title: Self-reported long-term cardiac morbidity in breast cancer patients: a retrospective cohort study in Germany (PASSOS Heart Study).
abstract: OBJECTIVE
  Improved survival after locoregional breast cancer has increased the concern about late adverse effects after therapy. In particular, radiotherapy was identified as a risk factor for major cardiac events in women treated until the 1990s. While modern radiotherapy with computerized planning based on 3D-imaging can help spare organs at risk, heart exposure may remain substantial. In a retrospective cohort study of women treated for locoregional breast cancer, we investigated whether current radiotherapy is associated with an elevated long-term cardiac morbidity risk.
  
  
  METHODS
  The study included 11,982 women diagnosed with breast cancer in Germany in 1998-2008. After an individual mortality follow-up, 9338 questionnaires on cardiac events before or after therapy and on associated risk factors were sent out in 2014. Based on 4434 questionnaires from women with radiotherapy, we used Cox regression to analyze the association between self-reported cardiac morbidity and breast cancer laterality as a surrogate measure of radiation exposure.
  
  
  RESULTS
  After a median follow-up of 8.3 years, there was no significant association of tumor laterality with cardiac morbidity in irradiated patients (458 events, hazard ratio for left-sided vs. right-sided tumors 1.07, 95% CI 0.89-1.29). Significant risk factors for any cardiac event included age at diagnosis, chemotherapy, hypertension, hypercholesteremia, and chronic kidney disease.
  
  
  CONCLUSIONS
  For contemporary radiotherapy, we found no evidence for a significantly elevated cardiac morbidity risk in left-sided versus right-sided breast cancer. Possible reasons for failing to confirm earlier reports on increased risk include shorter follow-up, application of newer radiotherapy techniques, and improved health monitoring.
authors.affiliation: Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Obere Zahlbacher Str. 69, 55131, Mainz, Germany. wollschlaeger@uni-mainz.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wollschläger
authors.affiliation: Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Obere Zahlbacher Str. 69, 55131, Mainz, Germany.
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Merzenich
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ulm, Prittwitzstr. 43, 89075, Ulm, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Schwentner
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ulm, Prittwitzstr. 43, 89075, Ulm, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.affiliation: Department of Radiation Oncology, University Hospital Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wiegel
authors.affiliation: Department of Radiation Oncology, University Hospital Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Bartkowiak
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Würzburg, Josef-Schneider-Strasse 4, 97080, Würzburg, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Wöckel
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Mainz, 55101, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Radiation Oncology and Radiation Therapy, University Medical Center Mainz, 55101, Mainz, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Schmidberger
authors.affiliation: Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Obere Zahlbacher Str. 69, 55131, Mainz, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Blettner
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000150:complications / Q000453:epidemiology* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006321:Heart / Q000503:physiopathology / Q000528:radiation effects; D006331:Heart Diseases / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D009017:Morbidity; D058958:Organs at Risk; D016016:Proportional Hazards Models; D011832:Radiation Injuries / Q000453:epidemiology* / Q000473:pathology; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D057566:Self Report
keywords: Breast cancer; Cardiac morbidity; Cohort study; Radiotherapy