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Every year 6,500 women die from breast cancer in Spain and the total incidence continues to increase. We talk about the current situation of this disease in our country with Javier Cortés, one of the leading experts in breast cancer worldwide.

Early diagnosis is key to the treatment of any disease, but in the case of breast cancer, currently, it is even more important. 99% of tumors that measure less than one centimeter are cured. This is how oncologist Javier Cortés, director of the International Breast Cancer Center (IBCC) de Barcelona, explains it.

Although the five-year survival rate for this cancer has improved significantly in the last 20 years (it stands at 82.8%) thanks to screening programs and innovation in treatments, there is still a long way to go. From the 35,000 new cases that were diagnosed last year, 5% were metastatic cancer – which nowadays still has no cure -. From all the above, it is also estimated that 30% will become metastatic.

The good news is that research continues and treatments with superior effectiveness to the traditional ones have been developed. Nevertheless, there are still many challenges to overcome. Even after being approved by the European Medicines Agency (EMA), some drugs can take up to two years to reach patients due to the lack of agreements between the different actors involved in the process.

QUESTION. Since 2002, the annual incidence rate of breast cancer in Spain has increased from 106.5 cases per 100,000 people to 132 last year. Why is this?

ANSWER. The precise reason is unknown. I think there are several factors that can justify it. The first is that the population is increasingly older; the second is that social awareness about breast cancer makes people get better checkouts more regularly; and third, that diagnostic techniques are more precise and, therefore, we are able to detect smaller tumors. 

As fourth, fifth, sixth… Risk factors known for breast cancer are increasingly present in our society: women smoke more, there is more obesity, fewer children per woman and they are born at later ages, there is less breastfeeding… The sum of all of this influences a greater incidence.

“Between 25 and 30% of all cancers could be avoided”

Q. 5-6% of those diagnosed are in the metastatic stage. Do you consider that the current screening program aimed at women between 50-69 years old is sufficient?

A . I am in favor of extending it. We have an increasingly older population, women live longer and therefore, from my point of view, I would extend breast cancer screening beyond 69 years of age and vice versa.

Q. In fact, 23% of breast cancer patients are under 50 years old, should this also be extended to younger ages?

A. I think so, in fact there are some countries in which the screening age has already started at 40-45 years. But of course, the problem is that, to establish clear screening programs, you first have to demonstrate that this has a global impact on the population and the prognosis. Therefore, it is not as easy as saying “come on, we will do it tomorrow.” I would consider it, but we would have to clearly define what the optimal age is and whether it should be done for all patients or only some of them.

Q. It is estimated that 20% of women who have had breast cancer will suffer a relapse. What factors increase the risk?

A. Triple negative tumors are tumors with a worse prognosis, patients who have many nodes in the armpit, tumors with aggressive characteristics, larger tumors and, of course, tumors that have responded worse to the treatments that have been given. In the context of primary or local cancer, these are all risk factors that increase the likelihood of relapse (size, nodes, subtype and response).

“We have very good treatments for breast cancer, but in many places they still do not offer them”

Q. And what can be done to reduce these numbers? 

A. Tumors must be diagnosed earlier, since cancers smaller than one centimeter are cured in 99% of cases. Then, to implement the treatments we have, since there are very good treatments and in many places they still do not offer them. Finally, be visited or treated by professionals who are experts in breast cancer. 

Q. Why are some of the available treatments not used? 

A. It is a complicated question, we would have to ask hospital by hospital. I think the budget impact is one reason. In addition, there are drugs that have been positioned in the clinic in a more restrictive manner regarding approval by the European Medicines Agency (EMA). It is incredibly sad that there are hospitals, even within the same city, where treatments are given whereas in others they are not. 

Q. Advances in diagnosis have given rise to tests such as liquid biopsy, which allows the tumor to be detected even before it is noticeable. How is it currently being used? 

A. Liquid biopsy is a tool that has different applications. At this moment it is already being used in the clinic but always in the presence of cancer. It is not yet being used, except outside of clinical studies, to predict cancer that we do not yet see or that is forming, or to predict which patients who have already had cancer will relapse or have metastases in the future. There are studies underway, with very nice data, but they are not yet being used. 

Where it is being used is in patients who have cancer, especially those who have metastases, with several purposes: to look for different molecular alterations in tumors, to look for resistance mutations, to determine whether to change treatments sooner or later. 

Q. Can it replace mammography in early detection programs? 

A. It is a good question, I don’t know if it can replace it, but I am certainly convinced that it can, at least, complement it. I think that liquid biopsy is going to play an important role in detecting cancer. In what context, in which patients, where to do it or where not, are some of the current questions. We still have a lot to know but it will be key in the future, for sure.

“We have seen that immunoconjugated antibody treatment works much better than chemotherapy”

Q. Treatments are also advancing and traditional approaches (surgery, chemotherapy and radiotherapy) have been joined by Trojan horse antibody treatment for HER2-positive metastatic breast cancer. Could you explain to us how exactly it works?

A. There are two types of antibody-based molecules: classic antibodies, which are basically proteins that stick to their receptor and block it, and immunoconjugates or Trojan horses, which are also an antibody but have chemotherapy molecules attached to them. In this way, in addition to blocking the receptor, what it does is internalize into the tumor cell and once inside, breaking the binding, the chemotherapy is free and attacks. It is like a Trojan horse because the chemotherapy is hidden in the antibody.

Q. What advantages does it offer compared to traditional treatments?

A. The main benefit is their effectiveness, we have seen that they work much better than chemotherapy. Furthermore, although they also have toxicity and the side effects are similar, sometimes they are somewhat better.

Q. What criteria are followed so that a patient can be prescribed this therapy?

A. Apart from the previous classification, tumors can be hormonal or non-hormonal. So, depending on whether they are hormonal or have received previous treatments, there are a series of conditions for the treatment to be of choice or not. Above all, patients should have already received previous treatment and have metastases.

Q. So it’s still not a first-line treatment, right?

A. Not today, there is a study that is underway, it is called Destiny Breast 06, which will probably be communicated at the end of this year and if this is the case, it will be applied to frontline patients.

“We must work together so that treatments reach patients sooner”

Q. Apart from HER2 positive patients, in 2023 the indication for this treatment was approved for HER2-Low (neither positive nor negative), how does it work in these cases?

A. HER2 is a protein that is in the membrane of practically all breast cells, tumor and non-tumor. We classify these tumor cells depending on the amount of HER2 as 0, 1, 2 or 3. When they have a lot of protein we say that they are HER2 positive, that is, they are tumors that depend on this protein to live and we treat them with anti-inflammatory drugs. HER2. There are others that have it but at lower levels and do not depend on this protein to live, so blocking HER2 does not matter to the cell, but we can use it as the entry for a Trojan horse. In these tumors that have lower expressions between 1-2, which are known as HER2-Low, immunoconjugated antibodies also work.

Q. HER2-Low occurs in 50% of breast cancers, so the approval may affect many patients, is that correct?

A. Yes, 15% of cases are HER2 positive and between 50-55% HER2-Low, so the impact is going to be very great. However, although one of them was approved in 2023, it is still pending reimbursement in Spain. 

I would like to make an appeal that, once the drugs are approved by the EMA (European Medicines Agency), we all work to try to get them to patients as soon as possible because sometimes in Spain it is taking up to two years.

Q. How could this time be reduced?

A. We would have to do the job together, between the Spanish Regulatory Agency, the Spanish Medicines Agency, the pharmaceutical companies… Try to reach agreements as soon as possible.

Q. There is a lot of talk about the chronification of metastatic breast cancer, what is the current situation?

A. Unfortunately, metastatic breast cancer is currently an incurable disease. In our country, about 6,500 women and more or less 100 or 150 men die each year as a result of breast cancer. So that pink ribbon for breast cancer, yes, and black ribbon for many as well.

However, we are seeing more and more patients who have the disease under control for longer and die as a result of another disease and not their breast cancer. We began to consider that some may have a chronic disease or, in quotes, potentially cured. For example, in 14-15% of patients with metastases and HER2-positive tumors, after five years of disease, with their treatment, the tumor has not reappeared. Are they cured? Probably yes, but to prove it we would have to stop all the treatments and see what happens, so today we say that it could become more chronic than cured because they continue with the treatments.

“Prevention has to start in schools, otherwise it is very difficult”

Q. Sometimes one has the feeling that we have been talking about innovative treatments for years and yet the numbers of patients with this and other conditions are still there. Obviously innovation is crucial for the advancement of science, but what can preventive medicine do? Are we really making progress in this sense?

A. It’s a great question. I think that throughout the world, unfortunately, much more work is done on the treatment than on the prevention of the disease. This is more complicated, but you have to work on it. For example, we have always said “no smoking”. If people stopped smoking, drinking and sunbathing in moderation, we would avoid between 25 and 30% of all cancers. However, we continue drinking, we continue smoking and, therefore, we continue trying… We have to start in schools, if we don’t do it there, it is very difficult.

Q. In this sense, in addition to the awareness campaigns about the importance of check-ups and self-examination that have been so effective in recent years, do you think it would be necessary to give more visibility to risk factors?

A. Absolutely. In fact, notice that we are doing well with tobacco, although logically we are lacking; also with alcohol, but we must talk more about the issue of physical exercise, sun prevention, healthy diets… I believe that there are a series of social action measures that can be implemented by health authorities and the media to try to have a slightly healthier life together.

Source: https://www.alimente.elconfidencial.com/bienestar/2024-02-01/cancer-de-mama-doctor-javier-cortes_3821332/