Physical activity linked to ‘survival advantage’ in breast cancer
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Rikki Cannioto, PhD, EdD, of Roswell Park Comprehensive Cancer Center, discussed her study linking physical activity before and after breast cancer treatment to reduced recurrence and mortality rates among patients with high-risk disease.
She told Healio how physical activity may impact survivorship of patients with metastatic breast cancer, limitations of her study and the most important take-home points from her research for clinicians.
Healio: Before this study, what did the research say about the link between physical activity and survival outcomes in breast cancer patients?
Cannioto: Over the past two decades, the relationships between physical activity performed before and after diagnosis with breast cancer has been consistently established in the literature, but some important limitations in the extant body of literature warranted further research. For example, most of the existing studies relied upon physical activity assessed during one time point only — either before or after diagnosis — and did not account for changes in activity throughout survivorship.
We felt it was important to take a comprehensive look at activity levels, because previous research about the relationship between physical activity and breast cancer recurrence is limited and inconsistent.
Our study relied heavily on the Diet, Exercise, Lifestyle and Cancer Prognosis (DELCaP) Study, led by Christine Ambrosone, PhD, and embedded in a SWOG therapeutic trial for breast cancer.
What made the new study unique is that we queried detailed physical activity habits before diagnosis and on several occasions after diagnosis, which yielded physical activity information at four different time points. Our study was prospective in nature, following patients throughout treatment and at 1 and 2 years after treatment completion.
The evidence we collected supports the association between consistent physical activity before and after treatment and decreased risk of recurrence.
And while mounting evidence has supported an inverse association between physical activity and breast cancer outcomes, the underlying mechanisms responsible for this association have not been elucidated. Our group is currently engaged in additional research to examine factors that may be driving the associations between recreational physical activity and improved breast cancer survival.
Healio: What did your study find was the effect of physical activity before and after breast cancer treatment?
Cannioto: The key finding pertaining to pre-diagnosis physical activity was that patients who reported meeting the minimum range of activity according to the Physical Activity Guidelines for Americans put out by the U.S. Department of Health and Human Services —150-300 minutes of moderate-intensity activity or 75-150 minutes of vigorous activity per week — experienced a significantly reduced hazard of recurrence (HR = 0.62; 95% CI, 0.43-0.88) and mortality (HR = 0.48; 95% CI, 0.31-0.75). This translates to a 38% decrease risk for experiencing breast cancer recurrence and a 52% decreased risk for dying among those patients meeting the minimum range of activity recommended by the Guidelines.
The strong inverse relationship between pre-diagnosis recreational physical activity and outcomes among those meeting the recommended activity levels reveals the broader health impact of these findings, suggesting that, even though exercise may not prevent breast cancer in all women, it is consistently associated with a survival advantage.
When considering pre- and post-diagnosis jointly, we observed inverse associations between meeting the minimum range of activity recommended by the Guidelines with both recurrence and survival. Specifically, we combined activity data from two time points (one before diagnosis and one after treatment completion at one or two-year follow-up) to represent four groups of patients — those who met the Guidelines at both times (yes/yes), those who did not meet the Guidelines pre-diagnosis but did postdiagnosis (no/yes), those who met the guidelines pre-diagnosis, but not postdiagnosis (yes/no) and those who did not meet the Guidelines at either time (no/no). Findings revealed that patients meeting the minimum Guidelines before diagnosis and at the 1-year follow-up after treatment was completed (yes/yes) experienced statistically significantly reduced hazards of recurrence (HR = 0.59; 95% CI, 0.42-0.82) and mortality (HR = 0.51; 95% CI, 0.34-0.77) compared with patients who did not meet the Guidelines at either time point.
In other words, patients consistently meeting the Guidelines before diagnosis and 1 year after diagnosis, when treatment was completed, experienced a 41% reduced risk for recurrence and a 49% reduced risk for mortality compared with those not meeting the Guidelines at either time point.
These observed associations became even stronger at the 2-year follow-up for both recurrence (HR = 0.45; 95% CI, 0.31-0.65) and mortality (HR = 0.32; 95% CI, 0.19-0.52). That is, patients meeting the guidelines before diagnosis and 2 years after diagnosis experienced a 55% decreased risk for recurrence and a striking 68% reduced risk for mortality compared with those not meeting the Guidelines at either time point.
Importantly, we also observed statistically significant reduced risk for recurrence (46%) and mortality (43%) among patients not meeting the Guidelines before diagnosis, but who met the Guidelines at the 2-year follow-up, demonstrating that beginning an exercise program after diagnosis was also associated with improved survival.
Importantly, the collective body of research, including our own work, reveals that post-diagnosis activity is more strongly associated with survival than pre-diagnosis activity, but research supports consistent associations for both.
Healio: How has physical activity been shown to impact survivorship of those with metastatic breast cancer?
Cannioto: There is limited data in the literature regarding the independent associations of physical activity and survival among patients with metastatic breast cancer. However, several studies have demonstrated that exercise is both feasible and safe for this population, and may be associated with improved quality of life. Collectively, these studies have shown that exercise adherence has been established among patients with metastatic breast cancer, demonstrating that this subgroup of patients tend to be highly interested in and willing to exercise.
At least one study has specifically reported on the association of physical activity and survival in metastatic breast cancer, and the findings are congruent with the overall body of literature, demonstrating an inverse association between physical activity and mortality among these patients. Specifically, researchers of the analysis published in Cancer Nursing reported that greater physical activity level at baseline was significantly associated with longer subsequent survival time (HR = 0.9; 95% CI, 0.84-0.97). Additionally, engaging in 1 extra hour per day of moderate activity lowered the risk for subsequent mortality by 23% (HR = 0.77; 95% CI, 0.65-0.92). Further, these results remained significant after controlling for demographic, medical, cancer, depression and stress-related factors such as cortisol levels (HR = 0.91; CI, 0.84–0.99).
Healio: What were the limitations of the study and how might future research overcome these limitations?
Cannioto: An important limitation of the study was that we assessed physical activity via self-report questionnaires, and participants did not wear activity trackers, which would provide us with objective data about the amount and intensity of physical activity performed throughout the study.
While many smaller studies that are randomized, controlled trials are now incorporating the use of activity trackers, this may not be feasible for large-scale epidemiological studies in which patients are followed for longer periods. Logistical or technical problems with tracking devices and/or compliance in wearing and updating the device over an extended study period may preclude the ability to use these devices over the long term. One way to overcome the individual limitations of subjective and objective methods of physical activity assessment is to use some combination of self-report questionnaires and activity trackers in future research.
Healio: What is the take-home message of your study for clinicians treating patients with breast cancer?
Cannioto: There were three key take-away messages from the study that are relevant to clinical oncology.
First, when we jointly examined physical activity before and after treatment, we demonstrated that patients with high-risk breast cancer who met the minimum physical activity Guidelines both before and after diagnosis experienced greater than a 50% reduced hazard for recurrence and mortality compared with those not meeting the Guidelines at either time point. The minimum physical activity Guidelines include a range of activity representing 150 to 300 minutes per week of moderate-intensity physical activity — for example, walking for exercise at a brisk pace at 3 mph — or 75 to 150 minutes of vigorous-intensity activity such as, jogging.
Second, we also noted that patients not meeting the minimum physical activity Guidelines prior to diagnosis, but who reported meeting the Guidelines after treatment (at 2-year follow-up) experienced statistically significantly reduced hazards for recurrence and mortality compared with patients not meeting the Guidelines at that time. These findings have important implications for clinical oncology because they suggest that a cancer diagnosis may serve as an impetus for increasing physical activity in some patients, and that among these patients, beginning an exercise program after treatment completion resulted in a survival advantage. These findings are similar to earlier findings our group reported with a different population of patients. Specifically, patients who reported beginning exercise only at the time of diagnosis or after diagnosis, but who had been previously inactive before diagnosis, experienced significant survival advantages compared with those who remained inactive.
Third, when we collectively considered all of the physical activity data from all four questionnaires, using a special type of analysis that accounted for how physical activity behavior varied over time, we observed striking inverse associations between mortality and any amount of consistent, regular, weekly exercise. That is, patients who consistently reported exercising regularly, but who did not meet the minimum physical activity Guidelines, also experienced significant survival advantages. These findings have important implications in the clinical oncology setting given that some patients and survivors may find the current minimal Guidelines overwhelming.
These findings coincide with our previous research based upon a different study population demonstrating that lower volumes of regular exercise also associated with significant survival advantages among cancer patients. The take-away message is for cancer patients and survivors to avoid inactivity and to aim to meet the minimum range of physical activity as recommended by the current Physical Activity Guidelines for Americans.
References:
- Cannioto RA, et al. Cancer Cause Control. 2019;doi:10.1007/s10552-018-1101-5.
- Cannioto RA, et al. J Natl Cancer Inst. 2020;doi:10.1093/jnci/djaa046.
- Palesh O, et al. Cancer Nurs. 2018;doi:10.1097/NCC.0000000000000525.
- HSS. Physical Activity Guidelines for Americans, 2nd edition. https://health.gov/sites/default/files/2019-09/Physical_Activity_Guidelines_2nd_edition.pdf. Accessed on June 23, 2020.
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