Prediagnosis Exercise Protective Against CVD After Breast Cancer

Batya Swift Yasgur, MA, LSW

September 30, 2019

Older women who exercised prior to a diagnosis of breast cancer may have a lower risk of cardiovascular events (CVEs) and mortality from cardiovascular disease (CVD) compared with those who did not engage in exercise, a new analysis from the Women's Health Initiative (WHI) suggests.

Investigators asked more than 4000 women who were diagnosed with breast cancer about their exercise habits prior to their diagnosis. Participants were followed for 8 years for incident CVEs and for 12 years for CVD death.

Prediagnosis exercise was associated with a 20% to 37% reduction in the risk of first CVEs.

"We found that when these patients exercised prior to their diagnosis of breast cancer, the risk of CVEs and death associated with heart disease was overall reduced years down the line after their cancer treatment," lead author Tochi M. Okwuosa, director of the cardio-oncology program, Rush University Medical Center, Chicago, Illinois, told theheart.org | Medscape Cardiology.

"This is relevant because we know that cancer treatment by itself increases the risk of heart attack, stroke, heart failure, and cardiovascular disease after treatment and down the line, even many years later, so it's interesting that exercise prior to treatment actually makes a difference in reducing risk caused by the treatment and also caused by advancing age," she said.

The study was published online September 24 in JACC: CardioOncology.

Better Treatment Tolerance

Cardiorespiratory fitness (CRF) can decline as much as 5% to 20% in women receiving chemotherapy-containing adjuvant therapy — an impact that can persist for years following treatment cessation, the authors write.

"I have noticed that patients who exercised prior to [chemotherapy] treatment for cancer tended to tolerate treatment better and recover faster, while those who had not exercised were more fatigued overall, sicker, took longer to recover, and maybe never even fully recovered their baseline exercise level prior to treatment," Okwuosa said.

"There were also cardiovascular benefits for people who had exercised prior to diagnosis, which interested me because I'm a cardiologist," she added.

Since exercise is known to improve CRF and the reserve capacity of all organs in the cardiovascular system, the researchers sought to determine the association between prediagnosis exercise and the risk of CVEs in women with primary breast cancer by drawing on data from the WHI — an observational study of postmenopausal women ages 50 to 79 years.

The initial study was conducted between October 1993 and December 1998. Women who completed that phase were offered the opportunity to enroll in an extension study. Those who did were followed annually from 2005 to 2010.

Participants in the current cohort (n = 4015) had a confirmed diagnosis of nonmetastatic primary breast cancer during the main WHI study.

"Exercise exposure" was assessed in baseline and follow-up questionnaires, in which patients were asked to report the frequency, duration, and intensity of leisure-time physical activity.

Each type of exercise (eg, walking, biking, or jogging) was translated into metabolic equivalent task (MET) values, based on the degree of exercise intensity.

These values were used to categorize exercise into quartiles: < 2.5 MET hours/week; 2.5 to < 8.6 MET hours/week; 8.6 to < 18 MET hours/week; and ≥ 18 MET hours/week.

Exercise data were collected at the visit closest to breast cancer diagnosis, which was between 5 years and 1 month before diagnosis.

The primary CVD outcome consisted of the first occurrence of newly diagnosed heart failure (HF), myocardial infarction (MI), angina, coronary revascularization, peripheral artery disease, carotid artery disease, transient ischemic attack, stroke, or cardiovascular death that took place after the breast cancer diagnosis.

The researchers also studied individual incident CVEs (MI, HF, coronary heart disease [CHD] death, and CVD death).

All models were adjusted for a variety of factors, including age at WHI enrollment, race/ethnicity, body mass index (BMI), cancer stage, education, use of hormone therapy, and family history.

The researchers additionally estimated the association between CVD outcomes and exercise levels defined by national exercise guidelines (≥ 9 MET hours/week referent to < 9 MET hours/week).

Median durations of study outcomes are listed below.

Table 1. Median Duration of Study Outcomes

Study Component

Median Duration (Interquartile Range)

Exercise Assessment to Breast Cancer Diagnosis

12 months (6 - 23 months)

Follow-up for Cardiovascular Events

8.2 years (6.0 - 10.6 years)

Death

12.7 years (10.4 - 14.9 years)

Good Cardiac Reserve

During the study, a total of 324 CVEs (including 89 MIs, 49 new diagnoses of HF, and 215 CVD deaths [96 attributed to CHD]) occurred.

With each increasing quartile of exercise, researchers found a decreasing trend in age-adjusted hazard ratio (HR), compared with the referent first quartile for the primary endpoint of CVEs (n = 342; annualized percentage, 1.14%) in both age- and multivariable-adjusted models.

Table 2. Risk for Primary Outcome (CVEs) by Level of Exercise

Cardiovascular Events

< 2.50 MET hours/week

2.50 < 8.625 MET hours/week

8.625 < 18.00 MET hours/week

≥ 18.00 MET hours/week

P value for trend

Age-adjusted HR (95% CI)

Referent

0.77 (0.58 - 1.03)

0.75 (0.56 - 0.99)

0.59 (0.43 - 0.80)

.0001

Multivariable-adjusted HR (95% CI)

Referent

0.80 (0.59 - 1.09)

0.9 (0.64 - 1.17)

0.63 (0.45 - 0.88)

.016

Secondary endpoints yielded similar findings across quartiles of increasing physical activity in cardiovascular death and CHD death. Although there were also similar age-adjusted trends for HF and MI, they did not reach significance.

Similarly, when examining CVEs based on exercise guidelines, only CHD death remained statistically significant on multivariable analyses comparing high to low exercise level (HR, 0.56; 95% CI, 0.35 - 0.89; P = .014).

The findings persisted, even when the researchers conducted a sensitivity analysis of a Medicare subset of participants (n = 1603), adjusting for treatment variables (eg, chemotherapy and/or radiation therapy and surgery).

"If you get sick, but you have good cardiac reserve because you were exercising in the first place, you can tolerate the illness better and recover better and faster afterwards," Okwuosa noted.

One More Tool

Commenting on the study for theheart.org | Medscape Cardiology, Christina M. Dieli-Conwright, PhD, MPH, associate professor, Department of Supportive Care Medicine, City of Hope medical center in Duarte, California, said it has a "fantastic take-home message — exposing oneself to exercise is going to be beneficial, especially in terms of cardiovascular events, and we know CVD has enormous mortality in women."

Dieli-Conwright, who was not involved in the study, said it "emphasizes the importance of exercising as primary prevention in breast cancer, since women diagnosed with breast cancer, especially at an early stage, are dying from CVD, despite surviving cancer."

In an accompanying editorial, Lindsay Peterson, MD, MSCR, of the Washington University School of Medicine, St Louis, Missouri, and Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, note that, as an increasing number of patients survive their breast cancer, CVD "is and will continue to become a major risk of morbidity and mortalities for survivors."

"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."

Okwuosa added that physical exercise has many health benefits and its role in preventing CVD following breast cancer treatment "is just one more tool in the pocket of PCPs [primary care providers] and other physicians to teach people about the beneficial effect of exercise."

The Women's Health Initiative (WHI) is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health & Human Services. Okwuosa has disclosed no relevant financial relationships. The other authors' disclosures are listed on the original paper. Peterson is supported by the American Cancer Society. Ligibel is supported by the Susan G. Komen Foundation and also receives product donations from Fitbit and Nestle Health Sciences to support the BWEL study. Dieli-Conwright has disclosed no relevant financial relationships.

JACC CardioOncology. Published online September 24, 2019. Full text, Editorial

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