Triple-negative phenotype is of adverse prognostic value in patients treated with dose-dense sequential adjuvant chemotherapy: a translational research analysis in the context of a Hellenic Cooperative Oncology Group (HeCOG) randomized phase III trial.

PURPOSE: It is well recognized that breast cancer is a heterogeneous disease. The purpose of the current study was to classify patients according to the immunohistochemical phenotype of their tumors in an effort to evaluate the outcome of the respective groups of patients and specifically of those with triple-negative breast cancer (TNBC) following dose-dense sequential adjuvant chemotherapy. METHODS: A total of 595 patients with high-risk breast cancer were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy with or without paclitaxel in the context of a randomized study. ER, PgR, HER2, Ki67, EGFR, and CK5 protein expression were evaluated in 298 formalin-fixed paraffin-embedded tumor samples by immunohistochemistry (IHC). HER2 was also evaluated by chromogen in situ hybridization (CISH). HER2 status and Ki67 protein expression differentiated luminal IHC subtypes (luminal B tumors being HER2 and/or Ki67-positive). RESULTS: Among the 298 tumors, the immunohistochemical panel classified 37 (12%) as luminal A, 198 (66%) as luminal B, 27 (9%) as HER2 enriched, and 36 (12%) as TNBC. The median follow-up time was 97 months. Patients with luminal A tumors had the best prognosis, with improved disease-free survival (log-rank, P = 0.033) and overall survival (P = 0.006) compared with the other three tumor subtypes. The three subtypes had an increased risk for relapse and death compared with luminal A in multivariate analysis, as well. No benefit from paclitaxel treatment was detected in any of the four subtypes or the total cohort. Hierarchical clustering based on mRNA expression of ER, PgR, and HER2 by quantitative RT-PCR identified patient groups that were comparable to the subtypes identified by IHC. CONCLUSIONS: The results of this study confirm that triple negative, luminal B and HER2-enriched phenotypes identified by IHC are of adverse prognostic value in high-risk breast cancer patients treated with dose-dense sequential adjuvant chemotherapy.

Estradiol and leptin as conditional prognostic IVF markers.

We studied the concentration of serum estradiol and serum and follicular fluid leptin in 200 women undergoing their first in vitro fertilization with embryo transfer (IVF-ET) program at the time of human chorionic gonadotrophin administration and oocyte retrieval, in an attempt to assess their concerted role on embryo quality and the prognosis of IVF outcome. Low serum (46.49 +/- 8.4 ng/ml) and follicular fluid (52 +/- 9.8 ng/ml) leptin levels were associated with a high number of 'good-quality' embryos (73.6%) and high implantation (11.2%) and pregnancy (35.8%) rates and were observed in women with normal peak estradiol levels of between 1000 and 2000 pg/ml. It appears that leptin and estradiol interact coordinately in a concentration-dependent manner to control IVF outcome. Further studies will be required to substantiate and clarify the mechanism of proposed conditional interaction between the two hormonal systems.

Local therapy of atrophic vaginal conditions with oestriol suppositories.

Twenty post-menopausal women were treated using oestriol vaginal suppositories (Ortho-Gynest). Subjective disturbances such as dyspareunia, pruritus, and kraurosis vulvae showed a good response to the therapy, while the anaplastic activity of the vaginal epithelium to the suppositories was shown by an increase in the vaginal superficial cells which followed the course of treatment. Side-effects were minimal and disappeared following cessation of treatment.