Discordant assessment of tumor biomarkers by histopathological and molecular assays in the EORTC randomized controlled 10041/BIG 03-04 MINDACT trial breast cancer

Accurate identification of breast cancer patients most likely to benefit from adjuvant systemic therapies is crucial. Better understanding of differences between methods can lead to an improved ER, PgR, and HER-2 assessment. The purpose of this preplanned translational research is to investigate the correlation of central IHC/FISH assessments with microarray mRNA readouts of ER, PgR, and HER-2 status in the MINDACT trial and to determine if any discordance could be attributed to intratumoral heterogeneity or the DCIS and normal tissue components in the specimens. MINDACT is an international, prospective, randomized, phase III trial investigating the clinical utility of MammaPrint in selecting patients with early breast cancer for adjuvant chemotherapy (n = 6694 patients). Gene-expression data were obtained by TargetPrint; IHC and/or FISH were assessed centrally (n = 5788; 86 %). Macroscopic and microscopic evaluation of centrally submitted FFPE blocks identified 1427 cases for which the very same sample was submitted for gene-expression analysis. TargetPrint ER had a positive agreement of 98 %, and a negative agreement of 95 % with central pathology. Corresponding figures for PgR were 85 and 94 % and for HER-2 72 and 99 %. Agreement of mRNA versus central protein was not different when the same or a different portion of the tumor tissue was analyzed or when DCIS and/or normal tissue was included in the sample subjected to mRNA assays. This is the first large analysis to assess the discordance rate between protein and mRNA analysis of breast cancer markers, and to look into intratumoral heterogeneity, DCIS, or normal tissue components as a potential cause of discordance. The observed difference between mRNA and protein assessment for PgR and HER-2 needs further research; the present analysis does not support intratumoral heterogeneity or the DCIS and normal tissue components being likely causes of the discordance.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015

The 14th St Gallen International Breast Cancer Conference (2015) reviewed new evidence on locoregional and systemic therapies for early breast cancer. This manuscript presents news and progress since the 2013 meeting, provides expert opinion on almost 200 questions posed to Consensus Panel members, and summarizes treatment-oriented classification of subgroups and treatment recommendation

New developments in hormone receptor-positive disease.

Of more than one million women diagnosed with breast cancer each year, approximately 700,000 have hormone receptor (HR)(+) disease. Although endocrine therapy has revolutionized breast cancer management and substantially improved outcomes in these patients, the optimal management of these patients remains a significant challenge. For instance, the threshold for adding adjuvant chemotherapy is a topic of continuing debate, and the most effective regimens that include endocrine therapy and chemotherapy are still under debate as well. Tumor markers, such as Ki-67, and host markers, such as cytochrome P450 2D6, are being studied as potential tools to offer more tailored adjuvant endocrine therapy. Current research suggests that luminal A and luminal B cancers are two completely different diseases, and work is being performed to better distinguish between these two disease types and deliver more effective therapy to individual patients. This article addresses these important outstanding issues with respect to HR(+) disease.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Ovarian cancer: new therapeutic concepts, renewed optimism.

Journal Articleinfo:eu-repo/semantics/publishe

Regarding the dilemma of adjuvant therapy in postmenopausal patients with node-positive, estrogen receptor-positive breast cancer: are we better informed?

CommentLetterinfo:eu-repo/semantics/publishe

Systemic treatment for locally advanced breast cancer: what we still need to learn after a decade of multimodality clinical trials.

Multimodality therapy of locally advanced breast cancer with initial chemo-(hormono)-therapy followed by locoregional treatment has become increasingly popular during the past decade. A paucity of large randomised clinical trials leaves the following unanswered questions: does systemic treatment impact on long-term control of distant metastases? What is the best treatment sequence? The most effective drug combination? The optimum treatment duration? Future prospects in the treatment of locally advanced breast cancer include the use of haematopoietic growth factors to increase the dose-intensity of neoadjuvant chemotherapy, the investigation of autologous bone marrow transplantation with high dose chemotherapy on a larger scale, the development of new approaches designed at interrupting the "autocrine loop" of breast cancer local growth factors and the introduction of diphosphonates in the adjuvant systemic therapy.Journal ArticleReviewinfo:eu-repo/semantics/publishe

Docetaxel in advanced ovarian cancer: preliminary results from three phase II trials. EORTC Early Clinical Trials Group and Clinical Screening Group, and the MD Anderson Cancer Center.

Docetaxel has been evaluated in 293 patients with advanced ovarian cancer in three phase II trials. All patients had previously received cisplatin and/or carboplatin as first-line treatment. In all three studies, treatment comprised docetaxel 100 mg/m2 as a 1 h intravenous infusion every 3 weeks, without premedication for hypersensitivity reactions or emesis. To date, 200 patients are evaluable for response. Of these, 63 patients achieved complete or partial response, giving an overall response rate of 31.5% (95% confidence interval 24-39%) for all evaluable patients, or 21.5% for all patients entered in the studies. Of the 57 patients whose disease had progressed either during previous therapy or within 4 months of discontinuing previous therapy, 13 (23%) responded to docetaxel (EORTC data). Major adverse effects of docetaxel observed in approximately half the patients (particularly those who received more than four courses) included skin reactions and fluid retention. Grade III or IV neutropenia was common but short-lived. Severe acute hypersensitivity reactions occurred in approximately 5% of patients. Docetaxel now warrants evaluation as part of first-line therapy. Studies aimed at reducing the incidence of fluid retention and skin reactions with docetaxel are ongoing.Clinical TrialClinical Trial, Phase IIJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe