Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors

Naomi B Boekel, Michael Schaapveld, Jourik A Gietema, Nicola S Russell, Philip Poortmans, Jacqueline C M Theuws, Dominic A X Schinagl, Derek H F Rietveld, Michel I M Versteegh, Otto Visser, Emiel J T Rutgers, Berthe M P Aleman, Flora E van Leeuwen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later.

METHODS AND MATERIALS: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses.

RESULTS: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00-1.83).

CONCLUSION: Radiation therapy regimens used in BC treatment between 1989 and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens increased the risk of CHF.

LanguageEnglish
Pages1061-72
Number of pages12
JournalInternational journal of radiation oncology, biology, physics
Volume94
Issue number5
DOIs
Publication statusPublished - 1 Apr 2016

Cite this

Boekel, N. B., Schaapveld, M., Gietema, J. A., Russell, N. S., Poortmans, P., Theuws, J. C. M., ... van Leeuwen, F. E. (2016). Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors. International journal of radiation oncology, biology, physics, 94(5), 1061-72. https://doi.org/10.1016/j.ijrobp.2015.11.040
Boekel, Naomi B ; Schaapveld, Michael ; Gietema, Jourik A ; Russell, Nicola S ; Poortmans, Philip ; Theuws, Jacqueline C M ; Schinagl, Dominic A X ; Rietveld, Derek H F ; Versteegh, Michel I M ; Visser, Otto ; Rutgers, Emiel J T ; Aleman, Berthe M P ; van Leeuwen, Flora E. / Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors. In: International journal of radiation oncology, biology, physics. 2016 ; Vol. 94, No. 5. pp. 1061-72.
@article{e975299cf4b84c018ac5b6cf5d3192da,
title = "Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors",
abstract = "PURPOSE: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later.METHODS AND MATERIALS: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses.RESULTS: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95{\%} confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95{\%} CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95{\%} CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95{\%} CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95{\%} CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95{\%} CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95{\%} CI 1.00-1.83).CONCLUSION: Radiation therapy regimens used in BC treatment between 1989 and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens increased the risk of CHF.",
keywords = "Age Factors, Aged, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Intraductal, Noninfiltrating, Cardiovascular Diseases, Cause of Death, Chemotherapy, Adjuvant, Cisplatin, Cohort Studies, Combined Modality Therapy, Confidence Intervals, Female, Fluorouracil, Heart, Heart Failure, Heart Valve Diseases, Humans, Lymphatic Irradiation, Mastectomy, Methotrexate, Middle Aged, Myocardial Ischemia, Netherlands, Radiotherapy, Registries, Risk Assessment, Survivors, Time Factors, Unilateral Breast Neoplasms, Journal Article, Research Support, Non-U.S. Gov't",
author = "Boekel, {Naomi B} and Michael Schaapveld and Gietema, {Jourik A} and Russell, {Nicola S} and Philip Poortmans and Theuws, {Jacqueline C M} and Schinagl, {Dominic A X} and Rietveld, {Derek H F} and Versteegh, {Michel I M} and Otto Visser and Rutgers, {Emiel J T} and Aleman, {Berthe M P} and {van Leeuwen}, {Flora E}",
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Boekel, NB, Schaapveld, M, Gietema, JA, Russell, NS, Poortmans, P, Theuws, JCM, Schinagl, DAX, Rietveld, DHF, Versteegh, MIM, Visser, O, Rutgers, EJT, Aleman, BMP & van Leeuwen, FE 2016, 'Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors', International journal of radiation oncology, biology, physics, vol. 94, no. 5, pp. 1061-72. https://doi.org/10.1016/j.ijrobp.2015.11.040

Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors. / Boekel, Naomi B; Schaapveld, Michael; Gietema, Jourik A; Russell, Nicola S; Poortmans, Philip; Theuws, Jacqueline C M; Schinagl, Dominic A X; Rietveld, Derek H F; Versteegh, Michel I M; Visser, Otto; Rutgers, Emiel J T; Aleman, Berthe M P; van Leeuwen, Flora E.

In: International journal of radiation oncology, biology, physics, Vol. 94, No. 5, 01.04.2016, p. 1061-72.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors

AU - Boekel, Naomi B

AU - Schaapveld, Michael

AU - Gietema, Jourik A

AU - Russell, Nicola S

AU - Poortmans, Philip

AU - Theuws, Jacqueline C M

AU - Schinagl, Dominic A X

AU - Rietveld, Derek H F

AU - Versteegh, Michel I M

AU - Visser, Otto

AU - Rutgers, Emiel J T

AU - Aleman, Berthe M P

AU - van Leeuwen, Flora E

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - PURPOSE: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later.METHODS AND MATERIALS: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses.RESULTS: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00-1.83).CONCLUSION: Radiation therapy regimens used in BC treatment between 1989 and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens increased the risk of CHF.

AB - PURPOSE: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later.METHODS AND MATERIALS: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses.RESULTS: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00-1.83).CONCLUSION: Radiation therapy regimens used in BC treatment between 1989 and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens increased the risk of CHF.

KW - Age Factors

KW - Aged

KW - Antineoplastic Agents

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Carcinoma, Intraductal, Noninfiltrating

KW - Cardiovascular Diseases

KW - Cause of Death

KW - Chemotherapy, Adjuvant

KW - Cisplatin

KW - Cohort Studies

KW - Combined Modality Therapy

KW - Confidence Intervals

KW - Female

KW - Fluorouracil

KW - Heart

KW - Heart Failure

KW - Heart Valve Diseases

KW - Humans

KW - Lymphatic Irradiation

KW - Mastectomy

KW - Methotrexate

KW - Middle Aged

KW - Myocardial Ischemia

KW - Netherlands

KW - Radiotherapy

KW - Registries

KW - Risk Assessment

KW - Survivors

KW - Time Factors

KW - Unilateral Breast Neoplasms

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ijrobp.2015.11.040

DO - 10.1016/j.ijrobp.2015.11.040

M3 - Article

VL - 94

SP - 1061

EP - 1072

JO - International Journal of Radiation Oncology Biology Physics

T2 - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 5

ER -