Prognostic significance of RACGAP1 mRNA expression in high-risk early breast cancer: a study in primary tumors of breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial.

PURPOSE: RACGAP1 is a Rac GTPase-activating protein involved in cell growth regulation, cell transformation and metastasis. The aim of the present study was to explore the prognostic and/or predictive significance of RACGAP1 mRNA expression on disease-free survival (DFS) and overall survival (OS) in high-risk early breast cancer patients and compare it to that of Ki67 protein expression and to the Nottingham prognostic index (NPI). METHODS: A total of 595 high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative dose-dense sequential chemotherapy with epirubicin followed by CMF with or without paclitaxel. RNA was extracted from 314 formalin-fixed paraffin-embedded primary tumor tissue samples followed by one-step quantitative RT-PCR for assessing RACGAP1 mRNA expression. RESULTS: High RACGAP1 mRNA expression (above the median) was associated with poor DFS (log-rank, p = 0.002) and OS (p < 0.001). High histological grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of RACGAP1. Results of the Cox multivariate regression analysis revealed that high RACGAP1 mRNA expression independently predicted poor overall survival (Wald's p = 0.008). High Ki67 protein expression was also an adverse prognostic factor for death (p = 0.016), while high NPI score values were not. CONCLUSIONS: High RACGAP1 mRNA expression, as assessed by qRT-PCR, was found to be of adverse prognostic significance in high-risk early breast cancer patients treated with dose-dense sequential chemotherapy. The utility of RACGAP1 mRNA expression in patient selection for treatment with aggressive chemotherapy regimens should be further explored and validated in larger cohorts.

Carboplatin/gemcitabine alternating with carboplatin/pegylated liposomal doxorubicin and carboplatin/cyclophosphamide in platinum-refractory/resistant paclitaxel - pretreated ovarian carcinoma.

OBJECTIVE: In this phase II study the efficacy and toxicity of an alternating chemotherapy regimen was examined in platinum-resistant relapsed epithelial ovarian cancer (EOC) patients. METHODS: Forty-five patients with platinum-refractory/resistant relapsed EOC, previously treated with carboplatin+paclitaxel+/-epirubicin were included. The regimen was consisted of gemcitabine 800 mg/m(2) (days 1+8) and carboplatin AUC 5, alternating with pegylated liposomal doxorubicin 30 mg/m(2) and carboplatin AUC 5, alternating with carboplatin AUC 5 and cyclophosphamide 600 mg/m(2), every 3 weeks for a total of 9 cycles. RESULTS: Among 38 patients with measurable disease, 39.4% (95% CI: 23.2-55.7) responded (five complete response and 10 partial response), while 30 out of 40 (75%) patients assessable by CA125 criteria had a serological response. Responses were more frequent in patients with platinum-free interval (PFI) 3-6 months than in those with PFI 0-3 months, but this was not statistically-significant. After a median follow-up of 19.5 months (range, 1.0-37+ months) the median progression-free survival was 7.1 months (95% CI: 3.4-10.8) and the median survival (OS) was 18.8 months (95% CI: 15.6-22.0). For patients with PFI 0-3 months PFS was 4.3 (95% CI: 0.8-7.8) months, while for those with PFI 3-6 months PFS was 8.9 (95% CI: 5.3-12.4) months (p=0.062). The regimen was well-tolerated and the main grade 3-4 toxicity was myelosuppression, palmar-plantar erythrodysesthesia, allergy and fatigue. CONCLUSION: This alternating regimen, including carboplatin, gemcitabine, liposomal doxorubicin and cyclophosphamide, is an active and well-tolerated treatment in platinum relapsed/refractory EOC patients.

Gastric metastases originating from breast cancer: report of 8 cases and review of the literature.

BACKGROUND: Breast cancer metastasis to the stomach is rare. It is very important to distinguish a breast cancer metastasis to the stomach from a primary gastric cancer on the basis of clinical, endoscopic, radiological and histopathological features, in order to administer the appropriate treatment. PATIENTS AND METHODS: Eight patients with breast cancer metastasis to the stomach were identified in our database between 1995 and 2008. The clinicopathological data and outcome from the medical records of these patients were then reviewed. RESULTS: The median age at initial breast cancer diagnosis was 59.5 years (range 44-75 years), while the median interval between the primary breast cancer and the gastric involvement was 41 months (range 2-82 months). The primary breast cancer histological subtype was mostly lobular carcinoma. All the biopsy specimens were estrogen receptor (ER), cytokeratin (CK) 7 and gross cystic disease fluid protein-15 (GCDFP-15) positive and CK-20 negative, while two of them (25%) were HER-2-neu positive. All the patients received chemotherapy and two of them were also treated with hormonal treatment. Two patients underwent surgical intervention, while one patient who had gastric involvement as the only metastatic site will proceed to surgical resection of the stomach. All these three patients were alive after 9, 39 and 44 months of follow-up, respectively. The response rate to chemotherapy was 50% (1 complete response [CR], 3 partial responses [PR]), and the median survival was 11 months (range, 1-44+ months). CONCLUSION: Breast cancer metastasis to the stomach can be differentiated from primary gastric cancer by comparing the biopsies from the gastric metastasis with the original histological slides from the primary breast tumor. Appropriate systemic treatment for metastatic breast carcinoma is the preferred treatment, whereas surgical intervention should be reserved for palliation or may be indicated in cases of solitary resectable gastrointestinal tract metastases.

Primary fallopian tube carcinoma: results of a retrospective analysis of 64 patients.

OBJECTIVE: The objective of this retrospective study was to determine the clinical outcomes of patients with primary fallopian tube carcinoma (PFTC) treated with paclitaxel and platinum analogue-based combination chemotherapy following primary cytoreductive surgery. METHODS: Sixty-four patients with the diagnosis of PFTC were identified through the gynecology service database and the tumor registry of 4 different institutions. The majority of patients (48/64, 75%) were treated with carboplatin AUC (area under curve) 6 and paclitaxel 175 mg/m(2) as a 3 h infusion. RESULTS: Among 28 patients with measurable disease, we observed 19 (68%) complete clinical and 7 (25%) partial responses for an overall response rate of 93%. After a median follow-up of 40 months (3+-134+ months), the 5-year survival rate of the entire population was 70% (median overall survival [mOS] not reached) and the median time to tumor progression (mTTP) was 81 months (95% CI: 53-109). Stage and residual disease were of prognostic significance. The mTTP was not reached in patients with stage I/II and was 38 months for patients with stage III/IV (p=0.004). The mOS for patients with stage I/II was not reached, whereas it was 62 months for those with stage III/IV (p=0.057). The mTTP was 86 and 23 months for patients with residual disease <2 cm and >2 cm, respectively (p<0.001). The mOS was not reached for patients with residual disease <2 cm, while it was 36 months for residual disease >2 cm (p<0.001). CONCLUSION: Optimally cytoreduced patients with PFTC treated with platinum and paclitaxel-based chemotherapy regimen have an excellent possibility of survival.

First-line chemotherapy of non-seminomatous germ cell tumors(NSGCTs).

Germ cell tumors (GCTs) account for the majority of testicular cancer cases occurring in men of young age and are divided into two main histologic groups, seminomas and non-seminomas. The introduction of cisplatin in the treatment of germ cell tumors was a breakthrough, classifying them among curable diseases. The identification of 3 subgroups of patients with non-seminomatous tumors (good-risk, intermediate and poor-risk), with different profiles concerning prognosis and response to treatment, supported clinical trials aiming to assess different treatment strategies and recommend the most effective and less toxic regimens. This review describes the toxic effects of therapy and the efforts aiming to overcome toxicity and improve treatment efficacy, focusing on the trials which form the basis of current standard treatment of non-seminomatous germ cell tumors.

Pancreatic cancer: current and future treatment strategies.

Pancreatic cancer is a disease with a high mortality rate and short survival, as a result of the high incidence of metastatic disease at diagnosis, the fulminant clinical course and the lack of successful therapeutic strategies. The administration of chemotherapeutic agents for the treatment of advanced disease has failed and currently, research focuses on the understanding of molecular pathways in order to investigate the role of targeted therapy. Trials on adjuvant and neo-adjuvant therapy of pancreatic cancer are also ongoing. This review presents the recent developments with newer chemotherapeutic and molecular-targeted agents, identifying the efforts for individualized treatment strategies.

The development of monoclonal antibody therapy in leukemias.

Conventional cytotoxic management of leukemia has less than optimal results, while it is associated with life-threatening toxic effects due to lack of specificity for hematopoietic cells. Therefore, novel therapeutic strategies with monoclonal antibodies (MAbs) are being explored for delivering chemotherapy or radiation directly to malignant cells. Recently, anti-CD33 antibodies have been engineered to target malignant myeloid and immature normal cells and have been used to deliver cytotoxic agents or radiation to leukemic cells. 131I-labeled anti-CD45 antibodies are used in combination with conventional chemotherapy in leukemic patients receiving marrow transplantation. Additionally, the emergence of Rituximab (against CD20) and Campath-1H (against CD52) for chronic lymphocytic leukemia (CLL) has provided encouraging clinical results for the prognosis of this disease. In conclusion, there has been ongoing research indicating that the approach of patients with leukemia through the application of MAbs might be safer and more effective than current treatment. Considering the preliminary data, MAb therapy appears to be a new, promising weapon in the oncologist's armentarium.

The prognostic significance of autoantibodies against dsDNA in patients with colorectal adenocarcinoma.

BACKGROUND: The tumors of the gastrointestinal system have been associated with various immune disorders. The goal of this study was to correlate the presence of the anti-dsDNA autoantibodies in the serum of patients with colorectal adenocarcinoma suffering from the prognosis of their disease. PATIENTS AND METHODS: We investigated 55 patients with colorectal adenocarcinoma, 26 patients with benign surgical disease and 40 healthy volunteers for the presence of anti-dsDNA autoantibodies pre-operatively and one month post-operatively, with an ELISA technique. RESULTS: The difference of prevalence of anti-dsDNA antibodies between the group of cancer patients and the two control groups was statistically significant (p < 0.001). After a 3-year follow-up, the difference of incidence of the recurrences between the positive and the negative group for anti-dsDNA autoantibodies of the CA patients was statistically significant (P < 0.01). CONCLUSION: The presence of anti-dsDNA autoantibodies in patients with colorectal cancer indicated a better outcome of the course of the disease.

Prognostic significance of autoantibodies against tropomyosin in patients with colorectal adenocarcinoma.

We examined, with an enzyme-linked immunoadsorbent assay (ELISA) method, the serum of 55 patients with Colon Adenocarcinoma (CA) for the presence of autoantibodies against tropomyosin (TMS), of IgM and IgG isotypes, before and 1 month after surgery. Twenty-six (26) patients with benign surgical diseases (BSD) (hernia or cholelithiasis) and 40 healthy volunteers were used as controls. Preoperatively, 20/55 (36.3%) of CA patients and 2/26 (7.7%) of BSD patients were positive for anti-TMS antibodies, while postoperatively, the positive samples were 22/55 (40%) and 2/26 (7.7%), respectively. The difference between the group of CA patients and the two control groups was statistically significant (p < 0.001). The presence of anti-TMS antibodies has been associated with better outcome of CA patients: 30 CA patients (30/55, 54.5%) had detectable anti-TMS antibodies either preoperatively or postoperatively and 25 CA patients (25/55, 45%) were completely negative in both occasions. In the first group of patients, four (4) recurrences were detected (4/30, 13.3%) while in the second group nine (9) recurrences were found (9/25, 36%). The difference between the two groups was statistically significant (p < 0.01). Anti-tropomyosin antibodies could be used as biological markers of prognosis in colon cancer patients.