Increased risk of CV death, HF and AF in breast cancer survivors
Cardiovascular outcomes in breast cancer survivors: a systematic review and meta-analysisLiterature - Galimzhanov A, Istanbuly S, Tun HN, et al. - Eur J Prev Cardiol. 2023 Jul 27;zwad243. [Online ahead of print]. doi: 10.1093/eurjpc/zwad243.
Introduction and methods
CVD has been recognized as an important cause of morbidity and mortality in breast cancer survivors [1-2]. CVD and breast cancer share risk factors, have common pathophysiological pathways, and many therapies that are used to treat breast cancer have toxic effects on the cardiovascular system [3-7]. There is increased literature that reports on cardiovascular outcomes in breast cancer survivors compared with the general cancer-free population. The relationship between breast cancer and cause-specific CVD is complex and remains incompletely understood. There is a need to quantify the future risk of CVD in breast cancer survivors for appropriate risk stratification.
Aim of the study
The aim of this meta-analysis was to determine the relative risk of cause-specific CVD in breast cancer patients compared with the general matched cancer-free population. Moreover, this meta-analysis also aimed to determine the absolute risk of cardiovascular outcomes in breast cancer survivors.
This was a systematic review and meta-analysis of studies published in PubMed, Web of Science, and Scopus before 23 March, 2023. In addition, studies were also retrieved from registries, journal websites, Biomed Explorer, Dimensions, and international meeting proceedings. In order to compare the risk of CV outcomes in breast cancer survivors and in the general population, 26 articles (n=836,301 patients) were included that reported on CV outcomes in patients with breast cancer at different stages as compared to those in the general matched cancer-free population. In order to estimate the incidence rate of CV outcomes in patients with breast cancer, 116 articles (n=2,111,882 patients) were included that provided original data on the incidence of CV outcome in breast cancer patients. Treatment strategy for breast cancer patients has been changed considerably after 1990. Therefore, studies before 1990 were excluded in this analysis. Follow-up time ranged from 1 to 11.8 years. The matching criteria varied considerably between studies, but all studies were matched for age, and in most reports the study arms were matched or statistical analyses were adjusted for race, socioeconomic status, comorbidities, and common CV risk factors.
The outcomes were CV death, HF, CAD, MI, any stroke, ischemic or hemorrhagic stroke, and AF. The same outcome definitions of the primary studies were used.
Risk of CV outcomes
- Patients with breast cancer had a higher risk of cardiovascular death compared with matched cancer-free controls during 0 to 5 years following breast cancer diagnosis (HR: 1.09; 95%CI: 1.07-1.11). There was no statistically significant difference in the risk of cardiovascular death between breast cancer survivors 8 to 11 years after breast cancer diagnosis and matched cancer-free controls (HR: 1.23; 95%CI: 0.99-1.52).
- Breast cancer survivors had a higher risk of HF as compared to matched healthy non-cancer controls during a period of 1 to2 years (HR: 1.21; 95%CI: 1.1-1.33), 2 to5 years (HR: 1.22; 95%CI: 1.11-1.33), and 5 to10 years (HR: 1.19; 95%CI: 1.1-1.29) after breast cancer diagnosis.
- Breast cancer survivors had an increased risk of AF compared to cancer-free controls for 0-3 years after breast cancer diagnosis (up to 3 months after diagnosis, HR: 1.64; 95%CI: 1.18-2.26; up to 3 months to 3 years after diagnosis, HR: 1.13; 95%CI: 1.05-1.21). There was no data available for >3 years post-diagnosis.
- The risk of CAD between breast cancer survivors and matched cancer-free controls was not different between 0 to 5 years and 5 to 8 years following follow-up (HR: 0.97; 95%CI: 0.90-1.02; and HR: 1.01: 95%CI: 0.92-1.10, respectively).
- Breast cancer survivors had a comparable risk of MI compared with matched cancer-free controls.
- Breast cancer survivors had a comparable risk of any stroke during 8 years following diagnosis compared with matched cancer-free controls (HR: 0.99; 95%CI: 0.83-1.19) or ischemic stroke (HR: 1.19; 95%CI: 0.94-1.51).
Incidence of CV outcomes
- The incidence of cardiovascular death, HF, and AF in breast cancer patients was 1.73 (95%CI: 1.18-2.53), 4.44 (95%CI: 3.33-5.92), and 12.95 (95%CI: 12.60-13.31) per 1000 persons years of follow-up, respectively.
- The incidence of CAD, MI, stroke, and ischemic stroke in breast cancer patients was 4.29 (95%CI: 3.09-5.94), 1.98 (95%CI: 1.24-3.16), 4.33 (95%CI: 2.97-6.30), and 2.64 (95%CI: 1.79-3.92) per 1000 person years of follow-up, respectively.
This meta-analysis showed that breast cancer was associated with an increased risk of cardiovascular death, HF, and AF, but not CAD, MI, or (ischemic) stroke. The increased risk for HF in breast cancer survivors persisted to 10 years after breast cancer diagnosis. Moreover, there was a time-dependent increase in the risk of AF in breast cancer survivors, with a relative higher risk in the first 3 months after diagnosis. These data highlight the importance to carefully asses breast cancer survivors for their cardiovascular risk factor profile and future CV risk, and to monitor the cardiovascular function long-term in these patients.