Recurrence/Cancer-Specific Survival Outcomes

Efficacy and mechanisms of nonlinear, targeted exercise treatment to improve recurrence and cancer-specific survival. We have several projects in this domain:

Phase II Trial of Aerobic Training in Metastatic Breast Cancer (R21-CA143254)

There is growing recognition and acceptance of the integral role of exercise following a breast cancer diagnosis. This emerging dogma is based, in large part, on evidence from randomized trials indicating that exercise improves symptom control as well as observational data suggesting that regular exercise is associated with substantial reductions in cancer-specific and all-cause mortality in women following a breast cancer diagnosis. Prior to launching a large-scale trial investigating the effects of exercise on disease outcome, it is first of crucial importance to gather informative pilot data to establish the safety, feasibility, and potential efficacy of exercise training in women with metastatic disease undergoing chemotherapy.

Against this background, we are conducting a randomized phase II trial to assess the safety and tolerability of the addition of aerobic training to standard therapeutic regimens compared to standard therapy alone (plus attention-control) among 72 women with metastatic breast cancer.

Aerobic Exercise for Men on Active Surveillance for Prostate Cancer (R01-CA181802)

Recent observational and preclinical evidence from our group suggests that aerobic exercise after diagnosis may lower risk of prostate cancer progression. While these results are intriguing, it remains unknown whether increasing aerobic exercise after diagnosis favorably alters prostate cancer biology.

Against this background, we are conducting a randomized clinical trial to test the effects of 24 weeks aerobic exercise versus usual care on the prostate microenvironment and cancer-related anxiety among men on active surveillance for prostate cancer.

(PQA5) Dose and Mechanisms of Exercise in Breast Cancer Prevention (R01-CA179992)

Breast cancer is the most commonly diagnosed malignancy in American women. Although tamoxifen is considered the standard chemopreventive strategy for women at high risk of breast cancer, it is medically contradicted in up to about 30 percent of high-risk women, associated with several adverse toxicities, and only effective for prevention of estrogen receptor positive (ER+) breast cancer. Thus, there is an urgent need for new, nontoxic strategies to prevent both ER+ and ER negative (ER–) breast cancer.

Observational studies indicate that regular exercise is consistently associated with a 20 to 30 percent reduction in both ER+ and ER– breast cancer incidence in both pre- and postmenopausal women. However, the host- and/or tumor-related mechanisms that underline this association as well as the optimal “dose” to modulate these effects have not been elucidated.

The objective of this grant is to elucidate the “dose-response” effect of exercise on inhibition of breast cancer initiation and the role of cytokine withdrawal to regulate this effect in preclinical and clinical studies.