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Breast Cancer Patients Face Higher Long-Term Afib Risk (CME/CE)

Action Points

  • In this large study, women with breast cancer had increased risk of atrial fibrillation (AF): For those ages <60, breast cancer was associated with incidence of AF during the first 6 months, and from 6 months to 3 years. For women ages >60, breast cancer was associated with incidence of AF from 6 months to 3 years, but not associated with increased incidence in the first 6 months post-diagnosis.
  • Note that the clinical significance of this study is unclear, but physicians should be aware that women with breast cancer may have a lower threshold for AF.

CME Author: Vicki Brower

Study Authors: Marie D’Souza, Laerke Smedegaard, et al.

Target Audience and Goal Statement:

Oncologists, cardiologists, internists, and family medicine specialists

The goal of the study was to determine the long-term incidence of atrial fibrillation (AF) in women with breast cancer.

Questions Addressed:

  • What is the long- and short-term incidence of atrial fibrillation (AF) in women with breast cancer as compared with the general population?
  • Do women with breast cancer have a higher incidence of AF as compared with the general population, and if so, might it be because of systemic inflammation produced by the cancer itself and/or treatments?

Study Synopsis and Perspective:

A population-based Danish study found that breast cancer was associated with incident AF, and this association differed according to age group and follow-up time periods.

Women ages <60 were more than twice as likely to have AF during the first 6 months after cancer diagnosis (HR 2.10, 95% CI 1.25-3.44), and risk was increased by 80% from 6 months to 3 years (HR 1.80, 95% CI 1.38-2.35), as compared with the general population, according to Maria D'Souza, MD, of Copenhagen University Hospital Herlev-Gentofte in Hellerup, Denmark, and colleagues.

Among patients ages >60, the incidence of AF was not elevated during the first 6 months after their breast cancer diagnosis (HR 1.13, 95% CI 0.95-1.34), but was increased from 6 months to 3 years after diagnosis (HR 1.14, 95% CI 1.05–1.25), also as compared with the general population, the researchers reported in HeartRhythm.

For the study, investigators used nationwide registries in Denmark to estimate the long-term incidence of AF in 74,155 patients (average age 62) diagnosed with breast cancer from 1998 to 2015. This group was compared with 222,465 age- and sex-matched individuals from the general population in a three-to-one ratio. Comorbidities and pharmacological treatment at baseline were similarly distributed between groups. Long-term incidence of AF was estimated using cumulative incidence curves and multivariable Cox regression models.

Also, several comorbidities known to increase risk of AF in the general population had similar associations in the study population:

  • Hypertension: HR 1.38 (95% CI 1.27-1.50)
  • Ischemic heart disease: HR 1.35 (95% CI 1.16-1.56)
  • Heart failure: HR 1.71 (95% CI 1.36-2.14)
  • Chronic kidney disease: HR 1.46 (95% CI 1.05-2.05)
  • Peripheral arterial disease: HR 1.80 (95% CI 1.38-2.36)
  • Chronic obstructive pulmonary disease: HR 1.86 (95% CI 1.58-2.20)
  • Chronic liver disease: HR 1.65 (95% CI 1.02-2.65)

Diabetes and thyroid disease were not associated with an increased risk of AF.

D’Souza and colleagues noted “an important angle to the increased incidence of AF; we observed a higher relative risk of AF in the youngest patients (compared with the background population) but found that the oldest patients had the highest absolute risk of developing AF.”

D’Souza’s group suggested that both cancer-induced systemic inflammation and side effects of cancer treatment may contribute to an increased risk of AF.

The relative increase in risk in the youngest (ages <60) patients might be due to "[age-related] differences in treatment modalities, with younger patients receiving more aggressive and cardiotoxic treatment than do older patients," they noted. They urged further study to clarify the role of systemic inflammation, particularly that due to conventional treatments, including radiotherapy, anthracycline, trastuzumab [Herceptin], and aromatase inhibitors.

Source References:

HeartRhythm 2019; DOI:10.1016/j.hrthm.2018.10.017

Editorial: HeartRhythm 2019; DOI:10.1016/j.hrthm.2018.11.016

Study Highlights: Explanation of Findings

Breast cancer patients showed an increased long-term risk of AF, with a risk of almost double for patients ages <60, compared with the background population both short- and long-term, whereas older women (ages >60) had similar short-term and marginally increased long-term incidence, compared with the same population.

Younger patients had a higher relative risk of AF, and older patients had the highest absolute risk of AF, according to this population-based Danish retrospective cohort study.

The researchers observed that patients with breast cancer “may have a lower threshold” for developing AF because breast cancer and its treatment induces inflammation, a known risk factor for AF. They also noted that certain breast cancer treatments are linked with heart failure, “and AF may serve as a marker for these cardiotoxic side-effects.”

While information on an association between breast cancer and AF is scarce, there is extant reporting on increased incidence of AF in women with breast cancer, and also on increased short term (<3 months) and neutral long-term risks of AF in cancer in general.

“Our findings should encourage doctors to focus on the risk of AF in patients with recent breast cancer in order to diagnose and treat as early as possible, and researchers to search for increased risk of AF looking at the cancer itself, treatment, genetic predisposition, and shared lifestyle risk factors,” the authors noted. “Ultimately, earlier treatment may result in better stroke prevention.” .

In an accompanying editorial, Ankur Karnik, MD, of Boston University School of Medicine, and colleagues wrote that while the study “supports further research into the potentially bidirectional relationship between cancer and AF … [its] clinical significance is uncertain.”

“Ultimately, the cumulative incidence at 3 years was low and similar for women with and without breast cancer (approximately 0.4% vs 0.2% before 60 years and 2.2% vs 2.4% after 60 years). Broad-based monitoring for AF in women with breast cancer is therefore not warranted at this time,” they wrote.

The editorialists also noted that the results must be considered in light of several factors. These included that “the 3 year follow-up may be too short a time for the cardiotoxic effects of breast cancer treatment to fully manifest; that analyses did not account for unmeasured confounding from body mass index … or for competing risk of death — three-year mortality risk was larger than the risk of AF in both groups.”

They also noted that obesity is a common risk factor for both breast cancer and AF, and that “inflammation may be a common process that increases risk for both conditions.” Ultimately, for the general population and breast cancer patients, the cumulative incidence at 3 years was low and similar in both populations.

Thus they stated that “broad-based monitoring for AF is therefore not warranted at this time.”

The editorialists also described how breast cancer treatment may contribute to AF “indirectly.” Ionizing radiation increases the risk of heart failure and ischemic heart disease in a dose-dependent fashion, both of which are risk factors for AF. Heart failure may also result from chemotherapy, with added hypertension. Increased medical visits may also increase AF detection.

The results are generalizable to women of European ancestry, the editorialists and authors noted. Study limitations included the fact that the comparatively higher mortality rate in breast cancer patients may have caused underestimation of their AF risks. Also, there was the potential for residual confounding due to lack of information on the breast cancer patients’ individual stage, cancer treatments, and prognosis.

  • Reviewed by
    Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco
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