Philippe Bedard, MD

2008-2009 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; Laura van 't Veer, PhD, Netherlands Cancer Institute; Giuseppe Viale, MD, PhD, University of Milan School of Medicine

In early 2007 the TRANSBIG Consortium, an international research network, launched the MINDACT clinical trial, which is testing a new strategy to individualize treatment for women with breast cancer. The goal of this trial is to assess the usefulness of a 70-gene signature (commercialized under the name of MammaprintTM) in determining the best treatment for women with breast cancer after their breast cancer has been surgically removed.

Developed by a member of the TRANSBIG Consortium, the Netherlands Cancer Institute, this 70-gene signature is a tool that can analyze genes in a patient's tumor and determine whether 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). Today, women whose cancer has spread to the surrounding lymph nodes are thought to be at higher risk for having their cancer return and are often treated with chemotherapy after their cancer has been removed. Previously, the 70-gene signature had only been validated in women whose cancer had not spread to their lymph nodes, and women with lymph node involvement were excluded from participating in MINDACT.

Since receiving a BCRF grant in October 2007, the TRANSBIG Consortium has demonstrated that the 70-gene signature can also be used to identify patients whose cancer involves 1 to 3 lymph nodes but have a low risk of recurrence. As a result, the MINDACT trial now includes women with 1 to 3 involved lymph nodes. Traditionally, women who are 70 years of age or older with breast cancer have not been allowed to participate in clinical trials studying new tests and treatments. So far, the 70-gene signature has only been tested in women less than 70 years of age, and the MINDACT trial does not allow older women to participate.

With continued support from the BRCF, TRANSBIG will be able to finalize testing the utility of the 70-gene signature in predicting the risk of relapse in elderly women diagnosed with breast cancer, which may lead to the inclusion of these patients in MINDACT. Ultimately, the hope is that doctors may use the 70-gene signature in the future to better identify women with breast cancer, regardless of lymph node involvement and age, who can be spared unnecessary chemotherapy following the surgical removal of their tumor.

Until now, it was thought that all HER-2 positive breast cancer patients needed adjuvant chemotherapy in addition to adjuvant trastuzumab and adjuvant endocrine therapy (if the hormonal receptors are positive). However, recent data seem to show that this population is quite heterogeneous. Using the 70-gene signature, for example, a significant proportion of women with HER-2 positive disease are predicted to have a low risk of recurrence. Hence, it may also be possible to safely spare these patients adjuvant chemotherapy, if these results are confirmed.

With the support of BCRF, the purpose of this study is to confirm that HER-2 positive breast cancer is heterogeneous and can be sub-divided into two subgroups with different prognosis as defined by the 70-gene signature, and can therefore be treated differently. The second step will be to characterize in detail the biology of these subgroups, using different available technologies, to better define the best treatment strategy for each.

Mid-year Progress Report:
HER-2 is protein on the surface of breast cancer cells that controls cancer cell growth and the spread of the cancer to other parts of the body. Approximately 1 in 5 women diagnosed with breast cancer have a distinct type of breast cancer with high levels of the HER-2 gene and/or protein (known as HER-2 positive breast cancer). In general, women with HER-2 positive breast cancer are thought to be at an increased risk of having their cancer return after surgery. The 70-gene profile (MammaPrint®) is a new test that analyzes genes expressed in a patient’s breast cancer to determine whether or a not the breast cancer is likely to return after surgical removal. Previously it was unknown whether the MammaPrint test could be used for patients with HER-2 positive disease.

With BCRF support, the researchers analyzed the outcome of 169 patients with confirmed HER-2 positive disease with a prior MammaPrint testing result. Surprisingly, the MammaPrint test classified 1 in 6 HER-2 positive patients as "low risk" for spread of their cancer. After accounting for known prognostic factors associated with outcome, MammaPrint "high risk" HER-2 positive tumors were 5 times more likely to spread after surgical removal than MammaPrint "low risk" HER-2 positive tumors. Surprisingly, in the group of HER-2 positive patients that did not receive chemotherapy or trastuzumab (Herceptin®; a treatment that inhibits the HER-2 protein), 7 out of 8 MammaPrint "low risk" patients did not experience a relapse at 10 years from their initial diagnosis. In addition, no relapses were seen in the group of patients with ER-positive, HER-2 positive MammaPrint "low risk" disease irrespective of treatment.

Bio:
Philippe Bedard received his medical degree from the University of Toronto where he was awarded the Cody Academic Silver Medal. Subsequently, he completed his Internal Medicine and Medical Oncology specialty training at the University of Toronto. He is a board certified fellow of the Royal College of Physicians and Surgeons of Canada and the American Board of Internal Medicine.

He is currently a clinical and translational research fellow with TRANSBIG, an international network of breast cancer translational researchers, under the supervision of Dr. Martine Piccart-Gebhart and Dr. Fatima Cardoso at the Jules Bordet Institute in Brussels, Belgium. His research interests include the use of prognostic signatures in early-stage breast cancer, the biology of HER-2 positive breast cancer, and clinical trials methodology. He has been recognized by the American Society of Clinical Oncology with a Merit Award. He is supported by a Canadian Association of Medical Oncologists RxD fellowship award for his ongoing research.