Evaluation of radiological and pathological prognostic factors in surgically-treated patients with bronchoalveolar carcinoma

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Metformin decreases circulating androgen and estrogen levels in nondiabetic women with breast cancer. Clin Breast Cancer

Abstract These are further data from a randomized controlled trial designed to test the effect of different doses of metformin in patients with breast cancer (BC) and without diabetes, with the aim of modifying the hormonal parameters linked to BC prognosis. A dose of 1500 mg/d of metformin causes significant reductions of the levels of free testosterone and estradiol. Introduction: Diabetic patients treated with metformin have a lower risk of developing BC or a better BC prognosis. Metformin might reduce cancer growth through direct antiproliferative effects or through indirect mechanisms, particularly the reduction of insulin. In a randomized study on nondiabetic BC patients in natural menopause with high testosterone levels, we observed a significant decrease in insulin and in testosterone levels with metformin 1500 mg/d compared with 1000 mg/d. We present the results of a new analysis of our study on the effect of metformin on the bioavailability of sex hormones. Patients and Methods: One hundred twenty-four eligible women were initially invited to take metformin 500 mg/d for 3 months. The 108 women who completed the first 3 months continued the study using 1000 mg/d for 1 month. The women were then randomized into 2 groups, and, for the subsequent 5 months, 1 group increased the dose to 1500 mg/d, and the other group continued with 1000 mg/d. Results: Ninetysix women completed the study, 43 receiving metformin 1500 mg/day, and 53 receiving 1000 mg/day. The women receiving 1500 mg/d showed a greater and significant reduction of free testosterone (À29%) and estradiol (À38%), a borderline significant reduction of estrone and insulin-like growth factor-1, and a nonsignificant reduction of androstenedione. They also showed a nonsignificant increase of dehydroepiandrosterone sulfate. Conclusion: Metformin does not interfere with the production of dehydroepiandrosterone sulfate. Besides, it decreases estradiol levels, basically through the reduction of testosterone. These hormonal changes might have clinical relevance

Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity

International audienceInvasive ductal carcinomas (IDC) of the breast with the triple negative phenotype (steroid hormone receptor absent, negative HER2 status) are characterized by poor clinical outcome. Additional tumor markers might allow identification of patients at higher risk. We evaluated clinical and biological features of 284 consecutive patients with pT1-3, pN1-3 M0 triple-negative IDC. Median follow-up was 70 months (interquartile range 59–94 months). Statistically significant worse disease-free and overall survival were observed in multivariate analysis, for patients with EGFR immunoreactivity in ≥50% invasive tumor cells (HR 2.39, 95% CI, 1.32–4.34,  = 0.004 for DFS; HR 2.34, 95% CI, 1.20–4.59  = 0.01 for OS). Age ≥ 70 years and PVI were additional independent predictors of reduced overall survival. EGFR immunoreactivity significantly correlates with worse prognosis in patients with triple-negative IDC, supporting further studies on the correlation between the degree of EGFR expression and outcome of triple negative breast cancer

Increasing steroid hormone receptors expression defines breast cancer subtypes non responsive to preoperative chemotherapy

International audienceThe predictive role of the degree of endocrine responsiveness to preoperative chemotherapy (PCT) is unclear. We reviewed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT. The incidence of pathological complete remission (pCR) and outcome were assessed with respect to the degree of estrogen (ER) and progesterone receptor (PgR) expression (ER and PgR absent, vs. ER or PgR 0–49%, vs. ER and PgR ≥50% of the cells positive). A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors (17.7%) versus patients with tumors expressing high ER and PgR (0%) (OR 14.4  < 0.001). Despite the higher incidence of pCR, a statistically significant worse disease-free survival (DFS), and overall survival (OS) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR (HR 6.4, 95% CI 3.5–11.6, for DFS; HR 3.6 95% CI 2.4–5.6 for OS). Response and outcome after PCT are correlated with the degree of expression of steroid hormone receptors. Studies on tailored preoperative therapies are needed