title: Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors.
abstract: OBJECTIVE
  To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Naomi B
authors.initials: NB
authors.lastname: Boekel
authors.affiliation: Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Schaapveld
authors.affiliation: Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.affiliation: Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Russell
authors.affiliation: Radiation Oncology, Institute Verbeeten, Tilburg, The Netherlands; Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Poortmans
authors.affiliation: Radiotherapy, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Theuws
authors.affiliation: Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Dominic A X
authors.initials: DA
authors.lastname: Schinagl
authors.affiliation: Radiation Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Derek H F
authors.initials: DH
authors.lastname: Rietveld
authors.affiliation: Steering Committee Cardiac Interventions Netherlands, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Michel I M
authors.initials: MI
authors.lastname: Versteegh
authors.affiliation: Registration and Research, Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands.
authors.forename: Otto
authors.initials: O
authors.lastname: Visser
authors.affiliation: Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Emiel J T
authors.initials: EJ
authors.lastname: Rutgers
authors.affiliation: Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Berthe M P
authors.initials: BM
authors.lastname: Aleman
authors.affiliation: Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: f.v.leeuwen@nki.nl.
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
mesh_terms: D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000209:etiology / Q000532:radiotherapy* / Q000601:surgery; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality*; D002423:Cause of Death; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000379:methods; D016001:Confidence Intervals; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006321:Heart / Q000528:radiation effects; D006333:Heart Failure / Q000209:etiology / Q000401:mortality; D006349:Heart Valve Diseases / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D006801:Humans; D015182:Lymphatic Irradiation; D008408:Mastectomy; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000209:etiology / Q000401:mortality; D009426:Netherlands; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D012042:Registries; D018570:Risk Assessment; D017741:Survivors; D013997:Time Factors; D000069584:Unilateral Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate