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EARLIER study findings that anthracycline- or trastuzumab-based treatment for breast cancer raises the risk for heart failure and cardiomyopathy (HF/CM) in select patients can now be extended to a more general population of women with the disease.


Data from clinical trials have demonstrated that although anthracycline and trastuzumab regimens are highly effective in improving disease-free survival among women undergoing treatment for breast cancer, anthracycline use is associated with an approximate 2% increase in HF/CM, and an approximate 4% increase when anthracycline therapy is followed by trastuzumab. However, such trials typically exclude older women (eg, women older than 70 years) and women with major comorbidities, rendering the effects of such treatments in these patient groups less understood.



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In order to evaluate real-world adjuvant anthracycline and trastuzumab use as well as incident HF/CM risk associated with adjuvant anthracycline and trastuzumab use in a population-based cohort of women with breast cancer, epidemiologist Erin J. Aiello Bowles, MPH, a research associate at Group Health Research Institute in Seattle, Washington, and colleagues conducted what they believe to be the first study to examine associations between anthracycline and trastuzumab administration and HF/CM in a cohort of breast cancer patients broader than Medicare-eligible women or clinical trial participants. Their population-based, retrospective cohort study focused on data from the health maintenance organization Cancer Research Network, involving 12,500 women in whom incident, invasive breast cancer was diagnosed between January 1999 and December 2007. None of the women had a diagnosis of HF/CM at the time of breast cancer diagnosis or at the initiation of chemotherapy. 


The researchers identified anthracycline, trastuzumab, and other chemotherapy use, as well as incident HF/CM following chemotherapy initiation. Among the study participants (mean age 60 years; range 22 to 99 years):


• 29.6% received anthracycline-based chemotherapy alone (without trastuzumab; however, some might have received additional chemotherapy such as cyclophosphamide)


• 0.9% received trastuzumab alone (without anthracycline; however, all but one woman received additional chemotherapy)


• 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. 


Compared with patients in the latter two groups, those receiving anthracycline and trastuzumab were younger than 65 years and had fewer comorbidities. Women receiving trastuzumab alone tended to be older with more comorbidities, whereas women receiving anthracycline, with or without trastuzumab, tended to be younger and without other illnesses. Both treatments were associated with heightened HF/CM risk compared with no chemotherapy.


“Compared with women who received no chemotherapy, our hazard ratios suggest a fourfold increase in the risk of HF/CM among women who received trastuzumab alone and a sevenfold increase in the risk of HF/CM for those who received anthracycline plus trastuzumab,” reported Bowles’ team in Journal of the National Cancer Institute (2012;104:1293-1305). ONA