A Review of the Charter and its Impact with Co-Founder of the Charter: Professor Gabriel Hortobagyi

Could you please tell me a little bit about your career and how you came to be involved with the charter?

Prof. Gabriel N Hortobagyi (Prof H.): I trained in medical oncology in Houston starting in 1974, and even during my training, I developed an approach to the treatment of patients with breast cancer that changed the sequence of treatments, starting with chemotherapy and going on to surgery later. That was later to be known as neoadjuvant chemotherapy. Simultaneously, others were also starting to investigate that approach including Professor Salmon in Arizona, Professors De Lena and Bonadonna in Milan, Italy, and Professor Khayat’s mentor, Professor Jacquillat, in Paris. As the initial results of such a modification of treatment became publicly available, Professor Jacquillat decided to organize a conference, an international conference at the Pitié-Salpetrière Hospital, and I was invited to that as a speaker. Professor Khayat was assigned to me to be my guide, my bodyguard in Paris during my stay, and we became friends. Of course, we had common interests in cancer research, in the area of breast cancer. As subsequent meetings were organized, this became the International Congress of Neoadjuvant Chemotherapy; later it was converted to the International Congress in Anti-Cancer Therapies (ICACT). ICACT was organized initially every three years, then every two years, and after Professor Jacquillat’s death, it was organized yearly and Professor Khayat, who inherited this from Professor Jacquillat, asked me and a couple of other people to help him organize the congress, and then it became a yearly activity. Very successful congress, 5,000-6,000 people from around the world coming to present and to listen to the presentations.

As the year 2000 approached, we realized that the world was changing but that some of the things that needed to change were not changing fast enough. We were making progress in science and in some parts of the world we were making progress in converting that science to practical benefits for patients, but in most of the world that was not happening. So, as the symbolic change in millennia was approaching, Prof Khayat, Prof. Benjamin and I, and others decided to make something special for the ICACT meeting in the year 2000 and to organize a special event, the World Summit on Cancer, inviting some of the leading thought leaders in biology, in science, and medical research, not only to make a huge splash about cancer research that year, but also to organize the Charter or Paris, which would highlight all that remains to be done for translating all the scientific progress into the patient’s benefit. That’s how it started, and it became a wonderful event, in part thanks to the energy and wonderful imagination of Professor Khayat, and the work of many people around the world. At that time we sat down with some folks from Europe, from North America, and with the help of a lovely lady, AnnaMaria DeSalva, to put into words what we thought should be a strong statement about how to empower patients with the latest in scientific research, and that this should be part of the movement for human rights.

We had multiple Nobel Prize winners, and a number of presidents, royalty, and statesmen of various sorts at the event, and we had the signing of the charter, with President Chirac’s support, at the Élysée Palace. Subsequently, a very large number of people around the world signed the charter. We also declared February 4th as the day to remember cancer and to remember the rights of patients, and that was later adopted by UNESCO. Today, World Cancer Day is celebrated every year on February 4th, so it has had a substantial impact on what we do.

From what I understand, the charter was designed to be an alliance between politicians, researchers, doctors, and patients to find a way to combat cancer in a way that is efficient but also fair to the patients. Would you agree with this assessment?

Prof. H: At the time the charter was written, there was this realization amongst us, that while the majority of cancer cases occurred outside of Europe and North America, the great majority of deaths from cancer also occurred outside of (Western) Europe and North America, and yet those parts of the world were not in the position to implement the progress in cancer care. It was clear that it would not be possible for just the physicians or the patients to implement those improvements in care. It required the concerted effort, and alliance, if you wish, of those who determine policy, meaning politicians and leaders in each country, physicians, scientists, and anyone who could influence the process, because a massive effort was needed in order to translate scientific progress in the benefit of patients everywhere. So yes, it was intended to create that energy, that association, that alliance between all those who could make this happen.

How successful have we been? Well, I think we have been partially successful. Certainly, progress in Cancer research has been dramatic over the past 24 years since the charter was signed, and several countries, including France, the UK, other European countries, Japan, China, certainly the United States, and Canada have invested heavily in supporting cancer research and this has helped propel this energy forward. What we know as cancer cures today is vastly different from what it was in the year 2000. 24 years later, we have made a whole lot of progress in diagnosis, prevention, treatment and survivorship of most malignancies.

What has not happened, where we have not had the impact that we wished to have is in much of the rest of the world. In those countries where insufficient budgets were assigned to the care of patients with cancer, the problem remains. As you know, even today, with many parts of the world at war, patients with cancer do not get access to high-quality care, access to the new medications, and the new procedures like high-quality radiation therapy to treat their cancer. We have not been able to reach those in power in many parts of the world to do that. In truth, there have been some parts of the world where in countries of intermediate resources this has had an impact. In many parts of Latin America, the Mediterranean Basin, the Middle East, and certainly in China and India there has been greater effort and greater resources put at the disposal of patients with cancer, but not to the extent that we were hoping for and we were aiming at. There is clearly a need to re-emphasize, to restate the state of the problem and the need to continuously make the effort and make the resources available for this purpose.

Something else that has changed, is that we have been much more successful in treating many cancers, including many different and hard-to-treat cancers like lung cancer, colorectal cancer, and certainly the hematological malignancies, and we also know today that many of the cancers we know are somewhat preventable. It is considered that anywhere from 15-25% of all cancers could be prevented with relatively inexpensive approaches to cancer prevention like changes in behavior, changes in diet, increased physical activity or exercise, and the eradication of certain infections that are known to result in many cases of cancers. If all of those preventive measures were applied to their fullest, we could reduce the incidence of cancer in general by anywhere from 15 to 25%. That has not received the emphasis around the world that cancer treatment has received.

Obviously, it is more dramatic for a patient who already has cancer to know that there is a treatment that can help them, than for a healthy person who doesn’t think about cancer because he’s healthy, right? Say, I’m going to exercise more, eat less, slim down, drink less alcohol, and smoke less because I want to reduce my risk of cancer. That’s not the way things work unless there is a concerted campaign. So, while these preventative interventions are inexpensive, what requires massive amounts of resources and support is for this to be shared with the public at large continuously, routinely, and regularly so that this becomes part of the culture, because otherwise, it’s not going to work. That Is an important part of greater emphasis in the future in prevention.

Another important part is that we have about 20 million new cases of cancer per year now, and even when we are successful in treating and curing those cancers, which we are in many cases–- in this part of the world probably 2/3 of the cases, in other parts world not as much but maybe half of the cases. Those patients who have been affected by cancer, which we call cancer survivors, carry that seal with them for the rest of their lives. Ther’’s the anxiety and fear of a reoccurrence, the return of their cancer. There is a stigma in many parts of society about what did this person do, what was the wrong they did so they got cancer as a punishment. The issue of survivorship, while it is being addressed more and more in our countries in Western Europe and North America, it has had much less support in other parts of the world and the quality of life of these patients is grossly affected in the absence of those efforts to improve survivorship.

Certainly, re-emphasizing the need for continued support for cancer research, the translation of the results of cancer research into the practical means for treating and preventing cancer, emphasizing cancer prevention measures, and emphasizing survivorship issues is the direction where we should be heading for the next 25 years if you wish, if not sooner. So, I think there’s much more work to be done and I think the charter would be a great instrument to use in an updated form to reinvigorate this movement.

You mentioned that the charter hasn’t had the influence you hoped it would be able to have in places like Africa or Latin America. What do you think would be needed from the more developed parts of the world in order to help them ease the socio-economic burden that comes with having so many cancer cases because the WHO and the International Agency for Research on Cancer (IARC) have released studies that over 70% of the cancer cases in the coming decades, are going to be in less developed regions in Africa. What is it that needs to be done to get these regions to that level where they can adequately treat and start preventing these diseases as well?

Prof. H: Ideally, there should be equality in the economies around the world and everybody should be equally prosperous. Now that’s totally idealistic and I don’t think it will ever happen. In the absence of that, I think a good point to aim at, is to continuously emphasize from the more prosperous parts of the world what can be accomplished, and what it takes to accomplish those goals, so that folks who live in countries of more limited resources, especially their leadership, know what they’re lacking, what they need to aim for because it’s a gradual process. This is not something that happens overnight. It didn’t happen overnight in France or the United States or the UK. It’s a process. So that’s something that we need to do and we need to do better. We have more tools at our disposal today. Through social media, for instance, we have relatively inexpensive ways to disseminate valid information. However, that requires access to the internet. Travel is certainly much easier, congresses are now being organized not only in the industrialized world but elsewhere. For instance, the American Society for Clinical Oncology (ASCO), on the one hand, and ESMO (European Society for Medical Oncology) on the other, organize yearly meetings in Asia, Australia, or New Zealand. So, those attract physicians and patients who beforehand were not able to or would not go to the yearly meetings to hear updates on what is going on, and what are the latest trends in treatment, prevention, and research.

All of those things help, but they need to be emphasized and they need to be emphasized publicly because most people do not care much about cancer one way or another until they are diagnosed with it. Most people are fortunately relatively healthy and they don’t have cancer, therefore they don’t listen to these messages unless they are repeated in multiple formats on multiple platforms at regular intervals. I think much can be done to accomplish those goals because the pressure from below, and the pressure from society on their leaders is also an important thing. It’s not sufficient for us as a conglomerate of scientists and committed physicians and philosophers and whatnot to just place pressure on country leaders. It is also important that they feel it from their electorate, the people who actually put them in power, and so both are important in reaching out to them and accomplishing these goals.

The other part that I should mention Is that sometimes the disparity between what should be done and what can be done is so great because of the resources required, that some leaders or some folks just throw up their arms and say we can’t do this. So, in order to address this, at least to a partial degree, several of us, and eventually several of our societies like ASCO and ESMO, have developed what is called resource-dependent guidelines. First developed by Ben Anderson and the Breast Health Global Initiative, several editions of resource-dependent guidelines were published. More recently, ASCO has developed resource-dependent guidelines for several different types of cancer, starting with breast cancer, where it is recognized that under optimal circumstances, and if everything could be done at the level science dictates, this is what we would do, but if we had only half of those resources, or a quarter, or one-tenth, then the minimum requirement would be this. Those guidelines have now been published several times, and have been updated, and I think those are helpful for countries of very limited resources to say ‘Well, the entire world says this is where we are aiming at, but at the very least we should have this.’ That type of effort, I think is very helpful to make people understand that there are some bare minimums of care or resources that are needed to be addressed or provided in any country, so as to provide a minimum of quality care for folks who develop this group of diseases. So that’s also an important contribution and it has practical implications, but it also has some messaging to the leadership of these various regions of the world to realize that they have obligations to their population. Obligations that can be met, at least to some extent, by making specific plans to implement these guidelines. Let’s face it, there are substantial resources all around the world: the question is, how are those resources allocated. If less was spent on weapons and armed forces, more would be available for basic needs of the population.

So it sounds like because of the disparity that you mentioned, the most realistic and effective way to raise awareness and increase the treatment options in these regions, would be to increase the communication and dissemination of this information, in particular the ASCO guidelines that you mentioned, not only to the countries where it’s needed but also to the more industrialized countries, so that general public is aware of how much it takes to run effective programs and that people need to be aware of this in order to understand this disease.

Prof. H: Absolutely. Now an additional tool might be available, in the sense that it’s not being used in the area of cancer. If you remember, in the 1980s a new disease was identified, AIDS, and a very effective coalition of activists was formed, first in the United States and Western Europe, they convinced the political powers that this was not just any disease, but that it needed some urgent emphasis and urgent help from the government. They were successful enough to not only make this a disease that was very rapidly deprived of the stigma that it initially had, but where a disproportionate amount of resources were dedicated to its research, to accelerate the development of treatments and eventually with the hope of developing vaccines, which is still in progress. While that was being done, and realizing that this was not limited to Western European and North American countries, but that the bulk of AIDS cases were occurring, again, in countries of limited resources, mostly Sub-Saharan Africa but also Asia and other parts, there was this concerted effort to get private foundations and governments involved to make effective treatments available outside of the industrialized world. As you know, today in much of Sub-Saharan Africa there is relatively in-expensive treatment available to patients with AIDS, and that has been a very dramatic development because it took a coalition of politicians, scientists, and members of the pharmaceutical industry to come together to make these treatments available at low cost. When the AIDS treatments first appeared, they were very expensive. Cancer treatments that are the latest rage today, are extremely expensive: $100,000 to $500,000 per patient per year. That’s not tenable for most countries around the world, including many in the industrialized world, so there needs to be that type of coalition again to emphasize the need to make these treatments, or preventive efforts, or whatever else it is that is needed available to those populations that need them the most. There are all those things that can be done and should be done, but that cannot be done in isolation. There needs to be that coalition in place where everybody is passionate about this cause.

Do you think that a revitalization or modification of the Charter would aid in or be beneficial to the creation of such a coalition?

Prof H: Certainly not doing it, would not help. Doing it and doing it effectively with the best communications tools and efforts, I think would go a long way towards re-energizing some members of the desired coalition. We don’t have the luxury of not doing it.

You’ve mentioned the concept of stigma a couple of times. One of the articles of the charter (Article II) specifically talks about this and combating the stigma surrounding cancer and cancer patients through education and increasing awareness for the fact that cancer diagnoses aren’t necessarily because a person did something, but that it can affect anyone regardless of habits. Do you think the charter has helped combat this stigma or that, at the very least, all the progress in terms of research, treatments, and information that is now available has improved people’s awareness about this?

Prof H: I think the Charter helped indirectly, but I think other forces were also at play so it’s hard to measure the relative contribution of the Charter to that. Sometimes when I lecture, I state that, for instance in the case of breast cancer, we have made a lot of progress, in part because of the progress in science and the development of more effective treatments and diagnostic tools, but that the media played an absolutely incredible role in this. In the 1950s and 60s, cancer was not a word you pronounced in public. You did not talk about cancer, you did not talk about money and you did not talk about sex in public. Those were topics that were off-limits. Because of that, patients who did develop breast cancer, for instance, or other types of cancer, didn’t talk about it, didn’t have information about it, and therefore their treatment was jeopardized and likely to be much less successful. Bringing this information into all the magazines, newspapers, and whatnot, and today you can hardly pick up a magazine, especially those dedicated to women’s interests, where there is not an article about cancer of some sort, how to treat it, how to prevent, how to live better, etc. I think that has had a major impact and that started even before the charter. I’m not trying to minimize the role of the charter in that process, but I’m just saying that there have been multiple forces at work to accomplish that. I think we have made a fair amount of progress with that, and I think in the industrialized world, the word cancer no longer carries that stigma. In many parts of the world, it still does, but that is something that can be addressed with education, and the dissemination of information and that’s a task that is relatively less expensive than the scientific process, the development of treatments, and making expensive treatments accessible to populations of limited resources.

So would you say it’s entirely possible to combat, and continue to combat, the stigma surrounding cancer?

Prof H: Correct.

Do you think the discovery of things such as the genetic links to certain cancers, or that certain viruses can cause particular cancers, has played into destigmatizing cancer?

Prof H: So somewhere between 10 to 20% of cancers are related to genetic predisposition, some more dramatic than others. For instance, the presence of a BRCA1 or BRCA2 gene mutation has a huge risk contribution to the development of breast cancer and other cancers in healthy populations. We also know that those mutations are more frequent in certain populations, for instance, Ashkenazi Jews and some other minority populations. Well, 50 years ago, had we known about it, that would have been hidden because you wouldn’t want to be considered someone at such high risk of getting cancer because that must be something due to something your family did that was horrible. Today, people actually feel empowered with having that information, and use that with great effectiveness to get better care. At least where I live, that is absolutely true, and in fact, whenever there are pockets of cancer cases in the neighborhood, there is immediately an effort by that neighborhood and their physicians to say ‘We need to do more research to see if there is a genetic component to this or something related to the environment’ or something of that sort. So yes, I think that type of information, if it is presented in the proper way, is empowering and it contributes to removing the stigma even. Laws forbidding the use of genetic information to discriminate in the workforce have also been very helpful.

Given all that we have discussed, aside from prevention and international collaboration, what is something you would like to see happen in the world of cancer research and cancer treatment in the next 20-25 years?

Prof H: So take the example of what we are doing today. We are 5,000 miles apart and we are able to connect and maintain a perfectly normal conversation about a variety of topics. When we started the ICACT conferences, none of this existed and therefore the only way a physician or patient had to update their knowledge and get new information, was to travel to where there was a meeting. The same thing happened with access to care. You could only access care if, as a patient, you went to your doctor’s office, unless you lived in a country where doctors still made house calls, which may still happen somewhere but not very often. Today, we have Telemedicine, which, in theory, should make it a whole lot easier for patients to access care, if they have access to the internet or the telephone. For physicians and other healthcare providers, this technology, which is relatively inexpensive, makes it possible to attend a meeting in its entirety without moving out of their office. During COVID-19, I attended meetings of ASCO, ESMO, AACR, and other organizations, sitting exactly here where I am now. So, this should empower all of us, because it should reduce the cost of education, and those resources could instead be repurposed for other worthy goals. For patients, this should also be empowering. You don’t need to run to the doctor’s office every single time you have a toothache, or pain, or a fever, or something like that.

The same thing with cancer treatment or prevention. Telemedicine can provide access for many patients who did not have it before. This is particularly true in areas of the world that are particularly disenfranchised. In the US, in Texas where I live, about a third of the counties don’t have a physician. It’s a huge state and if you have a small town of maybe 500 people, it’s not enough to support a full-time physician. That is also true in many parts of the world: Africa, Latin America, South Asia, etc. While it is not possible to force physicians to actually be there, you could, at a relatively low cost, set up and maintain a computer terminal. You can get a tablet today, or a computer terminal for very little cost. You can even do it on a cell phone. There could be a central instrument in town that everyone could have access to for telemedicine, for instance. So, there are many ways to make access possible and less expensive. Now reducing the costs of other interventions like surgery, radiotherapy, drugs, and immunotherapy, is more complicated because that takes really the entire coalition of the pharma, the physicians, the politicians, and the insurance companies to come together and come to an agreement that we are going to do this because we completely want to do this, but it is possible, as the AIDS movement has shown. We need to do that, and if we don’t do what we propose to do now with the re-invigoration and restatement of the charter, it’s unlikely to happen anytime soon, because inertia is the most likely mover of these things and inertia means that nothing will change unless someone wants to change it.

It appears that the common factors between the discussions with you, Prof. Khayat, and Dr. Harper are that there is a heavy emphasis on prevention, lifestyle education, and information dissemination and that this should be the focus in the coming decades, correct?

Prof H: That is correct, that is correct. Now within the information dissemination, there are different target populations and that needs to be emphasized. One huge one is of course the population at large. A second target population is physicians, especially non-specialist physicians so that they understand all the progress that has been made and what they need to be aware of. Next, the political regimes, the decision-makers, that determine what are the healthcare policies of each country, those should be targeted directly by information efforts, so that the necessary resources can be adjudicated and that the necessary directions in healthcare can be implemented in each region or country. So yes, those goals are all achievable with massive communication campaigns, but they need to be highly targeted.

Do you have anything else you would like to say regarding what we have discussed, or perhaps not discussed, so far?

Prof H: Well, I think the concept of bringing people of different backgrounds together is a very important one. Not only because a person alone can achieve far less than a group, but because whenever we bring a group with different backgrounds together, we learn from each other. We learn experiences each of us has had in different parts, in different aspects of our lives. I mentioned earlier what we have, or should learn from the AIDS groups, as they have been incredibly successful in their quest. We should learn from them, and we should not try to compete with them for resources but learn their techniques and how they were successful in implementing their efforts so that we are even more successful in what we can do. I’m especially impressed by the ability of the AIDS groups to reach an agreement with governments and pharmaceutical companies to provide low-cost treatment in areas of the world where that was considered not possible, and that is certainly a huge unmet need in the area of cancer. So, yes a coalition has multiple purposes but one of them is to learn from each other and continuously refine our objectives, our means, and our approaches to accomplishing what we want to accomplish.