Introduction
Physical activity and breast cancer
Biomarker studies in healthy women
Epidemiologic evidence relating exercise to proposed biomarkers
Systematic review of RCTs relating exercise to estrogens
Convincing biomarkers for postmenopausal breast cancer risk
Adiposity
Sex hormones
Trial name/reference, country | Sample sizea
| Study participants | Intervention arm prescription | Comparison group(s) |
---|---|---|---|---|
Figueroa et al., 2003, USA [37] | n = 24 EX; n = 28 CTL | • Mean body fat, 39 %; mean body weight, 67–71 kg • Inactive • No HRT use (HRT users analyzed separately) • Age 40–65 yr; mean, 57 yr | • 12 mo • 60–75 min/day, 3 days/wk, supervised • Resistance and weight-bearing aerobic exercise • 7 resistance exercises, 2 sets @ 70-80 % 1-RM + 25 min aerobic exercise @ 50-80 % HRmax
| Maintained usual level of physical activity |
Copeland et al., 2004, Canada [31] | n = 8 EX; n = 8 CTL | • Mean BMI 26 kg/m2 (EX); 32 kg/m2 (CTL) • No regular exercise in past year • No HRT use (HRT users analyzed separately) • Mean age, 54 yr | • 12 wk • 3 days/wk, supervised • Resistance training • By 1 month, progressed to 8 exercises @ 3 sets,10 repetitions each | Flexibility exercises 3 days/wk, unsupervised |
Physical Activity for Total Health Study, USA [35] | n = 87 EX; n = 86 CTL | • BMI 25–40 kg/m2, mean 30 kg/m2; body fat >33 % • Previously <60 min/week exercise that caused sweating • No hormone use past 6 mo • Age 50–75 yr; mean, 61 yr • 86 % non-Hispanic white | • 12 mo • 45 min/day, 5 days/wk (supervised and home-based) • Aerobic exercise • 60-75 % HRmax by wk 8 | Stretching controls |
Orsatti et al., 2008, Brazil [39] | n = 22 EX; n = 21 CTL | • Mean BMI 28–29 kg/m2, mean body fat 33-36 % • No previous leisure activity besides household • No hormone therapy past 6 mo • Age 40–70 yr; mean, 58–59 yr | • 16 wk preceded by 4-wk low-load adaptation period • 50–60 min/day, 3 days/week, supervised • Resistance training • 8 exercises @ 3 sets, 8–12 repetitions each, 60-80 % 1-RM | Asked not to change exercise habits |
Sex Hormones and Physical Exercise (SHAPE) study, the Netherlands [34] | n = 96 EX; n = 93 CTL | • BMI 22–40 kg/m2, mean 27 kg/m2; mean body fat 40-41 % • <2 hr/wk moderate sport/recreational activity and not adherent to international physical activity recommendations • No HRT use past 6 mo • Age 50–69 yr; mean, 58–59 yr | • 12 mo • 60 min/day, 2 days/wk supervised group session + 30 min/week home-based individual session • Supervised sessions: aerobic (20 min @ 60-85 % HRmax) and strength training (25 min) + warm-up, cool-down • Home-based sessions: brisk walking or cycling @ 60-80 % HRmax (30 min) | Asked to retain habitual exercise patterns |
Alberta Physical Activity and Breast Cancer Prevention (ALPHA) trial, Canada [32] | n = 160 EX; n = 160 CTL | • BMI 22–40 kg/m2, mean 29 kg/m2
• <90 min/wk recreational activity or if between 90–120 min/wk had maximal oxygen uptake <34.5 mL/kg/min • No hormone use • Age 50–74 yr; mean, 61 yr • 91 % white race | • 12 mo • 45 min/day, 5 days/wk (supervised and home-based) • Aerobic exercise, mainly walking or cycling • At least half of each workout @ 70-80 % heart rate reserve; achieved by wk 12 | Maintained usual level of activity |
Yoo et al., 2010, South Korea [33] | n = 11 EX; n = 10 CTL | • Mean BMI, 25–27 kg/m2
• No hormone use • Age >65 yr; mean age 71 yr | • 12 wk • 60 min/day, 3 days/wk, supervised • 45-min walking with two 1-kg ankle weights; 10-min warm-up + 5-min cool-down | Asked to maintain usual physical activity routine |
Kim et al., 2012, South Korea [38] | n = 15 EX; n = 15 CTL | • Mean BMI, 25 kg/m2; >32 % body fat, mean 36 % • <20 min exercise twice weekly • No hormone use • Mean age 54 yr | • 16 wk • 60 min/day, 3 days/wk, supervised • Aerobic exercise • Line dancing, attained 70-80 % HRmax by wk 12 | No exercise |
Nutrition and Exercise for Women (NEW) Trial, USA [36••] | n = 117 EX; n = 87 CTL; n = 118 DIET; n = 117 DIET + EX | • BMI >25.0 kg/m2, mean 30.9 kg/m2, mean body fat 47.2 % • Moderate-intensity physical activity <100 min/week • No hormone use past 3 months • Age 50–75 yr; mean, 58 yr • 85 % non-Hispanic white | • 12 mo • ≥ 45 min/day, 5 days/wk (3 supervised and 2 home-based) • Aerobic exercise with metabolic equivalent ≥ 4 •70-85 % HRmax for 45 min by wk 7 | 1)Reduced-calorie weight loss diet 2)Combined reduced-calorie weight loss diet + aerobic exercise 3)Requested not to change exercise or dietary habits |
Proposed biomarker | Average biomarker change for exercise-only groupb
| Evidence of adiposity change as a potential mediator of sex hormone change | Study reference |
---|---|---|---|
Circulating estradiol | −9.5%c; NS at 13 wk | ----- | [31] |
−7.7 %; NS at 3 mo −4.4 %; NS at 12 mo | Stronger decreases in exercisers who lost 0.5 % + body fat | [35] | |
No change at 12 mo | ----- | [37] | |
−8 %; NS over 12 mo | −11.7 % at 12 mo in exercise group who lost >2 % body fat Change in estradiol was significantly associated with change in % body fat | [34] | |
−12 % at 12 mo; p = 0.004 over 12 mo | Exercise effect was slightly attenuated but remained significant after statistical adjustment for body weight change Statistical tests for mediation implied mediation by change in % body fat or total body fat, but not intra-abdominal fat | ||
+20.5 % c; NS at 3 mo | ----- | [33] | |
−4.9 %, NS at 12 mo | The decrease in the DIET + EX group (−20.3 %) was significantly greater than for the EX group; p < 0.001 Significantly greater differences between change in EX versus CTL across subgroups of increasing weight loss (p-trend < 0.01) | [36••] | |
Circulating free estradiol | −8.2 %, p = 0.02 at 3 mo −6.1 %; NS at 12 mo | Stronger decreases in exercisers who lost 0.5 % + body fat | [35] |
+7.9 % c; NS at 16 wk | ----- | [39] | |
−7.3 %; NS over 12 mo | −11.4 % at 12 mo in exercise group who lost >2 % body fat Change in free estradiol was significantly associated with change in %body fat | [34] | |
−12.9 % at 12 mo; p = 0.001 over 12 mo | Exercise effect was slightly attenuated but remained significant after statistical adjustment for body weight change Statistical tests for mediation implied mediation by change in % body fat, total body fat, intra-abdominal fat | ||
−4.7 %, NS at 12 mo | The decrease in the DIET + EX group (−26 %) was significantly different than for the EX group; p < 0.001 Significantly greater differences between change in EX versus CTL across subgroups of increasing weight loss (p-trend = 0.001) | [36••] | |
Circulating estrone | −3.8 %, p = 0.03 at 3 mo −1.8 %; NS at 12 mo | Stronger decreases in exercisers who lost 0.5 % + body fat | [35] |
No change at 12 mo | ----- | [37] | |
−9.7 %; NS over 12 mo | −23.7 % at 12 mo in exercise group who lost >2 % body fat Change in estrone was significantly associated with change in % body fat | [34] | |
−5.4 %; NS over 12 mo | Remained NS after statistical adjustment for body weight change | [32] | |
−5.5 %, p = 0.01 at 12 mo | The decrease in the DIET + EX group (−11.1 %) was significantly greater than for the EX group; p = 0.01 Significantly greater differences between change in EX versus CTL across subgroups of increasing weight loss (p-trend < 0.01) | [36••] | |
Circulating sex hormone binding globulin (SHBG)d
| +5.7 %; NS at 3 mo +8.8 %; NS at 12 mo | Stronger increases in exercisers who lost 0.5 % + body fat | [35] |
−0.7 %; NS over 12 mo | +2.0 % at 12 mo in exercise group who lost >2 % body fat | [34] | |
+3.2 % at 12 months; p = 0.001 over 12 mo | Effect of exercise was no longer statistically different from controls after statistical adjustment for body weight change Statistical tests for mediation implied mediation by % body fat, total body fat, intra-abdominal fat | ||
+6.2%c; p < 0.001 at 16 wk | ----- | [38] | |
−0.7 %, NS at 12 mo | The change in the DIET + EX group (+25.8 %) was significantly different than for the EX group; p < 0.001 Greater difference between change in EX versus CTL groups with more weight loss, but p-trend NS | [36••] |