Saving Lives: Decades of Progress for Breast Cancer Survival

[00:00:00] Adam Walker: From Susan G Komen, this is Real Pink, a podcast exploring real stories, struggles, and triumphs related to breast cancer. We’re taking the conversation from the doctor’s office to your living room.

We still have a long way to go to conquer breast cancer, but we have made some big advances that are saving lives and making a difference. A new modeling study was recently published that the mortality rate for U. S. women with breast cancer decreased an estimated 58% between 1975 and 2019. Joining us on today’s show is Dr. Jennifer Caswell-Jin, MD, who is an assistant professor of medicine at Stanford Medicine, a former Komen grantee specializing in breast cancer and research, and a lead author on the study that published these findings. Dr. Caswell-Jin will help us understand why the mortality rate has gone down, the barriers that exist in getting the rate down further, and what the future of breast cancer looks like from her perspective. Welcome to the show.

[00:01:09] Jennifer Caswell-Jin: Thank you, so happy to be here.

[00:01:16] Adam Walker: I’m kind of excited about your research, so let’s start off a little bit more about that. It’s just great finding the mortality rate for women in breast cancer has decreased over the past few decades. We know there’s still more work to be done, but this is something absolutely big to celebrate. So can you walk us through what the contributing factors have been for the mortality rate going down?

[00:01:38] Jennifer Caswell-Jin: Yeah, great. That was absolutely the big motivating question for us in doing this research, right? And I want to just start by, it’s an absolute fact that breast cancer mortality has been going down over time. That’s not something new. We discovered for this study, that’s just known before we started the project. And the project was, try to understand why has that been happening? And the reason we know it is there’s this national cancer registry, called SEER stands for surveillance, epidemiology and end results. This was and this has existed since 1973.

It was a result of the National Cancer Act, that President Richard Nixon signed into law. One of those first, major efforts by the federal government to sharpen the focus on cancer mortality. We’re, of course, now in another one, with the cancer moonshot. But it’s really because of that effort that we know at all what is happening with cancer mortality in our country.

And so from here, we can directly observe that the chance that a woman dies of breast cancer, so that means the breast cancer mortality for the overall population, not only people who have been diagnosed with breast cancer, but just any woman’s chance of dying of breast cancer in a given year has been dropping over time, right?

We know that from SEER. When you look at the trend, you can see, so breast cancer mortality was actually pretty constant from 1975 to 1990. And then from 1990 until now, it’s just been steadily declining and that just keeps going. You can also see incidents from SEER, right? So that means, and if the chances of a woman being diagnosed with breast cancer in a given year, and that shows a very different pattern, right?

So incidents, it’s actually been rising over time, especially into the mid 1990s. And then it starts to level off. So we knew it was complicated, right? You look at these registry data, and it’s complicated. More breast cancers are being diagnosed and yet the chances of dying of breast cancer is holding constant and then it’s starting to decline and a lot has been changing, right?

Clearly, treatment is changing a lot for breast cancer over this time period across the spectrum of disease. And really the pace of that change is picking up over time, breast cancer screening, right? So mammography is also being used more and more, especially into the mid 1990s. It was being used more and more.

And it’s also improving how well it detects breast cancers so more recently, right? With the advent of digital technology, mammography is getting better. So there’s just this massive amount of change happening, right? And you really need modeling to start to disentangle. What is leading to what and where this mortality decline is coming from so to directly answer your question, right?

So using modeling we estimate it’s about half of the breast cancer mortality reduction since the 1970s is from improvements in the treatment of breast cancer that has not metastasized, right? So stage 1, 2 or 3 breast cancer about half of the reduction is from that. About a quarter of it is from improvements in treating metastatic breast cancer and about a quarter of it is improvement in breast cancer screening.

[00:04:47] Adam Walker: Wow, that’s fantastic. So can you tell us a little bit more about like the nature of how the study was conducted? I know you’re going back into past data and you mentioned that the trend was evident to the

community, but talk a little bit more about just how the study was conducted in general.

[00:05:03] Jennifer Caswell-Jin: Yeah, I’m really lucky. I work with this consortium of cancelling modeling groups. It’s called CISNET. it’s this National Cancer Institute funded program with a bunch of different models of how cancer kind of works. there were four models working on this project. One was from Stanford, right?

That’s my model; it’s led by Professor Sylvia Plevritis. There’s one model from M. D. Anderson Cancer Center, there’s one model from the University of Wisconsin in collaboration with the Harvard School of Public Health, and there’s one model from the Dana Farber Cancer Institute. So each of these models works differently, they each make different assumptions about how breast cancer develops, is detected, responds to treatment, progresses.

It’s really helpful to have different models, different groups thinking about things differently in a project like this, because then you know what you learn is robust and generalizable. You have to make a lot of assumptions and modeling, right? So it’s very helpful to have sort of independent groups thinking about how we’re going to model cancer.

Each of these 4 different models would simulate hundreds thousands of women, and then put these simulated women through a cancer journey. Where their breast cancer developed, they did, or didn’t undergo some kind of screening. They were diagnosed with some type of cancer at some stage. They got some treatment. They didn’t. And they ultimately died or didn’t die of their breast cancer. And all of the data for their sort of breast cancer journey, the chances that they get screening, what kind of screening they get the chances that they get treatment, what kind of treatment they get, that all comes from real world data, right?

So for example, like the breast cancer surveillance consortium has done a really beautiful job over the last decades of collecting data about how people are actually getting screened for breast cancer in the population. So we would use those data and be able to see changes. Over time put those as inputs into the model.

SEER itself gives us data about stage of diagnosis, type of breast cancer being diagnosed. So we can use that information and how that changes over time. So there’s all this kind of real data, and patterns that go into the models that are showing these changes over time. So then the models can say, “What would

they predict breast cancer mortality to be in say, 2005 in this kind of simulated population of women where things are happening to them, similar to the real world, what would they predict it to be in 2015?”

And then we can see, “do the models reproduce what we know to be true from Syria? Oh, interesting. Okay. And, they really do like quite well, right?” Sort of plot the mortality and SEER that we observe over time and plot the mortality in the models over time and they, reproduce the mortality well.

So then, now that we know that they’re working, that they reproduce what is true in the real world, now they can imagine alternative realities. Like, what would have happened to breast cancer mortality if we only treated breast cancer that never metastasized and we never treated metastatic breast cancer? What would mortality have looked like in that imagined world? what would have happened to mortality if we never did breast cancer screening, but we, as soon as the breast cancer was diagnosed, we used the full force of our treatments, but we never screened for breast cancer. What would mortality have looked like in that world?

So you can imagine all these different scenarios. And the models can simulate them all, and we call those counterfactual realities, right? Counterfactual. Well, so the factual reality models also simulate, and then they can simulate the counterfactuals. And from those, we can estimate what part of the observed mortality reduction is from each of the changes that occurred over time. And that’s where we get those numbers that I said at the beginning of a quarter of each of those changes.

[00:08:43] Adam Walker: Interesting. Oh, that’s fascinating. Okay. That’s really interesting, all right. So we know that it’s reduced over time, but has it been equally distributed across all patient populations or not?

[00:09:00] Jennifer Caswell-Jin: Yeah. So this is an extremely important question. The short answer is, definitely not right. We know from these real world data sources that there are disparities and who gets mammography screening and how often disparities and who gets the highest quality treatment. and who doesn’t have access to care or to good care, right?

And these disparities mean, that the benefits that we see across the population are going to be concentrated more in some groups than others. Being able to see right through modeling how much difference what are we doing to reduce breast cancer mortality? How much difference does that make?

Also means, we have a sense, right? Of how much room we have to improve, by increasing access to inequity of care. And when the paper was published, Gemma actually published a editorial on the paper that kind of made that exact point that you are making, right? Which is so much now that we can see the difference that has been made. What are we going to do about the fact that it’s not?

[00:10:00] Adam Walker: Yeah. Wow. That’s great. I love that you’re proactively looking into that, right? So I know that advancements in screening and detection get a lot of credit for improving breast cancer outcomes. Historically, I’m curious, were you surprised to see the better outcomes for patients with metastatic breast cancer also contributed to decreased mortality?

[00:10:22] Jennifer Caswell-Jin: Yeah, what a great question. It has a complicated answer, but it’s a really good question.

So I’m a breast oncologist. I take care of people with breast cancer. So that means, I am all too aware that women with metastatic breast cancer usually die of breast cancer. We generally think of cure as something that just doesn’t happen.

I want to qualify that a bit. I have patients in my practice. I take care of women with metastatic breast cancer who do seem to be functionally cured, right? So cure for metastatic breast cancer doesn’t actually seem entirely out of reach anymore. But it’s definitely rare, right? Really rare, too rare.

So how could it be that a quarter of the reduction in mortality is because of treating metastatic breast cancer when nearly all people with metastatic breast cancer die of breast cancer? So the answer to that, like I said, it’s very complicated, but it has to do with the pace of the advances in treatment that have been happening, right?

So when a new treatment for metastatic breast cancer is introduced, it can add years to people’s lives. If that was the last treatment for metastatic breast cancer ever introduced, when those people eventually died of their breast cancer, years later than they would have otherwise, we would see population mortality rebound.

But we don’t see that rebound. And that’s because the next treatment comes in and extends the lives of more people. It might be a different group of people, but on the population level, what we’re seeing is a continuous decline in

mortality, extended survival, even if people ultimately die of breast cancer has a major impact on population level mortality.

Only as long as we keep coming up with new and better treatments, which is what is happening. I think the question also brings up, right? Is population level mortality the best measure of what has been happening in breast cancer over the past decades? That is also a complicated question, right?

Because we’re definitely also seeing longer survival. People say, being human, there’s 100 percent mortality from being human, right? We all die eventually. On an individual level, it’s the length of survival. If we think of metrics of death that matters, not whether or not we die, we will.

The problem is, there’s a lot of bias in looking at survival and population level data, right? So mortality is directly observable. A person dies or doesn’t die of breast cancer. That we can just see in the CR data how long they live after breast cancer, not directly observable and really complicated, right?

Depends on when they were diagnosed, like if you diagnosed them earlier, it might look like they’re living longer when they’re actually living the same amount.

So it’s harder to use that kind of metric in a study like this, which is really important why we focus on mortality doesn’t have those biases, but there’s no question that survival is also lengthening.

And of course, that matters a lot.

[00:13:14] Adam Walker: I appreciate you walking through that, that’s all really, it’s really interesting. I wouldn’t have thought of it that way as the advanced, the treatment advances, it helps each group do better than the group before essentially.

So what barrier still exists that or cause it like, what’s keeping us, I guess that’s what I’m asking from getting the rate down further? And what are you most hopeful about as you look to the future for breast cancer research?

[00:13:41] Jennifer Caswell-Jin: Yeah, so barriers wise, we just talked right about access and equity.

I do think that’s a really crucial frontier to push on, I think as a community, right? It’s just as essential that we find ways to make sure we can get our really

effective interventions that we have. To everyone across the population as that we push on developing more and more effective interventions.

I have a lot of hope around that 2nd aspect, improving our treatments and our screening approaches. And I really, we shouldn’t let up on that, right? Funding for cancer research has made a huge difference. We’ve seen it accelerate over the past few years, there have been a lot of revolutions and how we study cancer on the technology side.

I really think if we keep pushing hard and we redo this analysis in 20 years, we’re going to see the mortality decline steepen. And I believe that I hope that, but I also think, if we don’t start investing heavily in implementation and access and equity, that’s going to be a barrier, right? We have to build the interventions and we also have to get them to everyone.

In terms of hope, I think, like I say, I believe and hope we’ll see the mortality decline steep in, I think in doing this project, it was really meaningful to me to see the pace of improvement over the last decades, better treatment, better screening. It was also really striking how much all of this matters, right?

So screening matters a lot. Treatment matters a lot; you kind of emphasized that earlier, we said we’ve heard a lot about how screening matters and yeah, screening definitely does matter. It matters a lot, but so does treatment of all stages of disease. It all contributes. And I think, one thing I wanted to bring up is how breast cancer is actually pretty unique among cancers in this way.

If you look at other cancers. It’s really screening and prevention that has led to the greatest mortality reductions over time. Like, if you look at lung cancer, lung cancer mortality has plummeted, mostly because lung cancer incidence has plummeted, right? Very different pattern to what we see in breast cancer, where we see incidence rise, but mortality goes down.

In lung cancer, it’s clearly, incidence goes down and that leads to mortality going down. This is tobacco cessation, right? Those efforts really worked on a public health level, but we are actually starting to see treatment improvements matter more for other cancers too. So like in lung cancer over the last five years, treatment improvements are suddenly now mattering, right?

Breast cancer may be led the field a little bit that way, but it’s starting to happen in other cancers. And I really do have a lot of hope that if we can keep pushing on every component, right? On prevention, on early detection, on treatment. You know of treat across the spectrum of the disease, that we’ll see the pace of

improvement continue to pick up speed, I definitely have a lot of hope about the future if i’m looking back on the past through this project.

[00:16:43] Adam Walker: Yeah, so do I. There’s I think there’s a lot to be hopeful for. So I understand you had a common funded research project connected to the efforts to reduce mortality I wonder could you tell us more about that work and how it fuels your efforts to study breast cancer mortality now?

[00:17:01] Jennifer Caswell-Jin: Yeah, definitely.

So I was a Komen postdoctoral fellow before I became faculty at Stanford. So this was probably about five years ago or so. Komen does a really good job, right? Investing in research and training across the spectrum. So I was one of those kind of early people in my career when I was a Komen fellow.

And it’s a little bit of a detour, right? But my Komen project was related to HER2 positive breast cancer. So this is the type of breast cancer where we’ve seen really the greatest impact of treatment over time. In the 1970s, HER2 positive breast cancer had the worst outcome of any type of breast cancer, and all of that changed really dramatically with the advent of HER2 targeted therapies, which have continued to improve.

My project was focused on understanding how HER2 positive breast cancers responded to HER2 targeted therapies by sampling them over time. we would get samples before treatment, right after treatment, later in treatment, sequence their DNA, sequence their RNA, look at their protein changes in the context of space within the biopsy.

Again, this is that revolution that I was referring to that’s happened in how we can interrogate cancer samples. And the goal was to see, well, two things. So first, could I find a marker of exquisite response to treatment so that HER2 targeted therapy alone, sparing them the chemotherapy toxicity.

Because now that we have HER2 targeted therapy, it used to be a really bad outcomes, like I said, and HER2 positive breast cancer, but now it’s not. So maybe we’re, we know that we are over treating a lot of people, but it’s hard to figure out who those people are. So that was part of the goal.

The other part was to see, could we better understand resistance to HER2 targeted therapies in those tumors that didn’t respond. We actually, we learned a

lot. Several, I think really important in my development as a scientist, but I think also, impactful papers came out of those projects.

And actually those types of questions are still a part of my research program today. I think it goes without saying, but of course, if we can overcome resistance to therapy, that is going to reduce breast cancer mortality, right? I also do think, that developing less toxic treatments will also reduce breast cancer mortality, right?

Because there’s less burden on the patient, less time off of work for disability, less having to find childcare because you’re too sick. And so all of those things are going to mean more people are going to be able to do it. More people are going to be able to take the potentially curative therapy. So again, just this idea, right?

Like that, if we push on every aspect, that’s what it’s going to take to reduce breast cancer mortality. I think deescalation, personalization becoming, coming up with less toxic treatment is, part of that.

[00:19:46] Adam Walker: Absolutely. All right. So last question, based on your research and your experience, what is one thing you want our listeners to know?

[00:19:58] Jennifer Caswell-Jin: Yeah, I can’t pick one thing.

[00:20:01] Adam Walker: Okay, what are a few things you want our listeners to know?

[00:20:06] Jennifer Caswell-Jin: Okay, well, I guess I would like to leave everyone with this sense of hope that I got from working on this project, right? I think that’s been a theme in our conversation today, right? Is hope. from looking back at the past for the future, and really it was like a hopeful experience for me, looking at all of this.

So I’d like to leave everyone with that. I think if you’re dealing with a breast cancer diagnosis, right? We have come with such, we’ve come such a long way and we’re going to continue to improve and we’re going to keep pushing and I think it’s going to get better and better. If you’re at risk of breast cancer, because maybe you have a genetic variant that predisposes you to breast cancer, or you have a strong family history of breast cancer, or honestly, you’re a woman, right?

We’re all at risk of breast cancer. Our screening and prevention options have also come a long way, right? Meet with a doctor, talk about your risk and what we can do about it. We actually can do a lot now. So I think, wherever we are in the journey, there’s hope in action because the tools that the community has built, they really do work.

But I guess for researchers, I think different. If you’re a researcher listening, I think that the message, and I know, this is that we have way more to do. So seeing progress should inspire us to work even harder because we know that the work leads to more progress.

[00:21:30] Jennifer Caswell-Jin: And I think that’s also been a big takeaway. From spending time with a history of breast cancer treatment and screening for me, is just the inspiration for pushing forward.

[00:21:41] Adam Walker: Yeah, I love that. there, there is a hope that it’s moving forward so quickly, and then there’s still so much more to do, and you’re working really hard to do it, and we we really appreciate the work that you do. Thank you for the work you’re doing and thank you for joining us on the show today.

[00:21:58] Jennifer Caswell-Jin: Thanks Adam and appreciate Komen, right? Obviously has a huge, footprint in that world.

[00:22:08] Adam Walker: Thanks for listening to Real Pink, a weekly podcast by Susan G Komen. For more episodes, visit And for more on breast cancer, visit Make sure to check out @Susan G Komen on social media. I’m your host, Adam. You can find me on Twitter @AJWalker, or on my blog,