Effects of Tamoxifen and Exemestane on Cognitive Functioning of Postmenopausal Patients With Breast Cancer: Results From the Neuropsychological Side Study of the Tamoxifen and Exemestane Adjuvant Multinational Trial

Schilder, Christina M.; Seynaeve, Caroline; Beex, L.V.A.M.; Boogerd, Willem; Linn, Sabine C.; Gundy, Chad M.; Huizenga, Hilde M.; Nortier, J.W.R.; Velde, Cornelis Jh van de; Dam, F. S. van; Schagen, Sanne B.

doi:10.1200/jco.2008.21.3553

Cited by 230 publications

(222 citation statements)

References 38 publications

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“…Accordingly, adjuvant endocrine therapy in postmenopausal breast cancer may influence cognitive function. Tamoxifen was negatively associated with cognitive functions in some reports (Paganini-Hill & Clark 2000, Collins et al 2009) and the TEAM trial confirmed these findings by showing that tamoxifen is significantly associated with lower functioning in verbal memory and executive functioning (Schilder et al 2010). Exemestane, on the other hand, did not show significantly worse outcomes for any cognitive domain compared with healthy controls.…”

Section: Cognitionsupporting

confidence: 67%

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

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Breast cancer is the most prevalent type of cancer in women and responsible for significant female cancer-related mortality worldwide. In the Western world, over 80% of breast cancers are hormone-receptor positive for which endocrine therapy is administered. The main anti-estrogen treatments in use consist of selective estrogen-receptor modulators, such as tamoxifen, and third-generation aromatase inhibitors (AIs), such as exemestane, letrozole, and anastrozole. In this review, the focus will lie on exemestane, its clinical use, and its side-effect profile. Exemestane is the only third-generation steroidal AI. Its efficacy as a first-line treatment in metastatic breast cancer has been demonstrated. Therefore, exemestane could be considered a valid first-line therapeutic option, but it also can be used in second-line or further situations. Exemestane is mostly used as part of sequential adjuvant treatment following tamoxifen, but in this setting it is also active in monotherapy. Furthermore, this AI has been studied in the neoadjuvant setting as presurgical treatment, and even as chemoprevention in high-risk healthy postmenopausal women. It may reverse side effects of tamoxifen, such as endometrial changes and thromboembolic disease but may also cause some inconvenient side effects itself. Additionally, there is a lack of total crossresistance between exemestane and nonsteroidal AIs as far as their anti-tumoral efficacy is concerned; moreover the two classes of AIs display a nontotal overlapping toxicity profile. Taking together, exemestane can be considered as a useful treatment option at all stages of breast cancer.

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Section: Cognitionsupporting

confidence: 67%

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

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show abstract

“…The tendency seems to be that subjective ratings of memory and concentration decrease after treatment with chemotherapy, and that breast cancer patients treated with chemotherapy also seem to be more likely than controls to perceive themselves as impaired [47]. It is also unclear whether tamoxifen used for postoperative endocrine therapy has an effect on cognitive function [48,49], and the effect of aromatase inhibitors, the first option for postmenopausal breast cancer, on cognitive function is also an important issue for further study [50,51].…”

Section: Discussionmentioning

confidence: 99%

Associations among baseline variables, treatment-related factors and health-related quality of life 2 years after breast cancer surgery

Taira

Shimozuma

Shiroiwa

et al. 2011

Breast Cancer Res Treat

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Provision of social support and rehabilitation for patients with physical, mental and functional problems after cancer treatment is important for long-term health-related quality of life (HRQOL). Effective use of human and financial healthcare resources requires identification of patients requiring rehabilitation. The objectives of the current study were to clarify the patterns of physical and psychosocial recovery over time, to evaluate the associations among baseline variables, treatment-related factors and HRQOL at 6 months, 1 and 2 years after breast cancer surgery, and to identify the significant factors predicting HRQOL at each point. A multicenter longitudinal study was performed to evaluate physical conditions, anxiety, depression and HRQOL at one month (baseline), 6 months, and 1 and 2 years after surgery in 196 patients (mean age: 53.3 years old) with early breast cancer and no postoperative recurrence. Physical conditions were evaluated using a patient-reported symptom checklist. HRQOL was rated using the Functional Assessment of Cancer Treatment scale-General (FACT-G) and the Breast Cancer subscale (FACT-B). Anxiety and depression were rated using the Hospital Anxiety and Depression Scale (HADS).More than 50% of patients had local problems of "tightness", "arm weakness" and "arm lymphedema", and systemic problems of "reduced energy, fatigue, and general weakness" postoperatively. The HRQOL score significantly improved one year after surgery, and scores for physical, emotional and functional well-being also increased with time, whereas the score for social well-being was highest at baseline and decreased with time. Depression and anxiety significantly improved with time. Concomitant disease, marital status and the presence of a partner, anxiety and depression at baseline, pathological lymph node involvement, and adjuvant intravenous chemotherapy were significant factors predicting FACT-G scores at 6 months and 1 and 2 years after surgery. Depression at baseline was a strong predictor of HRQOL up to 2 years after surgery. These results suggest that physical rehabilitation is required for tightness and lymphedema to improve long-term postoperative physical function. A further study of psychosocial interventions is required to improve depression and social well-being after breast cancer surgery.

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“…Mientras que en algunos trabajos se ha sugerido que el tamoxifeno sólo o asociado a QT puede contribuir al deterioro de la FC (34,35) , las evidencias resultan más débiles para los inhibidores de la aromatasa (36,37) y el bloqueo androgénico (31,38) .…”

Section: Cambios Hormonalesunclassified

Bases biológicas del deterioro de la función cognitiva inducido por los tratamientos antineoplásicos

et al. 2012

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Often patients treated with chemotherapy and/or radiotherapy suffer memory and attention problems. The exact mechanisms of action are unknown, although several explanations have been proposed. Both chemotherapy and radiotherapy have a direct toxic effect in the CNS, especially neural progenitor cells and the glia, which are responsible for maintaining neurogenesis in the hippocampus and white matter integrity. Besides the treatments can induce vascular damage in the brain, altering the immune response mediated by cytokines, and hormonal changes secondary to either chemotherapy or hormone therapy itself. The intensity of these effects would be modulated by several genetic factors that influence the ability of neuronal repair, pharmacodynamics and activity of neurotransmitters. Keywords: Cognitive function, cancer, chemotherapy, radiotherapy, chemobrain. ResumenA menudo los pacientes que reciben tratamiento con quimioterapia y/o radioterapia presentan problemas de memoria y de atención. Se desconocen los mecanismos exactos por los que esto se produce, aunque se han propuesto diversas explicaciones. Tanto la quimioterapia como la radioterapia poseen una acción tóxica directa en el SNC, especialmente sobre las células progenitoras neurales y las de la glía, que son las responsables de mantener la neurogénesis del hipocampo y la integridad de la sustancia blanca. A ello cabe añadir el daño que pueden inducir los tratamientos en la vascularización cerebral, la alteración de la respuesta inmune mediada por citoquinas, y los cambios hormonales ya sean secundarios a la quimioterapia o a la propia hormonoterapia. La intensidad de estos efectos estaría modulada por diversos factores genéticos que influyen sobre la capacidad de reparación neuronal, la farmacodinamia y la actividad de los neurotransmisores.

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Effects of Tamoxifen and Exemestane on Cognitive Functioning of Postmenopausal Patients With Breast Cancer: Results From the Neuropsychological Side Study of the Tamoxifen and Exemestane Adjuvant Multinational Trial

Cited by 230 publications

References 38 publications

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Associations among baseline variables, treatment-related factors and health-related quality of life 2 years after breast cancer surgery

Bases biológicas del deterioro de la función cognitiva inducido por los tratamientos antineoplásicos

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