Abstract P3-06-18: Increase of serum androgen and its metabolites in postmenopausal primary breast cancer patients with disease progression during neo-adjuvant exemestane treatment; JFMC 34–0601 TR

Abstract

Abstract BACKGROUND: We reported a positive correlation between body mass index (BMI) and clinical response to neo-adjuvant hormonal therapy (NAH) with steroidal aromatase inhibitor, exemestane, in post-menopausal breast cancer patients (Takada M et al. Breast 2012). Here, we examined the relationship between serum concentrations of sex steroids and BMI, and explored their predictive value for clinical response. PATIENTS AND METHODS: Among the 116 post-menopausal patients enrolled in the JFMC 34–0601 clinical trial of 24 weeks (wks) of NAH with exemestane, serums from 60 patients at pre-treatment, at 4wks and end of the treatment (24wks) were subjected to this study. Estradiol (E2), estrone (E1), dehydroepiandrosterone (DHEA), androstenedione (A-dione), 5-androstene-3β, 17β-diol (Aenediol), 5α-androstane-3β, 17β-diol (Aanediol) were measured using LC-MS/MS analysis and E1- sulfate (E1S) was by RIA. RESULTS: There were no significant correlations between pre-treatment concentrations of sex steroids and BMI, except for moderate correlation of E2 and BMI (p = 0.004). In multivariate analysis, E1 was an independent predictive factor for objective response [odds 6.0, 95% confidence interval (CI) 1.5 — 34.6, p = 0.011], as well as BMI. All of the estrogens decreased to under-detection levels (0.5 for E1 and E2, 5 pg/assay for E1S) at 4 wks of treatment, and maintained through to the end of treatment in almost all patients independently of clinical response. The geometric mean percentage changes in androgens after NAH were: DHEA −0.2% (95%CI −15.3% — +17.6%) for patients without progressive disease (non-PD) and +44.8% (95%CI +22.1% — +71.8%) for patients with progressive disease (PD); A-dione −2.3% (95%CI −17.3% — +15.4%) for non-PD and +45.6% (95%CI +28.3% — +65.3%) for PD; Aenediol −11.5% (95%CI −20.6% — −1.4%) for non-PD and +24.9% (95%CI +1.9% — +53.0%) for PD; Aanediol +21.3% (95%CI −5.5% — +55.8%) for non-PD and +56.3% (95%CI +5.3% — +132.0%) for PD, respectively. The changes in the concentrations of both DHEA and A-dione in patients with PD were statistically significant (p = 0.008 and p = 0.002, respectively). In all of the PD patients, the serum concentrations of DHEA and A-dione were increased after NAH. CONCLUSION: Pretreatment serum concentration of E1 was an independent predictive factor for clinical response to NAH with exemestane. Measurement of dynamics of the serum androgen concentrations might be helpful for monitoring treatment response, and mechanism of increase of androgens has a value for further investigation. Our results should be validated using a larger dataset. (UMIN ID; C000000345) Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-18.