While the risk of heart failure in breast cancer patients may be greater than previously recognized, there is growing concern that newer agents used to treat breast cancer may be increasing heart disease risk. A population-based, retrospective cohort study of 12,500 women diagnosed with invasive breast cancer has found that women treated with anthracycline and trastuzumab (Herceptin) appear to experience more cardiac problems than shown in previous studies.

“Both of these drugs are important for breast cancer survival,  but the risk of heart failure associated with them may be higher than previously estimated in clinical trials, and may persist longer (at least 5 years) than we thought,” said lead study author Erin Aiello Bowles, MPH, who is an epidemiologist at Group Health Research Institute, Seattle, Washington.  “Many women with breast cancer are eligible for chemotherapy treatment, and anthracyclines are some of the most commonly used types of chemotherapy for breast cancer. About 20% to 25% of these women are HER2 (human epidermal growth factor receptor-2)-positive and they are also eligible for trastuzumab treatment.”

Dr. Bowles said these new study findings are significant because an increasing number of women are surviving longer with breast cancer, making it more of a chronic disease. Based on current incidence rates, 12.4% of women (one of every eight women) born in the United States this year will develop breast cancer at some time during their lives.1 Although the majority of these women are expected to have good outcomes when treated with the current armamentarium, cardiac toxicities resulting from cancer therapies may have a greater impact the overall survival of some women.

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Bowles and her colleagues estimated real-world use of anthracyclines-trastuzumab combination and their association with heart failure and cardiomyopathy.2  The researchers looked at 12,500 women (mean age: 60 years; range: 22-99 years) diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007 at eight centers.  The researchers used administrative procedure and pharmacy codes to identify anthracycline, trastuzumab, and other chemotherapy use.  In the process, they also identified incident heart failure and/or cardiomyopathy following chemotherapy initiation and assessed the risk of heart failure and/or cardiomyopathy with time-varying chemotherapy exposures compared to no chemotherapy.

“We did this study for two reasons. First we wanted to see how often anthracycline and trastuzumab were being used in the community. And second, we wanted to estimate the risk of heart failure after using anthracycline and/or trastuzumab for breast cancer treatment in a general population. All previous studies risk estimates had come from either clinical trials, which have stringent eligibility criteria and may not be generalizable to all populations, or SEER (Surveillance and Epidemiology and End Results)-Medicare studies, which are only done in older women,” Bowles told ChemotherapyAdvisor.com.  

The study showed that patients receiving anthracycline and trastuzumab tended to be younger with less comorbidity than recipients of other chemotherapy or no chemotherapy.  Compared with no chemotherapy, the risk of heart failure and/or cardiomyopathy was higher in women treated with anthracycline alone and the risk was highly increased in women treated with trastuzumab alone or anthracycline plus trastuzumab (Table 1).

Table 1. Risk of Heart Failure/Cardiomyopathy (HF/CM) for Patients Who Received Treatment for Breast Cancer2

Women Receiving Breast Cancer Therapy (N=12,500) Risk for HF/CM
Anthracycline alone


HR=1.49 (95% CI: 1.11 to 1.76)

Trastuzumab alone 0.9% HR=4.12 (95% CI: 2.30 to 7.42)
Anthracycline and trastuzumab  3.5% HR=7.19 (95% CI: 5.00 to 10.35)
Other chemotherapy 19.5% HR=1.49 (95% CI: 1.25 to 1.77)

HF, heart failure; HR, hazard ratio; CM, cardiomyopathy.