A new study published in Annals on Oncology, a cancer-focused research journal, has found that trastuzumab (Herceptin) — a breast cancer drug — increases the risk of heart complications. Women who have diabetes and women with a history of heart disease are especially at risk.
The study analyzed the medical data of 45 women between the ages of 70 and 92 who had been treated with trastuzumab starting in 2005. Researchers found that 26.7% of the patients demonstrated heart problems that were caused by the drug. This rate was slightly higher than the rate demonstrated in younger and healthier women during the drug’s clinical testing phase. Trastuzumab caused 33% of the women with histories of heart disease to develop asymptomatic or symptomatic heart problems while only 9.1% of women without a history of heart disease developed those problems. Similarly, 33.1% of women with diabetes experienced new heart problems compared to only 6.1% of non-diabetic women. All but one of the women recovered fully once treatment with the drug was discontinued; five of the women renewed their treatment with the drug upon the disappearance of the problems.
Trastuzumab is currently the most-used medication for treating women with HER2 positive breast cancer, or the type of cancer that causes expression of the HER2 protein on the surface of the cancer cells. Elderly women are most at risk for breast cancer but trastuzumab has also been tested on younger, healthy women in clinical trials.
The study was conducted by Dr. César Serrano, a clinical fellow in Barcelona, Spain at the University Hospital Department of Medical Oncology Breast Cancer Centre. “This is the first study to specifically assess trastuzumab-related cardiac toxicity and the cardiovascular factors that are associated with an increased risk in a selected population of elderly breast cancer patients,” said Serrano of the study.
“Trastuzumab is generally well-tolerated and, although there are some concerns about it causing heart problems, until now few risk factors have been identified among patients in clinical trials, most of whom are usually younger than 70 years and have good general health,” continued Serrano. “Our study has demonstrated a significantly increased incidence of cardiac events among patients aged 70 and over with cardiovascular risk factors such as a history of cardiac disease and diabetes.
“Approximately 70% of all newly diagnosed cancers occur in patients older than 65 and, given the expected increase in the absolute number of elderly cancer patients over the coming decades in Western countries, there is an unmet need for information about the efficacy and safety of anti-cancer treatments in daily clinical practice. Data obtained in this report can serve to advise clinicians to be aware of symptomatic and asymptomatic cardiac dysfunction in elderly patients. We think that it is reasonable to refer elderly breast cancer patients to a cardiologist if one or more cardiovascular risk factors are present before or during treatment with trastuzumab. Moreover, a closer surveillance of early symptoms and cardiac function is highly recommended.”
Patients developed both asymptomatic and symptomatic cardiotoxicity after administration of trastumuzab. Asymptomatic cardiotoxicity occurs when no obvious symptoms of heart problems are apparent but scanning or echocardiography reveals that the heart’s left ventrible drops in function by 10% or more. Symptomatic cardiotoxicity shows apparent physical symptoms such as swelling of the limbs and shortness of breath; this type of cardiotoxicity includes congestive heart failure.
“One of the main characteristics of trastuzumab cardiotoxicity is its reversibility,” said Serrano. “It is a well-known phenomenon that differs from other chemotherapeutic agents such as anthracyclines. Reversibility normally happens with treatment discontinuation, but also can also occur spontaneously. The decision to reintroduce trastuzumab, or to continue with it, must be taken case-by-case together with a cardiologist.”