Besides the traditional therapeutic options, treatment with antibodies specific for the receptor tyrosine kinase HER-2/neu has been established as a standard therapy in the clinical management of ...advanced breast cancer. Ongoing clinical studies focus on the improvement of application protocols in order to minimize side effects and evaluate the potential therapeutic benefit of anti-HER-2/neu antibodies in combination with conventional chemotherapy. Various similar strategies to target other tumour-associated antigens or proangiogenic factors with inhibitory antibodies are currently investigated in promising preclinical and clinical trials. In addition, research efforts are made to develop procedures to generate tumour-specific cellular immune responses in breast cancer patients. Therapeutic vaccination is, however, still at an early stage of development, despite encouraging results of animal studies. We summarise and discuss vaccination strategies with tumour-specific proteins or peptides, pulsed dendritic cells, and modified tumour cells as well as antibody-based therapeutic concepts to target HER-2/neu, EGF receptor, MUC-1, uPA/uPAR, and VEGF.
Purpose
Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The ...Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion.
Methods
The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology.
Results
Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference.
Conclusions
In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.
Zusammenfassung
Die Prognose des Ovarialkarzinoms ist abhängig vom initialen Tumorstadium und vom postoperativen Tumorrest. Letzterer ist der wesentliche durch die chirurgische Therapie ...beeinflussbare Prognosefaktor. Der Beitrag stellt in Anlehnung an die aktuelle Leitlinie der Kommission Ovar der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO): „Diagnostik, Therapie und Nachsorge maligner Ovarialtumoren“ Empfehlungen zur chirugischen Behandlung des primären Ovarialkarzinoms dar. Patientinnen, die eine leitliniengerechte Therapie durchgeführt erhalten, haben eine höhere Überlebenswahrscheinlichkeit als Patientinnen, bei denen dies nicht der Fall ist. Beim frühen Ovarialkarzinom (FIGO I-IIA) ist die Durchführung einer systematischen Staging-Operation einschließlich der paraaortalen und pelvinen Lymphonodektomie notwendig. Im fortgeschrittenen Stadium sollen unter Berücksichtigung des Allgemeinzustandes der Patientin auch multiviszerale Resektionen durchgeführt werden, soweit dadurch Tumorfreiheit erreicht werden kann.
Zusammenfassung
Patientinnen mit lokoregionärem Mammakarzinomrezidiv bilden ein prognostisch sehr heterogenes Kollektiv, dieses kann kategorisiert werden anhand der erhaltenen Vortherapie und der ...Lokalisation des Rezidivs. Aufgrund der Assoziation mit prognostisch ungünstigen Faktoren des Primärkarzinoms haben Patientinnen mit regionären Lymphknotenmetastasen oder Thoraxwandrezidiven nach Mastektomie insgesamt eher eine ungünstige Prognose, während Patientinnen mit intramammärem Rezidiv ohne Lymphknotenbefall insbesondere bei positivem Rezeptorstatus eine deutlich bessere Prognose aufweisen. Die lokale Kontrolle durch Resektion, ggf. mit anschließender Radiatio, steht im Mittelpunkt der kurativen Therapie. Die postoperative systemische Therapie sollte risikoadaptiert erfolgen. Über die optimale Strategie kann derzeit aufgrund fehlender prospektiver Studien nur spekuliert werden.
•The OPBC and EUBREAST ranked 51 important questions in axillary management.•Guidelines should be developed for axillary imaging and de-escalation of surgery.•Research was recommended for ...de-escalation of radiotherapy.•Management of residual nodal disease after surgery remains unclear.
The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register.
One attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non-cross-resistant drugs to platinum-paclitaxel combination regimens. ...Gemcitabine was among the candidates for a third drug.
We performed a prospective, randomized, phase III, intergroup trial to compare carboplatin plus paclitaxel (TC; area under the curve AUC 5 and 175 mg/m(2), respectively) with the same combination and additional gemcitabine 800 mg/m(2) on days 1 and 8 (TCG) in previously untreated patients with advanced epithelial ovarian cancer. TC was administered intravenously (IV) on day 1 every 21 days for a planned minimum of six courses. Gemcitabine was administered by IV on days 1 and 8 of each cycle in the TCG arm.
Between 2002 and 2004, 1,742 patients were randomly assigned; 882 and 860 patients received TC and TCG, respectively. Grades 3 to 4 hematologic toxicity and fatigue occurred more frequently in the TCG arm. Accordingly, quality-of-life analysis during chemotherapy showed a disadvantage in the TCG arm. Although objective response was slightly higher in the TCG arm, this did not translate into improved progression-free survival (PFS) or overall survival (OS). Median PFS was 17.8 months for the TCG arm and 19.3 months for the TC arm (hazard ratio HR, 1.18; 95% CI, 1.06 to 1.32; P = .0044). Median OS was 49.5 for the TCG arm and 51.5 months for the TC arm (HR, 1.05; 95% CI, 0.91 to 1.20; P = .5106).
The addition of gemcitabine to carboplatin plus paclitaxel increased treatment burden, reduced PFS time, and did not improve OS in patients with advanced epithelial ovarian cancer. Therefore, we recommend no additional clinical use of TCG in this population.
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