Effects of exercise dose on endogenous estrogens in postmenopausal women: a randomized trial

Exercise dose comparison trials with biomarker outcomes can identify the amount of exercise required to reduce breast cancer risk and also strengthen the causal inference between physical activity and breast cancer. The Breast Cancer and Exercise Trial in Alberta (BETA) tested whether or not greater changes in estradiol (E2), estrone, and sex hormone-binding globulin (SHBG) concentrations can be achieved in postmenopausal women randomized to 12 months of HIGH (300 min/week) vs MODERATE (150 min/week) volumes of aerobic exercise. BETA included 400 inactive postmenopausal women aged 50–74 years with BMI of 22–40 kg/m2. Blood was drawn at baseline and 6 and 12 months. Adiposity, physical fitness, diet, and total physical activity were assessed at baseline and 12 months. Intention-to-treat analyses were performed using linear mixed models. At full prescription, women exercised more in the HIGH vs MODERATE group (median min/week (quartiles 1,3): 253 (157 289) vs 137 (111 150); P<0.0001). Twelve-month changes in estrogens and SHBG were <10% on average for both groups. No group differences were found for E2, estrone, SHBG or free E2 changes (treatment effect ratios (95% CI) from linear mixed models: 1.00 (0.96–1.06), 1.02 (0.98–1.05), 0.99 (0.96–1.02), 1.01 (0.95, 1.06), respectively, representing the HIGH:MODERATE ratio of geometric mean biomarker levels over 12 months; n=382). In per-protocol analyses, borderline significantly greater decreases in total and free E2 occurred in the HIGH group. Overall, no dose effect was observed for women randomized to 300 vs 150 min/week of moderate to vigorous intensity exercise who actually performed a median of 253 vs 137 min/week. For total and free E2, the lack of differential effect may be due to modest adherence in the higher dose group.

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Effects of a 1-Year Physical Activity Intervention on Markers of Hemostasis among Breast Cancer Survivors: A Randomized Controlled Trial

TH Open ◽

10.1055/s-0040-1721782 ◽

2021 ◽

Vol 05 (01) ◽

pp. e14-e23

Author(s):

Siv Kjølsrud Bøhn ◽

Inger Thune ◽

Vidar Gordon Flote ◽

Hanne Frydenberg ◽

Gro Falkenér Bertheussen ◽

...

Keyword(s):

Breast Cancer ◽

Physical Activity ◽

Postmenopausal Women ◽

Cancer Patients ◽

Physical Activity Intervention ◽

Intervention Group ◽

Factor Vii ◽

Breast Cancer Patients ◽

Hemostatic Factors

Abstract Introduction Physical activity may reduce the development of breast cancer. Whereas hypercoagulability has been linked to adverse outcomes in breast cancer patients, the effects of physical activity on their hemostatic factors are unknown. The study aimed to assess whether long-term (1 year) physical activity can affect hemostatic factors in breast cancer patients. Methods Fifty-five women (35–75 years) with invasive breast cancer stage I/II were randomized to a physical activity intervention (n = 29) lasting 1 year or to a control group (n = 26), and analyzed as intention to treat. Fibrinogen, factor VII antigen, tissue factor pathway inhibitor, and von Willebrand factor (VWF) antigen as well as prothrombin fragment 1 + 2, the endogenous thrombin potential and D-dimer, were measured in plasma before intervention (baseline), and then after 6 and 12 months. Results Maximal oxygen uptake (measure of cardiorespiratory fitness) decreased the first 6 months among the controls, but remained stable in the intervention group. We found no significant differences between the two study groups regarding any of the hemostatic factors, except a significantly higher increase in factor VII antigen in the intervention group. The effect of the intervention on VWF was, however, significantly affected by menopausal stage, and a significant effect of the intervention was found on VWF among postmenopausal women, even after adjustment for dietary intake. Conclusion Long-term physical activity had no effect on the majority of the hemostatic factors measured, but led to increased plasma concentrations of factor VII antigen and prevented an increase in VWF concentration after breast cancer treatment in postmenopausal women. The clinical impact of these findings for risk of vascular thrombosis warrants further studies.

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Walking speed, physical activity, and breast cancer in postmenopausal women

European Journal of Cancer Prevention ◽

10.1097/cej.0b013e328361627e ◽

2014 ◽

Vol 23 (1) ◽

pp. 49-52 ◽

Cited By ~ 5

Author(s):

Karen Kwan ◽

Rowan T. Chlebowski ◽

Anne McTiernan ◽

Rebecca J. Rodabough ◽

Michael J. La Monte ◽

...

Keyword(s):

Breast Cancer ◽

Physical Activity ◽

Postmenopausal Women ◽

Walking Speed

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Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.2.453 ◽

1998 ◽

Vol 16 (2) ◽

pp. 453-461 ◽

Cited By ~ 460

Author(s):

P Dombernowsky ◽

I Smith ◽

G Falkson ◽

R Leonard ◽

L Panasci ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Postmenopausal Women ◽

Objective Response ◽

Advanced Breast ◽

Megestrol Acetate ◽

Dose Effect ◽

Double Blind ◽

Once Daily ◽

Previously Treated

PURPOSE To compare two doses of letrozole and megestrol acetate (MA) as second-line therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS Five hundred fifty-one patients with locally advanced, locoregionally recurrent or metastatic breast cancer were randomly assigned to receive letrozole 2.5 mg (n = 174), letrozole 0.5 mg (n = 188), or MA 160 mg (n = 189) once daily in a double-blind, multicenter trial. Data were analyzed for tumor response and safety variables up to 33 months of follow-up evaluation and for survival up to 45 months. RESULTS Letrozole 2.5 mg produced a significantly higher overall objective response rate (24%) compared with MA (16%; logistic regression, P = .04) or letrozole 0.5 mg (13%; P = .004). Duration of objective response was significantly longer for letrozole 2.5 mg compared with MA (Cox regression, P = .02). Letrozole 2.5 mg was significantly superior to MA and letrozole 0.5 mg in time to treatment failure (P = .04 and P = .002, respectively). For time to progression, letrozole 2.5 mg was superior to letrozole 0.5 mg (P = .02), but not to MA (P = .07). There was a significant dose effect in overall survival in favor of letrozole 2.5 mg (P = .03) compared with letrozole 0.5 mg. Letrozole was significantly better tolerated than MA with respect to serious adverse experiences, discontinuation due to poor tolerability, cardiovascular side effects, and weight gain. CONCLUSION The data show letrozole 2.5 mg once daily to be more effective and better tolerated than MA in the treatment of postmenopausal women with advanced breast cancer previously treated with antiestrogens.

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