Behaviour of vaginal epithelial maturation and sex hormone binding globulin in post-menopausal breast cancer patients during the first year of tamoxifen therapy.

To evaluate the effect of tamoxifen on vaginal epithelial maturation and on oestrogen-related hepatic synthesis, we prospectively studied the karyopyknotic index (KPI), the maturation index (MI), expressed as a percentage of parabasal (MI-1), intermediate (MI-2) and superficial (MI-3) cells, as well as the serum levels of the oestrogen-dependent sex hormone binding globulin (SHBG). Tests were performed at baseline, after 1, 3, 6 and 12 months of therapy in 64 post-menopausal breast cancer patients. Basal KPI ranged from 0 to 9 (mean 1.5 +/- 0.3) and rose 13.5-fold to 21 +/- 2.5 (P = 0.000) after the first 30 days of tamoxifen. Absence of KPI rise was observed in 23% of patients. Pretreatment MI figures 1, 2 and 3 were 56.9 +/- 5.6, 41.7 +/- 5.4 and 1.4 +/- 0.3, respectively, and sharply shifted to the right (P = 0.000) after 1 month of therapy, indicating an increase of vaginal epithelial maturation. At baselines the SHBG mean value was 62.1 +/- 3.3 nmol/l and underwent an increase of 44% (P = 0.000) after 30 days of tamoxifen. All of these observed 1-month modifications remained stable up to the studied 12 months of therapy. Present findings indicate an early and persistent oestrogenic effect of tamoxifen on the vaginal epithelium and the hepatic synthesis of SHBG.

Liver function tests and lidocaine metabolism (MEGX test) during i.v. CMF therapy in breast cancer.

The measurement of monoethylglycinexylidide (MEGX test) is considered a sensitive method for the evaluation of hepatic metabolic capacity. The multidrug chemotherapy CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/ m2, 5-fluorouracil 600 mg/m2) is widely used in breast cancer patients but very few clinical studies have investigated its possible liver toxicity. We have prospectively evaluated the possible acute liver toxicity after a cycle (i.e. two courses) of CMF by means of the measurement of standard liver function tests and of MEGX, i.e. the main lidocaine (Lid) metabolite after the i.v. injection of Lid. Consecutive patients (n = 15), aged 43-68 years, were radically operated on because of M0 primary breast cancer and candidates for adjuvant CMF because of nodal axillary involvement (pN1) were studied. Tests were performed before the first (given at day 1) and 48 h after the second course (given at day 8) of an i.v. CMF regimen to be repeated every 28 days. Full blood count, serum ALT, AST, gamma-GT, alkaline phosphatase and albumin were measured with standard methods. To investigate the appearance of MEGX, blood samples were taken before, and 5, 10, 15, 20, 25, 30 and 60 min after i.v. Lid injection. MEGX serum concentration was measured by means of a fluorescent polarization immunoassay. We found no significant variation between pre- and post-CMF standard liver function tests with the exception of ALT levels, which, however, decreased (mean 48%, p < 0.05). The MEGX serum concentration was significantly increased over the sampling time period and the 42% mean rise was statistically significant (p < 0.001). Moreover, the post-CMF increase of circulating MEGX was steeper than the basal pre-CMF values. The slopes relating to the curves of MEGX formation over the first 20 min were 3.30 and 2.24, respectively (p < 0.001). In conclusion, no hepatic acute toxicity was observed during the CMF chemotherapy. Further studies are required to understand the meaning of the unexpected MEGX rise.