Search

Background: The overexpression of syndecan-1 in breast carcinomas correlates with poorer prognosis and an aggressive phenotype. The effect of syndecan-1 expression on tumor response to neoadjuvant chemotherapy was determined in locally advanced breast cancer., Patients and Methods: Semi-quantitative syndecan-1 immunohistochemistry was performed in pre-chemotherapy breast cancer biopsies of 37 patients undergoing high-dose neoadjuvant treatment with cyclophosphamide and epirubicin., Results: 43.2% of breast carcinomas stained positive for syndecan-1. Syndecan-1 expression was more frequent in ductal invasive carcinomas than in other histological types (p=0.062). The pathological response to chemotherapy was decreased in syndecan-1-positive patients: 37.5% of syndecan-1-positive vs. 19% of syndecan-1-negative patients attained pathologically "no change". No syndecan-1-positive patient showed complete remission. Also, a correlation between syndecan-1 immunostaining intensity and response to chemotherapy was observed. Of the responding tumors, none showed strong syndecan-1 expression (Score 3+), whereas 20% of the non-responding tumors were strongly syndecan-1-positive., Conclusion: Syndecan-1-expressing breast carcinomas show a trend towards a decreased response to chemotherapy.

Timing of systemic treatment in primary operable breast cancer is subject to extensive investigation, suggesting that pathologic complete remission (pCR) might improve survival in this setting. The German Adjuvant Breast Cancer Group previously demonstrated the feasibility of a dose-dense biweekly schedule of 4 cycles doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 (ddAT) +/- tamoxifen in the neoadjuvant setting to yield a pCR of 9.7% (Gepardo trial). Patients assigned to ddAT received prophylactic granulocyte colony-stimulating factor support (5 micro g/kg days 5-10). The current study (GeparDUO) was designed to assess whether the pCR rate, including no viable invasive and preinvasive tumor cells, achieved with ddAT was equivalent to sequential administration of doxorubicin/cyclophosphamide followed by docetaxel (AC-DOC) over 24 weeks in primary operable breast cancer. From June 1999 to September 2001, 913 patients were enrolled in this trial. In total, 395 patients randomized before August 1, 2000, were included in the second interim analysis. Safety data were available from 369 patients (ddAT, n = 191; AC-DOC, n = 178) demonstrating that toxicity of both regimens was tolerable. Grade 3/4 neutropenia occurred in 39.8% of patients receiving ddAT and in 69.3% of patients treated with AC-DOC. Efficacy data were available in 378 patients. A pCR occurred in 14.8% of the primary breast tumors. According to the recommendations of the data monitoring committee, recruitment to the study was halted as of September 2001 (n = 913/1000) due to the significant difference in pCR rates observed between the treatment arms. Surgery was documented in 380 patients. Breast conservation was possible in 288 cases (75.8%). The application of both schedules is safe and feasible in an outpatient setting. Although, results obtained from this interim analysis are encouraging, caution is recommended until the results obtained show statistical difference in pCR.