Increased efficacy of a dose-dense regimen of neoadjuvant chemotherapy in breast carcinoma: a retrospective analysis.

Neoadjuvant chemotherapy is being increasingly used in the treatment of breast carcinoma. We performed a single-center retrospective analysis of the results of neoadjuvant therapy in 376 breast carcinoma patients treated with three different regimens combining doxorubicin and paclitaxel (AT), dose-dense doxorubicin and cyclophosphamide with sequential weekly paclitaxel (DD AC-P), or the combination of trastuzumab with chemotherapy (DD AC-PT). The expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor (HER)-2 was determined immunohistochemically. Pathological response was determined in 318 patients. Pathological complete response (pCR) was observed in 18% of patients. The pCR rate was significantly higher in patients treated with DD regimen (22 vs. 13%) and younger than 55 years (23 vs. 13%). The pCR rate was higher in patients with triple negative (TN) tumors (43%) and tumors over-expressing HER-2 (HER-2+; 28%) compared to patients with ER- or PR-positive tumors not expressing HER-2 (ER/PR+HER-2-; 6%). In patients with TN tumors pCR rate was significantly higher after treatment with DD AC-P compared to AT (61 vs. 22%, p=0.005). pCR was associated with significantly improved relapse-free survival (RFS) and overall survival (OS), but when analysis was performed based on tumor phenotype, the difference was significant only in patients with TN tumors. In multivariate analysis, pCR, stage, and ER expression were significant predictors of RFS, while pCR, stage, ER and DD regimen were significant predictors of OS. In conclusion, present data indicate superiority of a DD regimen in obtaining pCR in patients with breast carcinoma treated with neoadjuvant chemotherapy. The difference in efficacy is due mostly to markedly higher pCR rate in patients with TN tumors.

Tumor-infiltrating lymphocytes predict response to neoadjuvant chemotherapy in patients with breast carcinoma.

Tumor-infiltrating leukocytes and other immunohistochemical parameters were evaluated in pretherapeutic biopsies and resection specimens in 73 patients undergoing neoadjuvant chemotherapy with doxorubicin and paclitaxel. Ten patients with pathological complete response had significantly higher p53 expression, CD3(+) lymphocyte and CD83(+) cell counts, and lower progesterone receptor expression. In the remaining 63 patients, a significant decrease in the percentage of Ki-67, vascular endothelial growth factor expression, CD68(+) monocytes, and increased CD31(+), CD34(+), and SMA(+) stromal vessels, maximal CD3(+) and CD56(+) lymphocyte, maximal and mean CD83(+) cell, maximal CD1a(+), and maximal and mean S100(+) cell counts were observed after neoadjuvant chemotherapy.

Expression of bcl-2 in breast cancer: correlation with clinicopathological characteristics and survival.

Breast cancer is the most common malignancy in women. It is an immensely heterogeneous disease, characterised by a broad variety of clinical development. The research in recent years has focused on finding new markers of prognosis. This study investigates the role of expression of the bcl-2 protein in breast cancer. We analysed bcl-2 expression in 57 women with primary breast carcinoma who were treated with neoadjuvant (primary) chemotherapy, followed by a surgical procedure. The bcl-2 expression was correlated with other clinicopathological characteristics of the tumour- histological grade, stage, expression of hormonal receptors, proliferation rate, and with the survival of the patients. No significant association of bcl-2 expression with either overall survival or disease free survival was found.

Pathological complete response in advanced gastrointestinal stromal tumor after imatinib therapy.

Gastrointestinal stromal tumor (GIST) is a rare neoplasm exhibiting, in most cases, mutations of c-kit. Recently it has been demonstrated that a majority of GIST patients with c-kit mutations respond to therapy with imatinib, a c-kit tyrosine kinase inhibitor. Although the response rate in patients treated with imatinib in prospective clinical studies is above 50%, complete response is rare, and the data on the use of imatinib as neoaduvant therapy facilitating radical surgery is still scanty. Here, we report on a patient with metastatic gastric GIST who underwent surgery after 6 months of imatinib therapy. No tumor cells were detected on pathological examination of resection specimen. This case report indicates that a pathological complete response could be achieved with imatinib therapy in patients with GIST, but a wider experience and longer follow-up is necessary to appreciate the prognostic significance of pathological complete response in GIST.

Brain metastases of epithelial ovarian carcinoma responding to cisplatin and gemcitabine combination chemotherapy: a case report and review of the literature.

BACKGROUND: Brain represents a rare site of metastasis in patients with epithelial ovarian carcinoma (EOC). CASE REPORT: We observed a case of multiple brain metastases in an EOC patient after complete response of a pelvic recurrence to platinum/paclitaxel chemotherapy. Complete response of brain metastases was observed after whole brain radiotherapy and subsequent chemotherapy by combination of cisplatin and gemcitabine. Three subsequent recurrences of brain metastases were controlled by re-treatment by the combination of 5-fluorouracil, cisplatin and gemcitabine. METHODS: Because of limited information on the outcome of EOC brain metastases in reported case series, a pooled analysis of the published reports in patients with EOC brain metastases was performed. Data were extracted from 46 reports that contained sufficient details on 189 individual patients. The survival was analyzed by the Kaplan-Meier method. Univariate and multivariate analyses were performed by the log-rank test and Cox method, respectively. RESULTS: The most favorable outcome was observed in patients treated by surgery combined with radiotherapy and/or chemotherapy. The survival was significantly better in reports describing only one or two cases, in patients diagnosed after 1992, in patients who received therapy in addition to symptomatic treatment, in patients treated by radiotherapy, chemotherapy and surgery, in patients without extracranial metastases and with single brain metastases. On multivariate analysis, the absence of extracranial metastases, treatment by chemotherapy, surgery and radiotherapy were independent positive predictors of survival. CONCLUSIONS: EOC brain metastases are responsive to chemotherapy. An aggressive multidisciplinary therapeutic approach including chemotherapy may lead to prolonged survival.