Breast Cancer - Joseph GLIGOROV, MD, PhD


Dr Joseph Gligorov

With 1.7 million new cases each year, breast cancer is the second most frequent form of cancer in the world, just behind lung cancer.  And its incidence is constantly rising, especially in rich countries, but also in developing countries.

In France today more than 90% of patients treated for breast cancer are still alive five years after their diagnosis, and most of them will be completely cured.  This progress can be attributed to early screening, to an improvement in the quality of care, and to advances in research.

The breast cancer patients who come to Tenon Hospital are treated in a center that is recognized as “expert” in breast disease, itself integrated into a large university hospital complex (Institut Universitaire de Cancérologie de l’Université Paris VI – the University Institute of Cancerology at the University of Paris VI).  Patients benefit from the most effective diagnostic and therapeutic tools available.  But also, thanks to the clinical and transfer research conducted in the field under the aegis of APREC, patients benefit from early access to the latest therapeutic innovations, sometimes several years before they are made available in the marketplace.

APREC has been a decisive agent in the progress achieved in breast cancer research through numerous projects (more than 50) that we have carried out in the past 20 years.  To illustrate this, we will briefly outline our activities in three areas:

First, in the realm of breast cancers called “HER2 positive”, that is those with overexpression of an oncogene called HER2 or c-erb-B2.  This involves around one case of breast cancer in five.  In France we have conducted the coordination of an international trial and offered our patients the first treatment targeting the HER2 protein: trastuzumab (Herceptin).  We have also conducted the coordination in France, and internationally, of two trials demonstrating the equivalence and simplicity of the use of this treatment in a subcutaneous form.  At the same time, we are also  overseeing the national coordination of an international trial aiming to demonstrate the superiority of the association of two anti-Her2 drugs, trastuzumab with lapatinib (Tyverb)).  Other trials currently in the works are exploring new very important anti-HER2 treatments such as pertuzumab (Perjeta), T-DM1 (Kadcyla) or everolimus (Afinitor).

A second area of research involves improving control over the tumor’s environment and notably the vascularization of breast cancers.  APREC has supported several research projects in this    realm, two recent ones of which are very promising, and for which we are awaiting the results in 2014. They involve the long-term use of an “anti-angiogenic molecule,” bevacizumab (Avastin).  We are overseeing the international and national coordination of these two projects.

Finally, a third area involves the “de-escalation strategies” of treatments.  The challenge is to obtain results that are at least as good as those obtained with less aggressive treatments.  APREC has supported and carried out the only medical-economic evaluation of the use of a new genomic tool (OncotypeDx™) enabling the establishment of a  scale of gravity for non-metastatic breast cancers, and for each level to determine whether it is of benefit or not to the patient  to prescribe preventive chemotherapy.  Another example: we are perfecting tracers for PET scanning that enable us to determine very early on whether a chemotherapy is effective or not: thus we can prevent certain patients from continuing an ineffective and yet toxic treatment, when usually we must wait three months to evaluate the efficacy of  a chemotherapy.

In the past ten years, APREC’s involvement in the progress of breast cancer treatments has resulted in more than a hundred scientific publications.


My name is Joseph Gligorov.  I am an oncologist, and I work in the oncology unit at Tenon Hospital, in Paris.  I am also a member of the Scientific Board of APREC, with a special focus on breast cancer, including the development of new anti-cancer drugs and strategies.

Looking briefly at the facts surrounding breast cancer, let’s recall some figures: it is the most frequent cancer in women throughout the world; there are more than one and a half million new cases each year.  It is the leading cause of death by cancer in women in developing countries, and the second most lethal cancer in developed countries.  And yet, by contrast, as regards therapeutic possibilities, it is a disease that within 50 years has gone from being considered an extremely fearsome form of cancer from which there was very little chance of survival, to one that today can be effectively treated, and more than 90% of women who are diagnosed are still alive five years after their diagnosis.  And a great majority of these women are probably ultimately  cured of their cancer.

Working with Drs. Victor Izrael and Jean-Pierre Lotz, we have been furthering the progress that has been made in the past fifty years, by developing very important bridges between, on the one hand, our daily place of clinical work, the hospital, the patients we see in consultation and whom we treat every day, and, on the other hand, the research facility APREC, and behind it, its laboratories and researchers.

At APREC, among the different projects in which we have participated, and there have been many, there have been several dozen new innovative projects per year, some of which I believe are crucial and will mention here.

The first has no doubt been our participation from the beginning in the development of new drugs that target a specific protein called HER2. Close to 20% of all breast cancers present an excessive amount of this protein on the cancer cell surface.  This protein unfortunately adds to the aggressive nature of the disease, and some teams initially in the U.S. had identified it and had synthesized antibodies to be used to neutralize it and potentially block the growth of cancer cells.   At the time when that drug began to be developed, we participated in the first preventative trials aimed at women who had had cancer, and for whom we wished to diminish the risk that the disease would return, and we used the drug within the framework of large international trials, notably in partnership with the BCIRG (Breast Cancer International Research Group).  Thanks to APREC, a large number of our patients have had a positive response, and today a very large majority of them are cured, whereas the drug was only available to other patients several years later.

Today there are antibodies that can be combined with chemotherapy.  This enables us, using the antibody as a Trojan Horse, to carry chemotherapy directly inside the cancer cell without affecting other cells.  One can see that this research, which is increasingly important for the development of new strategies, leads to more progress, and each day we can share that progress with our patients, thanks to APREC.

Secondly, we have been attempting to improve the treatment of certain breast cancers called hormone-dependent.  The great majority of breast cancers, 70 – 80%, show the presence of hormone receptors inside the cancer cell.  For a long time we have used and still use tamoxifen, which is a very useful drug, but we realized that it wasn’t sufficient for some patients.  Thus we have been able to participate in the development of new drugs that block the production of hormones, or that block the action of hormones. Here, too, APREC has enabled us to treat patients in our clinical oncology unit at Tenon Hospital with these new therapies, sometimes several years before the drugs become available to all.

Finally, translational research enables us to determine to whom we should and should not administer treatment, to seek the best possible understanding of which patients will benefit most from certain drugs.  This is why we have very strong partnerships both with biology and anatomic pathology labs within the University of Paris VI and at the University Institute of Cancerology, Paris-Sorbonne. We also have two direct partnerships with imaging labs, notably in radiology and nuclear medicine, and we are developing new radio-nuclide tracers to enable us to determine if there are targets present on the cellular level in some specific cases. This will allow us to use certain drugs in specific situations, perhaps without being forced to biopsy patients when the disease returns, and thus to spare them discomfort and inconvenience.

All of these activities are only a part of the research work that my colleagues and I are doing each day at APREC, concerning breast cancer as well as other cancers. Thanks to APREC, I believe we have made great progress for our patients, and are participating in global international progress.  This means that in the years to come breast cancer may perhaps still be a commonplace disease, but it will be one that will be curable in the very great majority of cases, and will no longer be a true scourge, rather an illness from which one can easily recover.

I thank you in advance for your much needed support.