Late effects of adjuvant chemotherapy for breast cancer on fine motor function.

BACKGROUND: Adjuvant chemotherapy for breast cancer has been associated with deterioration of fine motor skill. Which aspects of motor performance are underlying this problem is unclear but important because manual motor deterioration could affect quality of life. The current study aims to investigate late effects of adjuvant chemotherapy for breast cancer on fine motor function, using both speed and accuracy measures. METHOD: We compared fine motor function of 174 women who had received adjuvant Cyclophosphamide Methotrexate 5-Fluorouracil chemotherapy for breast cancer on average 20 years ago with that of a population sample of 195 women without a history of cancer. Fine motor function was measured with the Purdue Pegboard Test and the Archimedes spiral test. RESULTS: The group of chemotherapy-exposed breast cancer survivors was slower in drawing an Archimedes spiral than the reference group. Furthermore, in the chemotherapy-exposed subjects, we found that older age is related to more crossings of the spiral template, more return movements, and more deviations from the template. Such relationships were not observed within the reference group. No significant between-group differences were found for any of the Purdue Pegboard measures. CONCLUSIONS: Compared with a population-based reference group, Cyclophosphamide Methotrexate 5-Fluorouracil chemotherapy-exposed breast cancer survivors demonstrated motor slowing while drawing an Archimedes spiral, on average 20 years after completion of primary treatment. Furthermore, the Archimedes spiral test is a more sensitive measure than the Purdue Pegboard Test to assess fine manual motor performance in long-term breast cancer survivors following chemotherapy.

Global and focal white matter integrity in breast cancer survivors 20 years after adjuvant chemotherapy.

OBJECTIVES: To date, only four small studies have investigated the effects of adjuvant chemotherapy for breast cancer on the microstructure of cerebral white matter with magnetic resonance imaging (MRI). These studies, which were conducted shortly up to 10 years post-treatment, showed that chemotherapy is associated with focal loss of microstructural white matter integrity. We investigated the long-term effect of chemotherapy on white matter microstructural integrity by comparing the brains of chemotherapy-exposed breast cancer survivors to those of a population-based sample of women without a history of cancer. EXPERIMENTAL DESIGN: Diffusion tensor imaging (DTI) MRI (1.5 T) was performed in 187 CMF (cyclophosphamide, methotrexate, and 5-flourouracil) chemotherapy-exposed breast cancer survivors, mean age 64.2 (sd = 6.5) years, who had been diagnosed with cancer on average 21.2 (sd = 4.4) years before, and 374 age-matched cancer-free reference subjects from a population-based cohort study. Outcome measures were whole-brain microstructural integrity as measured by fractional anisotropy and mean/axial/radial diffusivity and focal white matter integrity, which was analyzed with tract-based spatial statistics. All analyses were adjusted for age, cardiovascular risk factors, education, and symptoms of depression. PRINCIPAL OBSERVATIONS: No significant group differences were observed in white matter integrity. However, within the breast cancer survivors, time since treatment was inversely associated with lower global and focal white matter integrity. CONCLUSIONS: This cross-sectional study suggests that among chemotherapy-exposed breast cancer survivors white matter microstructural integrity deteriorates with accumulating time since treatment. This warrants further investigation.

Cluster-like headache and a cystic hypothalamic tumour as first presentation of sarcoidosis.

INTRODUCTION: Sarcoidosis is a granulomatous, multisystem inflammatory disease of unknown cause, which presents with a wide variety of symptoms. We describe a rare case of a newly diagnosed sarcoidosis, with cluster-like headache as a presenting symptom. CASE: A 31-year-old man presented with cluster headache with a cystic lesion in the hypothalamus. A non-caseating granuloma consistent with the diagnosis sarcoidosis was found at biopsy. Pulmonary involvement was confirmed on positron electron tomography-computed tomography (PET-CT). Treatment with prednisone led to regression of the hypothalamic lesion. Headache attacks did not recur. DISCUSSION: Cluster-like headache with a cystic hypothalamic lesion as first presentation of sarcoidosis has never been reported. Their possible relationship seems to underline the role of the hypothalamus in the central pain-regulatory areas in the brain, but is not undisputed. This case clearly demonstrates once again the relevance of neuroimaging in new-onset cluster-like headache.

Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy.

PURPOSE: Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration. Whether chemotherapy has any long-term effects on cognition is largely unknown, yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the improved survival. We investigated whether cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer is associated with worse cognitive performance more than 20 years after treatment. PATIENTS AND METHODS: This case-cohort study compared the cognitive performance of patients with breast cancer who had a history of adjuvant CMF chemotherapy treatment (six cycles; average time since treatment, 21 years; n = 196) to that of a population-based sample of women never diagnosed with cancer (n = 1,509). Participants were between 50 and 80 years of age. Exclusion criteria were ever use of adjuvant endocrine therapy, secondary malignancy, recurrence, and/or metastasis. RESULTS: The women exposed to chemotherapy performed significantly worse than the reference group on cognitive tests of immediate (P = .015) and delayed verbal memory (P = .002), processing speed (P < .001), executive functioning (P = .013), and psychomotor speed (P = .001). They experienced fewer symptoms of depression (P < .001), yet had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance. CONCLUSION: Survivors of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago perform worse, on average, than random population controls on neuropsychological tests. The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy. This study suggests that cognitive deficits following breast cancer diagnosis and subsequent CMF chemotherapy can be long lasting.

Incidental findings on brain Magnetic Resonance Imaging in long-term survivors of breast cancer treated with adjuvant chemotherapy.

PURPOSE: Incidental brain findings defined as previously undetected abnormalities of potential clinical relevance that are unexpectedly discovered at brain imaging and are unrelated to the purpose of the examination are common in the general population. Because it is unclear whether the prevalence of incidental findings in breast cancer patients treated with chemotherapy is different to that in the general population, we compared the prevalence in breast cancer survivors treated with chemotherapy to that in a population-based sample of women without a history of any cancer. PATIENTS AND METHODS: Structural brain MRI (1.5T) was performed in 191 female CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil) chemotherapy-exposed breast cancer survivors. A reference group of 1590 women without a history of cancer was sampled from a population-based cohort study. All participants were aged 50 to 80 years. Five trained reviewers recorded the brain abnormalities. Two experienced neuro-radiologists reviewed the incidental findings. RESULTS: The cancer survivors had completed chemotherapy on average 21 years before. Of the 191 subjects, 2.6% had an aneurysm and 3.7% had a meningioma. The prevalence of meningiomas and aneurysms was not different between the groups. The prevalence of pituitary macro adenomas in the breast cancer survivors (1.6%) was higher than that in the reference group (0.1%) (OR=23.7; 95% CI 2.3-245.8). CONCLUSION: Contrary to commonly held opinions, we did not observe an increased prevalence of meningiomas in cancer survivors. Breast cancer survivors previously treated with chemotherapy are more likely to develop pituitary adenomas than persons without a history of cancer and chemotherapy treatment.

Persistent neurocognitive problems after adjuvant chemotherapy for breast cancer.

BACKGROUND: Neurocognitive problems have been observed in a number of women previously treated with adjuvant chemotherapy for breast cancer. The present study aims to combine the results of neuropsychological and electrophysiological techniques collected in patients with breast cancer treated with cyclophosphamide/methotrexate/5-fluorouracil (CMF) at different time points. PATIENTS AND METHODS: Patients with breast cancer treated with adjuvant CMF chemotherapy (n = 63) were examined with neuropsychological tests 1 year after treatment and compared with healthy women (n = 60; T1 portion of the study). Based on neuropsychological test performance, patients were classified as cognitively impaired or unimpaired. Four years later, behavioral and neurophysiological measures (T2 portion of the study) were collected during an information-processing task in a subgroup of patients (n = 26). At T2, we compared the results of cognitively impaired patients (n = 8) with those of patients classified as cognitively unimpaired at T1 (n = 18). RESULTS: In the initial neuropsychological assessment, 33.3% of the patients were classified as cognitively impaired, compared with 10% of healthy women. At T2, impaired patients who received CMF showed longer P3 latencies, lower P3 amplitudes, longer reaction times, and made more errors in an information processing task compared with unimpaired patients who received CMF. CONCLUSION: The results indicate the persistence of neurocognitive problems < or = 5 years after completion of chemotherapy and consistency across different assessment techniques.

ERP amplitude and latency in breast cancer survivors treated with adjuvant chemotherapy.

OBJECTIVE: Neurocognitive problems that were observed in a number of breast cancer survivors treated with adjuvant chemotherapy initiated a series of EEG studies to examine the neurophysiological basis of these deficits. The aim of the present study was to examine the effects of various regimens of adjuvant chemotherapy on the N1 and P3 component of the event-related potential (ERP) in breast cancer patients 3-6 years after treatment. METHODS: Fifty-three breast cancer patients treated with various chemotherapy regimens were compared to 23 stage I breast cancer patients not treated with chemotherapy. An auditory oddball task was used to study the amplitude, latency and structure of the potential field of the N1 and P3. RESULTS: Patients treated with chemotherapy showed lower P3 amplitudes than patients not treated with chemotherapy. Differences were also observed in P3 latency between patients treated with different chemotherapy regimens. CONCLUSIONS: Our results indicate a general effect of all chemotherapy regimens under study on P3 amplitude and a more specific chemotherapeutic effect on P3 latency. SIGNIFICANCE: The present study provides evidence for the notion that different chemotherapy regimens have different effects on brain functioning.

Electrophysiological correlates of information processing in breast-cancer patients treated with adjuvant chemotherapy.

Cognitive deficits are found in a number of breast-cancer patients who have undergone adjuvant (Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF)) chemotherapy, but the underlying mechanisms are still unclear. The objective of this study is to investigate information processing in these patients with concurrent registration of brain activity. Twenty-six breast-cancer patients treated with adjuvant CMF chemotherapy and a control group of 23 stage I breast-cancer patients not treated with chemotherapy were examined. Mean time since treatment for the CMF patients was 5.1 years after the last CMF course, and for the control patients 3.6 years after termination of radiotherapy. An information processing task was administered with concurrent EEG registration. Reaction times and the amplitudes and latencies of an Event Related Potential component (P3) in different task conditions related to input, central, and output processing of information were studied. Significant differences in latency and amplitude of the P3 component were found between the treatment groups with an earlier and reduced P3 in the chemotherapy group. Patients treated with chemotherapy had longer reaction times (although not significantly different) than the control group on all task conditions. Our data provide further evidence for long-term neurocognitive problems in breast-cancer patients treated with adjuvant (CMF) chemotherapy and offer new information regarding abnormalities in brain functioning in these patients.