International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationCardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors
Introduction
Breast cancer (BC) survival rates have substantially improved by earlier diagnosis and more effective treatment, such as more effective systemic therapy and more precise radiation therapy (RT). Radiation therapy reduces the risk of local recurrence and overall mortality in BC patients (1). However, it may expose the heart to radiation, which can increase the risks of cardiovascular disease (CVD) 2, 3, 4, 5, 6. Over the past 2 decades, changes in RT techniques likely reduced the radiation exposure of the heart. Yet only a few studies have assessed CVD morbidity 4, 6 and mortality 3, 8, 9, 10 among BC patients treated after the 1980s. These studies still showed increased risks of cardiovascular morbidity (ischemic heart disease [IHD] 4, 6, valvular heart disease [VHD] [6]) and mixed results on cardiovascular mortality 3, 8, 9, 10. However, the heart is mostly exposed from internal mammary chain (IMC) irradiation 5, 10, 11. It remains unclear whether risks are also increased after tangential breast irradiation alone.
Current chemotherapy regimens may also increase CVD incidence. In children, anthracycline-containing chemotherapy is associated with congestive heart failure (CHF) in a dose-dependent way 12, 13. However, few large studies on long-term CVD risks in BC survivors treated with anthracyclines were performed 14, 15.
With the growing number of BC survivors, it is important to better understand the risks associated with contemporary BC treatment. Therefore, we conducted a large, population-based study on CVD in BC survivors treated in 1989 or later.
Section snippets
Data collection procedures
A cohort comprising 72,045 female patients diagnosed with stage I to III BC as their first malignancy between 1989 and 2005, aged <75 years, was selected from the Netherlands Cancer Registry (NCR). The NCR has nationwide coverage since 1989 (16) and performs annual linkage with the population-based municipal personal records database for date of death. For both initial and subsequent malignancies, NCR provided dates of birth, diagnosis, and death, topography, morphology, stage, type of surgery,
Results
In total, 70,209 patients were available for analysis (Table 1). Characteristics did not differ between patients diagnosed with left- and right-sided BC. Median follow-up was 9 years (range, 0-21 years). During this time, 7435 patients experienced at least 1 cardiovascular event, including 2411 cardiovascular deaths, 5226 hospital admissions for CVD, and 2331 cardiovascular surgical interventions (Table E1; available online at www.redjournal.org).
Discussion
In this large, population-based cohort of BC patients we found that, compared with the general population, BC patients have a slightly lower CVD mortality risk. However, death due to VHD was more frequent. Moreover, left-sided RT after mastectomy increased the risk of any cardiovascular event, IHD, CHF, and VHD, compared with both surgery alone and right-sided RT. This increase seemed to be caused by IMC field as well as chest wall irradiation. The CVD risk after both left- and right-sided RT
References (24)
- et al.
Cardiotoxic effects of tangential breast irradiation in early breast cancer patients: The role of irradiated heart volume
Int J Radiat Oncol Biol Phys
(2007) - et al.
Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden
Radiother Oncol
(2011) - et al.
Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: Prospective cohort study of about 300,000 women in US SEER cancer registries
Lancet Oncol
(2005) - et al.
Cardiac dose estimates from Danish and Swedish breast cancer radiotherapy during 1977-2001
Radiother Oncol
(2011) - et al.
Exposure of the heart in breast cancer radiation therapy: A systematic review of heart doses published during 2003 to 2013
Int J Radiat Oncol Biol Phys
(2015) - et al.
Cause-specific mortality in long-term survivors of breast cancer: A 25-year follow-up study
Int J Radiat Oncol Biol Phys
(2006) - et al.
Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials
Lancet
(2011) - et al.
Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials
Lancet
(2005) - et al.
Risk of ischemic heart disease in women after radiotherapy for breast cancer
N Engl J Med
(2013) - et al.
Long-term risk of cardiovascular disease in 10-year survivors of breast cancer
J Natl Cancer Inst
(2007)
Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer
Br J Cancer
Chemotherapy and cardiotoxicity in older breast cancer patients: A population-based study
J Clin Oncol
Cited by (88)
High-Dose Ionizing Radiation Accelerates Atherosclerotic Plaque Progression by Regulating P38/NCOA4-Mediated Ferritinophagy/Ferroptosis of Endothelial Cells
2023, International Journal of Radiation Oncology Biology PhysicsExposure of the heart and cardiac valves in women irradiated for breast cancer 1970–2009
2022, Clinical and Translational Radiation OncologyNuclear medicine imaging methods of radiation-induced cardiotoxicity
2022, Seminars in Nuclear Medicine
This study was supported by Dutch Cancer Society grant NKI 2008-3994.
M.S. and J.A.G. contributed equally to this work.
B.M.P.A. and F.E.v.L. contributed equally to this work.
Conflict of interest: none.