Anthracyclines for breast cancer, lymphoma linked to higher congestive heart failure risk
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Treatment with anthracyclines for breast cancer or lymphoma correlated with more than two times higher risk for congestive heart failure than that of healthy controls, according to a study conducted at Mayo Clinic.
“Survivorship with cancer is improving year by year and decade by decade with new treatments,” lead author Hector R. Villarraga, MD, associate professor and cardio-oncologist at Mayo Clinic in Rochester, Minnesota, told Healio. “We don’t want to successfully treat a disease that 50 years ago was deadly, and then have these individuals succumb to heart disease because we forgot about their heart and other parts of their body. We have to be more conscientious and proactive in following these patients and controlling their cardiac risk factors.”
In the retrospective, population-based, case-control study, Villarraga and colleagues assessed data from the Rochester Epidemiology Project on 2,196 residents of Olmstead County, Minnesota, diagnosed with breast cancer or lymphoma between 1985 and 2010. The study also included a cohort of age-, sex- and comorbidity-matched healthy controls.
Villarraga spoke with Healio about the inspiration for this study, what it revealed and what clinicians can do to more closely monitor patients who received anthracycline treatment.
Healio: What prompted you to conduct this study?
Villarraga: I’ve been dedicated to the field of cardio-oncology for the last 8 years, and I thought this could give us a bit more information. The studies up until now have been done in databases from HMOs, so there is a referral bias. And if you have patients who are seen for breast cancer, lymphoma or any other cancer and you group them from institutions, you don’t know if that’s a true setting for incidence of heart failure. So, since we have the Rochester Epidemiology Project here around the clinic — where people get their care either here at Mayo or at another hospital — we had a setting that has been used for many, many other epidemiologic projects.
We looked at patients with breast cancer and lymphoma who could be followed for at least 20 to 25 years, and we matched them with controls at a ratio of 1 to 1.5. The controls had the same comorbidities (diabetes, hypertension or hyperlipidemia), age and gender. The only difference was that one group had cancer treatment and the other did not.
We followed about 1,500 controls and 800 patients for 25 years. We looked at incidence of heart failure in the cohort of patients who received anthracycline as primary treatment for their cancer.
Healio: What did you find?
Villarraga: From day 1, there was already a diversion in the curves showing the anthracycline group had greater incidence of heart failure than the group that did not receive anthracyclines. We further divided the patients with cancer into a group who did not receive anthracyclines for their cancer. When we compared these patients with controls, we saw the normal rate of heart failure in the community, which is around 3.5%. In our cohort with anthracycline exposure, the rate was between 7% and 8%. So, it was definitely linked to the medication. When we looked at it by dose, we didn’t see a difference. Other research has used a cutoff of 250 300 mg/m2 or 300 mg/m2 as being more cardiotoxic, but here we didn’t see it dependent on dose. It was just exposure or nonexposure.
Healio: Did the correlation between anthracycline exposure and heart failure persist over time?
Villarraga: Yes. The curves continued diverging and separating for 20 years of follow-up.
Healio: How much of a factor were the patients’ comorbidities and risk factors?
Villarraga: We thought initially that the risk factors could be driving it, but the beauty of this project is that patients were matched with controls who had the same diseases. So, it looked at the pure effect of the medication.
Healio: What are the implications of these findings?
Villarraga: Anthracyclines will probably need to continue to be used. The mainstay of cancer treatment, despite the development of new medications or subdrugs of anthracycline, is how we monitor patients. So, how should patients be monitored to avoid the development of heart failure? That’s where cardio-oncology comes in. We have algorithms for these patients. They need an echocardiogram at baseline and, depending on the risk factors, they need to be followed more carefully during and after treatment. They also need to be followed in the survivorship clinic.
We want to get the message to physicians to be more proactive — monitor these patients with echocardiograms and probably blood biomarkers like troponin. The guidelines state that once the patient finishes treatment, they have to be seen by their primary care physician every year. According to their symptoms or lack of symptoms, they have to be guided to diagnostic methods of double-checking how the heart is working.
Healio: What is next in your research on this?
Villarraga: We have many projects going on. One of them has prospectively enrolled about 350 patients with lymphoma. We are studying different imaging biomarkers to predict who will develop heart failure or just cardiac toxicity. Cardiac toxicity is defined as a drop in ejection faction greater than 10%. In this prospective group of patients with lymphoma, we saw changes in a new imaging marker called strain rate.
To evaluate this, we divide the left ventricle into 16 pieces and in each piece measure how it forms, how it stretches and how it contracts in three domains — x, y and z. So, we are physiologically dissecting the heart muscle. We have found that in looking at these patterns, we can predict who is going to develop heart failure or just cardiac toxicity.
For more information:
Hector R. Villarraga, MD, can be reached at Mayo Clinic, 200 First St. SW, Rochester, MN 55905; email: villarraga.hector@mayo.edu.
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