For the first time in neoadjuvant ABCSG trials, the RCB score is defined as primary study endpoint. approaches are aiming to increase the efficacy of neoadjuvant therapy. Inclusion of capecitabine might further increase pCR rates in selected patients, although data are not unanimous throughout the respective clinical trials. In patients harbouring BRCA-1 germline mutations, platinum derivatives are apparently promising. Emeramide (BDTH2) Novel Her2-targeted agents such as lapatinib Rabbit Polyclonal to PPP2R3C and pertuzumab are currently under investigation in several clinical trials, while the role of bevacizumab, a monoclonal antibody inhibiting angiogenesis, awaits future clarification. Keywords:Breast cancer, Chemotherapy, Neoadjuvant therapy, Targeted therapy == Abstract == Brustkrebs ist der hufigste bsartige Tumor bei Frauen. Traditionell stellt die Operation den ersten Behandlungsschritt dar, eine systemische Therapie wird meist danach verabreicht. Die Studie B-18 der NSABP (National Surgical Adjuvant Breast and Bowel Project) konnte nachweisen, dass kein Nachteil resultiert, wenn die systemische Therapie vor einer Operation verabreicht wird. Als Vorteil zeigte sich eine signifikant hhere Rate an brusterhaltenden Operationen. Moderne neoadjuvante Regime enthalten Anthrazykline und Taxane, wodurch ein pathologisch komplettes Ansprechen (pCR) bei etwa 20% der Patientinnen erzielt wird. Bei tripel-negativen Tumoren wurde eine berlegene Wirksamkeit beobachtet. Mit pCR-Raten von bis zu 50% ist Trastuzumab, ein gegen den Her2-Rezeptor gerichteter monoklonaler Antikrper, die erste zielgerichtete Therapie, die Eingang in die neoadjuvante Behandlung Her2-positiver Tumore gefunden hat. Bei einem Teil der Patientinnen scheint eine Erweiterung der Chemotherapie um zustzliche Zytostatika wie Capecitabin die pCR-Raten zu steigern, allerdings sind die diesbezglichen Ergebnisse klinischer Studien nicht einhellig. Bei Frauen mit erblicher BRCA-1-Mutation knnten Platinderivate eine besondere Wirksamkeit aufweisen. Bei Her2-positiven Tumoren werden alternativ oder additiv zu Trastuzumab Substanzen wie Lapatinib und Pertuzumab in klinischen Studien getestet, bislang vorliegende Ergebnisse erscheinen vielversprechend. Die Rolle von Bevacizumab, einem Antikrper gegen den Gefwachstumsfaktor VEGF, im neoadjuvanten Setting ist unklar, und weitere Ergebnisse mssen abgewartet werden. == Introduction == The term breast cancer as understood today summarizes a heterogeneous group of malignancies with major disparities in terms of prognosis and treatment response. The Stanford Group first established the classic intrinsic classification of luminal, human epidermal growth factor receptor 2 (Her2)-positive, normal-like, and basal-like cancers [1]. Herein, luminal is once more separated into luminal A highly oestrogen-dependent and therefore oestrogen receptor- and progesterone receptor-positive with low grading and a low proliferation rate and a less endocrine-responsive subtype called Emeramide (BDTH2) luminal B. Emeramide (BDTH2) The Her2-positive subtype describes highly consistent Her2-positive cancers as defined by immunohistochemistry or fluorescence-in-situ-hybridization (FISH). Basal-like breast cancers have a gene expression profile similar to the profile of myoepithelial cells of the basal epithelial layer of milk ducts [1]. Typically, those tumours are characterized by the lack of Her2 as well as hormone receptor (HR) expression; therefore, in the clinical routine setting, the term triple-negative tumour is often used as surrogate for the basal-like subtype, with approximately 80% concordance [2]. While targeted treatment options are available for HR-positive and Her2-positive tumours, chemotherapy remains the mainstay of treatment for triple-negative disease. It was recently suggested that so-called core basal-likes were related to tumours harbouring germline BRCA-1 mutations [3]. This, in terms, lead to the assumption that certain treatment strategies such as inhibitors of PARP-1 or platinum salts might prove fruitful in the treatment of triple-negative breast cancers [4]. == Breast Cancer and Neoadjuvant Therapy == Starting in the 1970ies, preoperative systemic therapy was initially administered in cases of locally advanced inoperable breast cancer only [5]. Since those days, the concept of neoadjuvant treatment has evolved to become a standard in operable Emeramide (BDTH2) disease also, with the objective Emeramide (BDTH2) to increase the rate of breast conservation [6]. A milestone in this process was National Surgical Breast and Bowel Project (NSABP) trial B-18 which established equal efficacy of 4 cycles of doxorubicin plus cyclophosphamide, whether given before or after operation [7]. Over the last 30 years, a broad spectrum of different chemotherapeutic drugs has been studied in the neoadjuvant setting. Based upon those results, the respective consensus statements of the 2009 2009 and 2011 St. Gallen Conferences state that neoadjuvant chemotherapy regimens should contain an anthracycline and a taxane [8,9]; as for the duration of.