TRANSBIG’s first clinical trial, MINDACT (MIcro-array for Node negative and 1 to 3 lymph node Disease may Avoid ChemoTherapy) is a multicentre, prospective, phase III trial coordinated by the European Organisation for Research and Treatment of Cancer (EORTC). The trial aims to compare the 70-gene prognostic signature test with currently used clinical-pathological methods to assess the risk of breast cancer recurrence in patients with lymph node negative disease i.e. the tumour has not yet spread.
By using the genomic test in addition to traditional methods, it is hoped that more accurate risk assessment can be achieved, sparing many lymph node negative patients from chemotherapy and its potential side effects.
The trial also aims to determine the best treatment in terms of chemo- and hormonal therapies.
In November 2008, the MINDACT trial reached the pilot phase, involving the first 800 patients enrolled. Preliminary results demonstrated
the logical feasibility of the trial, a
high compliance rate among physicians and patients, and that the overall process (using frozen materials) provides good quality data and biological materials.
Patient recruitment has continued and aims to increase from 150 to 200 per month, ultimately to reach 6,000 women during 2011 to the end of 2012.
Initially, physicians were involving more lower risk patients than expected, pointed out Dr Fatima Cardoso, Assistant Professor in Medical Oncology (Jules Bordet Institute, Brussels, Belgium) and Scientific Director of the TRANSBIG network, probably because they had reservations about chemotherapy not being given. This was discouraging. ‘We thought we were only ones in the world that believed in the genomic test,’ Dr Cardoso said. However, there is now less scepticism because people are far more comfortable about genetic signatures than five years ago, she pointed out. Concern that genomic tests would end the role of pathologists has also changed. ‘This is an important new tool, to be incorporated with all the others we have,’ added Dr Cardoso.
BIG, created in 1996 by leading European opinion leaders, now involves research participants based in European countries*, Canada, Latin America, Asia and Australasia, linking with about 3,000 specialised hospitals and research centres.
In Germany, for example, the Deutsche Krebshilfe, a non-government organisation that promotes cancer research and education, is providing over a million euros to fund the ten-year MINDACT study.
Working on establishing the genetic signature of the tumour, Professor Ulrike Nitz, director of the Niederrhein Breast Centre in Mönchengladbach, coordinates the MINDACT study in Germany. ‘Every tumour has its own specific molecular “finger print”, which allows us to assess the relapse risk,’ she explained. This signature is determined using micro-array technology that can analyse many thousands of genes simultaneously.
The traditional method to assess cancer aggressiveness, i.e. the risk of recurrence, is based on clinical/pathological criteria, such as the patient’s age, tumour size, microscopic tumour cells grading, hormone receptors and whether the cancer has spread to lymph nodes. If high-risk is assessed, breast cancer patients receive adjuvant chemotherapy.
Based on the micro-array technology, the gene signature (commercial name: MAMMAPRINT), which was identified by the Netherlands Cancer Institute, individually defines which genes of a woman’s tumour are active or not, presenting data for tumour recurrence prognosis.
Node-negative breast cancer patients who are particularly at risk of cancer recurrence can voluntarily participate in the MINDACT study. Patients who will undergo chemotherapy are randomly selected, a procedure that is an important criterion for the validity of the study and which provides the framework for determining whether the new genetic signature reliably indicates the breast cancer relapse risk. All patients – those receiving chemotherapy and those not – are to be closely monitored.
In the future, Prof Nitz said: ‘We expect to be able to spare 20% of the women from strenuous chemotherapy without compromising their chances of survival.’
* Austria, Belgium, Cyprus, Czech Republic, Denmark, France, Germany, Greece, Ireland, The Netherlands, Italy, Luxembourg, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom.