Active Voice: Exercise and Breast Cancer Survival
By Kerry S. Courneya, Ph.D.
Viewpoints presented in SMB commentaries reflect opinions of the authors and do not necessarily reflect positions or policies of ACSM.
Kerry S. Courneya, Ph.D., is a professor and Canada research chair in physical activity and cancer at the University of Alberta in Edmonton, Canada. His research program focuses on physical activity and cancer survivorship including how exercise may help cancer survivors cope with treatments, recover after treatments and extend long-term survival.
This commentary presents Dr. Courneya’s views on the topic of a research article which he and his colleagues published in the September 2014 issue of Medicine & Science in Sports & Exercise® (MSSE).
Exercise has many positive outcomes for cancer patients and survivors including improvements in health-related fitness, symptom management and quality of life. Nevertheless, perhaps the most compelling question for cancer patients and oncologists is whether exercise can improve cancer outcomes. A growing number of observational studies have suggested that physical activity after a breast cancer diagnosis is associated with a lower risk of breast cancer-specific and all-cause mortality. Of course, there are many explanations for why physically active breast cancer survivors may live longer than inactive breast cancer survivors—and these explanations may be unrelated to the causal effects of exercise. Phase III randomized controlled trials would provide a definitive answer to this question, but there are methodological and logistical challenges in conducting such studies.
My colleagues and I had an opportunity to follow up on a randomized controlled trial that we conducted between 2003 and 2005. We reported the results in the September 2014 issue of MSSE. The Supervised Trial of Aerobic versus Resistance Training (START) was originally designed to examine the independent effects of aerobic exercise and resistance exercise on health-related fitness and patient-reported outcomes in 242 breast cancer patients receiving adjuvant chemotherapy. We observed several effects in the START trial that prompted us to consider a long-term follow up of cancer outcomes; most notably we found a higher chemotherapy completion rate in the resistance exercise group. While the START trial was not originally designed to examine breast cancer outcomes, we felt it provided an opportunity to obtain preliminary data similar to a phase II randomized drug trial.
In 2012, we abstracted all the events in the START trial including recurrences, second cancers and deaths, and calculated the key survival outcomes of disease-free survival (DFS), overall survival (OS), distant disease-free survival (DDFS; which consists of death from any cause, distant recurrence or second primary invasive cancer) and recurrence-free interval (RFI). The two exercise arms were combined for analysis (n=160), and we also explored selected subgroups. Much to our pleasant surprise, we found that the eight-year DFS was 82.7 percent for the exercise groups compared with 75.6 percent for the control group (Hazard ratio [HR]=0.68, 95 percent CI=0.37-1.24). Moreover, we observed even stronger effects for OS (HR=0.60, 95 percent CI=0.27 to 1.33), DDFS (HR=0.62, 95 percent CI=0.32 to 1.19), and RFI (HR=0.58, 95 percent CI=0.30 to 1.11). In subgroup analyses, there was a suggestion that exercise had stronger effects in women who were overweight/obese, had stage II/III cancer, estrogen-receptor (ER) positive tumors, human epidermal growth factor receptor-2 (HER2) positive tumors, received taxane-based chemotherapies and optimal chemotherapy dosing.
We concluded from our exploratory follow-up that there was a suggestion that exercise during adjuvant chemotherapy may improve cancer outcomes, although we cautioned that none of the effects achieved statistical significance. We offered several speculative explanations for the possible effect of exercise but, perhaps, the most welcomed explanation would be that exercise potentiates the effects of cytotoxic chemotherapy (i.e., acts as a chemosensitizer). If these findings were to hold up in a large phase III trial, this would indeed be a practice-changing paradigm shift for oncology. Unfortunately, it does not appear that there are any ongoing or planned phase III trials on this question. Consequently, our serendipitous phase II data, along with more targeted observational and mechanistic studies, may be our best evidence of a survival benefit for the foreseeable future.