Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor-positive breast cancer. Despite this treatment, however, some patients have a relapse. methodsWe conducted a double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival. resultsOf the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported -183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04). conclusionsExemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment.

No abstract

Given the improvement in mortality rates associated with breast cancer, the importance of understanding the long-term neuropsychological consequences of chemotherapy is becoming increasingly vital. This study applies meta-analytic techniques to the scant literature on the relationship between contemporary adjuvant chemotherapy treatment for breast cancer and cognitive dysfunction as examined through neuropsychological indices. Seven studies (involving more than 300 participants) were selected from over 200 potential articles, based on three inclusion criteria: presence of breast cancer, administration of chemotherapy treatment, and use of neuropsychological tests. From these, nine treatment-control comparisons were used to generate 129 Hedge's d effect sizes across the cognitive domains of simple attention, working memory short- and long-term memory, speed of processing, language, spatial abilities, and motor function. Small to medium cumulative effect sizes, showing diminished cognitive function for chemotherapy treatment groups compared to control groups, were obtained for each of the eight cognitive domains. Overall, these results suggest that women who undergo adjuvant chemotherapy as treatment for breast cancer may experience subtle yet consequential cognitive decline.

These data suggest that hormonal therapies exert a subtle negative influence on cognition in breast cancer patients. Further analyses indicated that this effect was not fully accounted for by demographic factors or fatigue. Methodological limitations of the current study are addressed, along with recommendations for future studies in this area.

These data suggest that there is a subtle negative impact of chemotherapy on cognitive function in breast cancer patients shortly following completion of treatment, but that this resolves within 1 year. However, given that our control group comprises breast cancer patients receiving hormonal therapy, and indications that hormonal therapy may also adversely affect cognition, such conclusions must be considered tentative.