5-Fluorouracil, epirubicin and cyclophosphamide versus epirubicin and paclitaxel in node-positive early breast cancer: a phase-III randomized GONO-MIG5 trial.

The study was designed to compare an anthracycline-containing regimen to a regimen combining both anthracycline and paclitaxel as adjuvant therapy for high-risk breast cancer patients. In this multicenter, randomized phase-III trial, node-positive early breast cancer patients were randomly assigned to receive either 6 cycles of FEC (5-fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2), day 1, every 3 weeks) or 4 cycles of EP (epirubicin 90 mg/m(2) and paclitaxel 175 mg/m(2), day 1, every 3 weeks). The primary endpoint was overall survival (OS). Secondary endpoints included toxicity and event-free survival (EFS). From 1996 to 2001, 1055 patients were enrolled. At a median follow-up of 12.8 years, 335 deaths had been recorded. The 10-year OS was 73 % (95 % CI 69-77) in the FEC arm and 74 % (95 % CI 70-78) in the EP arm (p = 0.405). The 10-year EFS was 51 % (95 % CI 45-56) in the FEC arm and 49 % (95 % CI 44-55) in the EP arm (p = 0.572). No difference in the hazard of death was observed (HR for EP 0.85, 95 % CI 0.68-1.06, p = 0.15). Patients treated with FEC experienced more frequently nausea and vomiting, stomatitis, and leukopenia as compared to patients treated with EP. Toxicities which occurred more frequently with EP were anemia, fever, myalgias, and neurotoxicity. Our study failed to demonstrate a superiority of an adjuvant treatment with four EP as compared to six FEC in node-positive breast cancer patients.

Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers.

The purpose of this article is to evaluate the prognostic value of androgen receptor (AR) expression in patients with estrogen receptor (ER)-positive breast cancer, treated with endocrine therapy, with or without the addition of chemotherapy. A consecutive series of 953 patients with ER-positive breast cancer, treated between 1998 and 2003, was selected. Repeated immunohistochemistry confirmed the expression of ER in the tumor of 938 patients. AR expression was measured by immunohistochemistry. The Kaplan-Meier method, logrank test and multivariate Cox models were used to explore the impact of AR expression on time to relapse (TTR) and disease specific survival (DSS) in all patients and in subgroups treated with chemo-endocrine therapy or endocrine therapy alone. AR immunoreactivity was assessable in 859 tumors and positive in 609 (70.9%). AR expression was a significant marker of good prognosis for TTR (P = 0.001) and DSS (P < 0.001). This effect was particularly evident in the group of patients receiving chemo-endocrine therapy (TTR (P = 0.015) and DSS (P < 0.001)). Cox models confirmed AR as an independent variable for both TTR (P = 0.003, HR 0.444, 95%CI 0.258-0.765) and DSS (P < 0.001, HR 0.135, 95%CI 0.054-0.337). Thus, we focused on ER-positive luminal B breast cancer that may be selected for chemotherapy because of their more aggressive immunophenotype. In this subset AR expression identified a group of patients with better prognosis for TTR (P = 0.017, HR 0.521, 95%CI 0.306-0.888) and DSS (P = 0.001, HR 0.276, 95% CI 0.130-0.588). AR expression is an independent prognostic factor of better outcome in patients with ER-positive breast cancers.

Micropapillary ductal carcinoma in situ of the breast: an inter-institutional study.

The clinical significance of micropapillary growth pattern in ductal carcinoma in situ is controversial and the impact of nuclear grading in terms of recurrence of this lesion is yet to be clarified. Our aim was to evaluate, on a series of micropapillary in situ carcinomas, the histological features correlated with recurrence and whether the micropapillary subtype had a different behavior from other non-micropapillary ductal carcinoma in situ. We collected 55 cases of micropapillary in situ carcinomas from four institutions. All cases were reviewed for nuclear grade, extent, necrosis, microinvasion and tested for estrogen and progesterone receptors, Ki67, HER2, EGFR and p53 expression. Clinical data, type of surgery and follow up were obtained for all patients. Our results showed that the nuclear grade is crucial in determining the biology of micropapillary carcinoma in situ, so that the high nuclear grade micropapillary ductal carcinoma in situ more frequently overexpressed HER2, showed higher proliferation index, displayed necrosis and microinvasion and was more extensive than low/intermediate nuclear grade. Logistic regression analysis confirmed the high nuclear grade (Odds ratio: 6.86; CI: 1.40-33.57) as the only parameter associated with elevated risk of local recurrence after breast-conserving surgery. However, the recurrence rate of 19 micropapillary carcinoma in situ, which were part of a cohort of 338 consecutive ductal carcinoma in situ, was significantly higher (log-rank test, P-value=0.019) than that of non-micropapillary, independently of the nuclear grade. In conclusion, although nuclear grade may significantly influence the biological behavior of micropapillary ductal carcinoma in situ, micropapillary growth pattern per se represents a risk factor for local recurrence after breast-conserving surgery.