Thursday, October 4, 2007

Increased CV risk in breast-cancer patients examined

Increased CV risk in breast-cancer patients examined

The (heartwire)

Durham, NC - The increased risk of cardiovascular disease in women who have received treatment for breast cancer is examined in a new review paper in the October 9, 2007 issue of the Journal of the American College of Cardiology.

The authors, led by Dr Lee Jones (Duke University Medical Center, Durham), explain that the risk of cardiovascular disease in women who have received treatment for breast cancer is increased in many ways. "Cardiovascular clinicians need to understand this risk, and diagnostic, preventive, and/or therapeutic strategies that effectively address this need are urgently required," they say.

Jones et al note that breast cancer is the most common malignancy in American women, with approximately 213 000 new cases diagnosed in 2006. Although the incidence of breast cancer has increased by 0.2% per year between 1997 and 2000, improvements in detection and therapy have resulted in significant survival gains, with breast-cancer-specific mortality decreasing almost 24% between 1990 and 2000. As a result, approximately 2.3 million American women are now living with a previous history of breast cancer, with sufficient survival to be at risk for cardiovascular disease.

The authors report that many of the chemotherapeutic agents used in breast-cancer management are associated with acute and long-term cardiac complications. Anthracycline-containing regimens are well recognized to trigger dose-dependent, cumulative, progressive cardiac dysfunction, manifested as decreased LVEF and, ultimately, symptomatic congestive heart failure; radiotherapy also causes adverse cardiac events.

They point out that while endocrine therapy has not been clearly associated with cardiovascular injury, the new aromatase inhibitors have been associated with more cardiovascular events than tamoxifen, albeit a slightly lower incidence of thromboembolic events. Thus, longer-term follow-up is required to fully assess the associated cardiovascular risks.

In addition, the HER-2-directed treatment trastuzumab (Herceptin, Genentech) is associated with a heart-failure incidence of between 2.0% and 4.1% and asymptomatic cardiac dysfunction rates of between 3.0% and 18.0%; angiogenesis inhibitors are also known to be associated with cardiovascular complications, with reports of arterial thromboembolic events, increase in cardiac troponin, reductions in LVEF, and, most commonly, hypertension.

Jones et al also note that unfavorable lifestyle changes also come into the equation. "Physical activity and body weight are two major independent risk factors for cardiovascular disease that are often neglected when evaluating cardiovascular consequences of breast-cancer therapy. It has been reported that, on average, early breast-cancer patients decreased their physical activity by two hours per week from before to after diagnosis. Furthermore, more than 70% of breast-cancer patients gain between 2.5 to 6.2 kg of body weight during treatment," they write.

And to complicate matters still further, Jones et al explain that the presence of preexisting cardiovascular risk factors is itself a strong predictor for the development of breast-cancer-therapy-induced cardiovascular injury, making the likely lifetime risk for cardiovascular disease much greater. "Recent estimates suggest that physical inactivity confers a risk of breast cancer among white women of 2% to 15%, with overweight and obesity being associated with a 34% and 63% increased breast-cancer risk, respectively. It could be speculated, therefore, that physical inactivity and obesity rates may be even greater among early breast-cancer patients that, in turn, may translate into greater cardiovascular disease risk independent of the effects of adjuvant therapy."

Multiple-hit hypothesis

The authors refer to all these different causes of increased cardiovascular risk in breast-cancer survivors as the "multiple-hit" hypothesis. "We speculate that the consequences of the 'multiple hit' will become an increasingly important issue in the management of women with early breast cancer. Overall, this information is of critical importance to cardiovascular physicians, who will increasingly be called upon to evaluate and treat these women," they write.

Jones et al say that although the current and future consequences of the "multiple-hit" hypothesis will be clinically devastating, it is currently not possible to predict which patients are at increased risk of late-occurring cardiovascular disease. As current monitoring techniques (eg, echocardiography, radionuclide angiography) have limited ability to detect early cardiac damage, newer, more sensitive imaging modalities (single-photon-emission computed tomography, MRI, exercise or dobutamine stress testing) as well as novel biochemical markers (brain natriuretic peptide, troponin I) that allow more accurate detection and quantification of subclinical cardiac damage are being explored, they add.

They recommend that a formal baseline cardiovascular risk assessment, using either Framingham or Reynolds risk scores, be performed before adjuvant therapy for breast cancer. "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. Unfavorable risk factors should to be managed, ideally before the initiation of 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, although further research would be required before making such a recommendation universal," they conclude.


Jones LW, Haykowsky MJ, Swartz JJ, et al. Early breast cancer therapy and cardiovascular injury. J Am Coll Cardiol 2007; 50:1435-1441.

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