Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy

Abstract

A limited number of studies have associated adjuvant chemotherapy with structural brain changes. These studies had small sample sizes and were conducted shortly after cessation of chemotherapy. Results of these studies indicate local gray matter volume decrease and an increase in white matter lesions. Up till now, it is unclear if non-CNS chemotherapy is associated with long-term structural brain changes. We compared focal and total brain volume (TBV) of a large set of non-CNS directed chemotherapy-exposed breast cancer survivors, on average 21 years post-treatment, to that of a population-based sample of women without a history of cancer. Structural MRI (1.5T) was performed in 184 chemotherapy-exposed breast cancer patients, mean age 64.0 (SD = 6.5) years, who had been diagnosed with cancer on average 21.1 (SD = 4.4) years before, and 368 age-matched cancer-free reference subjects from a population-based cohort study. Outcome measures were: TBV and total gray and white matter volume, and hippocampal volume. In addition, voxel based morphometry was performed to analyze differences in focal gray matter. The chemotherapy-exposed breast cancer survivors had significantly smaller TBV (-3.5 ml, P = 0.019) and gray matter volume (-2.9 ml, P = 0.003) than the reference subjects. No significant differences were observed in white matter volume, hippocampal volume, or local gray matter volume. This study shows that adjuvant chemotherapy for breast cancer is associated with long-term reductions in TBV and overall gray matter volume in the absence of focal reductions. The observed smaller gray matter volume in chemotherapy- 123Breast Cancer Res Treat (2012) 132:1099-1106 DOI 10.1007/s10549-011-1888-1 exposed survivors was comparable to the effect of almost 4 years of age on gray matter volume reduction. These volume differences might be associated with the slightly worse cognitive performance that we observed previously in this group of breast cancer survivors.

Neurocognitive function of lymphoma patients after treatment with chemotherapy

“…Consistent with this explanation was that the median time since completion of chemotherapy was approximately 55 months for our participants at the time of neuropsychological testing, whereas assessments of cognitive function in other studies took place sooner after chemotherapy completion [7,8,16]. However, such an explanation does not simply rule out future cognitive impairment as previous studies also showed chemotherapy to be associated with cognitive impairment approximately 10 years later [10] and reductions in total brain volume and overall gray matter volume approximately 20 years later [13]. Clearly, longitudinal studies with a baseline neuropsychological examination before initiation of chemotherapy and neuropsychological examinations on both the shorter and longer term after completion of chemotherapy are needed in order to precisely locate the time window(s) when cognitive impairment occurs.…”

“…Furthermore, from a neuro-epidemiological perspective, it is important to examine whether treatment with chemotherapy in (late) adulthood accelerates cognitive decline and increases the risk of dementia. A previous study of breast cancer patients showed that treatment with chemotherapy was associated with reductions in overall gray matter volume about 20 years later [13].…”

Challenges in research on the neural basis of „chemobrain”

“…Examinations of cortical structure using magnetic resonance imaging (MRI) have demonstrated reductions of both gray and white matter volume when comparing chemotherapy-treated patients with either healthy controls [25] or untreated patients [26]. Prospective studies have revealed that both frontal and temporal cortex showed the most pronounced volume reductions [27,28].…”

Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls

“…The exact mechanisms of this dysfunction remain unclear, although there is emerging evidence that chemotherapy may accelerate cognitive and brain aging. For example, one study noted that gray matter atrophy in chemotherapy-treated (C+) BC survivors was comparable to the effect of 4 y of additional aging (3). Additionally, a previous epidemiological study demonstrated that C+ BC survivors were at higher risk for dementia than nonchemotherapy-treated survivors (C−) (4).…”