Prevalence of Cerebral Small-Vessel Disease in Long-Term Breast Cancer Survivors Exposed to Both Adjuvant Radiotherapy and Chemotherapy

Purpose 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. Patients and 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. Conclusion 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.