His specialty, the immunotherapy, is the way that is opening new hopes to patients with some of the tumors more aggressive “He is chronifying tumors with a very poor prognosis, such as breast cancers triple negative. This tumor is very aggressive, causes relapses and occurs mainly in young women, ”explains the head of Immunotherapy at the Institute of Oncology (IOB), who works in the Breast Cancer Unit of the Ruber Juan Bravo University Complex, in Madrid.
Triple negative breast cancer is a complicated tumor because it expresses neither hormonal receptors nor the HER2 molecule and therefore has no treatments aimed at those targets. The only thing against him is chemotherapy, which does not work in the long term. But things, finally, begin to change.
Woman today What do you mean when you say that chemotherapy does not work in the long term against this tumor?
Esther Holgado When you first gave it, the response lasted about 12 weeks. Then there was a relapse, because the tumor cells learn to defend against chemotherapy. In fact, the second round usually works about nine weeks and the third, only four.
M.H. Is that why there is talk of a bad prognosis?
HEY. The survival of these patients was short. Triple negative breast cancer is more like lung cancer than other breast tumors because it has many genetic alterations. Luckily, we now know that the cancers that have the most mutations are the ones that respond best to immunotherapy.
M.H. That is, the rest of breast cancers do not have so many mutations.
HEY. That's why your tumor cells are not so inflamed. In contrast, tumors with more mutations are more able to warn the immune system that something bad is happening, so the lymphocytes of the immune system are directed to the tumor to attack it. The bad thing is that certain tumors manage to inactivate the response and thus prevent the attack.
M.H. In which tumors is immunotherapy working?
HEY. In those with more mutations. In addition to triple negative breast cancer, in lung, bladder, kidney, melanoma, head and neck, lymphomas or Merkel carcinoma.
M.H. Can all patients with triple negative breast cancer benefit from immunotherapy?
HEY. No, and that must be made very clear. At the moment it only works for patients with metastatic triple negative breast tumors that express the PD-L1 protein. They represent 41% of patients with this type of tumor. The challenge is to discover the mechanisms that the tumor develops to survive the treatments. Other proteins are being investigated, for example LAG-3.
Reality and promise
- Immunologists James P. Allison and Tasuku Honzo won the Nobel Prize in Medicine in 2018 for discovering proteins that some types of cancer develop to prevent immune system attacks. Allison, who works at the MD Anderson Cancer Center in Houston, identified the CTLA-4 protein and discovered how to take the brake off so that the T cells (T lymphocytes) in our defenses attack certain types of cancer cells. Honzo, who works at the University of Kyoto, identified the PD-1 protein, which also slows T cells.
- “Oncologists had always wondered why the immune system did not act against cancer, when it is a huge threat. Now we know that if we block PD-1, PDL-4 and CTLA-4 proteins, we get T cells to attack tumor cells, ”explains Dr. Loose.
- Today there are inhibitors of CTLA-4, PD-1 and PD-L1 that are used in melanoma and lung cancers, triple negative breast, bladder, head and neck, kidney, Merkel carcinoma or squamous cell carcinoma. "Thanks to them, patients who had survivals for months now live for years," says the oncologist.
- There are more drugs of this type that will come out soon and even more under study. “Many studies on immunotherapy have been presented at the congress of the European Society of Medical Oncology this year. It is a reality and also a very promising field of study, ”concludes Esther Holgado.
M.H. How many cancer patients are candidates to benefit from it?
HEY. In general, they respond between 20% and 30% of patients. In some cases of lung cancer and melanoma, the response is greater. In triple negative breast tumors prolongs survival by 10 months and with a good quality of life. We are chronifying that tumor.
M.H. Why should these patients also be given chemotherapy?
HEY. Because when tumor cells die from chemotherapy, the immune system can identify chemicals that release those cells when they die and thereby recognize and attack them.
M.H. Is it about being smarter than cancer cells?
HEY. I usually say that tumor cells are like cockroaches. They always manage to survive. They are the smartest cells we have in the human body. The fight against them is a continuous battle.
M.H. Is immunotherapy free of side effects?
HEY. They are not frequent, but when they appear they are usually related to inflammatory processes, that is, with pathologies such as thyroiditis, hepatitis, colitis, myocarditis … The good thing is that we have learned to handle them. We put treatments as soon as the first symptom appears.
M.H. What kind of studies do you do?
I do clinical trials with new drugs. I also work with the National Cancer Research Center. For example, if I need to know why patients with these types of breast tumors develop skin metastases, CNIO experts help us understand why it is happening. Thanks to this, we will see many advances in immunology. ›› + Info: www.esmo.org.
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