Small cell carcinoma of vulva: curative multimodal treatment in face of resistance to initial standard chemotherapy.

Background And Purpose: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease, which has a slightly better prognosis than small cell lung cancer, but still dismal. Gynecologic small cell malignancies tend to show a better survival than similar histologies of other regions. However, of five reported cases of vulvar manifestation only one patient was disease-free at the time of publication with limited follow-up.

Evaluation of ERalpha, PR and ERbeta isoforms in neoadjuvant treated breast cancer.

The actual predictive value of oestrogen receptor (ER) beta for treatment decisions in breast cancer is still unclear. Retrospective studies using preoperative systemic therapy (PST) revealed that chemotherapy but also endocrine therapy can lead to alterations in expression levels of ERalpha and progesterone receptor (PR). The main purpose of this study was to compare ERbeta expression levels before and after neoadjuvant chemotherapy or endocrine therapy and to explore a possible predictive value of ERbeta.

Number of hysteroscopies and the time interval between hysteroscopy and surgery: influence on peritoneal cytology in patients with endometrial cancer.

Aim: Hysteroscopy is a routine procedure for the diagnosis of endometrial cancer (EC). Moreover, with implementation of sentinel lymph node technique, a second hysteroscopy is necessary for technetium injection before performing lymphadenectomy. As yet, no data are available showing whether the time interval between hysteroscopy and definitive surgery, or the number of preoperative hysteroscopies, have an influence on the intraperitoneal cytology results.

Integrating bevacizumab, everolimus, and lapatinib into current neoadjuvant chemotherapy regimen for primary breast cancer. Safety results of the GeparQuinto trial.

Background: Safety data for combining bevacizumab, everolimus, or lapatinib with anthracycline- and taxane-based neoadjuvant chemotherapy for breast cancer are limited.

Patients And Methods: The neoadjuvant GeparQuinto trial investigates the addition of (i) bevacizumab to four cycles epirubicin/cyclophosphamide (EC) followed by four cycles docetaxel (Taxotere) in patients with human epithelial growth factor receptor (HER)2-negative tumors, (ii) everolimus to weekly paclitaxel in patients with HER2-negative tumors not responding to EC ± bevacizumab, and (iii) lapatinib instead of trastuzumab to EC-docetaxel in patients with HER2-positive tumors to improve the rate of pathological complete response. Tolerable dose, need for supportive treatments, and early signals for toxic effect were evaluated in a planned safety analysis of 270 patients.

Management of fertility preservation in young breast cancer patients in a large breast cancer centre.

Purpose: The increase of breast cancer in young women under 40 years and the increasing age of women at the time of the birth of their first child underlines the importance to implement counselling for fertility-preserving strategies in the management of breast cancer care. We present the fertility-preserving procedures performed after routine counselling for primary breast cancer patients in a large certified breast cancer centre.

Materials And Methods: Since November 2006, patients aged below 40 years with histologically confirmed breast cancer are routinely counselled on fertility-preserving possibilities before breast surgery and chemotherapy in the fertility centre of the University Women's Hospital in Tuebingen.

Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial.

Purpose: This study was aimed at detecting and characterizing circulating tumor cells (CTC) before and after neoadjuvant therapy (NT) in the peripheral blood of patients with breast cancer.

Experimental Design: The clinical trial GeparQuattro incorporated NT approaches (epirubicin/cyclophosphamide prior to randomization to docetaxel alone, docetaxel in combination with capecitabine, or docetaxel followed by capecitabine) and additional trastuzumab treatment for patients with HER2-positive tumors. We used the Food and Drug Administration-approved CellSearch system for CTC detection and evaluation of HER2 expression and developed HER2 immunoscoring for CTC.

Clinical Recommendations of DEGRO and AGO on Preferred Standard Palliative Radiotherapy of Bone and Cerebral Metastases, Metastatic Spinal Cord Compression, and Leptomeningeal Carcinomatosis in Breast Cancer.

Background: To provide guidance for clinical practice on preferred standard palliative radiotherapy (RT) of different sites of metastasis for breast cancer patients based on current published evidence complemented by expert opinion.

Methods: The breast cancer expert panel of the German Society for Radiation Oncology (DEGRO) and members of the Working Party of Gynecologic Oncology (AGO) Breast Committee formulated recommendations based on the panel's interpretation of the level of evidence referring to the criteria of evidence-based medicine added to the AGO grades of recommendation.

Results: For different types and sites of metastasis, distinct therapeutic goals (alleviation of symptoms, pain relief, local tumor control, prevention or improvement of neurological deficits, stabilization of the spine or other bones) require complex approaches considering individual factors (i.

ATP chemosensitivity testing of new antitumor duplex drugs linking 3`-C-ethynylycytidine (ECyd) and 2´-deoxy-5-fluorouridine (5-FdU) in comparison to standard cytostatica and combinations thereof.

Background: 2´-Deoxy-5-fluorouridylyl-(5´-5´)-3´-C-ethynylcytidine [5-FdU(5´-5´)ECyd] and 3´-C-ethynylcytidinylyl-(5´->1-O)-2-O-octadecyl-sn-glycerylyl-(3-Ο->5´)-2´-deoxy-5-fluorouridine [ECyd-lipid-5-FdU] are antitumor active duplex drugs and these heterodinucleoside phosphate analogues could be cleaved in vivo by wide-spread phosphodiesterases into different antitumor active antimetabolites.

Methods: We cultured breast MCF-7, MDA-MB-231 and ovarian OVCAR-29 and OAW-42 cancer cell lines and used the luminometric measuring of the ATP tumor chemosensitivity assay to assess the in vitro activity of 5-FdU(5´-5´)ECyd and ECyd-lipid-5-FdU in comparison to standard single cytostatic agents and combinations thereof currently used in anticancer therapies. To allow comparison between samples and different regimens IndexSUM was determined based on the percentage tumor cell growth inhibition at each test drug concentration.

Optimal treatment for patients with ectopic pregnancies and a history of fertility-reducing factors.

Purpose: With most ectopic pregnancy (EP) cases now diagnosed and treated early, a major concern has become future reproductive outcome. The aim of this study was to evaluate long-term reproductive outcome after salpingotomy versus salpingectomy in patients with and without additional fertility-reducing factors.

Methods: As part of a prospective follow-up study, 261 patients underwent laparoscopic management of EP at our institution.

Clinical Relevance of Disseminated Tumor Cells in the Bone Marrow and Circulating Tumor Cells in the Blood of Breast Cancer Patients.

Subclinical tumor cell spread, as the putative precursor stage of subsequent solid metastases, can be assessed in breast patients via the detection of disseminated tumor cells (DTC) in bone marrow aspirates or circulating tumor cells (CTC) in the peripheral blood with immunocytochemical and molecular techniques. In the context of a growing number of treatment strategies for cancer patients in the adjuvant setting as well as in the metastatic situation, markers predicting therapy efficacy are urgently needed. The detection of DTC or CTC may become one of the most interesting parameters not just for the prediction of survival or therapy monitoring but also for the characterization and specific targeting of residual tumor cells.

HER2 status on persistent disseminated tumor cells after adjuvant therapy may differ from initial HER2 status on primary tumor.

Background: Persistence of disseminated tumor cells (DTCs) is observed in 10 to 15% of breast cancer patients and is associated with poor prognosis. These patients might benefit from secondary adjuvant targeted therapy. The aim of this study was to assess HER2 status of persistent DTCs to determine whether the use of HER2-targeted agents might be a therapeutic option in patients with tumor cell persistence.

Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells.

Introduction: The role of circulating tumor cells (CTCs) in blood of primary breast cancer patients is still under investigation. We evaluated the incidence of CTCs in blood, we evaluated the correlation between CTCs and disseminated tumor cells (DTCs) in the bone marrow (BM), and we characterized CTCs for the expression of HER2, the estrogen receptor (ER) and the progesterone receptor (PR).

Methods: Blood of 431 patients with primary breast cancer were analyzed for EpCAM, MUC1 and HER2 transcripts with the AdnaTest BreastCancer (AdnaGen AG, Germany).

Bisphosphonate-associated osteonecrosis of the jaw in breast cancer patients: recommendations for prevention and treatment.

Osteonecrosis of the jaw (ONJ) is a rare but severe disease which has been diagnosed in women with breast cancer on a bisphosphonate (BP) therapy. Thus, the German society of senology appointed a multidisciplinary task force to establish a consensus on the use of bisphosphonates in breast cancer patients with bone metastases, considering in particular the possible risk of ONJ. This report summarizes the results and recommendations for the prevention and treatment of ONJ in breast cancer patients receiving BP.

Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients.

Introduction: The persistence of circulating tumor cells (CTC) in breast cancer patients might be associated with stem cell like tumor cells which have been suggested to be the active source of metastatic spread in primary tumors. Furthermore, these cells also may undergo phenotypic changes, known as epithelial-mesenchymal transition (EMT), which allows them to travel to the site of metastasis formation without getting affected by conventional treatment. Here we evaluated 226 blood samples of 39 metastatic breast cancer patients during a follow-up of palliative chemo-, antibody - or hormonal therapy for the expression of the stem cell marker ALDH1 and markers for EMT and correlated these findings with the presence of CTC and response to therapy.

Disseminated tumor cells in bone marrow may affect prognosis of patients with gynecologic malignancies.

Introduction: The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of breast cancer patients is associated with poor prognosis. Several studies demonstrated that tumor cell dissemination may occur in gynecologic cancer and affect clinical outcome. The aim of our study was to evaluate the incidence of DTC and to assess their prognostic significance in patients with gynecologic malignancies.

Selective microdochectomy after ductoscopic wire marking in women with pathological nipple discharge.

Background: To investigate the diagnostic reliability of selective microdochectomy after direct ductoscopic wire marking of suspect lesions in patients with pathological nipple discharge.

Methods: Selective microdochectomy due to pathological discharge was performed in 33 patients with mean age of 51.7 years.

Mammotome versus ATEC: a comparison of two breast vacuum biopsy techniques under sonographic guidance.

Purpose: The study evaluates the differences between the Mammotome (MT) and ATEC (A) vacuum biopsy (VB) of the breast in terms of diagnostic reliability, biopsy duration and complications.

Methods: In a prospective randomized study, 62 ultrasound-guided VBs of the breast were performed. MT and A were compared using Mann-Whitney U test.

Membrane-initiated effects of progesterone on proliferation and activation of VEGF in breast cancer cells.

Objective: Progesterone influences mammary gland development and probably breast cancer tumorigenesis and functions by regulating a broad spectrum of physiological processes. We investigated receptor membrane-initiated actions of progesterone in MCF-7 breast cancer cells via progesterone receptor membrane component 1 (PGRMC1).

Design And Method: The expression of PGRMC1 in breast cancer was verified by immune fluorescent analysis of paraffin sections.

A laminin-rich basement membrane matrix influences estrogen receptor beta expression and morphology of MDA-MB-231 breast cancer cells.

The expression of the estrogen receptor beta (ERbeta) has been shown to play an important role in breast cancer. There is emerging hope that ERbeta and its isoforms will be used as prognostic markers or as therapeutic targets in the clinical management of breast cancer. Many studies indicate that ERbeta is down regulated during carcinogenesis.

Bisphosphonate-induced osteonecrosis of the jaw (ONJ): Incidence and risk factors in patients with breast cancer and gynecological malignancies.

Objective: Since 2003, multiple cases of bisphosphonate-induced osteonecrosis of the jaw (ONJ) were reported. The aim of this study was to describe the incidence and risk factors of ONJ in patients with breast cancer or gynecological malignancies receiving bisphosphonates (BP).

Methods: ONJ was recorded for all patients with breast cancer or gynecological malignancies treated with intravenous bisphosphonates at the Department of Gynecology and Obstetrics, University Hospital Tuebingen during April, 1999 and May, 2006.

Micrometastatic spread in breast cancer: detection, molecular characterization and clinical relevance.

Immunocytochemical or molecular assays allow the detection of single disseminated tumor cells (DTCs) in the bone marrow (BM) or the peripheral blood in 10% to 60% of breast cancer patients without signs of metastasis. Results from recently reported studies suggest that circulating tumor cell (CTC) levels may serve as a prognostic marker and be used for early assessment of therapeutic response in patients with metastatic breast cancer. In early stage breast cancer, however, the impact of CTCs is less well established than that of DTCs in BM, where several clinical studies demonstrated that such cells are an independent prognostic factor at primary diagnosis.

Breast cancer proteomics reveals correlation between estrogen receptor status and differential phosphorylation of PGRMC1.

Introduction: Breast tumors lacking the estrogen receptor-alpha (ER-alpha) have increased incidence of resistance to therapy and poorer clinical prognosis.

Methods: Whole tissue sections from 16 cryopreserved breast cancer tumors that were either positive or negative for the ER (eight ER positive and eight ER negative) were differentially analyzed by multiplex imaging of two-dimensional PAGE gels using 54 cm isoelectric focusing. Differentially detected spots of Progesterone Receptor Membrane Component 1 (PGRMC1) were shown to differ in phosphorylation status by differential two dimensional polyacrylamide gel electrophoresis of phosphatase-treated tumor proteins.

Tumor cell dormancy: implications for the biology and treatment of breast cancer.

Despite progress made in the therapy of solid tumors such as breast cancer, the prognosis of patients even with small primary tumors is still limited by metastatic relapse often long after removal of the primary tumor. Therefore, it has been hypothesized that primary tumors shed tumor cells already at an early stage into the blood circulation. A subset of these disseminated tumor cells may persist in a state of so-called "dormancy".