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Erlangen, Germany

Von Wolff M.,University of Bern | Montag M.,University of Bonn | Dittrich R.,University Womens Hospital | Denschlag D.,Hochtaunus Kliniken | And 2 more authors.
Archives of Gynecology and Obstetrics | Year: 2011

Purpose Fertility preservation methods are playing an increasing role in women up to the age of 40 years because of rising survival rates in those affected by cancer. However, balanced practical recommendations concerning all relevant fertility preservation, to support doctors in counselling and treating patients, are still rare. Methods These recommendations were prepared by the network FertiPROTEKT (http://www.fertiprotect.eu), a collaboration of around 70 centres in Germany, Switzerland and Austria. The recommendations were developed by specialists in reproductive medicine, reproductive biology and oncology, which gave a comprehensive overview of all named techniques as well as their benefits and risks. Furthermore, practice-orientated recommendations for the individual use of fertility preservation methods for various indications such as breast cancer, Hodgkin's lymphoma and borderline ovarian tumours are given. Results Various options such as ovarian stimulation and cryopreservation of unfertilised or fertilised oocytes, cryopreservation and transplantation of ovarian tissue, GnRH-agonist administration and transposition of the ovaries can be offered. All the techniques can be performed alone or in combination within a maximum of 2 weeks with low risk and different success rates. Conclusions Fertility preservation in women has become an option with realistic chances to become pregnant after cytotoxic therapies. The information provided allows a well balanced and realistic counselling and treatment. © The Author(s) 2011.


Stute P.,University Womens Hospital | Reichenbach A.,University Clinic of Muenster | Szuwart T.,University Clinic of Muenster | Kiesel L.,University Clinic of Muenster | Gotte M.,University Clinic of Muenster
Maturitas | Year: 2012

Objectives: Postmenopausal hormone therapy (HT) increases local estrogen formation in breast tissue. The enzymatic substrates depend on transmembrane anion transporting polypeptides (OATPs) to reach intracellular enzymes. The aim of this study was to investigate the effect of testosterone (T) on the expression of OATP-1A2, OATP-2B1, and OATP-3A1 in malignant (MCF-7, BT-474) and non-malignant (HBL-100) breast cells in vitro. Study design: Cells were incubated in RPMI 1640 medium containing 5% steroid-depleted fetal calf serum for 3d, and subsequently incubated in the absence or presence of T, anastrozole (A), and T+A (10 -6 M) for 24 h at 37 °C. Main outcome measures: OATP expression was determined by immunocytochemical staining. Expression intensity was graded as low, moderate, or strong. Hormone receptor (AR, PR, ESR1, ESR2) expression was investigated by qPCR and Western blotting. Rank variance analysis was performed for statistical analysis (p ≤ 0.05). Results: OATP-1A2, OATP-2B1, and OATP-3A1 expression was present in all untreated breast cell lines examined, with OATP-1A2 and OATP-3A1 being the predominant ones. There was a trend for a higher baseline expression in untreated HBL-100 and BT-474 in comparison to MCF-7 cells, which was significant for OATP-2B1. T treatment led to decreased OATP-1A2, -2B1, and -3A1 expression in BT-474 and HBL-100 cells, respectively. In contrast, in MCF-7 cells, OATP-2B1 expression was significantly increased. T-induced upregulation of AR and PR protein expression in BT-474 and MCF-7 cells was reduced by A treatment. Conclusions: T may constitute a signal for differential regulation of mammary OATP expression. In non-malignant breast cells T seems to have a beneficial effect by reducing the availability of substrates for the intracellular formation of potent estrogens. © 2012 Elsevier Ireland Ltd. All rights reserved.


Von Minckwitz G.,German Breast Group | Von Minckwitz G.,University Womens Hospital | Fontanella C.,German Breast Group | Fontanella C.,University of Udine
Breast | Year: 2013

The relationship between achievement of a pathologic complete response (pCR) and favorable long-term outcome varies among breast cancer subtypes. We aimed to highlight which neoadjuvant treatment strategy could be most successful in each breast cancer subtype. A recent FDA meta-analysis on randomized neoadjuvant breast cancer trials suggests that the survival differences of patients with or without a pCR were less pronounced in luminal A-like tumors, despite the overall favorable prognosis of these patients. Moreover, even though the strong prognostic effect of pCR in HER2 positive and TNBC, the NOAH study was the only trial which showed a trend in surrogacy of pCR for long-term outcome in HER2-positive subtype. Results from GeparTrio study suggest that patients with hormone-positive tumors might need a response-guided approach, with either an intensification of treatment in case of an early response or a change to other chemotherapy in case of no early response. Furthermore, data from German neoadjuvant trials confirm that an increasing number of chemotherapy cycles is associated with a higher pCR rate, especially in patients with HER2-positive/hormone-positive tumors. In line with these suggestions, Tryphaena study showed a pCR rate that exceeding the 60% threshold, the highest pCR results presented in a large multicenter study. In TNBC, the highest pCR rate in the German neoadjuvant studies was obtained with the simultaneous application of docetaxel, doxorubicin and cyclophosphamide for 6 cycles. However, as shown in GaparQuinto and NSABP 40 trials, treatment effect in TNBC might be further maximized by adding bevacizumab, and two randomized neoadjuvant trials are expected this year to report data on the efficacy of carboplatin. © 2013 Elsevier Ltd.


von Minckwitz G.,German Breast Group | von Minckwitz G.,University Womens Hospital
Hematology/Oncology Clinics of North America | Year: 2013

Lessons have recently been learned in the use of neoadjuvant chemotherapy. This article explains how diagnosis of a pathologic complete response (pCR) can avoid an unfavorable prognosis in patients with high-risk breast cancer; how the surrogacy of pCR for long-term survival remains questionable; how translational biomarker studies have not been helpful in identifying patients with a high chance of treatment benefit; assessment of the prognosis of patients without a pCR for identifying patients at high risk and which clinical trials will be available for these patients in the near future; and which patients might require less locoregional treatment. © 2013 Elsevier Inc.


Konecny G.E.,University of California at Los Angeles | Paepke S.,TU Munich | von Minckwitz G.,German Breast Group c o GBG Forschungs GmbH | von Minckwitz G.,University Womens Hospital
Breast | Year: 2014

Neoadjuvant systemic chemotherapy is a possible therapeutic approach for the treatment of locally advanced operable, primarily non-operable or inflammatory breast cancer. Neoadjuvant systemic chemotherapy is an option for breast cancer patients who would require adjuvant chemotherapy otherwise based on clinical and histological examination and imaging. The use of neoadjuvant systemic therapy in operable breast cancer is currently increasing because of its advantages that include higher rates of breast conserving surgery and the possibility of measuring early in-vivo response to systemic treatment. The timing of axillary sentinel lymph node diagnosis (i.e. before or after neoadjuvant chemotherapy) is critical in that it may influence the likelihood of axillary preservation. It is not yet clear if neoadjuvant therapy might improve outcomes in certain subgroups of breast cancer patients. Neoadjuvant treatment modalities require a close collaboration between oncology professionals, including surgeons, gynecologists, medical oncologists, radiation oncologists, radiologists and pathologists. The most important parameter for treatment success and improved overall survival is the achievement of a pathologic complete response (pCR), although the role of pCR in patients with luminal A like tumours might be less informative. Identification of patient subgroups with high pCR rates may allow less invasive surgical or radiological interventions. Patients not achieving a pCR may be candidates for postoperative clinical trials exploring novel systemic treatments. © 2014 Elsevier Ltd.

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