A new study has found significant rates of heart damage from chemotherapy, especially for the combination of anthracycline chemotherapy (typically, Adriamycin) plus Herceptin (trastuzumab). The study was designed to investigate the association between treatment with anthracycline chemotherapy, Herceptin, or both, and heart failure in women with breast cancer.
Clinical trials have documented the association between cardiotoxic chemotherapy for breast cancer and congestive heart failure. However, clinical trial participants do not represent typical breast cancer patient populations since they typically contain younger and otherwise more healthy women.
The study included 13,497 women from eight Cancer Research Network (CRN) health plans who were diagnosed with invasive breast cancer during the period 1999 to 2007. The Cancer Research Network consists of the research programs, enrolled populations, and data systems of 14 U.S. health maintenance organizations. To conduct the study, the authors used data from the Cancer Research Network Virtual Data Warehouse (VDW) to determine whether each woman was exposed to anthracycline chemotherapy alone, Herceptin alone, anthracycline plus Herceptin, other chemotherapy, or no chemotherapy. The authors also determined whether each woman had heart failure before her breast cancer diagnosis, developed heart failure after starting breast cancer treatment, or was not diagnosed with heart failure. The authors calculated the associations between heart failure and exposures for each treatment category while adjusting for age, health plan, breast cancer stage, year of diagnosis, and co-existing medical conditions.
A total of 6,420 (46.2%) of the study population received no chemotherapy, 3,857 (28.6%) received anthracycline chemotherapy only, 157 (1.2%) received Herceptin only, 470 (3.5%) were treated with both, and 2,748 (20.4%) received other chemotherapy. A total of 1,041 (7.7%) of the women were diagnosed with heart failure after starting treatment. Anthracycline use alone was found to be associated with 1.19 times the risk of heart failure compared to no chemotherapy. Herceptin alone was associated with 3.02 times the risk of heart failure compared to no chemotherapy; anthracycline plus Herceptin was associated with 6.05 times the risk; and other chemotherapy was associated with 1.36 times the risk.
These associations strengthened after excluding women from the analysis who already had heart failure before their breast cancer diagnosis or who were diagnosed with heart failure fewer than 60 days after breast cancer diagnosis.
The authors conclude that the combination of anthracycline plus Herceptin, in particular, is associated with an elevated risk of heart failure in the community setting.
Comments regarding the study
While Herceptin plus anthrocycline chemotherapy appears to be an effective treatment combination for HER2 overexpressing (HER2+) breast cancer, the study results indicate that the combination greatly elevates the risk of heart damage. A delay between completion of anthracycline chemotherapy and treatment with Herceptin may be advisable, especially for those with pre-existing risk factors for heart disease. Clinical trials have reported a 2% to 3% risk of heart failure during the first five years after treatment (with a higher, but unknown, incidence over longer periods of time).
The present study reports a 7.7% rate of heart failure in a typical breast cancer patient population. The most common symptom of heart damage is shortness of breath, which may begin during chemotherapy or months or years afterwards. Breast cancer patients should undergo a cardiovascular work-up before starting chemotherapy and be monitored during therapy and afterwards for signs of cardiomyopathy.
Selected breast cancer studies
Adjuvant Trastuzumab in HER2-Positive Breast Cancer
Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant Trastuzumab in HER2-Positive Breast Cancer. New England Journal of Medicine. Massachusetts Medical Society; 2011; 365:1273-1283 10.1056/nejmoa0910383
Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden
McGale P, Darby SC, Hall P, Adolfsson J, Bengtsson N, Bennet AM, et al. Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden. Radiotherapy and Oncology. Elsevier BV; 2011; 100:167-175 10.1016/j.radonc.2011.06.016
Pathology of late-onset anthracycline cardiomyopathy
Bernaba BN, Chan JB, Lai CK, Fishbein MC. Pathology of late-onset anthracycline cardiomyopathy. Cardiovascular Pathology. Elsevier BV; 2010; 19:308-311 10.1016/j.carpath.2009.07.004
Early identification of trastuzumab-related cardiotoxicity with speckle-tracking echocardiography.
Maurea N, De Lorenzo C, Coppola C, Ragone G, Di Pietro E, Schiattarella G, et al. Early identification of trastuzumab-related cardiotoxicity with speckle-tracking echocardiography.. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2010; 28:e11096-e11096 10.1200/jco.2010.28.15_suppl.e11096
Aged garlic extract protects against doxorubicin-induced cardiotoxicity in rats
Alkreathy H, Damanhouri ZA, Ahmed N, Slevin M, Ali SS, Osman AM. Aged garlic extract protects against doxorubicin-induced cardiotoxicity in rats. Food and Chemical Toxicology. Elsevier BV; 2010; 48:951-956 10.1016/j.fct.2010.01.005
Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology
Eschenhagen T, Force T, Ewer MS, de Keulenaer GW, Suter TM, Anker SD, et al. Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. European Journal of Heart Failure. Wiley; 2011; 13:1-10 10.1093/eurjhf/hfq213