70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.

The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.)

The Breast International Group. a new spirit of collaboration in breast cancer research for the new millennium.

The Breast International Group (B.I.G.-aisbl), an official non-profit organisation since 1999, is an association whose members are well established clinical breast cancer research groups located around the world. Inspired by the American 'Intergroup' model, B.I.G. functions as a 'consortium of consortia': it is a partnership among independent co-operative groups, each with its own extensive network of affiliated centres, hospitals, laboratories and investigators. Through B.I.G. groups draw on combined resources to reduce the wasteful duplication of efforts and to achieve results in breast cancer research impossible for any individual group in a comparable period of time. International collaboration through a mechanism like B.I.G. will become increasingly frequent in the future, especially as we move towards exploring therapies targeted at subgroups of patients with specific tumour molecular profiles.Journal Articleinfo:eu-repo/semantics/publishe

Vision and collaboration: essential ingredients for the future of breast cancer research. Editorial overview

SCOPUS: ed.jinfo:eu-repo/semantics/publishe

The EORTC strategy for the early 2000's.

Letterinfo:eu-repo/semantics/publishe

La nouvelle génération des études cliniques sur le cancer du sein: la bonne drogue et la bonne cible.

The principal mission of the Breast International Group (Big), Transbig, and the Breast European Adjuvant Study Team (Breast), all located at the Jules Bordet Institute in Brussels, is to accelerate and facilitate the initiation and conduct of large and difficult breast cancer clinical trials. This is made possible through the excellent network of research groups, scientists, physicians and many other collaborators deeply committed to academic clinical and translational research. A clear example of this collaboration is the HERA trial (Herceptin Adjuvant trastuzumab in HER2 positive early breast cancer) that contributed to a change of clinical practice and improved the prognosis for this particular patient population. In addition, there is an important new generation of adjuvant trials, for example, Mindact, which is evaluating the use of microarray technology in treatment decision making, and the Altto and Neo-Altto studies, which have just started and are evaluating lapatinib, a small tyrosine kinase molecule given either adjuvantly or neo-adjuvantly, alone, sequentially or in combination with trastuzumab, in patients with HER2 positive early breast cancer. The latter studies, with their strong translational research component, aim to determine which tumour profiles will best benefit from lapatinib as opposed to treatment with trastuzumab alone.English AbstractJournal ArticleReviewinfo:eu-repo/semantics/publishe

TRANSBIG: The way forward in breast cancer research

info:eu-repo/semantics/publishe

Better translation from bench to bedside: breakthroughs in the individualized treatment of cancer.

This article reflects on progress made in recent years with respect to bench-to-bedside research in breast cancer. It shows how the advent of molecular oncology-accompanied by high-throughput experimental methods and "omics" technologies-has led researchers to realize that breast cancer is a heterogeneous disease for which a "one size fits all" approach to patient treatment is no longer optimal. This, in turn, has contributed to a change in thinking about clinical trial design. Using several examples of clinical trials being run under the umbrella of the Breast International Group, including the recently launched Microarray In Node-negative Disease may Avoid ChemoTherapy study and Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization study, the article looks at how translational research and biological specimen collection has become a central component of clinical research design in a relatively short period of time. This, plus an evolution in research culture that has resulted in increased international collaboration among research networks, groups, and centers, will arm researchers with the tools needed to develop truly individualized cancer treatments for patients in the future.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Adjuvant chemotherapy in elderly patients with breast cancer: a survey of the Breast International Group (BIG).

BACKGROUND: To collect oncologists' experience and opinion on adjuvant chemotherapy in elderly breast cancer patients. MATERIALS AND METHODS: A questionnaire was circulated among the members of the Breast International Group. RESULTS: A total of 277 oncologists from 28 countries participated in the survey. Seventy years is the age cut-off commonly used to define a patient as elderly. Biological age and the biological characteristics of the tumor are the most frequently used criteria to propose adjuvant chemotherapy to an elderly patient. Combination therapy with cyclophosphamide, methotrexate and fluorouracil on days 1 and 8 is the most frequently prescribed regimen. Great interest exists in oral chemotherapy. CONCLUSION: There is interest among those who responded to the survey to validate a comprehensive geriatric assessment for use as a predictive instrument of toxicity and/or activity of anticancer therapy and to evaluate the role of a treatment option that is potentially less toxic and possibly as effective as polychemotherapy.Journal Articleinfo:eu-repo/semantics/publishe

Struggle as metaphor in European Union discourses on unemployment.

This study looks at how, over a period of several years, unemployment in two genres (speeches and Presidency Conclusions) generated in organizations of the European Union (EU) is constructed both as a `problem' and a `fight' and how these formulations can be viewed as closely connected under an overarching metaphor of `struggle'. A synthesis of discourse analytic and cognitive-semantic analyses, this article begins by demonstrating how struggle is invoked and then proceeds to decompose the notion into several categories, using statistical analysis to show their distribution. Ultimately, it is demonstrated that the differences between the two genres are connected to their respective purposes and target audiences, with Presidency Conclusions examples of internal organizational discourse and commissioners' speeches as external organizational discourse. The similarities between the two genres reflect the functions of the struggle metaphor in EU discourses of unemployment in general, the ways in which its dimensions serve various legitimizing functions in these genres' capacity as political discourse, and the connection between discourses on unemployment and the prevailing EU economic philosophy