More Prominence Urged for Heart Risks in Breast Cancer Treatment

DURHAM, N.C., Oct. 12 -- Oncologists need to think heart when treating early breast cancer, according to clinicians here.

The "multiple hits" on heart health from both breast cancer treatment and post-diagnosis lifestyle changes necessitate need more aggressive cardiovascular risk management, they said.

Only indirect evidence supports this additive risk, said Lee W. Jones, Ph.D., of Duke University Medical Center here, and colleagues. But, the consequences are likely to become increasingly important for oncologists and cardiologists treating these women, they said in a review article in the Oct. 9 issue of the Journal of the American College of Cardiology.

"While we may achieve what amounts to miracle cures and have stupendous success, that comes, at times, with a price," said coauthor Pamela S. Douglas, M.D., also of Duke.

Further research is needed before making a universal risk management recommendation for women with breast cancer, the researchers said. But they suggested making a formal cardiovascular risk assessment with Framingham or Reynolds risk scores at baseline before adjuvant therapy.

"Consideration should be given to more aggressive management of risk factors than might otherwise be indicated, in view of the 'multiple-hit' hypothesis presented here," they said.

They added, "All women should be counseled about the value of a healthy lifestyle, and a program of individualized primary prevention should be undertaken as described in the American Heart Association guidelines." Ideally this should be before beginning adjuvant breast cancer treatment.

The researchers noted that many of these women are already at risk for cardiovascular disease. Studies have shown 62% of breast cancer patients are either overweight or obese and 36% are sedentary.

Then, after diagnosis, women typically decrease their physical activity by two hours a week with even greater reductions for those who receive multimodal breast cancer treatment, the investigators said. And, more than 70% of breast cancer patients gain 5.5 to 13.7 pounds during adjuvant therapy.

These factors, although of unknown value in predicting elevated cardiovascular disease morbidity and mortality in breast cancer versus the general population, "are often neglected when evaluating cardiovascular consequences of breast cancer adjuvant therapy," they said.

Direct and indirect effects of breast cancer treatment then add to this risk, the researchers said.

Anthracycline-based chemotherapy has gotten the lion's share of attention for decreased left ventricular ejection fraction leading to heart failure, but "virtually all adjuvant therapies are associated with unique and varying degrees of cardiovascular injury," they said.

Modern radiation techniques have been associated with cardiac perfusion defects in 50% to 63% of women in prospective studies.

Tamoxifen increases the occurrence of thromboembolic events. Decreases in serum estrogen with aromatase inhibitors have raised concern over adverse cardiovascular effects, although longer-term follow-up with this class of drugs is needed to determine the full impact on heart health, the researchers said.

Trastuzumab (Herceptin) also has relatively short follow-up for cardiovascular effects in clinical trials, but already a 2.0% to 4.1% heart failure occurrence rate and 3.0% to 18.0% occurrence rate of asymptomatic cardiac dysfunction have been reported.

Angiogenesis inhibitors bevacizumab (Avastin), sorafenib (Nexavar), sunitinib (Sutent), and investigational vascular disrupting agents are already associated with cardiovascular complications, including hypertension, arterial thromboembolic events, cardiac troponin increases, and left ventricular ejection fraction reductions.

Pre-existing heart disease risk factors may also increase the likelihood of breast cancer treatment-related cardiovascular complications, the researcher said.

Overall, breast cancer patients' cardiovascular risk profiles after primary therapy were worse than age- and gender-matched controls in two pilot studies by Dr. Jones' group, "supporting our contention of the 'multiple hit.'"

"Thus, as women progress through the selected treatment regimens, they will be subjected to a series of sequential or concurrent cardiovascular insults coupled with lifestyle perturbations that collectively leave patients with overt or sub-clinical cardiovascular disease," they said.

"At a minimum, these insults enhance susceptibility to further cardiovascular injury and, ultimately, risk of premature cardiovascular disease mortality," they concluded.

The consequences of multiple cardiovascular hits are likely to become increasingly important in early breast cancer management, the researchers said.

"Overall, this information is of critical importance to cardiovascular physicians who will increasingly be called upon to evaluate and treat these women," Dr. Jones and colleagues said.