Abstract
Background and Objective
The purpose of the present review was to study the impact of endocrine therapy (ET) on the cognitive outcomes of breast cancer patients.
Materials and Methods
We systematically searched the literature using the MEDLINE (1966–2015), Scopus (2004–2015), ClinicalTrials.gov (2008–2015) and Cochrane Central Register (CENTRAL) databases, as well as the references of the electronically retrieved articles.
Results
Twelve studies were included in the present systematic review, which assessed the cognitive function of 2756 patients. Among these patients, 2381 received ET, whereas the remaining 375 served as controls (placebo or no therapy). The majority of patients were postmenopausal, and the minimum follow-up period was 3 months and the maximum 2 years. Treatment with ET seems to be accompanied by altered cognitive abilities, including verbal memory, verbal fluency, motor speed, attention and working memory. Tamoxifen seems to be related to decreased cognitive performances compared with treatment with an aromatase inhibitor.
Conclusions
ET among breast cancer patients seems to negatively alter the cognitive outcomes of breast cancer patients. However, the methodological heterogeneity of the included studies, as well as the relatively small follow-up period, render imperative the conduct of further studies in the field.
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References
Theriault RL, et al. Breast cancer, version 3.2013: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2013;11(7):753–60 (quiz 761).
Cardoso F, et al. ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Ann Oncol. 2014;25(10):1871–88.
Andre F, et al. Breast cancer with synchronous metastases: trends in survival during a 14-year period. J Clin Oncol. 2004;22(16):3302–8.
Wilson S, Chia SK. Treatment algorithms for hormone receptor-positive advanced breast cancer: applying the results from recent clinical trials into daily practice-insights, limitations, and moving forward. Am Soc Clin Oncol Educ Book. 2013. doi:10.1200/EdBook_AM.2013.33.e20.
Mouridsen H, Gershanovich M. The role of aromatase inhibitors in the treatment of metastatic breast cancer. Semin Oncol. 2003;30(4 Suppl 14):33–45.
Morandi P, et al. The role of aromatase inhibitors in the adjuvant treatment of breast carcinoma: the MD Anderson Cancer Center evidence-based approach. Cancer. 2004;101(7):1482–9.
Aydiner A, Tas F. Meta-analysis of trials comparing anastrozole and tamoxifen for adjuvant treatment of postmenopausal women with early breast cancer. Trials. 2008;9:47.
Davies C, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805–16.
Jim HS, et al. Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy. J Clin Oncol. 2012;30(29):3578–87.
Liberati A, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.
Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence Working Group. “The Oxford Levels of Evidence 2”. Oxford Centre for Evidence-Based Medicine. Available at: http://www.cebm.net/index.aspx?o=5653.
Guyatt G, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94.
Bender CM, et al. Memory impairments with adjuvant anastrozole versus tamoxifen in women with early-stage breast cancer. Menopause. 2007;14(6):995–8.
Legault C, et al. Effects of tamoxifen and raloxifene on memory and other cognitive abilities: cognition in the study of tamoxifen and raloxifene. J Clin Oncol. 2009;27(31):5144–52.
Schilder CM, et al. Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: cross-sectional findings from the neuropsychological TEAM-side study. Acta Oncol. 2009;48(1):76–85.
Collins B, et al. Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study. Psychooncology. 2009;18(8):811–21.
Biglia N, et al. Effects of surgical and adjuvant therapies for breast cancer on sexuality, cognitive functions, and body weight. J Sex Med. 2010;7(5):1891–900.
Breckenridge LM, et al. Cognitive limitations associated with tamoxifen and aromatase inhibitors in employed breast cancer survivors. Psychooncology. 2012;21(1):43–53.
Schilder CM, et al. 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. J Clin Oncol. 2010;28(8):1294–300.
Schilder CM, et al. Self-reported cognitive functioning in postmenopausal breast cancer patients before and during endocrine treatment: findings from the neuropsychological TEAM side-study. Psychooncology. 2012;21(5):479–87.
Danhauer SC, et al. Positive and negative affect, depression, and cognitive processes in the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) Trial. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2013;20(5):532–52.
Lejbak L, Vrbancic M, Crossley M. Endocrine therapy is associated with low performance on some estrogen-sensitive cognitive tasks in postmenopausal women with breast cancer. J Clin Exp Neuropsychol. 2010;32(8):836–46.
Ganz PA, et al. Cognitive function after the initiation of adjuvant endocrine therapy in early-stage breast cancer: an observational cohort study. J Clin Oncol. 2014;32(31):3559–67.
Hurria A, et al. The effect of aromatase inhibition on the cognitive function of older patients with breast cancer. Clin Breast Cancer. 2014;14(2):132–40.
Jenkins V, et al. Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study. Psychooncology. 2004;13(1):61–6.
Shilling V, et al. The effects of hormone therapy on cognition in breast cancer. J Steroid Biochem Mol Biol. 2003;86(3–5):405–12.
Bell MJ, Terhorst L, Bender CM. Psychometric analysis of the Patient Assessment of Own Functioning Inventory in women with breast cancer. J Nurs Meas. 2013;21(2):320–34.
Stanczyk FZ, Bhavnani BR. Use of medroxyprogesterone acetate for hormone therapy in postmenopausal women: is it safe? J Steroid Biochem Mol Biol. 2014;142:30–8.
Phillips KA, et al. Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial. Breast Cancer Res Treat. 2011;126(1):221–6.
Newhouse P, et al. Tamoxifen improves cholinergically modulated cognitive performance in postmenopausal women. Neuropsychopharmacology. 2013;38(13):2632–43.
Newhouse P, et al. Tamoxifen improves cholinergically modulated cognitive performance in postmenopausal women. Neuropsychopharmacology. 2013;38(13):2632–43.
Dohanich GP, Fader AJ, Javorsky DJ. Estrogen and estrogen-progesterone treatments counteract the effect of scopolamine on reinforced T-maze alternation in female rats. Behav Neurosci. 1994;108(5):988–92.
Gibbs RB. Estrogen replacement enhances acquisition of a spatial memory task and reduces deficits associated with hippocampal muscarinic receptor inhibition. Horm Behav. 1999;36(3):222–33.
Singh M, et al. Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague–Dawley rats. Brain Res. 1994;644(2):305–12.
Feng Z, Cheng Y, Zhang JT. Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats. J Pineal Res. 2004;37(3):198–206.
Gibbs RB. Impairment of basal forebrain cholinergic neurons associated with aging and long-term loss of ovarian function. Exp Neurol. 1998;151(2):289–302.
Gibbs RB. Oestrogen and the cholinergic hypothesis: implications for oestrogen replacement therapy in postmenopausal women. Novartis Found Symp. 2000;230:94–107 (discussion 107–11).
Linke R, Schwegler H, Boldyreva M. Cholinergic and GABAergic septo-hippocampal projection neurons in mice: a retrograde tracing study combined with double immunocytochemistry for choline acetyltransferase and parvalbumin. Brain Res. 1994;653(1–2):73–80.
Easton A, et al. A specific role for septohippocampal acetylcholine in memory? Neuropsychologia. 2012;50(13):3156–68.
Teles-Grilo Ruivo LM, Mellor JR. Cholinergic modulation of hippocampal network function. Front Synaptic Neurosci. 2013;5:2.
Duka T, Tasker R, McGowan JF. The effects of 3-week estrogen hormone replacement on cognition in elderly healthy females. Psychopharmacology (Berl). 2000;149(2):129–39.
LeBlanc ES, et al. Hormone replacement therapy and cognition: systematic review and meta-analysis. JAMA. 2001;285(11):1489–99.
Sherwin BB. Estrogen and cognitive aging in women. Neuroscience. 2006;138(3):1021–6.
Keenan PA, et al. Prefrontal cortex as the site of estrogen’s effect on cognition. Psychoneuroendocrinology. 2001;26(6):577–90.
Maki PM. Estrogen effects on the hippocampus and frontal lobes. Int J Fertil Womens Med. 2005;50(2):67–71.
Dumas J, et al. Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: evidence for the critical period hypothesis. Horm Behav. 2008;53(1):159–69.
Dumas J, et al. Estrogen treatment effects on anticholinergic-induced cognitive dysfunction in normal postmenopausal women. Neuropsychopharmacology. 2006;31(9):2065–78.
Halbreich U, et al. Possible acceleration of age effects on cognition following menopause. J Psychiatr Res. 1995;29(3):153–63.
Newhouse P, Dumas J. Estrogen-cholinergic interactions: implications for cognitive aging. Horm Behav. 2015;74:173–85.
Nicholson RI, Johnston SR. Endocrine therapy: current benefits and limitations. Breast Cancer Res Treat. 2005;93(Suppl 1):S3–10.
Gibbs RB. Estrogen therapy and cognition: a review of the cholinergic hypothesis. Endocr Rev. 2010;31(2):224–53.
Folkerd EJ, et al. Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer. J Clin Oncol. 2012;30(24):2977–80.
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No sources of funding were used to conduct this systematic review.
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Ioannis Bakoyiannis, Eleousa-Alexandra Tsigka, Despina Perrea, and Vasilios Pergialiotis have no conflicts of interest to declare.
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Bakoyiannis, I., Tsigka, EA., Perrea, D. et al. The Impact of Endocrine Therapy on Cognitive Functions of Breast Cancer Patients: A Systematic Review. Clin Drug Investig 36, 109–118 (2016). https://doi.org/10.1007/s40261-015-0364-9
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DOI: https://doi.org/10.1007/s40261-015-0364-9