Trastuzumab Is Cardiotoxic in Some Elderly Patients With Breast Cancer

Older patients with breast cancer who have a history of heart disease and/or diabetes have an increased risk of cardiotoxicity during treatment with trastuzumab, according to Spanish researchers.

Cesar Serrano, MD, and colleagues at Vall d’Hebron University Hospital in Barcelona reviewed the records of 45 women aged ≥70 years who had received at least 1 dose of a trastuzumabbased regimen for early or advanced breast cancer and at least 2 left ventricular ejection fraction (LVEF) assessments while on treatment. All patients in the series had undergone treatment since 2005 at the hospital’s breast cancer unit.

The study found that 12 (26.7%) women experienced trastuzumab-related cardiotoxicity.

Overall, 33% of women with a history of cardiac disease developed trastuzumab-related asymptomatic or symptomatic cardiotoxicity compared with 9.1% of women without a history of cardiac disease (P = .017). Also, 33.3% of diabetic women developed asymptomatic or symptomatic cardiotoxicity versus 6.1% of nondiabetic women (P = .010).

Serrano and associates said that the study, to their knowledge, is the first to comprehensively examine trastuzumab-related cardiotoxicity and the cardiovascular risk factors (CRFs) associated with an increased risk in a selected population of elderly patients with breast cancer.

The researchers pointed out that trastuzumab is a current standard of care in human epidermal growth factor receptor (HER)-2 positive patients with breast cancer. Cancer incidence increases dramatically with age, and roughly 70% of new cancers are diagnosed in patients aged >65 years. Breast cancer is most common in elderly women. However, clinical trials including patients treated with trastuzumab have been reserved for women aged ≤65 years who have an optimal performance status. Thus, results to date are relevant only for “a relatively young and otherwise healthy patient population” and cannot be necessarily applied to the entire population.

Because of trastuzumab’s established benefits and the absence of known predictive risk factors for cardiotoxicity in elderly patients with breast cancer, the investigators decided to determine the agent’s cardiac safety profile in this population of patients in a routine clinical practice setting.

In the study, the New York Heart Association classification system was used to document symptomatic cardiotoxicity. Asymptomatic cardiotoxicity was defined as an absolute drop in LVEF ≥10%, resulting in a final LVEF <50% or an absolute drop >20%.

Results showed that 3 of 24 (12.5%) patients with early breast cancer and 5 of 21 (23.8%) patients with advanced disease experienced asymptomatic cardiotoxicity. Four women with advanced breast cancer, or 8.9% of the entire study population, developed symptomatic congestive heart failure.

All 8 asymptomatic patients with asymptomatic cardiac events had a complete recovery after they stopped taking trastuzumab. The drug was reintroduced in 4 patients, only 1 of whom had a repeat asymptomatic LVEF drop, which improved without treatment withdrawal. The median time to recovery was 6 weeks.

Of the 4 patients who developed symptomatic congestive heart failure, 3 recovered their cardiac function at a median of 5 weeks after discontinuing trastuzumab and receiving standard cardiac therapy; 1 patient was able to resume trastuzumab without any additional problems. The fourth patient did not recover cardiac function and had only slight improvement, so her physician decided not to resume any cancer treatment. The patient died 3 months later due to progression of her cancer.

While elderly patients with breast cancer who have a history of cardiac disease and diabetes had a significantly increased incidence of cardiac events in this study, other established CRFs, such as high blood pressure and a history of cigarette smoking, did not increase trastuzumab-related cardiotoxicity.

Serrano and colleagues said that their findings “can serve to advise clinicians to be aware of symptomatic and asymptomatic cardiac dysfunction in elderly patients, especially in those with 1 or more CRFs.”

It is especially important to carefully monitor early symptoms and cardiac function in older patients with breast cancer who are slated for trastuzumab treatment, given that the mortality rate at 5 years after a diagnosis of congestive heart failure is around 50% in patients aged ≥65 years. Physicians should consider referring elderly patients with breast cancer to a cardiologist if 1 or more CRFs are present prior to or during trastuzumab therapy.

Finally, the authors pointed out in a news release that the decision to reintroduce trastuzumab in patients in whom the drug has been withdrawn because of cardiotoxicity must be made in tandem with a cardiologist on a caseby- case basis.

Serrano C, Cortes J, De Mattos-Arruda L, et al. Trastuzumab- related cardiotoxicity in the elderly: a role for cardiovascular risk factors [published online ahead of print August 9, 2011]. Ann Oncol. doi:10.1093/annonc/mdr348.