title: Prevalence of cerebral small-vessel disease in long-term breast cancer survivors exposed to both adjuvant radiotherapy and chemotherapy.
abstract: OBJECTIVE
  Adjuvant radiotherapy and chemotherapy for breast cancer have been related to transient ischemic attacks and stroke. To date, no studies have investigated the relationship between these adjuvant therapies and subclinical cerebral small-vessel disease in survivors of breast cancer. We compared white matter lesion (WML) volume and prevalence of brain infarctions and cerebral microbleeds (CMBs) between breast cancer survivors exposed to adjuvant radiotherapy and chemotherapy (aRCeBCSs) for primary disease and a population-based reference group.
  
  
  METHODS
  Multimodal magnetic resonance imaging (1.5 T) was performed in 187 aRCeBCSs who received primary breast cancer treatment on average more than 20 years before this study and 374 age-matched reference women without a history of cancer. WML volume was segmented using fully automated software. Experienced raters reviewed all scans for cortical infarctions, lacunar infarctions, strictly lobar CMBs, and deep/infratentorial CMBs with or without lobar CMBs. Within the aRCeBCS group, we also analyzed the association between relative radiotherapy exposure to the carotid artery and prevalence of WML volume and CMBs.
  
  
  RESULTS
  The aRCeBCS group had a higher prevalence of both total CMBs and CMBs in a deep/infratentorial region than the reference group. No between-group differences were observed in the prevalence of infarctions or WML volume. Exposure of the carotid artery to radiation was not associated with WML volume or CMBs.
  
  
  CONCLUSIONS
  More CMBs were found in the aRCeBCS group than in the population-based controls. These vascular lesions potentially mark cerebrovascular frailty that could partially explain the well-documented association between chemotherapy and cognitive dysfunction. No support was found for a radiotherapy-related origin of CMBs.
authors.affiliation: Vincent Koppelmans, University of Michigan, School of Kinesiology, Ann Arbor, MI; Vincent Koppelmans, Meike W. Vernooij, Caroline Seynaeve, and M. Arfan Ikram, Erasmus University Medical Center, Rotterdam; Vincent Koppelmans, Willem Boogerd, and Sanne B. Schagen, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; and Monique M.B. Breteler, German Center for Neurodegenerative Diseases and University of Bonn, Institute for Medical Biometry, Informatics, and Epidemiology, Bonn, Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Koppelmans
authors.affiliation: Vincent Koppelmans, University of Michigan, School of Kinesiology, Ann Arbor, MI; Vincent Koppelmans, Meike W. Vernooij, Caroline Seynaeve, and M. Arfan Ikram, Erasmus University Medical Center, Rotterdam; Vincent Koppelmans, Willem Boogerd, and Sanne B. Schagen, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; and Monique M.B. Breteler, German Center for Neurodegenerative Diseases and University of Bonn, Institute for Medical Biometry, Informatics, and Epidemiology, Bonn, Germany.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: Vincent Koppelmans, University of Michigan, School of Kinesiology, Ann Arbor, MI; Vincent Koppelmans, Meike W. Vernooij, Caroline Seynaeve, and M. Arfan Ikram, Erasmus University Medical Center, Rotterdam; Vincent Koppelmans, Willem Boogerd, and Sanne B. Schagen, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; and Monique M.B. Breteler, German Center for Neurodegenerative Diseases and University of Bonn, Institute for Medical Biometry, Informatics, and Epidemiology, Bonn, Germany.
authors.forename: Willem
authors.initials: W
authors.lastname: Boogerd
authors.affiliation: Vincent Koppelmans, University of Michigan, School of Kinesiology, Ann Arbor, MI; Vincent Koppelmans, Meike W. Vernooij, Caroline Seynaeve, and M. Arfan Ikram, Erasmus University Medical Center, Rotterdam; Vincent Koppelmans, Willem Boogerd, and Sanne B. Schagen, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; and Monique M.B. Breteler, German Center for Neurodegenerative Diseases and University of Bonn, Institute for Medical Biometry, Informatics, and Epidemiology, Bonn, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.affiliation: Vincent Koppelmans, University of Michigan, School of Kinesiology, Ann Arbor, MI; Vincent Koppelmans, Meike W. Vernooij, Caroline Seynaeve, and M. Arfan Ikram, Erasmus University Medical Center, Rotterdam; Vincent Koppelmans, Willem Boogerd, and Sanne B. Schagen, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; and Monique M.B. Breteler, German Center for Neurodegenerative Diseases and University of Bonn, Institute for Medical Biometry, Informatics, and Epidemiology, Bonn, Germany.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Vincent Koppelmans, University of Michigan, School of Kinesiology, Ann Arbor, MI; Vincent Koppelmans, Meike W. Vernooij, Caroline Seynaeve, and M. Arfan Ikram, Erasmus University Medical Center, Rotterdam; Vincent Koppelmans, Willem Boogerd, and Sanne B. Schagen, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; and Monique M.B. Breteler, German Center for Neurodegenerative Diseases and University of Bonn, Institute for Medical Biometry, Informatics, and Epidemiology, Bonn, Germany.
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
authors.affiliation: Vincent Koppelmans, University of Michigan, School of Kinesiology, Ann Arbor, MI; Vincent Koppelmans, Meike W. Vernooij, Caroline Seynaeve, and M. Arfan Ikram, Erasmus University Medical Center, Rotterdam; Vincent Koppelmans, Willem Boogerd, and Sanne B. Schagen, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; and Monique M.B. Breteler, German Center for Neurodegenerative Diseases and University of Bonn, Institute for Medical Biometry, Informatics, and Epidemiology, Bonn, Germany. s.schagen@nki.nl.
authors.forename: Sanne B
authors.initials: SB
authors.lastname: Schagen
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000209:etiology*; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000209:etiology*; D008833:Microcirculation / Q000187:drug effects / Q000528:radiation effects; D008875:Middle Aged; D017741:Survivors