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Published in: Breast Cancer Research 1/2020

01-12-2020 | Breast Cancer | Research article

Long-term risk of ischemic heart disease after adjuvant radiotherapy in breast cancer: results from a large population-based cohort

Authors: Anna-Karin Wennstig, Charlotta Wadsten, Hans Garmo, Irma Fredriksson, Carl Blomqvist, Lars Holmberg, Greger Nilsson, Malin Sund

Published in: Breast Cancer Research | Issue 1/2020

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Abstract

Background

Adjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of ischemic heart disease (IHD). We examined the incidence of IHD in a large population-based cohort of women with BC.

Methods

The Breast Cancer DataBase Sweden (BCBaSe) includes all women diagnosed with BC from 1992 to 2012 (n = 60,217) and age-matched women without a history of BC (n = 300,791) in three Swedish health care regions. Information on comorbidity, educational level, and incidence of IHD was obtained through linkage with population-based registries. The risk of IHD was estimated by Cox proportional hazard regression analyses and cumulative incidence by the Kaplan-Meier method.

Results

Women with BC had a lower risk of IHD compared to women without BC with a hazard ratio (HR) of 0.91 (95% CI 0.88–0.95). When women with left-sided BC were compared to right-sided BC, an increased HR for IHD of 1.09 (95% CI 1.01–1.17) was seen. In women receiving RT, a HR of 1.18 (95% CI 1.06–1.31) was seen in left-sided compared to right-sided BC, and the HRs increased with more extensive lymph node involvement and with the addition of systemic therapy. The cumulative IHD incidence was increased in women receiving left-sided RT compared to right-sided RT, starting from the first years after RT and sustained with longer follow-up.

Conclusions

Women given RT for left-sided BC during 1992 to 2012 had an increased risk of IHD compared to women treated for right-sided BC. These women were treated in the era of three-dimensional conformal RT (3DCRT), and the results emphasize the importance of further developing and implementing RT techniques that lower the cardiac doses, without compromising the beneficial effects of RT.
Literature
1.
go back to reference McGale P, Darby SC, Hall P, Adolfsson J, Bengtsson NO, Bennet AM, et al. Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden. Radiother Oncol. 2011;100(2):167–75.CrossRef McGale P, Darby SC, Hall P, Adolfsson J, Bengtsson NO, Bennet AM, et al. Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden. Radiother Oncol. 2011;100(2):167–75.CrossRef
2.
go back to reference Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987–98.CrossRef Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987–98.CrossRef
3.
go back to reference van den Bogaard VA, Ta BD, van der Schaaf A, Bouma AB, Middag AM, Bantema-Joppe EJ, et al. 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. 2017;35(11):1171–8.CrossRef van den Bogaard VA, Ta BD, van der Schaaf A, Bouma AB, Middag AM, Bantema-Joppe EJ, et al. 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. 2017;35(11):1171–8.CrossRef
4.
go back to reference Harris EE, Correa C, Hwang WT, Liao J, Litt HI, Ferrari VA, et al. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol. 2006;24(25):4100–6.CrossRef Harris EE, Correa C, Hwang WT, Liao J, Litt HI, Ferrari VA, et al. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol. 2006;24(25):4100–6.CrossRef
5.
go back to reference Roychoudhuri R, Robinson D, Putcha V, Cuzick J, Darby S, Moller H. Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study. BMC Cancer. 2007;7:9.CrossRef Roychoudhuri R, Robinson D, Putcha V, Cuzick J, Darby S, Moller H. Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study. BMC Cancer. 2007;7:9.CrossRef
6.
go back to reference Taylor CW, Nisbet A, McGale P, Darby SC. Cardiac exposures in breast cancer radiotherapy: 1950s-1990s. Int J Radiat Oncol Biol Phys. 2007;69(5):1484–95.CrossRef Taylor CW, Nisbet A, McGale P, Darby SC. Cardiac exposures in breast cancer radiotherapy: 1950s-1990s. Int J Radiat Oncol Biol Phys. 2007;69(5):1484–95.CrossRef
7.
go back to reference Nilsson G, Holmberg L, Garmo H, Duvernoy O, Sjogren I, Lagerqvist B, et al. Distribution of coronary artery stenosis after radiation for breast cancer. J Clin Oncol. 2012;30(4):380–6.CrossRef Nilsson G, Holmberg L, Garmo H, Duvernoy O, Sjogren I, Lagerqvist B, et al. Distribution of coronary artery stenosis after radiation for breast cancer. J Clin Oncol. 2012;30(4):380–6.CrossRef
8.
go back to reference Correa CR, Litt HI, Hwang WT, Ferrari VA, Solin LJ, Harris EE. Coronary artery findings after left-sided compared with right-sided radiation treatment for early-stage breast cancer. J Clin Oncol. 2007;25:3031–7.CrossRef Correa CR, Litt HI, Hwang WT, Ferrari VA, Solin LJ, Harris EE. Coronary artery findings after left-sided compared with right-sided radiation treatment for early-stage breast cancer. J Clin Oncol. 2007;25:3031–7.CrossRef
9.
go back to reference Taylor CW, Povall JM, McGale P, Nisbet A, Dodwell D, Smith JT, et al. Cardiac dose from tangential breast cancer radiotherapy in the year 2006. Int J Radiat Oncol Biol Phys. 2007;25(21):3031–7. Taylor CW, Povall JM, McGale P, Nisbet A, Dodwell D, Smith JT, et al. Cardiac dose from tangential breast cancer radiotherapy in the year 2006. Int J Radiat Oncol Biol Phys. 2007;25(21):3031–7.
10.
go back to reference Wennstig AK, Garmo H, Hallstrom P, Nystrom PW, Edlund P, Blomqvist C, et al. Inter-observer variation in delineating the coronary arteries as organs at risk. Radiother Oncol. 2017;122(1):72–8.CrossRef Wennstig AK, Garmo H, Hallstrom P, Nystrom PW, Edlund P, Blomqvist C, et al. Inter-observer variation in delineating the coronary arteries as organs at risk. Radiother Oncol. 2017;122(1):72–8.CrossRef
11.
go back to reference Taylor C, Correa C, Duane FK, Aznar MC, Anderson SJ, Bergh J, et al. 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. 2017;35(15):1641–9.CrossRef Taylor C, Correa C, Duane FK, Aznar MC, Anderson SJ, Bergh J, et al. 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. 2017;35(15):1641–9.CrossRef
12.
go back to reference Goldvaser H, Barnes TA, Seruga B, Cescon DW, Ocana A, Ribnikar D, et al. Toxicity of extended adjuvant therapy with aromatase inhibitors in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2018;110(1):31-9. Goldvaser H, Barnes TA, Seruga B, Cescon DW, Ocana A, Ribnikar D, et al. Toxicity of extended adjuvant therapy with aromatase inhibitors in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2018;110(1):31-9.
13.
go back to reference Khosrow-Khavar F, Filion KB, Al-Qurashi S, Torabi N, Bouganim N, Suissa S, et al. Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol. 2017;28(3):487–96.CrossRef Khosrow-Khavar F, Filion KB, Al-Qurashi S, Torabi N, Bouganim N, Suissa S, et al. Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol. 2017;28(3):487–96.CrossRef
14.
go back to reference Sawyer DB. Anthracyclines and heart failure. N Engl J Med. 2013;368(12):1154–6.CrossRef Sawyer DB. Anthracyclines and heart failure. N Engl J Med. 2013;368(12):1154–6.CrossRef
15.
go back to reference Ryberg M, Nielsen D, Cortese G, Nielsen G, Skovsgaard T, Andersen PK. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J Natl Cancer Inst. 2008;100(15):1058–67.CrossRef Ryberg M, Nielsen D, Cortese G, Nielsen G, Skovsgaard T, Andersen PK. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J Natl Cancer Inst. 2008;100(15):1058–67.CrossRef
16.
go back to reference Rehammar JC, Jensen MB, McGale P, Lorenzen EL, Taylor C, Darby SC, et al. Risk of heart disease in relation to radiotherapy and chemotherapy with anthracyclines among 19,464 breast cancer patients in Denmark, 1977-2005. Radiother Oncol. 2017;123(2):299–305.CrossRef Rehammar JC, Jensen MB, McGale P, Lorenzen EL, Taylor C, Darby SC, et al. Risk of heart disease in relation to radiotherapy and chemotherapy with anthracyclines among 19,464 breast cancer patients in Denmark, 1977-2005. Radiother Oncol. 2017;123(2):299–305.CrossRef
17.
go back to reference Boekel NB, Jacobse JN, Schaapveld M, Hooning MJ, Gietema JA, Duane FK, et al. Cardiovascular disease incidence after internal mammary chain irradiation and anthracycline-based chemotherapy for breast cancer. Br J Cancer. 2018;119(4):408–18.CrossRef Boekel NB, Jacobse JN, Schaapveld M, Hooning MJ, Gietema JA, Duane FK, et al. Cardiovascular disease incidence after internal mammary chain irradiation and anthracycline-based chemotherapy for breast cancer. Br J Cancer. 2018;119(4):408–18.CrossRef
18.
go back to reference Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.CrossRef Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.CrossRef
20.
go back to reference Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.CrossRef Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.CrossRef
22.
go back to reference Jagsi R, Griffith KA, Koelling T, Roberts R, Pierce LJ. Rates of myocardial infarction and coronary artery disease and risk factors in patients treated with radiation therapy for early-stage breast cancer. Cancer. 2007;109(4):650–7.CrossRef Jagsi R, Griffith KA, Koelling T, Roberts R, Pierce LJ. Rates of myocardial infarction and coronary artery disease and risk factors in patients treated with radiation therapy for early-stage breast cancer. Cancer. 2007;109(4):650–7.CrossRef
23.
go back to reference Lamont EB, Christakis NA, Lauderdale DS. Favorable cardiac risk among elderly breast carcinoma survivors. Cancer. 2003;98(1):2–10.CrossRef Lamont EB, Christakis NA, Lauderdale DS. Favorable cardiac risk among elderly breast carcinoma survivors. Cancer. 2003;98(1):2–10.CrossRef
24.
go back to reference Damiani G, Basso D, Acampora A, Bianchi CB, Silvestrini G, Frisicale EM, et al. The impact of level of education on adherence to breast and cervical cancer screening: evidence from a systematic review and meta-analysis. Prev Med. 2015;81:281–9.CrossRef Damiani G, Basso D, Acampora A, Bianchi CB, Silvestrini G, Frisicale EM, et al. The impact of level of education on adherence to breast and cervical cancer screening: evidence from a systematic review and meta-analysis. Prev Med. 2015;81:281–9.CrossRef
25.
go back to reference Elshof LE, Schmidt MK, Rutgers EJT, van Leeuwen FE, Wesseling J, Schaapveld M. Cause-specific mortality in a population-based cohort of 9799 women treated for ductal carcinoma in situ. Ann Surg. 2018;267(5):952–8.CrossRef Elshof LE, Schmidt MK, Rutgers EJT, van Leeuwen FE, Wesseling J, Schaapveld M. Cause-specific mortality in a population-based cohort of 9799 women treated for ductal carcinoma in situ. Ann Surg. 2018;267(5):952–8.CrossRef
26.
go back to reference Nilsson G, Witt Nystrom P, Isacsson U, Garmo H, Duvernoy O, Sjogren I, et al. Radiation dose distribution in coronary arteries in breast cancer radiotherapy. Acta Oncol. 2016;55(8):959–63.CrossRef Nilsson G, Witt Nystrom P, Isacsson U, Garmo H, Duvernoy O, Sjogren I, et al. Radiation dose distribution in coronary arteries in breast cancer radiotherapy. Acta Oncol. 2016;55(8):959–63.CrossRef
27.
go back to reference Wennstig AK, Garmo H, Isacsson U, Gagliardi G, Rintela N, Lagerqvist B, et al. The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors. Radiat Oncol. 2019;14(1):40.CrossRef Wennstig AK, Garmo H, Isacsson U, Gagliardi G, Rintela N, Lagerqvist B, et al. The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors. Radiat Oncol. 2019;14(1):40.CrossRef
28.
go back to reference Lancet. 2005;365(9472):Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials, 1687–717. Lancet. 2005;365(9472):Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials, 1687–717.
29.
go back to reference Amir E, Seruga B, Niraula S, Carlsson L, Ocana A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299–309.CrossRef Amir E, Seruga B, Niraula S, Carlsson L, Ocana A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299–309.CrossRef
Metadata
Title
Long-term risk of ischemic heart disease after adjuvant radiotherapy in breast cancer: results from a large population-based cohort
Authors
Anna-Karin Wennstig
Charlotta Wadsten
Hans Garmo
Irma Fredriksson
Carl Blomqvist
Lars Holmberg
Greger Nilsson
Malin Sund
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2020
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-020-1249-2

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