Increases in CVD risk factors linked to worse survival in breast cancer

Home Blog Increases in CVD risk factors linked to worse survival in breast cancer

by Kristin Jenkins, Contributing Writer, MedPage Today

All-cause mortality risk was significantly increased in patients with breast cancer and coronary artery disease (CAD), and each additional cardiovascular disease risk factor (CVD-RF) was associated with a lowering of overall and progression-free survival, researchers found.

Analysis of survival outcomes data from five Phase II/III breast cancer trials showed that each additional CVD-RF was associated with an increased risk of death (hazard ratio [HR] 1.23, P=0.002), reduced progression-free survival (HR 1.12, P=0.05), and marginally reduced cancer-free survival (HR 1.15, P=0.07).

Similarly, the presence of comorbidities such as diabetes, CAD, and hypertension, but not hypercholesterolemia, was associated with an increased risk of a subsequent cardiac event in all patients (HR per CVD-RF 1.41, P < 0.001), according to Dawn L. Hershman, MD, of New York-Presbyterian/Columbia University Medical Center in New York City, and colleagues.

As shown in the study online in the Journal of Clinical Oncology, the presence of CAD was associated with a more than two-fold increased risk of eventual cardiac event (HR 2.65, P< 0.001), and diabetes was associated with a two-fold increased risk of a cardiac event (HR 2.00, P=0.002). In adjuvant studies, there was a more than three-fold increased risk of cardiac events among participants with hypertension (HR 3.20, P=0.006) or CAD (HR 3.44, P< 0.001).

Cardiovascular disease is now the primary cause of death in patients with breast cancer, but the relationship between cardiovascular risk factors, long-term cardiac events, and breast cancer is not well understood, the researchers said.

"We have an opportunity to develop and study interventions that comprehensively improve the health and well-being of cancer survivors, and we need to recognize and treat comorbid conditions to improve survival outcomes," Hershman told MedPage Today.

She noted that since patients in clinical trials are often the most compliant to treatment, the mortality risks may actually be higher in patients not eligible for clinical studies. It is important to encourage patients with early-stage and advanced breast cancer to follow up with their primary care physicians and "continue to manage their cardiovascular risk factors to reduce their risk of dying from non-cancer causes."

In an earlier study, the researchers found that compliance with medical or behavioral treatment for diabetes, hypertension, CAD, and high cholesterol often dropped off when breast cancer was diagnosed. "These chronic conditions may not be perceived as being as important," Hershman explained. "However, they do impact survival and adverse outcomes, and this should be emphasized to patients."

For the study, the authors analyzed data from 1999 to 2011 in five SWOG (formerly known as the Southwest Oncology Group) breast cancer trials, identifying 1,406 women with baseline diabetes, hypertension, hypercholesterolemia, and CAD using trial records linked to Medicare claims.

The primary outcome was overall survival, with deaths included from any cause. The files of patients with both baseline and follow-up claims data were examined for acute ischemic events or acute heart failure.

A total of 842 participants were put into a survival cohort, and 736 patients were put into a cardiac-event cohort. Median age was 70 at baseline, and median follow-up was 6 years. Hypertension and hypercholesterolemia were the most prevalent conditions in both cohorts.

Out of 1,460 women, 87% with early-stage and advanced disease had one or more CVD-RFs, 62% had two or more, and one-third had three or more. Even in women with advanced cancer, the number of significant CVD-RFs was associated with overall survival and risk of a cardiac event, the study showed.

Although there was no association between any of the individual CVD-RFs and overall survival, the exception was hypercholesterolemia, which was associated with improved overall survival (HR 0.73, P=0.01), the researchers reported. Hypercholesterolemia was also associated with improved rates of progression-free survival (HR 0.80, P=0.04), and cancer-free survival (HR 0.76, P=0.05).

In studies of women with advanced cancer, the association between hypercholesterolemia and better survival rates was even stronger: Overall survival was "considerably improved" (HR 0.65, P=0.006), as was progression-free survival (HR 0.68, P=0.005) and cancer-free survival (HR 0.62 ,P=0.003), the investigators said, pointing to the use of statins as a possible explanation.

"Statins are considered first-line therapy in the prevention of cardiovascular mortality in patients with hypercholesterolemia and have been associated with improved disease-free survival in patients with breast cancer." More study is needed to clarify this relationship, particularly the effect of hypercholesterolemia in advanced breast cancer, the researchers added.

There were no statistically significant associations between any of the risk factors and cardiac events in studies of women with advanced cancer, with the exception of diabetes (HR 2.37, P=0.03). Similarly, there was no significant association seen between obesity and overall survival in advanced studies.

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