Abstract
Purpose
To study the late cardiac toxicity of breast radiation therapy (RT) in Asian women.
Methods
Female breast cancer patients in Korea who underwent breast conservation surgery followed by RT from 1990–2012 were identified from two large registries at institution and population levels. Cumulative incidences of acute coronary events (ACE) or cardiac mortality were estimated in relation to the laterality of breast cancer using a competing risks analysis.
Results
In an analysis of 2577 women from a single institution, 3.7% were obese (body mass index ≥30), and 3.4% were ever-smokers. Patients with a history of hypertension, diabetes, or coronary artery disease were 17.5, 5.7, and 2.8%, respectively. The mean heart doses were 6.2 and 1.5 Gy for left- and right-sided tumors, respectively. With a median follow-up of 7 (range 1–23) years, the overall and breast cancer-specific survivals at 10 years were 94.9 and 96.5%, respectively. The 10-year cumulative incidence of ACE was 2.96%. The mean time to ACE was 5.2 ± 3.9 years (range 1–17). There was no clinically relevant difference in rates of ACE between left-sided and right-sided patients, with an adjusted hazard ratio of 1.16 (CI 0.59–2.29). An analysis of 24,235 women in a nationwide registry validated these negative findings with respect to cardiac mortality, with an adjusted hazard ratio of 1.52 (CI 0.37–6.25). Increasing age, a higher body mass index, and a history of hypertension or ischemic heart disease were identified as risk factors.
Conclusions
Our findings reassure that excess risk from breast RT may be small in healthy women, most of who not smoke, weigh less, and have fewer risk factors. A validation using a larger data set of National Health Insurance Corporation is ongoing.
Similar content being viewed by others
References
Darby SC, Ewertz M, McGale P et al (2013) Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 368(11):987–998. doi:10.1056/NEJMoa1209825
van den Bogaard VA, Ta BD, van der Schaaf A et al (2017) Validation and modification of a prediction model for acute cardiac events in patients with breast cancer treated with radiotherapy based on three-dimensional dose distributions to cardiac substructures. J Clin Oncol. doi:10.1200/JCO.2016.69.8480
Taylor CW, Kirby AM (2015) Cardiac side-effects from breast cancer radiotherapy. Clin Oncol (R Coll Radiol) 27(11):621–629. doi:10.1016/j.clon.2015.06.007
Health status: causes of mortality - OECD. Stat. (2017) Retrieved 2 Feb 2017, from http://stats.oecd.org/Index.aspx?QueryId=30115#
Kontis V, Bennett JE, Mathers CD et al (2017) Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble. Lancet. doi:10.1016/S0140-6736(16)32381-9
Ahn SH, Son BH, Kim SW et al (2007) Poor outcome of hormone receptor-positive breast cancer at very young age is due to tamoxifen resistance: nationwide survival data in Korea—a report from the Korean Breast Cancer Society. J Clin Oncol 25(17):2360–2368. doi:10.1200/JCO.2006.10.3754
Jeong K, Shim SJ, You SH et al (2009) A study of the radiotherapy techniques for the breast including internal mammary lymph nodes. Radiat Oncol J 27(1):35–41. doi:10.3857/jkstro.2009.27.1.35
Suh CO, Shin HS, Cho JH et al (2004) The 1998, 1999 patterns of care study for breast irradiation after breast-conserving surgery in Korea. J Korean Soc Ther Radiol Oncol 22(3):192–199
Gray RJ (1988) A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16:1141–1154
Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509
Cohen GR, Yang SY (1994) Mid-P confidence intervals for the Poisson expectation. Stat Med 13(21):2189–2203
Kim Z, Min SY, Yoon CS et al (2014) The basic facts of korean breast cancer in 2011: results of a nationwide survey and breast cancer registry database. J Breast Cancer 17(2):99–106. doi:10.4048/jbc.2014.17.2.99
Bradshaw PT, Stevens J, Khankari N et al (2016) Cardiovascular disease mortality among breast cancer survivors. Epidemiology 27(1):6–13. doi:10.1097/EDE.0000000000000394
Ministry of Health and Welfare, Korea National Health and Nutrition Examination Survey (2017) Retrieved 2 Feb 2017, from http://kosis.kr/eng/statisticsList/statisticsList_01List.jsp?vwcd=MT_ETITLE&parentId=D#SubCont
Taylor C, Correa C, Duane FK et al (2017) Estimating the Risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials. J Clin Oncol. doi:10.1200/JCO.2016.72.0722
Khera AV, Emdin CA, Drake I et al (2016) Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med 375(24):2349–2358. doi:10.1056/NEJMoa1605086
Lloyd-Jones DM, Hong Y, Labarthe D et al (2010) Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond. Circulation 121(4):586–613. doi:10.1161/CIRCULATIONAHA.109.192703
Caram ME, Guo C, Leja M et al (2015) Doxorubicin-induced cardiac dysfunction in unselected patients with a history of early-stage breast cancer. Breast Cancer Res Treat 152(1):163–172. doi:10.1007/s10549-015-3454-8
Ayres LR, de Almeida Campos MS, de Oliveira Gozzo T et al (2015) Trastuzumab induced cardiotoxicity in HER2 positive breast cancer patients attended in a tertiary hospital. Int J Clin Pharm 37(2):365–372. doi:10.1007/s11096-015-0070-y
Playdon MC, Bracken MB, Sanft TB et al (2015) Weight gain after breast cancer diagnosis and all-cause mortality: systematic review and meta-analysis. J Natl Cancer Inst 107(12):djv275. doi:10.1093/jnci/djv275
Guenancia C, Lefebvre A, Cardinale D et al (2016) Obesity as a risk factor for anthracyclines and trastuzumab cardiotoxicity in breast cancer: a systematic review and meta-analysis. J Clin Oncol 34(26):3157–3165. doi:10.1200/JCO.2016.67.4846
McGale P, Darby SC, Hall P et al (2011) Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden. Radiother Oncol 100(2):167–175. doi:10.1016/j.radonc.2011.06.016
Boero IJ, Paravati AJ, Triplett DP et al (2016) Modern radiation therapy and cardiac outcomes in breast cancer. Int J Radiat Oncol Biol Phys 94(4):700–708. doi:10.1016/j.ijrobp.2015.12.018
Harris EE, Correa C, Hwang WT et al (2006) Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol 24(25):4100–4106. doi:10.1200/JCO.2005.05.1037
Rutter CE, Chagpar AB, Evans SB (2014) Breast cancer laterality does not influence survival in a large modern cohort: implications for radiation-related cardiac mortality. Int J Radiat Oncol Biol Phys 90(2):329–334. doi:10.1016/j.ijrobp.2014.06.030
Giordano SH, Kuo YF, Freeman JL et al (2005) Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst 97(6):419–424. doi:10.1093/jnci/dji067
Luepker RV (2016) Falling coronary heart disease rates: a better explanation? Circulation 133(1):8–11. doi:10.1161/CIRCULATIONAHA.115.019862
Lopez-Jimenez F, Batsis JA, Roger VL et al (2009) Trends in 10-year predicted risk of cardiovascular disease in the United States, 1976 to 2004. Circ Cardiovasc Qual Outcomes 2(5):443–450. doi:10.1161/CIRCOUTCOMES.108.847202
Chang JS, Park W, Kim YB et al (2013) Long-term survival outcomes following internal mammary node irradiation in stage II–III breast cancer: results of a large retrospective study with 12-year follow-up. Int J Radiat Oncol Biol Phys 86(5):867–872. doi:10.1016/j.ijrobp.2013.02.037
Kim KH, Noh JM, Kim YB et al (2015) Does internal mammary node irradiation affect treatment outcome in clinical stage II–III breast cancer patients receiving neoadjuv ant chemotherapy? Breast Cancer Res Treat 152(3):589–599. doi:10.1007/s10549-015-3505-1
Poortmans PM, Collette S, Kirkove C et al (2015) Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med 373(4):317–327. doi:10.1056/NEJMoa1415369
Whelan TJ, Olivotto IA, Parulekar WR et al (2015) Regional nodal irradiation in early-stage breast cancer. N Engl J Med 373(4):307–316. doi:10.1056/NEJMoa1415340
Acknowledgements
This article was supported by the Korean Breast Cancer Society.
Author information
Authors and Affiliations
Consortia
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Chang, J.S., Ko, B.K., Bae, J.W. et al. Radiation-related heart disease after breast cancer radiation therapy in Korean women. Breast Cancer Res Treat 166, 249–257 (2017). https://doi.org/10.1007/s10549-017-4398-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-017-4398-y