Exercise and Cardiovascular Outcomes in Older Women With Breast Cancer: The Heart of the Matter ^∗ Open Access

Introduction

Every year, more than 100,000 women over the age of 65 years are diagnosed with breast cancer, making this the fastest-growing group of breast cancer patients (1). Breast cancer in older women differs in a number of ways from cancers in younger women. Histologically, older women are more likely to develop cancers that are hormone receptor positive, HER2/neu negative, and of lower tumor grade than younger women (2). Breast cancer is also often diagnosed at a later stage in older women, with tumors being more likely to be larger in size and more likely to involve lymph nodes, possibly related to less frequent screening (2). This may contribute to the worse breast cancer outcomes seen in older women, because the risk of breast cancer mortality increases with increasing age (3).

Recurrence and mortality outcomes in older women vary significantly by stage, histological characteristics, and the presence of pre-existing comorbidities, with non–breast cancer deaths accounting for an increasingly larger proportion of overall mortality with increasing age and number of comorbidities. For example, a Surveillance, Epidemiology, and End Results (SEER) Program Medicare analysis of 63,566 women over the age of 66 years diagnosed with breast cancer between 1992 and 2000 found that cardiovascular disease was the primary cause of mortality in study participants, accounting for 15.9% of all deaths (95% confidence interval [CI]: 15.6% to 16.2%) (4). Breast cancer was the second most common cause of mortality, accounting for 15.1% of deaths (95% CI: 14.8% to 15.4%). Cardiovascular disease was the most common cause of mortality for all patients with stage I breast cancer, whereas women with higher stage and grade cancers, as well as women with hormone receptor–negative tumors, were more likely to die of breast cancer. With increasing age, women of all stages were more likely to die of causes other than breast cancer. Age and the presence of comorbidities were associated with higher risk of both breast cancer–related and all-cause mortality, underscoring the potential importance of treatment tolerance and functional status on outcomes in older women with breast cancer.

Cardiorespiratory fitness (CRF) is an important moderator of functional status in older adults (5); declines in CRF have been associated with an increase in coronary heart disease and cardiovascular events (6). CRF has also been shown to be a prognostic factor in breast cancer, with individuals with higher CRF being at lower risk of breast cancer–related mortality (7,8). CRF declines with age at about 5% per decade, with a more rapid decline in women over the age of 60 (9). Additionally, studies have shown that breast cancer patients have lower CRF than healthy women and that CRF declines further in cancer patients after adjuvant therapy (10).

Several studies have demonstrated that exercise interventions can help to prevent decreases in CRF during breast cancer treatment and can lead to improvements in CRF in post-treatment breast cancer survivors, although data in older women are limited (11–14). Higher levels of physical activity have also been linked to a lower risk of developing and dying of breast cancer, with a recent review of 16 studies of breast cancer survivors demonstrating that women who engaged in the highest levels of physical activity after diagnosis had a lower risk of breast cancer mortality (hazard ratio [HR]: 0.72; 95% CI: 0.60 to 0.85) compared with inactive women (15,16).

In addition to the strong association between physical activity and breast cancer outcomes, a recent study demonstrated that recreational physical activity patterns after breast cancer diagnosis are also related to lower risk of cardiovascular events in breast cancer patients (17). In this analysis of 2,973 breast cancer survivors (mean age of 57 years), individuals who engaged in >9 metabolic equivalent (MET)-h/week of recreational physical activity had a 23% lower risk of cardiovascular events (95% CI: 0.67 to 0.88; p = 0.002) compared with less active individuals. In women over the age of 70, this benefit was even more pronounced, with an approximately 36% lower risk of cardiovascular events for those engaging in >9 MET-h/week compared with less (17).

In this issue of JACC: CardioOncology, Okwuosa et al. (18) provide additional evidence that higher levels of physical activity before diagnosis are associated with lower risk of cardiovascular events in women with breast cancer. The study evaluated the relationship between physical activity patterns before breast cancer diagnosis and cardiovascular outcomes (including heart failure, myocardial infarction, angina, coronary revascularization, peripheral and coronary artery disease, transient ischemic attack, stroke and cardiovascular death). Notably, almost two-thirds of the study population were over the age of 65 at the time of breast cancer diagnosis, and 40% were over age 70. The authors found that individuals in the top quartile of pre-diagnosis physical activity levels (reporting a median activity level of 18 MET-h/week of recreational physical activity) had a significantly lower risk of cardiovascular events (HR: 0.63; 95% CI: 0.45 to 0.88; p for trend = 0.016) and coronary heart disease death (HR: 0.41; 95% CI: 0.21 to 0.78; p for trend = 0.006) than inactive individuals. Additionally, individuals meeting current physical activity recommendations (9 MET-h/week) before a diagnosis of breast cancer had a 46% lower risk of coronary heart disease death (95% CI: 0.35 to 0.89) compared with those not meeting recommendations (<9 MET-h/week).

This study thus continues to demonstrate an important role of exercise in supporting favorable outcomes in older women with breast cancer. However, studies show that only one-third of breast cancer patients meet guideline recommendations of 150 min of moderate or vigorous physical activity per week, and very few engage in 18 MET-h of exercise per week (19). In the general population, older females are the least likely demographic to meet the recommended amounts of physical activity (20). Although many studies have demonstrated that it is feasible to increase physical activity in breast cancer patients during and after cancer treatment, many of these studies have focused on supervised exercise programs, which makes it difficult to scale this work to clinical populations. Additionally, few trials have focused on older breast cancer patients, who may have additional barriers to the implementation of exercise programs. Thus, work is needed to develop scalable interventions to increase physical activity in large groups of individuals, especially in older breast cancer survivors.

In conclusion, this study adds to the growing body of observational data that physical activity and exercise may impact morbidity and mortality in cancer patients. As more and more patients survive their breast cancer, cardiovascular disease is and will continue to become a major risk of morbidity and mortality for survivors. Finding strategies to help patients engage in recommended amounts of physical activity before and after a breast cancer diagnosis will be critical to improving outcomes in women with early breast cancer, in particular in the rising number of older adults with breast cancer.

Footnotes