Director at the Yale Cancer Center, Dr. Eric Winer, MD talks about a possible new treatment for metastatic breast cancer.
Interview conducted by Ivanhoe Broadcast News in October 2022.
Certainly is a lot different these days than it was when someone was diagnosed with cancer that had spread 20 years ago, 30 years ago, correct?
WINER: Yes. Our treatment 30 years ago wasn’t great. We had a limited number of chemotherapy drugs that we could use, and we had an even more limited number of hormonal therapy agents. We didn’t have any so-called truly targeted agents other than the hormonal therapies. At that point in time, there was virtually no one who was cured of their metastatic breast cancer. We can debate whether today people are cured or not. Not only were people not cured, but they tended not to live a very long time, meaning months to a year or two. A few live longer than that. I think more than anything else, people suffered a lot. We had inadequate drugs to control pain and to control nausea. We just didn’t pay attention to symptom control the way we do today. People spent a lot of time not only dealing with the fact that they were facing a shortened survival, but they just felt terrible.
How has that changed particularly in the last couple of years?
WINER: I think it’s changed over the last 10-20 years, and it’s changed in one very important way or there’s one important concept that underlies this. That is that all breast cancer and all metastatic breast cancer isn’t one disease. We are talking about a family of diseases. In the treatment of metastatic breast cancer, there are a number of variables we have to pay attention to. Important among those variables are whether the tumor is so-called HER2-positive. This means whether there’s the HER2 protein highly present on the cancer cell, whether it’s triple-negative, or whether it’s estrogen receptor positive. Beyond that, that still doesn’t tell us everything. We need to know someone’s prior history and whether they’ve received treatment for cancer before. We also need, as clinicians, to get some sense of the tempo of a woman’s individual problem, and how much cancer there is. All of those factors go into making treatment decisions, with perhaps the most important being one that I left out, which is what a patient wants.
About what percentage of women’s cancers now are metastatic and are we doing a better job at identifying earlier so that there are fewer?
WINER: To some degree. Probably about five percent of all women come to medical attention when the cancer has already spread to other parts of their body. I’m not just talking about spreading to the lymph nodes underneath the arm, but spreading to the bones, to the liver, to the brain, to lymph nodes at very distant places.
Where does it spread?
WINER: Metastatic cancer can spread to almost any place. The common sites are the bones, soft tissue, which means skin and lymph nodes, and other non-organs. The liver, the lungs, the brain. Every once in awhile, breast cancer can spread to other places like the inside of the bowel or the inside of the bladder. Those aren’t very common.
What percentage?
WINER: About five percent of people when they’re initially diagnosed have metastatic breast cancer. A much larger number develop metastatic breast cancer after their initial diagnosis. A woman is treated for breast cancer and one, or two, or five, or 15 years later develops metastatic breast cancer. For those women who develop metastatic breast cancer, truly 15 or 20 years later, we’re always truly scratching our heads saying, “where was it all this time?” I don’t have a good answer to that. Certain subtypes of breast cancer, particularly hormonally sensitive or estrogen receptor positive breast cancer tend to recur as often later as earlier.
What are you and your colleagues able to do now for these patients that you couldn’t have done a decade, two decades ago? What options and what hope is there for women who have cancer either that is diagnosed late where that they thought they were never going to see again and here it is?
WINER: I think women need to understand that oftentimes they can live for many, many years in spite of having metastatic breast cancer. Is it something that we can cure? In most cases, probably not today.For the small number of women who come to medical attention initially having had the cancer spread someplace and where it has not spread very extensively, and particularly if it’s one of those subtypes of breast cancer that are very sensitive to treatment, there probably is some number of women who truly are cured. The case I think that is most notable for all of us is a woman with HER2-positive breast cancer, where we’ve made tremendous progress in terms of drug development. Women are living much, much longer with HER2-positive metastatic breast cancer than they ever did. Some number of patients who at their initial diagnosis have metastatic breast cancer, and it’s in a small number of other places. Some of those women are probably cured with drug therapy alone.
What do you recommend for a woman who has metastatic breast cancer?
WINER: We have many Phase 1 trials and have an investigator who’s been very involved in drug development for years and years and is highly experienced. If we didn’t have clinical trials and if hundreds of thousands of women hadn’t signed up for clinical trials over these past 30 years, we wouldn’t know anything. A drug doesn’t get from the test tube to the pharmacy shelf without a big intervening step. That big intervening step is a series of clinical trials so that we can determine that the drug is safe, and effective, and better than other things that we have. That is absolutely critical. Sometimes people say the best treatment is on a clinical trial. In truth, if we knew it were the very best treatment then it probably wouldn’t be a clinical trial anymore, it would be standard. In clinical trials, we’re often looking for a better treatment. In a Phase 3 trial, where there’s a randomization, we are looking at the best available care and something that a lot of doctors and scientists and patient advocates, and others have reviewed and say maybe this is better. That is one reason to participate. In terms of earlier phase clinical trials, Phase 1, these are the earliest of clinical trials and they’re typically testing brand new drugs that haven’t been tried in people before or sometimes they’ve been tried a little bit in people. People often talk about first in human trials. Thirty years ago when we did those trials, it wasn’t very frequently that we saw a patient get better. The purpose of those trials is to test the safety of the drug and- to test the safety of the drug and to identify the doses that are most appropriate. But the intent, even 30 years ago when you treated a patient, was to make that patient better. We knew that that didn’t happen very often, but in someone who had no other options, he or she might decide to participate in the trial. It’s different today. What is different about it is that our understanding of cancer is far better than it ever was. We understand the molecular underpinnings of cancer. We understand the genes that drive the behavior of the cancer in many situations. What that lets us do is it allows us to pair the clinical trial- the specific clinical trial with this specific patient. We all have this sense that with that approach we’re doing far better with the earliest phase clinical trials in terms of helping patients than was the case in the past.
What would you say to a woman who’s diagnosed this week with advanced cancer, or whose cancer after years of laying dormant has come back? How do you counsel your patients and what what kind of hope is there?
WINER: It always depends on the individual patient, and it depends on a whole variety of parameters that we have to look at in that individual patient, the subtype of breast cancer, how much cancer she has. Then something about how quickly the cancer seems to be changing. In a woman who had breast cancer 15 years ago, and now it has come back, it’s taken 15 years to come back, that probably says something about the behavior of the cancer. In many women like that, cancer is going to be something that, that woman lives with for years and years and years and years. That is increasingly becoming true for other sub-types of breast cancer as well. If a woman is diagnosed with HER2-positive metastatic breast cancer, she can expect to live many years. What do I mean by many? I mean more than five or 10. But we have so many different treatments. This is where I think as oncologists, we sometimes have the hardest time having these conversations because, yes, there’s effective treatment, but at the same time, in all likelihood, eventually the cancer will probably threaten someone’s life. The truth is, as long as someone continues to stay ahead of the science, and the science keeps coming up with new treatments, who knows? If a woman who’s diagnosed with metastatic breast cancer today, with our available treatments, is destined to live eight years, 10 years, four years, whose to say that in the intervening time, we’re not going to have something better? I’m not suggesting that people have to go into a massive denial, that doesn’t work. However, I do think that if one can possibly do it, being both somewhat realistic and very hopeful is a nice mix.
Will you see cure for cancer in your lifetime?
WINER: I don’t think cancer is one disease. I can’t answer it generically for all of cancer. I think there are already many cures. We know with surgery alone, we cure some people, with surgery and radiation, we cure others, with surgery and chemotherapy or surgery and hormonal therapy or surgery and immunotherapy, we cure people. Fifteen years ago, virtually everybody with metastatic melanoma died of their disease. Today, a patient with metastatic melanoma gets immunotherapy. Somewhere in the range of 30-40 percent of those patients are alive and cancer-free five years later. Are they cured? Some, yes, some, no. However it’s remarkable. I believe that what we will see is step-by-step in increasing number of individuals with cancer who are cured of their cancer. There is also a big but here, and that but is you have to be able to get the cancer treatment. In a country where we have huge problems with cancer care disparities and health care disparities in general, where a man or a woman living in one city doesn’t get the same care as one who lives in another, or if you live in Washington DC and you have breast cancer, your chance of surviving is dramatically impacted by whether you’re black or white. We are going to get to a point, and I think we’re going to be at that point sooner than many people believe, where for the vast majority of cancers, the big question isn’t going to be, do we have the right drugs, do we have the right surgery, do we have the right anything? It is going to be can we get that treatment to someone? Can we support them during the treatment so they complete the treatment? Can we take care of them afterwards?
Is it ambitious?
WINER: I think the cancer moonshot is ambitious. I think it’s critically needed because cancer research desperately needs more funding, and this is the time when we want to step on the gas. We want to put that funding in because we’re so close. Cancer moonshot addresses a whole range of different topics from how to better take care of cancer survivors, to how to cure more children with refractory cancers, to getting people to work more closely together and making sure that in our clinical trials, we have a varied population. We are not just doing clinical trials in white people because the conclusions may not apply to others. The overarching thesis is that we want to reduce cancer mortality by 50 percent over the course of the next 25 years through a combination of screening and applying appropriate therapy and developing new drugs for refractory cancers and delivering the care. In truth, if we are not doing better than that 25 years from now, I would be disappointed. I think in 25 years, we ideally should be decreasing cancer mortality by at least 50 percent if not more. I think it’s going to take a lot of teamwork and money.
How far into your mind does it go?
WINER: One has to set realistic goals, and not all goals can be moonshot goals or totally aspirational goals. But in my aspirational view of this, I’d like to see us decrease cancer mortality by more than 50 percent. I think a big part of that though is trying to eliminate cancer care disparities. If we don’t do that and we don’t make a big dent in that and we don’t provide great care to everyone, state of the art care to everyone, then I don’t think we can achieve it. Ending with, which is that the better our cancer treatment gets, the more tragic it is that we can’t deliver it to everyone.
END OF INTERVIEW
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