantitative synthesis were available from 18 RCTs (1994 participants) for total estradiol and from 5 RCTs (1245 participants) for free estradiol. The overall effect of physical activity was a statistically significant decrease of both total estradiol (standardized mean difference [SMD] -0.12; 95 % confidence interval [CI] -0.20 to −0.03; P = 0.01; I2 = 0 %) and free estradiol (SMD −0.20; 95 % CI −0.31 to −0.09; P = 0.0005; I2 = 0 %). Subgroup analyses suggest that this effect is independent of menopausal status and is more noticeable for non-obese women and for high intensity exercise. Meta-analysis for secondary outcomes found that physical activity induces a statistically significant decline of free testosterone, androstenedione, dehydroepiandrosterone–sulfate and adiposity markers, while a significant increase of SHBG was observed.ConclusionsAlthough the effect is relatively modest, physical activity induces a decrease in circulating sex hormones and this effect is not entirely explained by weight loss. The findings emphasize the benefits of physical activity for women.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0647-3) contains supplementary material, which is available to authorized users.

Telomeres ensure genome integrity during replication. Loss of telomeric function leads to cell immortalization and accumulation of genetic alterations. The association of telomere length (TL) with breast cancer prognosis is examined through a systematic review. Electronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2015, and relevant reviews were searched. Studies that evaluated TL (blood and/or tumor) in association with breast cancer survival or prognostic factor were included. Thirty-six studies met inclusion criteria. Overall risk of bias was critical. Eight studies reported survival outcomes. Overall, there was a trend toward an association of longer telomeres with better outcomes (tumor, not blood). Of the 33 studies reporting associations with prognostic factors, nine adjusted for potential confounders. Among the latter, shorter telomeres were associated with older age (blood, not tumor), higher local recurrence rates (normal tissue), higher tumor grade (tumor), and lower physical activity (blood), which were reported in one study each. TL was not associated with molecular subtype (blood, one study), family history (tumor, one study), chemotherapy (blood, three of four studies), and stress reduction interventions (blood, two of two studies). Although major methodologic differences preclude from drawing conclusive results, TL could be a valuable breast cancer prognostic marker. Cancer Epidemiol Biomarkers Prev; 26(1); 3-10. ©2016 AACR.

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The role of progesterone receptor (PR) status on the association between obesity and prognosis of estrogen receptor positive (ER+) breast cancer (BC) remains poorly understood. We aim to examine whether this association varies according to the tumor PR status. Data for 3,747 women diagnosed with nonmetastatic ER+ invasive BC between 1995 and 2010 were analyzed. Women were classified according to their body mass index (BMI) (<18.5, 18.5–24.9, 25.0–29.9 or ≥30.0 kg/m2). Tumor PR status (PR−, PR+) was evaluated by immunohistochemistry. Hazard ratios (HR) for survival outcomes were estimated using multivariable Cox regression models. Effect modification was assessed on both additive and multiplicative scales using relative excess risk due to interaction and ratio of HRs, respectively. After a median follow‐up of 5.9 years (range: 3.4–9.2), women with PR− tumors and underweight (HR = 2.76, 95% CI: 1.40–4.91), overweight (HR = 2.02, 95% CI: 1.43–2.81) or obese (HR = 2.51, 95% CI: 1.67–3.65) had increased risk of all‐cause mortality, when compared to normal weight women with PR+ tumors. A similar pattern of associations was observed for BC‐specific mortality. In contrast, women with PR+ tumors had similar risks for both mortality outcomes, regardless of BMI. On the additive scale, all‐cause mortality was modified by PR status for overweight and obese women, whereas for BC‐specific mortality, it was only modified for underweight women. The same observations were found on the multiplicative scale. These results suggest that poorer survival associated with low and high BMI among women diagnosed with ER+ BC may depend on the tumor PR status.