The effects of adjuvant chemotherapy on cognition in women with breast cancer—preliminary results of an observational longitudinal study

Shilling, Valerie; Jenkins, Valerie; Morris, R.; Deutsch, G.P.; Bloomfield, David

doi:10.1016/j.breast.2004.10.004

Cited by 188 publications

(156 citation statements)

References 25 publications

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“…The effects were most pronounced in intact females, compared with males and ovariectomized females. Our data suggest that this kind of regulation could underlie memory deficits in women who suffer from breast cancer and who are treated with aromatase inhibitors for therapeutical reasons (Dowsett and Haynes, 2003;Shilling et al, 2005).…”

Section: Introductionmentioning

confidence: 76%

“…Clinical pilot studies have demonstrated that aromatase-inhibitors affect cognition and memory deficits in women treated with these inhibitors (Shilling et al, 2001(Shilling et al, , 2005Dowsett et al, 2005). Letrozole is easily transported across the blood-brain barrier after systemic application and exerts an inhibitory influence on hippocampal estrogen synthesis, as it does in other regions of the body (Zhou et al, 2010).…”

Section: Aromatase Inhibitors In the Therapy Of Breast Cancermentioning

confidence: 99%

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Aromatase Inhibition Abolishes LTP Generation in Female But Not in Male Mice

Vierk

Glassmeier²,

Zhou³

et al. 2012

Journal of Neuroscience

152

137

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Inhibitors of aromatase, the final enzyme of estradiol synthesis, are suspected of inducing memory deficits in women. In previous experiments, we found hippocampal spine synapse loss in female mice that had been treated with letrozole, a potent aromatase inhibitor. In this study, we therefore focused on the effects of letrozole on long-term potentiation (LTP), which is an electrophysiological parameter of memory and is known to induce spines, and on phosphorylation of cofilin, which stabilizes the spine cytoskeleton and is required for LTP in mice. In acute slices of letrozole-treated female mice with reduced estradiol serum concentrations, impairment of LTP started as early as after 6 h of treatment and progressed further, together with dephosphorylation of cofilin in the same slices. Theta-burst stimulation failed to induce LTP after 1 week of treatment. Impairment of LTP was followed by spine and spine synapse loss. The effects were confirmed in vitro by using hippocampal slice cultures of female mice. The sequence of effects in response to letrozole were similar in ovariectomized female and male mice, with, however, differences as to the degree of downregulation. Our data strongly suggest that impairment of LTP, followed by loss of mushroom spines and spine synapses in females, may have implications for memory deficits in women treated with letrozole.

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Section: Introductionmentioning

confidence: 76%

Section: Aromatase Inhibitors In the Therapy Of Breast Cancermentioning

confidence: 99%

Aromatase Inhibition Abolishes LTP Generation in Female But Not in Male Mice

Vierk

Glassmeier²,

Zhou³

et al. 2012

Journal of Neuroscience

152

137

View full text Add to dashboard Cite

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“…Hence, increasing attention is paid to negative side effects. In several neuropsychological CTC 2 , FEC 3 ) [1,7,9,25,[34][35][36]38,42,43]. These deficits range from very subtle to more severe and are observed in a wide range of brain functions, including memory, concentration, and speed of information processing [25], and can be noticed up to 10 years after completion of cytotoxic treatment [1].…”

Section: Introductionmentioning

confidence: 99%

Long-lasting suppression of hippocampal cell proliferation and impaired cognitive performance by methotrexate in the rat

Seigers

Schagen

Beerling³

et al. 2008

Behavioural Brain Research

213

135

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Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. AbstractMethotrexate (MTX) is a cytostatic agent widely used in combination with other agents as adjuvant chemotherapy for breast cancer and is associated with cognitive impairment as a long-term side effect in some cancer patients. This paper aimed to identify a neurobiological mechanism possibly responsible for this cognitive impairment using an animal model.The first study explored the hypothesis that MTX reduces neuronal cell proliferation. A dose-dependent long-lasting decrease in hippocampal cell proliferation was shown with Ki-67 immunocytochemistry, following a single intravenous injection of MTX (37.5-300 mg/kg). Animals treated with MTX also showed a dose-dependent transient decrease in body weight gain.In the second study, the effect of MTX (250 mg/kg) on two spatial learning tasks was examined. Animals treated with MTX learned the Morris water maze task adequately; however, these animals showed a longer latency time to cross the platform location in the probe trial, reflecting an impairment of spatial memory function. In the novel object recognition task, animals treated with MTX failed to distinguish a novel object from a familiar one, indicating a decrease in the comparator function of the hippocampus.Our studies indicated that, in the rat, MTX has a dose-dependent negative effect on hippocampal cell proliferation, and on cognitive behavior. These findings suggest that adverse effects of certain cytotoxic agents on hippocampal cell proliferation may have a potential contributory role in cognitive impairment observed in humans after chemotherapy.

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“…The first 3 reports that were published on longitudinal studies provided further support for this hypothesis. [8][9][10] Thus, the existence of chemo brain has become almost universally accepted, 11 although many details of the concept are controversial or obscure. The reported rates of cognitively impaired patients vary widely, reflecting different definitions of impairment.…”

mentioning

confidence: 99%

Cognitive function during neoadjuvant chemotherapy for breast cancer

Hermelink

Untch

Lux

et al. 2007

Cancer

313

116

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BACKGROUND.It is believed widely that chemotherapy‐induced cognitive impairment occurs in a subgroup of patients with breast cancer. However, recent reports have provided no evidence that chemotherapy affects cognition. In this study, the authors questioned whether cognitive compromise in patients with breast cancer is attributable to chemotherapy. In addition, the effects of therapy‐induced menopause and of the erythropoiesis‐stimulating factor darbepoetin α on cognitive performance were assessed.METHODS.A battery of neuropsychological tests was used to assess cognitive performance in 101 patients with breast cancer before neoadjuvant chemotherapy (T1) and toward the end of neoadjuvant chemotherapy (T2) with combined epirubicin, paclitaxel, and cyclophosphamide with concomitant darbepoetin α. Repeated‐measures multiple analyses of variance and a reliable‐change approach were used for statistical analyses.RESULTS.At T1, the group means ranged below the test norms in 5 of 12 cognitive tests. At T2, multiple analyses of variance (MANOVA) indicated a significant overall improvement in the test results (P < .001). After correcting for practice effects, cognitive decline predominated in 27% of patients, whereas improvement predominated in 28% of patients. Cognitive performance was not related significantly to self‐reported cognitive problems, anxiety and depression, menopause, or darbepoetin α administration.CONCLUSIONS.Even before chemotherapy, a subgroup of patients with breast cancer showed cognitive compromise that was unrelated to anxiety or depression. During chemotherapy, cognitive function remained stable in most patients, improved in a subgroup, and deteriorated in another subgroup. The deterioration may have been caused by side effects of chemotherapy, but it also may have been related to currently unidentified factors that cause prechemotherapy cognitive compromise. Therapy‐induced menopause and darbepoetin α did not appear to influence cognition. Cancer 2007. © 2007 American Cancer Society.

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The effects of adjuvant chemotherapy on cognition in women with breast cancer—preliminary results of an observational longitudinal study

Cited by 188 publications

References 25 publications

Aromatase Inhibition Abolishes LTP Generation in Female But Not in Male Mice

Aromatase Inhibition Abolishes LTP Generation in Female But Not in Male Mice

Long-lasting suppression of hippocampal cell proliferation and impaired cognitive performance by methotrexate in the rat

Cognitive function during neoadjuvant chemotherapy for breast cancer

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