"This year we will have the first genomic diagnostic test for breast cancer, which will benefit about 70% of newly diagnosed women"
Head of the Translational Genomics Group at the Vall d'Hebron Institute of Oncology (VHIO) and oncologist at the Vall d'Hebron University Hospital.
For his research on breast cancer diagnosis and treatment, he has been awarded with the Career Catalyst Research Grant by the American foundation Susan G. Komen for the Cure, a prize given for the first time in Spain and endowed with €345,000. .
Aleix Prat is Doctor of Medicine from the Autonomous University of Barcelona (UAB), head of the Translational Genomics Group at the Vall d'Hebron Institute of Oncology (VHIO) and oncologist at the Vall d'Hebron University Hospital. He currently directs two research projects aimed at improving the diagnosis of different breast cancers and specifying their treatment. The first project has succeeded in improving the current classification of breast cancer through the genomic analysis of tumors. The first genomic diagnostic test for breast cancer, which will benefit about 70% of women diagnosed with this disease, is expected to be on the market later this year. The other research project seeks to identify which patients with HER2 + breast cancer need only anti-HER2 therapy without chemotherapy.
The aim of the two research projects is to reduce mortality and improve the quality of life of patients with more effective and less aggressive treatments, such as avoiding chemotherapy.
We want to improve the quality of life of women with breast cancer and to do this we must be cautious when applying chemotherapy treatments because they are toxic and sometimes the benefits are very small. However, we must not forget that the new targeted or biological drugs we are working with are also toxic and have side effects. In fact, chemotherapy is also a targeted treatment, as it has a very specific function. For example, there are chemotherapy drugs that break down the DNA of the cell. Which drugs are targeted and which are not? What is chemotherapy and what is not? Sometimes this distinction is not clear, and in the end what we are seeking are treatments that show an acceptable balance between efficacy and toxicity.
But in the end does it seem that the new tests you are working with will improve the quality of life of the women involved?
Yes, it does. We are looking for other less invasive and less painful treatments for patients with breast cancer. For example, we have opened channels that allow us to have a more precise and accurate prognosis of the disease and avoid chemotherapy in patients who have a very low chance of their cancer reappearing. This group of patients may represent 15 to 20% of all diagnosed cases.
New channels that all focus on projects based on genomics. Is that the idea?
Yes, genomic studies in breast cancer have made us aware of the complexity of breast cancer and being aware of that complexity is helping us make more accurate treatment decisions. However, we still have a long way to go. The future lies in discovering how to use this molecular information to improve the diagnosis and treatment of this disease.
The project awarded the grant is a good example of this philosophy. Will it be possible to improve the prognosis of HER2+ tumours and provide quality of life for these patients?
Today, the combination of a series of targeted drugs and chemotherapy has reduced the mortality of HER2+ breast cancer, which accounts for 20% of all breast cancers diagnosed in Catalonia. Now, thanks to this grant, we intend to identify a priori patients with HER2+ breast cancer, who will probably not need to undergo chemotherapy. The trial, which has already been started in 12 hospitals throughout the country through the cooperative group SOLTI, will allow us to identify through genomics which group of patients newly diagnosed with HER2+ breast cancer is cured with anti-HER2 drug administration therapy and surgery without chemotherapy. We hope to have this genomic test in about 3 years.
How many women will benefit from this new test?
Approximately 20% of all patients diagnosed with HER2+ breast cancer could be cured without chemotherapy treatments.
In addition to this research, at the VHIO you have led a project that already improves the treatment of breast cancer affecting about 70% of women.
Yes, we know that the group called Luminal, the most common of all breast cancers, consists of two groups. Thanks to genomic studies we have observed that group "A" tumours have a more benign behaviour and anti-hormonal drug therapy is sufficient, but group "B" tumours have a more complicated prognosis, are more resistant to anti-hormone drugs and require chemotherapy. In our current study we compared the current histopathological definition with the genomic definition to see whether or not there was any discrepancy and we found that the genomic and histopathological diagnoses have a discrepancy of up to 40%. Studying this discrepancy, we found a histopathological marker, which we actually already had in all the histopathological reports but did not know how to use, which is the progesterone receptor, and we found that it was a good marker to distinguish between Luminal A and Luminal B disease and therefore to identify patients with Luminal A tumours that do not need chemotherapy. This new definition has recently been included in the international consensus guidelines on the management of breast cancer.
Have you eliminated the discrepancy?
Although we have improved the previous situation, there is still disagreement and genomics always wins. In fact, this is one of the messages of our research. Therefore, we have to succeed in bringing genomics into daily clinical practice.
How will introducing this genomic test into daily clinical practice affect the management of patients?
What the test will tell us in a reliable way is what kind of breast cancer the patient has and what the 10-year prognosis is, i.e. what probability the patient has of their cancer recurring. With all the data available, the patient may also decide whether or not it is worth undergoing chemotherapy for a specific percentage of benefit. In other cases, the risk of the cancer recurring is so low that chemotherapy is not worthwhile because the benefits do not outweigh the toxicities in the short and long term. The information provided by these genomic tests is much more precise and accurate than what we have today. All this results in a better quality of life.
Will there soon be a genomic test to diagnose breast cancer?
Yes, possibly this month or next we will have this test in Catalonia and the United States, as it has been approved by Europe and by the FDA. At VHIO we are finishing the trial phase of this genomic test, since we are directly involved in a Spanish trial by the cooperative group, GEICAM, involving 200 patients with Luminal A and B breast cancer.
How many women could it be applied to and how would it improve their treatment?
I can’t tell you a definite number. At first we will probably be strict when requesting this test, because the cost is high and we cannot request it for everyone. So we will apply it in selected cases and the percentage will depend largely on the criteria we decide in order to clarify those cases where we have most doubts. To begin with, we will probably use this test in 10% of patients newly diagnosed with breast cancer to decide whether or not to treat them with chemotherapy. In the future, I sincerely believe we will use the test for everyone.
And in the end how many women could avoid chemotherapy with this test?
Of all the women who take the test, 30% will not have to undergo chemotherapy. These are estimates, and we realize it is not a very high percentage, but allowing these women to avoid chemotherapy or better determining the risk of the cancer recurring are two very important elements in improving the quality of life of these patients, and allowing them to take decisions based on this information and the recommendation of their oncologist.
Does the future consist of personalized medicine in clinical practice?
Partly, yes. However, it should be said that the term "personalized" is starting to be replaced by "accurate" or "precise", because personalizing or individualizing is probably impossible. And in the end we are still based on the results obtained in groups of patients: groups of similar patients but not individual patients. The goal is to be more precise and accurate, and these genomic tests provide us with precision and accuracy. Thanks to genomic research we know that breast cancer is not a single disease but includes four entities, each with its own characteristics. And we now realize that treating all breast cancers in the same way does not make sense.