Lifestyle Interventions to Improve Cardiorespiratory Fitness and Reduce Breast Cancer Recurrence
Disclosures of potential conflicts of interest provided by the authors are available with the online article at asco.org/edbook.
As patients are living longer after a cancer diagnosis, survivorship is becoming increasingly important in cancer care. The sequelae of multimodality therapies include weight gain and decreased cardiorespiratory fitness, which increase cardiovascular risk. Evidence suggests that physical activity reduces the risk of breast cancer recurrence and death. Avoidance of weight gain after therapy also improves outcomes after a diagnosis of breast cancer. Prospective randomized trials must be performed to determine the benefits of specific physical activity and dietary habits for survivors of breast cancer. This review outlines the important physiologic changes that occur with antineoplastic therapy and the important role of exercise and diet.
Breast cancer survivors have reduced cardiorespiratory fitness secondary to impaired cardiovascular reserve.
Exercise training is an effective intervention to improve cardiorespiratory fitness; however, the physiologic mechanisms underpinning this favorable adaptation are unknown.
Concomitant diet and exercise interventions may abrogate breast cancer therapy–induced accelerated CVD sequelae, particularly in overweight/obese women.
Epidemiologic evidence supports the participation in exercise before and after breast cancer diagnosis because it is a contributing factor in decreasing breast cancer recurrence, breast cancer–related mortality, and overall mortality.
Breast cancer is the most frequently diagnosed cancer among women and the second leading cause of cancer death in the United States.1 Breast cancer mortality has decreased by nearly 40% during the last 3 decades as a result of advances in prevention, early detection, and treatment.2 As a result of improved survival and population aging, breast cancer is evolving into a disease of older survivors who face an important new set of health care challenges. Nearly one-third of breast cancer survivors have a peak oxygen uptake (peak VO2)—the gold standard measure of cardiorespiratory fitness—that is below the threshold level required for full and independent living.3 A consequence of reduced fitness is decreased survival in healthy populations.4
In accordance with the multiple-hit hypothesis, unfavorable lifestyle factors (e.g., sedentary lifestyle, sarcopenic obesity) coupled with the adverse effects of anticancer therapy result in reduced physiologic and functional reserve capacity. Interventions that improve cardiovascular health and body composition outcomes (e.g., increased muscle mass, decreased visceral adiposity) may play an important role in improving cardiorespiratory fitness, reduce breast cancer recurrence, and improve mortality.
The aim of this chapter is to briefly review the mechanisms responsible for reduced peak VO2 in survivors of breast cancer and the role of exercise training to improve peak VO2 and the role of diet, weight reduction, and exercise in the moderation of cardiovascular disease sequelae, reduction of breast cancer recurrence, and improvement in mortality.
Breast cancer survivors with normal resting left ventricular (LV) systolic function have a peak VO2 that is 19% (5.5 mL/kg/min) lower than healthy age-matched noncancer controls.5-10 The magnitude of the decline in peak VO2 is greatest during the short-term period after completing adjuvant therapy.3,11 Lower levels of cardiorespiratory fitness, as measured by peak VO2, may also have important prognostic implications and result in shorter survival in women with metastatic disease.3 Thus, an important goal is to maintain an optimal level of cardiorespiratory fitness across the breast cancer survivorship continuum.
Given that VO2 is equal to the product of cardiac output and arterial-venous oxygen content difference, the reduced peak VO2 among breast cancer survivors may be due to central (cardiac) or peripheral (skeletal muscle and its microvasculature) factors that result in decreased oxygen delivery to and/or extraction by the active muscles.5,12
To date, only one study has examined the acute hemodynamic cardiopulmonary response to maximal aerobic exercise in 47 survivors of breast cancer with normal resting LV systolic function (mean age, 59; mean LV ejection fraction, 64%) and 11 age-matched healthy controls.6 As shown in Fig. 1, the decreased peak VO2 in survivors of breast cancer was primarily due to a lower stroke volume and cardiac output, as heart rate and arterial-venous oxygen difference during maximal cycle exercise were not significantly different between groups.6 The mechanism responsible for the reduced maximal exercise stroke volume was not examined; however, it may be the result of increased LV afterload as maximal systemic vascular resistance was 11% higher in breast cancer survivors compared with controls.6
Oxygen extraction is directly related to muscle oxygen diffusive conductance (e.g., transport of O2 from hemoglobin to muscle mitochondria) and inversely related to muscle blood flow.12 Accordingly, our finding that maximal arterial-venous oxygen difference was not different between survivors of breast cancer and healthy controls despite a lower maximal cardiac output6 (muscle blood flow) suggests that abnormalities in skeletal muscle microvascular and/or mitochondrial function may play an important role in limiting breast cancer survivors exercise performance.5 To attenuate the decline (during adjuvant therapy) or increase peak VO2 (post-adjuvant therapy), therapies should focus on improving cardiovascular and skeletal muscle function.
Exercise training is an effective intervention to improve peak VO2, physical functioning, and quality of life, and reduces symptoms of fatigue in breast cancer survivors.13 The magnitude of the change in peak VO2 with training appears to be related to the volume of exercise performed, and the threshold workload required to obtain a clinically significant large increase in peak VO2 (effect size > 1) was 600 intensity-minutes in a 10-week supervised exercise training program performed for 90 minutes per week at 70% peak VO2.14 Although the mechanisms underpinning the exercise-training mediated improvement in peak VO2 have not been studied, they may be due to favorable changes in cardiac, peripheral vascular, or skeletal muscle function.5
Breast cancer survivors who are obese have a significantly higher overall, and breast cancer–related, mortality compared with their counterparts who are at a baseline healthy weight within 12 months after diagnosis.15 There is increasing evidence demonstrating that breast cancer survivors are at a higher risk of morbidity and mortality. Indeed, compared with sex- and age-matched counterparts, patients with breast cancer have an increased incidence of risk factors for cardiovascular disease (CVD; e.g., obesity, hypertension, diabetes, dyslipidemia, exercise intolerance)16 and CVD-specific morbidity (e.g., coronary artery disease and heart failure). Moreover, in survivors older than age 65, CVD is the leading cause of mortality.17,18 As prolonged administration of anticancer therapies becomes increasingly common19 and novel targeted therapies with potentially adverse cardiovascular safety profiles are included in treatment strategies,20 the incidence of CVD morbidity and mortality among breast cancer survivors will likely continue to rise. Thus, defining the feasibility and efficacy of innovative interventions that can attenuate CVD sequelae are of primary research and clinical importance.
Exercise, a pleiotropic stimulus leading to physiologic adaptation across multiple organ systems,21 improves insulin sensitivity, decreases lipids, and lowers blood pressure with concomitant improvements in peak VO2 in noncancer settings.22-26 Although comparatively less information is available in oncology settings, recent observational data of patients with breast cancer indicate that adherence to national exercise guidelines for adult patients with cancer (i.e., ≥ 9 MET hours/week) was associated with an adjusted 23% reduction in the risk of CVD events compared with not meeting the guidelines (< 9 MET hours/week; p = .0002).27 The association with exercise did not differ according to age, most CVD risk factors, menopausal status, or anticancer treatment,27 suggesting that, for many patients with breast cancer, exercise is a potent intervention that can modulate CVD sequelae. However, the protective effects of exercise did not extend to women with a body mass index (BMI) of 35 kg/m2 or greater.27 As a result, additional interventions may be required for patients with excess CVD risk associated with obesity.
Based on promising data indicating that weight control, physical activity, and/or diet quality reduce cancer recurrence and improve cancer-specific overall survival, the American Cancer Society issued Guidelines on Nutrition and Physical Activity for Cancer Survivors, which call for maintenance of a healthy body weight, regular physical activity regardless of BMI, and modest weight loss for cancer survivors who are overweight or obese.28 Importantly, concomitant diet and exercise interventions in nononcology overweight/obese settings have been shown to improve LV function, exercise capacity, glucose, lipid, and blood pressure control, inflammation markers, body composition, and skeletal muscle function.29 Thus, the synergistic benefits of multicomponent interventions could represent an optimal approach to offset CVD in patients with breast cancer.
The incidence of common risk factors for both CVD and cancer such as hypertension (up to 55%),30 diabetes (up to 10%),31 hyperlipidemia (up to 20%),32 obesity (up to 62%),33 and low exercise tolerance (up to 37%)3 likely increase the risk of CVD morbidity and mortality34 For example, Hooning et al examined the long-term causes of mortality among 7,425 women treated for early-stage breast cancer and found that after a median of 13.8 years, survivors diagnosed with one CVD risk factor at any time during the study follow-up had a 1.4- to 3.1-fold higher risk of CVD-related mortality relative to age-matched women among the general population.16,17 Moreover, Playdon et al reported that a weight gain of more than 5% from diagnosis to post-treatment was associated with a 12% increase in the risk of all-cause mortality compared with weight maintenance in a meta-analysis involving 23,832 patients with early-stage breast cancer.33 Similarly, among 3,993 women with early-stage disease (5.8 years postdiagnosis), those with a BMI greater than 30 kg/m2 (classified as obese) had a CVD mortality rate 1.65 times that of women with a normal BMI (18.5–24.9 kg/m2), and each 5 kg weight gain was associated with a 19% increase in CVD mortality.35 These findings highlight the importance of identifying women at the greatest risk of accelerated CVD sequalae so targeted interventions can be initiated.
Evidence from nononcology trials indicate that multicomponent interventions may be critical for improving outcomes such as body composition, peak VO2, and biomarkers linked to CVD outcomes. For example, in 107 obese adults (BMI > 30 mg/kg2) were randomly assigned to one of four groups for 52 weeks: (1) 27 patients in the control group, (2) 26 patients in the diet group, (3) 26 patients in the exercise group, and (4) 28 patients in the diet and exercise group.36 Peak VO2 improved more in the diet and exercise group than in the diet or exercise alone groups (increases of 17% vs. 10% vs. 8%, respectively; p < .001), whereas body weight decreased by 10% in the diet alone group and by 9% in the diet-exercise group, but did not decrease in the exercise group or the control group (p < .001). Similarly, in 439 postmenopausal women who were overweight/obese and randomly assigned to: (1) a reduced calorie, weight loss diet (diet; 118 patients); (2) moderate-to-vigorous intensity aerobic exercise (exercise; 117 patients); (3) a combination of a reduced calorie, weight loss diet and moderate-to-vigorous intensity aerobic exercise (diet and exercise; 117 patients); or (4) control (87 patients),37 leptin concentrations, a key regulator of energy homeostasis, metabolism, and adiposity, decreased in all of the intervention groups, but the greatest reduction occurred with diet and exercise (-40%). Taken together, these findings suggest that a combination of weight loss and an exercise program could provide greater improvement in multiple outcomes compared with either intervention alone in overweight/obese populations.
To date, the potential cardioprotective properties of multimodal interventions in patients with breast cancer have received limited attention; however, preliminary observational data indicate that adherence to diet and exercise guidelines improves patient morbidity and mortality. For example, among 938 breast cancer survivors in the Iowa Women’s Health Study (mean age, 79; 8.6 years postdiagnosis),38 adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) prevention guidelines for weight control, physical activity, and diet was associated with lower all-cause mortality (hazard ratio [HR] 0.67; 95% CI, 0.50–0.94), and a 40% reduction in CVD-specific mortality. The majority of trials of patients with breast cancer have examined the efficacy of either exercise alone to improve functional outcomes (e.g., VO2peak) or diet alone to direct weight management or weight loss. As a result, only approximately six trials have investigated the effect of a combined diet and exercise intervention among patients with breast cancer. For example, 90 postmenopausal patients with breast cancer receiving adjuvant chemotherapy were randomly assigned to (1) a calcium-rich diet intervention (attention control), (2) calcium-rich diet and exercise, or (3) calcium-rich diet with high fruit and vegetable, low-fat diet and exercise. Demark-Wahnefried et al39 reported that the high fruit and vegetable arm substantially attenuated therapy-induced increases in appendicular body fat. Similarly, Morey et al40 reported that among 641 older, overweight, long-term survivors of breast (289 patients), prostate (261 patients), and colorectal (91 patients) cancer randomly assigned to either a 12-month home-based program of telephone counseling promoting exercise and diet, or wait-list control, weight loss was significantly greater in counseling groups compared with the wait-list control group (2.06 vs. 0.92 kg, respectively; p < .001).
The Life After Cancer Epidemiology (LACE) study examined the impact of dietary adherence in 1,901 women diagnosed with early-stage breast cancer. A prudent dietary pattern was defined by a high intake of fruits, vegetables, whole grains, and poultry, whereas a Western diet was defined by high intake of red and processed meats and refined grains. The prudent diet was associated with a significant decrease in risk of overall death (trend p = .02; HR for highest quartile 0.57; 95% CI, 0.36–0.90) and death from non–breast cancer causes (trend p = .003; HR for highest quartile 0.35; 95% CI, 0.17–0.73) independent of physical activity, body habitus, or tobacco use. In contrast, a Western diet was related to an increasing risk of overall death (trend p = .05) and death from non–breast cancer causes (p = .02). Interestingly, both dietary patterns were not associated with reduced risk of breast cancer recurrence or breast cancer–specific mortality.41
The Women's Health Initiative Dietary Modification primary breast cancer prevention trial randomly assigned 48,835 postmenopausal women with no prior history of breast cancer and normal mammograms to undergo dietary intervention or to a control group. The dietary intervention reduced dietary fat intake to 20% of calories, increased fruit and vegetable intake (five servings a day), and increased grains to six servings a day. During year 1, intervention group members participated in 18 group sessions and then quarterly maintenance meetings. The control group participants received dietary guidelines. Although the incidence of breast cancer was not significantly decreased among women in the low-fat diet group, women in the intervention group had improved overall survival at 8.5 years (HR 0.65; 95% CI, 0.45–0.94; p = .02. At the 16-year mark, breast cancer-specific mortality was still lower than those in the control group (234 vs. 443 deaths, respectively; HR 0.82; 95% CI, 0.70–0.96; p = .01). Women with baseline waist circumference of 88 cm or greater and higher baseline levels of dietary fat intake had a stronger interaction in terms of deaths after breast cancer.42
The randomized phase III WINS trial evaluated whether dietary fat reduction affected relapse-free survival among 2,437 patients with early-stage breast cancer receiving standard-of-care treatment. Women with a dietary fat intake greater than 20% of calories were randomly assigned to a dietary intervention group or a control group. Women were given a fat-gram goal by centrally trained, registered dietitians implementing a low-fat eating plan. Women in the intervention arm underwent 8 biweekly individual counseling sessions, were subsequently contacted every 3 months, and self-monitored their fat-gram intake using a “keeping score” book. Fat intake was externally monitored by unannounced 24-hour telephone recalls performed annually for 5 years. Women enrolled in the intervention group consumed 9.2% calories from fat and lost nearly 6 pounds. Although there was no survival benefit at 19.4 years, an exploratory subgroup analysis of the group with estrogen negative tumors showed higher median survival of 13.6 years in the intervention group compared with 11.7 years in the control arm (HR 0.46; p = .006).42
Although these findings are promising for patients with breast cancer with, or at high risk of obesity, the long-term implications of acute multimodal interventions on CVD morbidity and mortality are unknown. To this end, the Look AHEAD (Action for Health in Diabetes) study examined the incidence of a composite cardiovascular outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalized angina) over 9.6 years in 5,145 overweight or obese individuals with type 2 diabetes randomly assigned to a diet and exercise intervention or control.43 Although improvements in weight loss, fitness, and CVD risk factors were greater in the intervention group, there was no significant difference between the intervention and control group in CVD morbidity and mortality (403 vs. 418 events, respectively; 1.83/100 person-years vs. 1.92/100 person-years, respectively; HR 0.95; 95% CI, 0.83–1.09; p = .505).43 Thus, the effect of multimodal interventions in patients with breast cancer on outcomes other than weight loss, or in patients with concomitant comorbidities such as hypertension, dyslipidemia, diabetes, or exercise intolerance, are important areas for further research.
In summary, given that patients with breast cancer now live long enough to be at risk for therapy-induced CVD morbidity and mortality, a research agenda that addresses the nature and magnitude of therapy-related CVD could define important targets for interventions. To this end, observational data indicating that exercise-induced modification of CVD events is attenuated in obese breast cancer survivors27 suggest that, for a subset of patients with breast cancer who are overweight or obese, multimodal interventions may be critical to abrogating accelerated CVD. Prospective trials are needed to define the role of diet and exercise in the management of CVD sequelae in overweight and obese breast cancer survivors.
The role of exercise in secondary prevention and breast cancer–related mortality is not well-defined. However, the known physiologic effects of exercise suggest that it may have an important role. Exercise may reduce adverse outcomes associated with fat accumulation such as an altered hormonal environment and adipokine production, which may act to promote tumor development and growth.44 Randomized, controlled trials of physical activity among postmenopausal women who are overweight demonstrated declines in serum levels of androgen, estrogen, and leptin—hormones important for tumorigenesis.45-47 For these reasons, exercise may be a modifiable behavior that has the potential to change important breast cancer outcomes. In the next section, we review the salient data on the impact of exercise on breast cancer recurrence and mortality.
The majority of studies examining this question have been observational cohort studies based on patient self-reporting, an important limitation. The landmark study is the Nurses’ Health Study, a prospective observational study of 2,987 female registered nurses with stage I to III breast cancer between 1983 and 1998.48 The women were followed every 2 years until 2002 or time of death, and answered questions about their physical activity over the prior year. After adjusting for factors predictive of survival after breast cancer, compared with women who engaged in less than 3 MET-hours/week of physical activity, the relative risk (RR) of death from breast cancer was 0.80 (95% CI, 0.60–1.06) for 3 to 8.9 MET-hours/week; 0.50 (95% CI, 0.31–0.82) for 9 to 14.9 MET-hours/week; 0.56 (95% CI, 0.38–0.84) for 15 to 23.9 MET-hours/week; and 0.60 (95% CI, 0.40–0.89) for 24 or more MET-hours/week (trend p = .004). After multivariable adjustment, the RR of breast cancer recurrence was 0.83 (95% CI, 0.64–1.08) for 3 to 8.9 MET-hours/week; 0.57 (95% CI, 0.38–0.85) 9 to 14.9 MET-hours/week; 0.66 (95% CI, 0.47–0.93) for 15-23.9 MET-hours/week; and 0.74 (95% CI, 0.53–1.04) for 24 or more MET-hours/week as compared with women who engaged in less than 3 MET-hours/week of physical activity (trend p = .05). Interestingly, the RR for each adverse outcome was lowest for the intermediate level of activity, equivalent to walking 3 to 5 hours per week at an average pace. The protective benefit was similar among nonobese and obese women, but the benefit was particularly apparent in women with hormone-responsive tumors. The RR of breast cancer death for women with hormone-responsive tumors who engaged in 9 or more MET-hours/week of activity compared with women with hormone-responsive tumors who engaged in less than 9 MET-hours/week was 0.50 (95% CI, 0.34–0.74). An important limitation of this study is that the participants were mostly non-Hispanic whites and occupationally homogenous.48
The Collaborative Women’s Longevity Study (CWLS) and the Life After Cancer Epidemiology (LACE) study used the same measure of physical activity as the Nurse’s Health Study, but found different results.49,50 In CWLS, a total of 4,482 eligible women age 20 to 79 diagnosed with invasive breast cancer stages I to III between 1988 and 2001 completed the questionnaire of physical activity a median of 5.6 years after diagnosis. After adjusting for relevant factors, women who engaged in greater levels of activity had a significantly lower risk of dying from breast cancer (HR 0.65; 95% CI, 0.39–1.08 for 2.8 to 7.9 MET hours/week; HR 0.59; 95% CI, 0.35–1.01 for 8.0 to 20.9 MET hours/week; and HR 0.51, 95% CI, 0.29–0.89 for > 21 MET hours/week; trend p = .05). Results were similar for overall survival (HR 0.44; 95% CI, 0.32–0.60 for > 21.0 vs. < 2.8 MET hours/week; trend p < .001) and were similar regardless of a woman’s age (although the majority of women were age > 50), stage of disease, and BMI. Similar to the Nurse’s Health Study, no benefit was demonstrated for vigorous-intensity activity and most of the participants were Caucasian. 50
In the LACE study, 1,970 women age 18 to 79 with stage I to III breast cancer from 1997 to 2000 completed the physical activity questionnaire the prior 6 months only. Age-adjusted results suggested that higher levels of physical activity were associated with reduced risk of recurrence and breast cancer mortality (trend p = .05 and .07, respectively, for highest versus lowest level of hours per week of moderate physical activity), but were not significant after adjusting for prognostic factors and other variables. Of note, in multivariable analyses, there remained a significant protective association between physical activity and all-cause mortality (HR 0.66; 95% CI, 0.42–1.03; trend p = .04). A strength and unique characteristic of this study is that it contained 20% minorities. It is hypothesized that the lack of power and healthier nature of the participants led to the null results of this study.49
Several studies have looked at exercise in breast cancer at several time points, an advantage over the studies that evaluate a single point in time. The Health, Eating, Activity, and Lifestyle (HEAL) study was a prospective, observational study of 933 women age 18 and older diagnosed with stage I to III cancer between 1995 and 1998 that measured activity levels the year prior to diagnosis and 2 years after diagnosis. Compared with women who were inactive both before and after diagnosis, women who increased physical activity after diagnosis had a 45% lower risk of death (HR 0.55; 95% CI, 0.22–1.38), and women who decreased physical activity after diagnosis had a fourfold greater risk of death (HR 3.95; 95% CI, 1.45–10.50). Although the risk reductions were observed for total deaths, the majority of deaths were from breast cancer.51 Similarly, the Women’s Health Initiative (WHI) study measured activity at diagnosis and 3 or 6 years post diagnosis in 4,643 postmenopausal women. Women participating in at least 9 MET hours/week (approximately 3 hours per week of brisk walking) of physical activity after diagnosis had lower breast cancer mortality (HR 0.61; 95% CI, 0.35–0.99; p = .049) and lower all-cause mortality (HR 0.54; 95% CI, 0.38–0.79); p < .01). Even in women who were inactive prior to diagnosis, those who increased or maintained physical activity of at least 9 MET hours/week after diagnosis had lower all-cause mortality (HR 0.67; 95% CI, 0.46–0.96).52
The Women’s Healthy Eating and Living Study (WHEL) similarly measured activity at baseline and 1 year in 2,361 women age 18 and older with stage I to III breast cancer. Adherence to activity guidelines was associated with a 35% lower mortality risk (HR 0.65; 95% CI, 0.47–0.91; p < .01). There was no effect seen on breast cancer events, although deaths were mostly secondary to breast cancer. Unlike the WHI study, in WHEL the change in activity during 1 year was not associated with improved outcomes, potentially secondary to shorter interval between reports.53 The Shanghai Breast Cancer Survival Study (SBCSS) assessed exercise at three time points (6, 18, and 36 months post-diagnosis) in 4,826 Chinese women age 20 to 70 between 2002 and 2006. After adjusting for several covariates, exercise during the first 36 months post-diagnosis was inversely associated with total mortality and recurrence/disease-specific mortality with HRs of 0.70 (95% CI, 0.56–0.88) and 0.60 (95% CI, 0.47–0.76), respectively, regardless of stage and BMI. They observed a dose-response relationship between mortality rates and exercise duration and MET scores, and the mortality association was only among estrogen- and progesterone receptor–negative patients.54 The clear strength of this study is that it evaluated more than two time points; however it is uncertain if this study can be applied to a Western breast cancer population.
Data from randomized controlled trials are limited. The Supervised Trial of Aerobic versus Resistance Training (START) trial randomly selected 242 patients with breast cancer between 2003 and 2005 to usual care, supervised aerobic, or resistance exercise during chemotherapy.55 The trial was originally designed to examine the independent effects of aerobic and resistance exercise on quality of life, health-related fitness, and other patient-reported outcomes. As an exploratory analysis, overall survival and disease-free survival was estimated. Eight-year disease-free survival was 82.7% for the exercise groups compared with 75.6% for the control group (HR 0.68; 95% CI, 0.37–1.24; log-rank p = .21). In exploratory subgroup analyses, the strongest effects were among women who were overweight or obese, had stage II/III cancers, estrogen receptor–positive tumors, HER2-positive tumors, and received taxane-based chemotherapies and optimal chemotherapy dosing.56 This study is limited by its exploratory nature but is certainly hypothesis-generating. Phase III studies comparing exercise to usual care in breast cancer survivors are warranted.
Supportive data from randomized controlled trials are lacking, but epidemiologic evidence supports the participation in exercise before and after breast cancer diagnosis to decrease breast cancer recurrence, breast cancer–related mortality, and overall mortality. The American Cancer Society encourages cancer survivors to engage in 150 minutes per week of moderate or 75 minutes per week of vigorous aerobic exercise.28
Decreased cardiorespiratory fitness, obesity, and a sedentary lifestyle negatively impact the outcomes of breast cancer survivors. Lifestyle interventions to improve survival are of much interest. However, there is a paucity of prospective, randomized clinical trial data to suggest specific exercise and dietary recommendations to improve cardiovascular fitness and reduce breast cancer–specific mortality in this population. Prospective, randomized studies that address interventions are necessary to guide breast cancer survivors.
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc.
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Research Funding: Amgen (Inst), Genentech (Inst), Novartis (Inst)
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