Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial.

BACKGROUND: Several studies have reported discordant results regarding the impact of the CYP2D6 phenotype on both the effectiveness and the degree of endocrine symptoms associated with tamoxifen. Other studies have suggested that menopausal symptoms may be a predictive factor to tamoxifen response. METHODS: We investigated the relationship between the CYP2D6-predicted phenotype and tamoxifen response in a nested case-control study among women from the International Breast cancer Intervention Study (IBIS-I), which evaluated tamoxifen in the preventive setting. RESULTS: In this retrospective analysis of the tamoxifen-treated women in the IBIS-I study, 9 women (16.6%) who developed oestrogen receptor-positive invasive breast cancer had a 2D6 poor or intermediate metaboliser phenotype compared with 45 (20.6%) controls. Adjusted matched logistic regression revealed no significant difference between cases and controls for extensive vs intermediate metaboliser phenotype (OR=0.81 (0.30-2.23), P=0.7) or extensive vs poor metaboliser phenotype (OR=1.02 (0.31-3.32), P=0.9). Controls in the tamoxifen group with a poor metaboliser phenotype developed nonsignificantly fewer hot flushes compared with those with an extensive metaboliser phenotype (OR=0.40 (0.12-1.31)), but those with the intermediate phenotype developed nonsignificantly more hot flushes (OR=1.38 (0.58-3.29)) in an unadjusted analysis. CONCLUSION: Data from the preventive IBIS-I study did not support an association between the CYP2D6 phenotype and breast cancer outcome or the development of endocrine symptoms in tamoxifen-treated women.

Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract.

OBJECTIVE: Black cohosh, a popular herbal treatment for menopausal symptoms, has been implicated in a number of hepatotoxicity case reports. The purpose of this investigation was to analyze data gained from clinical trials on the effect of black cohosh on liver function. METHODS: A meta-analysis of randomized, double-blind, and controlled clinical trials was conducted. These studies primarily evaluated the efficacy and safety of the isopropanolic black cohosh extract (iCR) in perimenopausal and postmenopausal women. Raw data on liver function values of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltranspeptidase were considered in this analysis, if these data at baseline and after 3 to 6 months of treatment were available. Standard methods of descriptive statistics were used in this analysis. RESULTS: Five studies involving a total of 1,117 women were included in the meta-analyses. A total of 1,020 women (test population=517 and reference population=503) completed the studies. Perimenopausal and postmenopausal women (40-60 y) were treated daily with iCR (corresponding to 40-128 mg drug) for 3 to 6 months. The meta-analyses of the standardized mean differences in the "test" versus "reference" showed no significant effects and no differences between double-blind, placebo-controlled and other trials. The overall fixed effect ± SEM was 0.055 ± 0.062 (P=0.37) for aspartate aminotransferase and 0.063 ± 0.062 (P=0.31) for alanine aminotransferase. The nonsignificant effects concerned the overall analyses of all included studies as well as the proportion of placebo-controlled studies. CONCLUSIONS: The results of this meta-analysis of five randomized, double-blind, and controlled clinical trials showed no evidence that iCR has any adverse effect on liver function.