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Congestive HF risk elevated in patients with breast cancer, lymphoma
ORLANDO, Fla. — Patients with breast cancer or lymphoma have a threefold elevated risk for congestive HF compared with adults without a history of cancer, according to new data presented at the American College of Cardiology Scientific Session.
Carolyn M. Larsen, MD, assistant professor of medicine at Mayo Clinic in Scottsdale, Arizona, and colleagues conducted a retrospective study of participants from the Rochester Epidemiology Project, matching 900 patients with breast cancer or lymphoma with 1,500 controls with no cancer history and followed them for new-onset congestive HF from 1985 to 2010 (median, 8.5 years).
“There was a gap in the existing knowledge of the long-term cardiovascular risk associated with anthracycline-based chemotherapy, which many patients with breast cancer and lymphoma receive,” Larsen told Cardiology Today. “This is a clinically important area because understanding the magnitude and duration of cardiovascular risk that breast cancer and lymphoma patients and survivors face is an essential step in developing guidelines for long-term clinical follow-up and surveillance imaging in this group of patients.”
Compared with those without a history of cancer, patients with breast cancer or lymphoma had elevated risk for new-onset congestive HF (HR = 3.65; 95% CI, 2.55-5.24). The curves began to separate at 1 year and were still separate at 20 years, Larsen and colleagues found.
After adjustment for CAD, hypertension, hyperlipidemia, obesity, sex and radiation therapy, the researchers identified the following as independent risk factors for congestive HF in patients with breast cancer or lymphoma:
- cumulative doxorubicin dose of at least 300 mg/m2 (HR = 2.34; 95% CI, 1.34-4.07);
- age at diagnosis (HR for age 80 years vs. 60-69 years = 3.06; 95% CI, 1.23-7.31); and
- diabetes (HR = 2.39; 95% CI, 1.24-4.59).
“While only a minority of breast cancer and lymphoma patients and survivors develop heart failure, our study demonstrates that 20 years after cancer diagnosis, they remain at increased risk of heart failure,” Larsen said in an interview. “Clinically, this is important to understand because it highlights the importance of ongoing surveillance such as assessing for signs and symptoms of heart failure at clinical follow-up visits in cancer patients and survivors.”
The findings on doxorubicin dose and diabetes are “important as it may help clinicians identify which cancer patients are at highest risk of heart failure and may benefit from closer follow-up,” she said.
Although the study did not answer the question of what doctors can do to mitigate the risk for congestive HF in patients with cancer, “we believe it is important that doctors screen for and help their patients in modifying coexisting cardiovascular risk factors including diabetes, hypertension, obesity, smoking and sedentary lifestyle to reduce their lifetime risk of cardiovascular disease, including heart failure,” Larsen said. “Cancer treatment can be lifesaving and we do not want to discourage treatment. We do want to make sure we are helping cancer patients and survivors care for their hearts during and after cancer therapy.” – by Erik Swain
Reference:
Larsen CM, et al. Abstract 1105-066. Presented at: American College of Cardiology Scientific Session; March 10-12, 2018; Orlando, Fla.
Disclosure: Larsen reports no relevant financial disclosures.
Perspective
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Right now, there are no long-term cohorts to follow adult survivors of breast cancer and lymphoma for adverse CV effects from anthracyclines; this is in contrast to pediatric cancer survivors, where we know how prevalent conditions such as HF, hypertension and diabetes are in these patients. To my knowledge, this [new research] is [from] one of the largest retrospective studies of HF in adult survivors of breast cancer and lymphoma, and its findings are consistent with others indicating increased risk for HF associated with anthracycline treatment over many years of survivorship. This is as good as it will get for the data at this point, because we do not prospectively follow these patients.
These data provide a huge rationale for trials. If you apply for a grant to study CV events in the adult survivor population, you are asked, how do you know that the CV risk is higher or that it is related to cancer treatments given many years ago? While this study was not prospective and could be biased, it shows a strong signal that CVD, particularly HF, is very relevant in these patients. Further evidence was provided by another study of patients in Olmstead County, Minnesota, which found that patients who underwent radiation treatment for breast cancer had elevated risk for HF with preserved ejection fraction (Saiki H, et al. Circulation. 2017;doi: 10.1161/CIRCULATIONAHA.116.025434). We are learning that HF risk in these patients is most likely related to anthracyclines, but there may also be risks from radiation, and we may be dealing with different HF phenotypes. In a recent report from Danish registries, preexisting CV risk factors were shown to increase HF risk among 2,508 survivors of non-Hodgkin lymphoma with a hazard risk of 2.86 when two or more CV risk factors were present (Salz T, et al. J Clin Oncol. 2017;doi:10.1200/JCO.2017.72.4211).
The American Society of Clinical Oncology clinical guideline on cardiac dysfunction published in 2017 as well as the National Comprehensive Cancer Network survivorship guideline published in 2015 acknowledge this risk and introduced the concept of doing a single echocardiogram after treatment with anthracyclines in patients with CV risk factors. Unfortunately, that is still not regular practice in the oncology community. There is a unique opportunity in the oncology professional societies to introduce awareness of HF risk in the survivorship care plan and to acknowledge that while we don’t have randomized trial data, we know that these patients develop HF later, and we must recognize that they are at risk. Typical randomized trials do not have long enough follow-up to detect this. But we should emphasize that an assessment of CV risk factors and a follow-up echocardiogram should be part of a survivorship plan. Oncologists need to initiate this conversation with the patient, from the time of diagnosis, through the balance of his or her life, which is when survivorship starts. Assessment of CV risk and cardiac function need to happen after treatment, not only before. There many unknowns, but we cannot even talk about this issue if patients are never even sent for an echocardiogram after completion of therapy.
Aggressive treatment of breast cancer and lymphoma is necessary, as recurrence rates in the first few years are high. We should never select the inferior oncology treatment based on possible HF risk years later. However, we have to recognize that approximately 5% to 10% of these patients will have reduced EF over time. We know from the HF literature that if we start treating patients when their EF is 40%, a number of them will be saved, but if we don’t detect HF until the EF is 20% and has been so for 6 months or more, the HF is irreversible. These patients are at much higher risk for developing HF than the general population.