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Older breast cancer patients face HF, cardiomyopathy after trastuzumab
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Older women with breast cancer treated with trastuzumab or trastuzumab plus anthracyclines experienced common complications such as heart failure and cardiomyopathy, according to study results.
Newer biologic therapies, such as the monoclonal antibody trastuzumab, have been reported to increase heart failure (HF) and cardiomyopathy (CM) in clinical trials, especially in combination with anthracycline chemotherapy. However, clinical trials of trastuzumab (Herceptin, Genentech) characteristically have enrolled younger women without cardiac comorbidities, and some trials excluded elderly patients due to concerns about the drug’s safety profile.
Jersey Chen
“Given the increasing number of long-term breast cancer survivors exposed to newer breast cancer therapies with the potential for myocardial injury, preventing and managing cancer therapy-induced cardiotoxicity represent an important point of collaboration between oncologists and cardiologists to reduce the burden of HF and CM,” Jersey Chen MD, MPH, of the Yale University School of Medicine, and colleagues wrote.
Chen and colleagues analyzed data from the SEER-Medicare linked database from 2000 to 2007 to assess the relationship between adjuvant trastuzumab and anthracycline therapy in older women with early-stage breast cancer and the development of HF or CM.
The researchers identified 45,537 women aged 67 to 94 years with early-stage breast cancer. Chen and colleagues calculated 3-year incidence rates of HF or CM in mutually exclusive treatment groups: trastuzumab (with or without nonanthracycline chemotherapy), anthracycline plus trastuzumab, anthracycline (without trastuzumab and with or without nonanthracycline chemotherapy), other nonanthracycline chemotherapy, or no adjuvant chemotherapy or trastuzumab therapy.
The investigators determined HF or CM events through administrative Medicare claims.
Adjusted 3-year HF or CM incidence rates were higher for patients receiving trastuzumab (32.1 per 100 patients) and anthracycline plus trastuzumab (41.9 per 100 patients) compared with those who received no adjuvant therapy (18.1 per 100 patients, P<.001), study results showed. The addition of trastuzumab to anthracycline therapy added 12.1 HF/CM events to the first year of follow-up, 17.9 to the second year of follow-up and 21.7 events to the third year.
Of the 8,837 patients who received adjuvant therapy, the percentage of those who received trastuzumab or anthracycline plus trastuzumab increased from 2.6% in 2000 to 22.6% in 2007 (P<.001). On average, women treated with trastuzumab, anthracycline plus trastuzumab or anthracycline were younger, had more Elixhauser comorbidities and had fewer cardiovascular conditions compared with patients who did not receive adjuvant therapy.
Also, patients with breast cancer of higher stage or higher grade, as well as those with larger tumor size, greater number of positive lymph nodes or who underwent mastectomy, were more likely to be treated with trastuzumab, anthracycline plus trastuzumab or anthracycline (P<.001).
“Our findings illustrate that the incidence of HF or CM is high for older women in general, regardless of the presence of breast cancer,” Chen and colleagues wrote. “This suggests that there is a potentially important role for cardiologists before initiation of cancer therapy to optimize patients who are at high risk for developing HF or CM and to detect early signs and symptoms of HF or CM after treatment. Ongoing research evaluating the role of cardiac biomarkers for predicting risk of HF or CM during cancer therapy may prove useful for identifying patients who may benefit from early cardiology referral.”
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