Introduction: It is generally accepted that estrogens play a protective role in cognitive function. Therefore, it can be expected that subtotal estrogen deprivation following aromatase inhibition will alter cognitive performance. Methods: In a cross-sectional study we investigated 80 postmenopausal women with breast cancer. Memory and spatial cognition were compared across 4 treatment groups: tamoxifen only (TAM, n = 22), aromatase inhibitor only (AI, n = 22), TAM followed by AI (‘SWITCH group', n = 15), and patients with local therapy (LT) only (surgery and radiation, n = 21). Duration of the 2 endocrine monotherapy arms prior to the assessment ranged from 1 to 3 years. The ‘SWITCH group' received 2-3 years TAM followed by at least 1 year and at most 3 years of AI. Memory and spatial cognition were investigated as planned comparisons. Investigations of processing speed, attention, executive function, visuoconstruction and self-perception of memory were exploratory. Results: With regard to general memory, AI patients performed significantly worse than the LT group (p = 0.013). Significant differences in verbal memory did not remain significant after p-value correction for multiple testing. We found no significant differences concerning spatial cognition between the groups. Conclusion: AI treatment alone significantly impairs general memory compared to the LT group.

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Many patients with breast cancer complain about concentration and memory problems in connection with systemic therapy. A number of studies investigating the possible decrease in cognitive abilities were published in the 1980s. Numerous studies showed impaired performance of patients receiving chemotherapy. The results concerning profile, extent, and duration of cognitive impairments are, however, non-uniform. Increasing interest has been focused in the last years on effects of endocrine therapy on cognitive capacity – especially concerning the effects of the almost complete estrogen depletion caused by aromatase inhibitors. Often, the published studies did not evaluate particular effects of endocrine therapy without considering interference of cytotoxic treatment. Furthermore, the different endocrine medications (antiestrogens vs. aromatase inhibitors) were usually not regarded separately despite different mechanisms of action. Hence, the results of past investigations are also controversial. In the future, prospective trials with larger samples are necessary. Differentiation between chemotherapy and endocrine therapy is essential. Likewise, different types of endocrine therapy should be examined separately.

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