NEW YORK (Reuters Health) - The chemotherapy combination of anthracycline and trastuzumab (Herceptin) increased women's risk of heart failure sevenfold in a new retrospective cohort study - and anthracycline wasn't all to blame.
The risk of heart failure or cardiomyopathy "was highly increased in patients treated with trastuzumab alone," the researchers reported in a paper released August 30 by the Journal of the National Cancer Institute.
Earlier randomized controlled trials also showed a link between the drugs and heart failure risk. But researchers said those risks may have been underestimated because the studies were limited to younger women without comorbidities.
"The rates of heart failure might actually be higher than what clinical trials have estimated to be associated with these drugs," lead researcher Erin Bowles from Group Health Research Institute in Seattle, Washington told Reuters Health.
She and her colleagues used data from eight study sites in the Cancer Research Network, on 12,500 women diagnosed with invasive breast cancer in 1999-2007 (mean age, 50 years). Of those women, 29.6% were treated with anthracycline only, 0.9% with trastuzumab alone, and 3.5% with a combination of the two drugs. Another 19.5% received other chemotherapy and the remaining women weren't treated with chemotherapy.
Compared with no chemotherapy, the risk of heart failure over a median follow-up of 4.4 years was higher for women treated with anthracycline alone (aHR = 1.40), with trastuzumab alone (aHR = 4.12), and with the drugs combined (aHR = 7.19).
The heart failure incidence was higher among women who were older at diagnosis, but hazard ratios associated with chemotherapy use decreased with increasing age, the researchers reported.
"My main hope is that the results will give clinicians pause when they are recommending trastuzumab to women who are of a different age or health status from women who participated in the trials," said Dr. Ann Geiger, a population researcher from Wake Forest Baptist Medical Center in Winston-Salem, North Carolina, who wrote an editorial on the study.
"It is a very powerful and important treatment and we also need to be very careful about how we use it," she said.
The findings shouldn't stop clinicians from prescribing trastuzumab altogether - alone or in combination with anthracycline, Bowles said. Instead, each woman's personal circumstances, including her underlying risk factors, should be considered individually.
"It depends on their age, what else is going on in their life, any other comorbidities they might have, (and) their personal risk of heart failure," she said. "It's really hard to say whether these results will influence treatment decisions. Certainly they would help inform them."
Dr. Geiger agreed that the potential heart risks of chemotherapy drugs, and not just their anti-cancer benefits, need to be considered at the time of diagnosis.
"People are making a decision in the throes of a breast cancer diagnosis, and your focus is appropriately very immediate, and it is hard to weigh something that seems very far away," she told Reuters Health.
Researchers and physicians may have gotten a bit too excited about trastuzumab before a full analysis of its harms was finished, Dr. Geiger added.
"It's very clear from this paper (that) people jumped on the proverbial band wagon early out of a sincere desire to help their patients, and we just need to be careful with that."
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