Breast cancer patients showed increased long-term risk of atrial fibrillation (AF), with a short-term risk for younger women as well, a population-based Danish study indicated.
Women younger than age 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), according to Maria D’Souza, MD, of Copenhagen University Hospital Herlev-Gentofte in Hellerup, Denmark, and colleagues.
The association differed significantly between age groups and follow-up time periods. Among patients older than age 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), the authors reported online in HeartRhythm.
“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,” noted D’Souza. “Ultimately, earlier treatment may result in better stroke prevention.”
In an accompanying editorial, Ankur Karnik, MD, of Boston University School of Medicine, and coauthors 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.”
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.
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.
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.
D’Souza and coauthors 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.”
The relative increase in risk in the youngest (<60 years) 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.
Editorialists wrote 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.”
Likewise, the study authors suggested that the comparatively higher mortality rate in breast cancer patients may have caused underestimation of their AF risk. Another limitation was the potential for residual confounding due to lack of information on the breast cancer patients’ individual stage, cancer treatments, and prognosis.
This study was funded by the Danish Heart Foundation, Copenhagen, Denmark and the VELUX Foundations, Copenhagen, Denmark.
D’Souza, Madelaire, and Smedegaard disclosed receiving grants from the Danish Heart Foundation. In addition, D’Souza, Fosbøl, Smedegaard, and Torp-Pedersen disclosed various grants/personal fees. Other authors reported no conflicts of interest.