Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG.

Purpose: Most patients with advanced ovarian cancer develop recurrent disease. For those patients who recur at least 6 months after initial therapy, paclitaxel platinum has shown a modest survival advantage over platinum without paclitaxel; however, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. Thus, an alternative regimen without significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer patients.

Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patients with chemotherapy-sensitive metastatic breast cancer.

Purpose: To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients.

Patients And Methods: Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m2/d for 4 days), cyclophosphamide (1,500 mg/m2/d for 4 days), and carboplatin (200 mg/m2/d for 4 days), followed by autologous stem-cell transplantation.

Results: One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm.

Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO.

Background: The combination of carboplatin and paclitaxel is the standard of care for the treatment of ovarian cancer, yet rates of recurrence and death remain high. We performed a prospective randomized phase III study to examine whether sequential administration of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer.

Methods: A total of 1308 patients with previously untreated ovarian cancer (International Federation of Gynecology and Obstetrics stages IIB-IV) were randomly assigned to receive six cycles of paclitaxel and carboplatin followed by either four cycles of topotecan (TC-Top; 658 patients) or surveillance (TC; 650 patients) on a 3-week per cycle schedule.

Neutropenic event risk and impaired chemotherapy delivery in six European audits of breast cancer treatment.

Goals Of Work: The aims of this study were to assess chemotherapy treatment characteristics, neutropenic event (NE) occurrence and related risk factors in breast cancer patients in Western Europe.

Materials And Methods: Six retrospective audits of breast cancer chemotherapy were combined into a dataset of 2,860 individuals. NEs were defined as neutropenia-related hospitalisation, dose reduction > or = 15% or dose delay > or = 7 days.

[Adjuvant therapy with trastuzumab (Herceptin) in primary breast cancer].

The results of four randomized international multicentric trials evaluating the therapeutic benefit of Herceptin in the adjuvant treatment of HER2-neu positive primary breast cancer have been reported. These reports showed that even after short term follow up one year of Herceptin resulted in improved disease free, metastases free and overall survival. Design and results of these four studies and the recommendations of national and international societies for the use of Herceptin in the adjuvant setting will be discussed.

C-KIT expression in ductal carcinoma in situ of the breast: co-expression with HER-2/neu.

The proto-oncogene c-KIT (CD117) is highly expressed in normal breast epithelium and is decreased in invasive breast cancer. In this study, we analyzed the protein expression and the mutational status of c-KIT in ductal carcinoma in situ (DCIS) of the breast and correlated these findings with nuclear grade, architectural pattern, and expression of HER-2, estrogen receptor (ER)-alpha, and progesterone receptor (PR). C-KIT, HER-2, ER, and PR expression were analyzed immunohistochemically in 106 cases of paraffin-embedded DCIS (85 pure DCIS and 21 DCIS with concurrent carcinoma).

The role of surgery in recurrent ovarian cancer.

The role of cytoreductive surgery (CS) in recurrent ovarian cancer (ROC) has not been clearly defined. We performed a retrospective study evaluating criteria for CS in ROC. Twenty-five institutions documented their patients with CS for invasive epithelial ROC performed 2000-2003.

Bone metastases in vulvar cancer: a rare metastatic pattern.

Bone metastases from a vulvar carcinoma are exceptionally rare with only five reported cases in the literature. We report on a patient who was initially treated with radical vulvectomy and bilateral inguinal lymphadenectomy for a vulvar cancer (pT2, pN2 (6/37), M0; G2). Due to a positive nodal status, adjuvant radiation of the vulva and the pelvis was performed additionally.

Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial.

Background: Breast cancer with extensive axillary-lymph-node involvement has a poor prognosis after conventional treatment. In trials with historical controls, high-dose chemotherapy produced improved outcomes. We compared an intensive double-cycle high-dose chemotherapy regimen with an accelerated conventionally dosed regimen in high-risk breast cancer in a multicentre trial.

Pegylated liposomal doxorubicin and carboplatin in advanced gynecologic tumors: a prospective phase I/II study of the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR).

Background: Single-agent platinum and single-agent pegylated liposomal doxorubicin (PLD) are both effective in the treatment of gynecologic malignancies. Based on evidence that combination platinum-containing regimens offer superior efficacy versus single-agent regimens, we conducted this study to determine the maximum tolerated dose (MTD) of PLD in combination with carboplatin.

Patients And Methods: In this phase I/II dose-finding study, six courses of PLD (20, 30, 40 or 50 mg/m2) and carboplatin (AUC 6) were administered every 28 days to women with advanced gynecologic malignancies.

Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.

Background: Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy.

Methods: This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy.

Radiation-induced capsule tissue reactions around textured breast implants in a rat model.

Capsule fibrosis and other complications around various filled breast implants were evaluated in a rat radiation model after 12 months of implantation. Model implants, one per rat, were implanted subcutaneously. One month after subcutaneous implantation, high voltage radiation followed one half each group.

[Mammographic breast density and breast cancer risk during HRT].

Higher breast density leads to a higher risk of breast-cancer coming along with a reduced sensitivity of mammography, the most important method for early diagnosis of breast cancer. HRT leads to an increase in breast density in up to (1/3) of treated women. Combined regimes of estrogen-progestin show a stronger influence than estrogen only.

Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group.

Purpose: Dose-dense and sequential administration of cytotoxic drugs are current approaches to improve outcomes in patients with early-stage breast cancer.

Methods: This phase III study investigated 913 women with untreated operable breast cancer (T2-3, N0-2, M0) randomly assigned to receive either doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 every 14 days for four cycles with filgrastim support (ADOC), or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 21 days followed by docetaxel 100 mg/m2 every 21 days for four cycles each (AC-DOC). The primary end point was the incidence of pathologic complete (invasive and noninvasive) response (pCR) in the breast and axillary nodes.

High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer.

Background: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer.

Patients And Methods: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest.

Androgen receptor expression in ductal carcinoma in situ of the breast: not a helpful marker for classification such as estrogen receptor alpha and progesterone receptor.

Androgen receptor (AR) is known to be expressed in approximately 70 to 90% of invasive breast cancers, but there are still conflicting data in terms of AR expression in ductal carcinoma in situ (DCIS). The aim of this study was to evaluate AR expression in DCIS and to compare these results with nuclear grading and with other common endocrine-related markers. On this basis the authors performed immunohistochemical staining for estrogen receptor (ER)-alpha and ER-beta, progesterone receptor (PR), pS2, her-2/neu, and AR in 59 cases of DCIS (24 low grade, 5 intermediate grade, 30 high grade).

Anthracycline and trastuzumab in breast cancer treatment.

This study was designed to evaluate the cardiac safety of the combined treatment of HER2-positive metastatic breast cancer patients with trastuzumab (Herceptin) plus epirubicin and cyclophosphamide (EC) in comparison with EC alone in HER2-negative metastatic breast cancer patients. Patients included those with metastatic breast cancer without any prior anti-HER2 treatment, anthracycline therapy, or any other chemotherapy for metastatic disease. This was a nonrandomized, prospective, dose-escalating, multicenter, open-label, phase I study in Germany.

A phase II study of paclitaxel, carboplatin, and gemcitabine in previously untreated patients with epithelial ovarian cancer FIGO stage IC-IV (AGO-OVAR protocol OVAR-8).

Purpose: A multicenter, nonrandomized, phase II study was initiated to evaluate the tolerability, toxicity, and activity of paclitaxel, carboplatin, and gemcitabine combination in previously untreated ovarian cancer.

Patients And Methods: Chemonaive patients who had radical debulking surgery for primary epithelial ovarian cancer International Federation of Gynecology and Obstetrics (FIGO) IC-IV received sequentially paclitaxel 175 mg/m(2), carboplatin AUC 5, and gemcitabine 800 mg/m(2) on day 1 and gemcitabine 800 mg/m(2) on day 8, every 3 weeks.

Results: From October 2001 to July 2002, 55 patients were treated and evaluated.

In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study.

Background: Response to the first two cycles of preoperative chemotherapy might differentiate subgroups of breast cancer patients with high or minimal chances for a pathologic complete response (pCR) and may be used as an in vivo chemosensitivity test.

Methods: Breast cancer patients were treated with two cycles of TAC (docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2) every 21 days). Patients whose tumors showed a response received four more cycles.

Future options with trastuzumab for primary systemic and adjuvant therapy.

HER2 positivity can be detected early in breast cancer development and is associated with a poor outcome. Primary systemic therapy with trastuzumab (Herceptin; F. Hoffmann-La Roche, Basel, Switzerland) in combination with taxanes and other cytotoxic agents has been studied in phase II clinical trials in women with HER2-positive breast cancer.

[Management of breast cancer treatment -- a multidisciplinary approach].

The management of breast cancer care poses very high expectations on implementing the treatment recommendations and guidelines for diagnostic procedures into routine treatment. Most recently a majority of these tasks has been transferred to the responsibilities of the breast centers being established all over Germany these days. Guidelines on treatment and diagnostic procedures and minimal invasive techniques have therefore been discussed among 1 300 colleagues and experts at the Duesseldorfer Symposium in June 2004.

Estrogen receptor alpha and beta, progesterone receptor, pS2 and HER-2/neu expression delineate different subgroups in ductal carcinoma in situ of the breast.

Antiestrogen therapy of ductal carcinoma in situ (DCIS) has become a more common option in reducing risk of developing invasive cancer. Previously, estrogen receptor alpha (ER-alpha) was evaluated as the only predictive factor. Immunohistochemical staining was performed for ER-alpha, estrogen receptor ER-beta, progesterone receptor (PR), pS2 and her-2/neu in 59 cases of ductal carcinoma in situ (DCIS).

Cardiac safety of trastuzumab in combination with epirubicin and cyclophosphamide in women with metastatic breast cancer: results of a phase I trial.

This prospective, parallel-group, dose-escalation study evaluated the cardiac safety of trastuzumab (Herceptin) plus epirubicin/cyclophosphamide (EC) in women with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) and determined an epirubicin dose for further evaluation. HER2-positive patients received standard-dose trastuzumab plus epirubicin (60 or 90 mg/m(2))/cyclophosphamide (600 mg/m(2)) 3-weekly (EC60+H, n=26; EC90+H, n=25), for four to six cycles; 23 HER2-negative patients received EC alone (90/600 mg/m(2)) 3-weekly for six cycles (EC90). All patients underwent thorough cardiac evaluation.

Secretory carcinoma of the breast: a distinct variant of invasive ductal carcinoma assessed by comparative genomic hybridization and immunohistochemistry.

Secretory carcinomas (SCA) are distinguished from infiltrating ductal carcinomas (IDC) of the breast by their characteristic histomorphology and more favorable prognosis and by the expression of a chimeric tyrosine kinase that is encoded by the ETV6-NTRK3 fusion gene. On this basis, we evaluated 13 SCAs (12 of them with ETV6-NTRK3 gene fusion) by molecular and immunohistochemical (IHC) methods. DNA was obtained from 8 of 13 microdissected SCAs and was analyzed for genetic alterations (GA) by comparative genomic hybridization (CGH).