Laura van 't Veer, PhD

2009-2010 BCRF Project:
The Breast International Group and TRANSBIG, Brussels, Belgium
(made possible by generous support from Roche)
Co-investigators: Martine Piccart-Gebhart, MD, PhD, Jules Bordet Institute; Fatima Cardoso, MD, Jules Bordet Institute; Phillippe Bedard, MD, Jules Bordet Institute; Giuseppe Viale, MD, PhD, University of Milan School of Medicine

In February 2007 an international research network known as the TRANSBIG Consortium launched the innovative MINDACT clinical trial (Micro array In Node negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy). The goal of this trial is to determine if a new test should be used to help doctors decide upon the best treatment for women diagnosed with early stage breast cancer. This new test, known as the 70-gene signature (or MammaPrint™), analyzes the genes of a patient's tumor to see if a cancer is likely to come back (in which case treatment with chemotherapy after surgery is probably needed) or not (in which case chemotherapy can safely be avoided).

MINDACT is an ongoing complex multinational clinical trial that has been recruiting patients since March 2007 and is now recruiting about 140 patients per month. The trial had a predefined "pilot phase" consisting on the first 800 patients enrolled. This important milestone was achieved in November 2008. Since the trial is contingent upon the comparison of the 70-gene signature with the standard clinical and pathological risk factors that doctors routinely use to decide whether a patient should be treated with chemotherapy, it is important to ensure that the pathological assessment of tumor specimens is consistent across the centers participating in the study. Previous studies have shown that there may be discrepancies in the assessment of histological grading, hormonal receptor status and HER-2 protein overexpression and/or gene amplification in up to 20% of cases between different pathological laboratories.

The goal of the current study is to retest the key pathological characteristics of the first 800 patients enrolled in the trial in a high quality pathology laboratory and evaluate how discrepancies in pathological assessment with local testing may affect the underlying assumptions for the ongoing MINDACT trial. In addition, the traditional pathological assessment of key markers at the protein level will be compared with expression of the gene using a new technology known as whole genome microarray. Ultimately, the hope is that in the future doctors can reliably distinguish women with breast cancer who can be spared unnecessary chemotherapy with those who need additional therapy to prevent a recurrence of their breast cancer.

Bio:
Laura van 't Veer is Head of Molecular Pathology at The Netherlands Cancer Institute, Amsterdam. She received her M.Sc. degree in Biology (1984) at the University of Amsterdam and a PhD in Medicine (1989) at the University of Leiden, The Netherlands. She did her postdoctoral training at the Cancer Center of the Harvard Medical School and The Massachusetts General Hospital, Boston, USA (1989-1991) and The Netherlands Cancer Institute (1992-1993). In 2003 she was one of the founders of the Netherlands Cancer Institute spin-off, the molecular profiling company Agendia.

Dr. van 't Veer is first author of a study showing that microarray genomics technology can predict which breast tumors will likely metastasize and which will not (Nature 2002, NEJM 2002). When these findings are implemented into daily clinical practice, the amount of so-called adjuvant treatments with chemotherapy for (pre-menopausal) breast cancer patients could be reduced by up to thirty percent. This microarray test now called MammaPrint, is central to the work of the translational research network TRANSBIG (Translational Research Breast International Group). The MINDACT trial is worldwide the first large scale clinical trial implementing genomics.

Dr. van 't Veer received for this work the 2007 European Society of Medical Oncology (ESMO) life-time achievement award for translational research in breast cancer.