What does the beginning of breast cancer look like? What happens at the very start that turns normal breast tissue into the first stages of cancer, and by recognizing these early molecular changes and pathway alternations, could we not only improve our understanding of the evolution of breast cancer, but also one might hope find a way to stop it before it even begins.
These questions are hardly philosophical. They go to the heart of important research that has been and is being led by Dr. Anna Maria Storniolo. Dr. Storniolo is a professor of clinical medicine in the Department of Hematology and Oncology at the Indiana University School of Medicine.
She is also director of the Catherine Peachey Breast Cancer Prevention Program, a comprehensive program providing risk assessment and counseling for women who may be at risk for developing breast cancer. She also has been a BCRF grantee since 2007.
Chris Riback: Dr. Storniolo, thanks for joining me. We’ll get into the various threads that you research: pregnancy and ethnicity, and the incredible tissue repository that you oversee. In reading and researching about you and your work, the thing that jumps out to me is the beginning. It feels like you want to understand the very start of breast cancer, almost the genesis from a range of angles and perspectives. Is that right? Have I interpreted your background accurately?
Dr. Storniolo: Yes, actually amazingly accurate. I was listening to your introduction, and I was wondering how I was going to be able to expand upon it since you explained it so beautifully. That’s exactly what we are all about, and the tissue bank allows us an opportunity to do that unlike we’ve had in the past.
“At its very elementary level, we need to find out how normal becomes abnormal.” – Dr. Storniolo
So that’s exactly what we’re all about. At its very elementary level, we need to find out how normal becomes abnormal. And now that we finally have all the molecular tools or many more molecular tools than we had 10 or 15 years ago to actually drill down into all of these cellular pathways, I think we can begin to understand how all of the various triggers in our normal breasts function and by understanding the normal triggers, hopefully we can begin to understand how that can go wrong.
Chris Riback: What draws you to the start? It’s the logical place to begin, and we all, growing up, kind of learn, “Well, if you want to figure something out, start at the beginning.” I have the privilege to talk with researchers like you, and it’s always incredibly interesting for me to learn about what motivates them to conduct their studies from their unique perspectives. Because some people start at the beginning, and others are investigating life end or cancer or breast cancer in older patients and longevity. And there are all these different entry points where while everyone’s kind of after the same goal: prevention, life quality, curing. For you, is it the science or is there something about the beginnings of things that happens to fascinate you personally?
Dr. Storniolo: I think this whole area came to me … Much of science begins in the laboratory and goes to the clinic. In my situation, I’m not a laboratory scientist, so my ideas and my passion begins in the clinic, and then I begin to think how can we fix this? How can we make things better? And then it becomes increasingly clear that we need to fix it at the very beginning. And in running the prevention program, which we began in early 2000s, I meet many many women who some people would call the worried well, but whose no two stories are the same. The common thread is they’re all very worried. They’re all very aware that this is a disease that, in many ways, is random, but certainly is common, and they all want to be able to do something to reduce their risk, but more importantly, to help other women, both their own families, their friends, et cetera, et cetera. So being faced with this day in, day out, and feeling, at least, at the beginning, as if I was a well-trained, hand-holder, I came across this opportunity with the tissue bank to have an enormous impact.
Chris Riback: Tell me about the tissue bank. What is it and how did it start?
Dr. Storniolo: Basically, there I was in the early 2000s, maybe 2002, 2003, at a scientific conference, and there was a mixture of basic scientists and clinicians in the room. The keynote speaker was from the National Cancer Institute, and one of the scientists from the audience rose and said, “I have this amazing idea, but to finish pursuing it, I will need normal breast samples.” And the speaker looked right at her and said, “Well, you’re going to wait a long time because they don’t exist.” And for me, and actually for a good friend of mine who happens to be an advocate, that was an “aha” moment.
Chris Riback: Yeah, it sounds like one. Yeah, tell me why.
Dr. Storniolo: Well, because it sounded like, “Well, that can’t be that hard. What do you mean you don’t have normal tissue?” There are millions of healthy women out there who, I think would help you out if you asked them, and therein started this journey.
I have to tell you. We were naïve, and this was an era where it was very difficult to do quote unquote “science” without a very specific defined end. So banking tissue for general purposes was not well looked upon by institutional review boards, so we had to tread very lightly and make partners of our IRBs and or lawyers. I learned a lot about clinical research in general, because at the very crux was the woman. And one wonderful Saturday, at the time I was a soccer mom, I went to the games that Saturday, and I purposely went around and asked about 25 women I didn’t know about this project.
I introduced the project, I introduced myself, and I said if we ever made this happen, and you were asked to have a breast biopsy, and donate the tissue for research, would you do that? I think everyone but one person looked at me and said, “Well, of course I would. Why wouldn’t I?”
And these were women I had never seen before in my life in a suburb watching their kids play soccer. I thought to myself, “Why is the institution … Why is science putting all these roadblocks in my way?” The thing that should be the biggest roadblock is not a problem at all. In fact, they’re happy to do it, and I can tell you that 4,900 women later, I was proven right.
Therein started the journey and I call tell you that once you have the material with which to work, the ideas are infinite. So it really has been, from that very start, that “aha” moment of we really can compare normal to abnormal, and we really can get at the basis of what happens at the very start. We don’t have to look at what happens at the end because, lord, by the time we get to the end, there have been hundreds of molecular changes, and it’s really, really hard to track back and know what was step number one with Breast Cancer Research Foundation money, we’ve been able to set up our own laboratory, and we have a research scientist.
And in fact, she has been able to do some amazing work. We have a cadre of women who donated tissue and then, unfortunately, within two or three or four years, called us to tell us that they had developed breast cancer. And many of these had developed breast cancer, interestingly, in the same breast from which they had donated tissue. Now I always thought that the interesting thing would be to compare their cancers to their normal tissue, but Dr. Natascia Marino, our scientist, actually corrected me and said to me, “Think about this, Anna Maria.” She said, “That tissue that they donated from two or three years earlier cannot possibly be normal because cancer doesn’t happen.”
We know the biology well enough. Cancer doesn’t happen in two to three years. It didn’t go from completely normal to clearly malignant in two to three years, so clearly, that quote unquote “original” susceptible normal is going to give us some clues.
Chris Riback: You can almost reverse engineer.
Dr. Storniolo: Oh my god, and I can tell you … Talk about “aha” moments. That was “aha” moment number two. It’s like, “Oh my god, that’s why we set this whole thing up, and it’s coming true.”
Indeed, and the work is ongoing, but what she has done is begin to look at those quote unquote “susceptible normals” and compare them after accounting for matching them for age and race and points in their menstrual cycle and everything else you could possibly match for because we have so many other samples. But she has compared them to random normals in the bank that had not gone on and developed cancer, and in fact, the preliminary data, she’s not finished her work. But the preliminary data has shown really interesting differences that clearly are pointing to changes along known pathways of malignancy: proliferation, abnormalities along delayed cell death, et cetera, et cetera.
It’s too early to say, but I really think we’re on to something. I really think we’re on to beginning to identify pathways and targets where very early changes occur. So that’s an example that’s happening in our lab, but many people are using the samples and looking at all kinds of questions, all kinds of molecular manifestations of different risk factors.
They’re looking at what is the molecular version of having women that have very, very early first periods versus very, very late first periods. Because having your first month period very early is a risk factor, and so, again, you can parse out every single risk factor and look at it from a molecular basis partly because we have the cancers and you can ask those same risk questions of the women with the cancers.
Just as importantly, we’ve asked those risk questions of our women without cancer, and so you can even compare normals, if you will, within the bank itself. So the beauty is, as everyone knows because I was asked this question all the time at the beginning, well of course normal isn’t one thing.
That’s why we’re going to try to get you as many versions of normal as we possibly we can. We’re going to try to get you racially. We’re going to try to mimic the racial composition of this country, we’re going to try to get you young, we’re going to try to get you old.
Believe it or not, women come in and volunteer when they’re pregnant. Women come in and volunteer when they’re nursing, so we have pregnancy samples, lactating samples. We have really, really just a wealth of information that I think can lead to a lot of important science.
Chris Riback: What you just described was among the things in looking at your work, and your research, it really just blew me away. I mean when I have these conversations, and when one learns more about breast cancer and breast cancer research, and for families who are living it, and people who are living it, the examples of bravery are kind of everywhere.
There are these impressive, unbelievable stories and examples of individual and collective bravery. But you really tapped into a different angle on the bravery. You described women you maybe … you called them the “worried well.” But some of them are just the … I think, you’ll tell me if I’m wrong, are just the caring well, or the loving well, or the I want to do what I can to help well.
And they go in, and they are voluntarily giving you, and giving the bank, this healthy tissue, and then off of that healthy tissue, as you’ve just described so well, you’re able to run innumerable … I can imagine, you’ve said it earlier, you know, the range of possibilities. Once you have that bank and once you start thinking of ideas, they’re just innumerable I can imagine. Just listening to you now, my brain is exploding thinking of all the things that I would want to know and particularly all the factors that you align and the data that you collect against this issue and from these individuals beyond that.
Do I have that right? Do you view it as a small form of bravery?
Dr. Storniolo: Oh my god. First of all, by far, this is the most humbling thing I have ever done. We’re having a collection by asking multiple women to come on one day. We call them collections and we usually have anywhere from a 120 to 180 women come on the same day so that we can have our surgeons and radiologists do the procedure all in one day, and we’re not constantly trickling women in. It takes a lot of volunteers.
We’re doing a collection this coming Saturday here in Indianapolis. By the way we’re coming to New York on November 11th. This is our 10th year. It still amazes me that women who do not know me from Adam do this because they want to help.
It is by far the most humbling I’ve ever done in my life. As my son would say, as cheesy as that sounds. I’ve heard the following more than one time as women are leaving, I try to personally thank as many women as I can, and so I’ll say thank you so much for giving part of yourself. You’ll never know how important this is, and they’ll look back and here’s a woman who just went through …
I mean it’s no different from a diagnostic breast biopsy. They will look at me with an ice pack in their bra, and they will look at me and say, “Oh no, thank you. Besides the day my children were born and the day I got married, this has been the most important day in my life.”
And I still get chills every time I say that.
Chris Riback: I got chills listening to you say it.
Dr. Storniolo: It is amazing.
Chris Riback: And the phrase that you used, thank you for giving a part of yourself. That’s I mean …
Dr. Storniolo: I think what they feel is many of them … Not all, but many of them can give money, but I think what they feel is that otherwise the only way you can participate in a clinical trial, unfortunately, is to have the disease. And they feel so helpless in fighting this disease that affects so many women. Everybody knows somebody with breast cancer, and so I really feel like this is their opportunity to really help in a way that even money doesn’t help.
And you know that this is their way of saying “I did something in my life to help stop this disease,” and the stories are unbelievable that you hear, but the amazing thing is how many people don’t have a direct relative or how many people are just there because they read about it in the paper and they just thought, “Wow, this is an amazing thing. I just have to come and help.”
You know it just, again, in this world where you can’t turn on the TV without hearing something terrible, it’s just wonderful to know that there are still many, many, many amazing people out there.
Chris Riback: You know, you said something earlier as well that struck me. Two things in fact. First one was that one of those “aha” moments where you realized that there is not this bank of tissue, of cancer-free tissue of people volunteering. And you’re like, “Wait a minute. First of all, why isn’t there?” And secondly, why don’t we just ask people? A lot of times if you ask someone something, you know, what’s the worst they can say? In fact, quite often, they’ll say yes. And the second thing that I’m kind of connecting it with. Your statement that you’re not, correct me if I have this wrong, a laboratory scientist. Oftentimes, and maybe with research or innovation or breakthroughs like this, is that what it takes?
I mean do you think the fact that you were … I don’t what to call you an outsider by any stretch, but you were outside of that, you know, strict scientific lab, scientific zone. Do you think that was part of what made you the type of person who would look at what might seem simple, might seem obvious to an outsider or a layperson like me, but within the family of scientists …
Dr. Storniolo: Well you know, I was at a point even then and I’m certainly at a point of my career now that I find my direct work with patients incredibly, incredibly fulfilling. And being at an academic institution, the opportunity to learn constantly is a privilege, and almost to me, part of my compensation, kind of the icing of the cake.
And I’m not under the pressure of having to have things work all the time. And so I see myself more as a scientific facilitator or a collaborator, and so I felt like I was in the right place to be able to make this happen because I had the luxury of I don’t know …The luxury of time, the luxury “academic time.” I had the wherewithal. I mean I had a partnership with Connie Rufenbarger, again, this amazing go-getter advocate that, initially, with the Peachey Fund money, we made it happen. And then we got more significant funding.
You know, it’s interesting because it’s taken the better part of 10 years to get some of the more established scientific institutions to come around stop using reduction mammoplasty, which is the leftover issue from when a woman has a breast reduction, which is clearly not normal tissue.
Or worst yet, that the tissue nearby a tumor, which is called adjacent normal, which has been used as quote unquote “normal” in experiments. That obviously is not normal, so it’s taken people a while to stop using that simply because they’ve always used that. That’s what’s been used in all of these other experiments, and so to break rank and switch over is going to take time. They’re going to have to repeat their experiments, et cetera, et cetera.
All of that requires extra time. They’re going to have to worry about their next grant, their next publication. I didn’t have all of that stress. It’s been incredibly frustrating to try to break through all of that. I’m happy to say we have finally. BCRF and all of my co-grantees have been incredibly helpful in that respect, but again, at the beginning, I don’t think I was daunted by any of that. My feeling was if it doesn’t work, I can say I tried. You know, I’m not wasting anyone’s money. Let’s make a go of it, if it doesn’t work, it doesn’t work. I think sometimes you just need people a little bit outside. You’re right, a little bit of an outsider to help things out.
I probably will never get an R01. That’s just not what I’m about, but I think science hopefully has room for a lot of different types of contributors, and BCRF is, I know you probably hear this from everybody, but BCRF is humbling to me because they have recognized what I do even though I am an outsider, and I’m not the typical type of scientist that usually is sitting in that room. And yet, I’m recognized as one of them. It is humbling and it just is a wonderful thing. I’m still great with them.
Chris Riback: Yeah, it really comes across in the stories that you tell and the ways that you tell them. What you were saying earlier about the honor that you feel, just from doing the work. You convey it in a way, I mean I feel it. I would imagine that working with those women who are giving of themselves and then doing the research that you’re doing and trying to come to the answers that you’re trying to find … To put it mildly, that’s not a bad life’s work. And obviously it’s not your entire life’s work.
Dr. Storniolo: You know, it’s interesting Chris because I’ve said this to my husband. When you don’t care who gets the credit, it’s an incredibly liberating thing. It is amazing what you can get done if you don’t care who gets the credit.
Chris Riback: That’s a great life lesson. That’s not a breast cancer research lesson. Maybe in one part it is. Actually to some extent, it goes to the heart of some of the philosophy behind BCRF, the collaboration, that I hear a great deal about with every scientist and researcher that I talk to, but that’s a life lesson.
Dr. Storniolo: I have three grown sons, and I’ve been really … And they’ve watched this. I mean one of them is an MD PHD candidate, so he’s in a hardcore lab. I mean he’s really, I think, watched me go through this and kind of how atypical its been, but it’s been so satisfying. It doesn’t really whether I’m first author. It doesn’t matter to me. What matters is that the work that’s done, and I don’t put down people where it does matter. It just … it’s not my thing, so I get to have fun watching other people succeed, as long as the work gets done. It’s just wonderful. I’m old enough that all that stuff doesn’t matter anymore. It’s just a privilege to be able to participate in all of it.
Chris Riback: Well maybe for the next conversation, after you talk to your own son, I’ll have you talk to my kids as well, and maybe impart some of this onto them. I do want to ask just one more about one of areas of research because that struck me an important, and I think so many people would have questions about: pregnancy. That’s one of the areas that you’re researching, and looking at the tissue at the different stages. And specifically, the role of pregnancy in protecting the breast from developing cancer. What’s the working hypothesis? What do you hope to identify? And where are you on that?
Dr. Storniolo: Well, pregnancy is a very funny thing. Pregnancy appears to protect the woman if the pregnancy is an early pregnancy and is neutral if the pregnancy is a late pregnancy. That’s the first level of, at least, at the epidemiologic observation. If you have pregnancies under 30, they appear to be protective. If you have pregnancies later in your life, they’re not bad, they’re just neutral. Having said that, there’s a period of time immediately after your pregnancy, and the duration of that period is a bit controversial. Some people say a year, some people say a little longer, that the breast appears to be at somewhat increased risk, which is a bit puzzling because that’s also the period where people nurse.
Now again, that happens to be an epidemiologic observation. Now you’ve got to tease out everything in between, which is some of those women nursed, some of those women didn’t nurse. We know that lactation is obviously a good thing for the breast, so I think what the work that the lab is doing is trying to get at some of those questions. That work is really, really in its earliest stages, but again, that’s one of things we’re looking at.
Chris Riback: Yeah, it’s a fascinating area that I’m sure people will watch on.
Dr. Storniolo: The breast is a very puzzling organ for something that changes as many times as it changes, it’s a puzzling organ.
Chris Riback: And this may be simplistic, silly question or thought, but as I was reading about it, I was finding it interesting, and reading about your research, I was finding it interesting to what extent the body and nature takes care of itself. I mean I guess at some stage, for some of us, it turns against itself as well, but your comments on how pregnancy obviously furthers our species, so it’s natural part of life. It can be, in the best cases, beneficial, and at the worst case, neutral. Lactation, again, the advancement of life, and part of the core of who we are as a species. The benefits of that. Just fascinating to think about or to read about the ways in which evolution. That body protects … Are those …
Dr. Storniolo: Yeah, yeah. And then you think about that from a philosophical point of view, then you get frustrated with how many different ways you try to mess that up. You’ve got it absolutely right.
Chris Riback: It comes across. One other area: ethnicity. That’s another area that you’ve done research. What are you looking for here and what stage is that research at?
Dr. Storniolo: That actually is moving along because it’s well known that self-reported ethnicity is not at all accurate, and for many reasons, people simply don’t know, and we are beginning to understand that ethnic differences are very important in understanding the basic genetic composition of kind of what we’re born with and where we start. So we did it to characterize every single donation we have as many different ways that we can. So we basically have done it now for all our tissue donors simply to have one more way of saying this is what this tissue is. It’s striking. It really is striking to compare.
We haven’t done a complete comparison of self-reported versus genomics, but the differences, at least from what just we’re looking at randomly, are pretty striking. And I’ve learned something about myself. I had no idea, but which makes sense, which is I’m an immigrant. I came from Italy, and it breaks it down to European versus Middle Eastern and then African et cetera, et cetera. And I learned that I was 27% Middle Eastern. Now since I was born in Sicily and everybody and their brother, historically, has been through Sicily, that kind of makes sense, but I had no idea.
Chris Riback: Yeah, fascinating.
Dr. Storniolo: So it is fascinating. It’s just one more way of characterizing what you’re looking, which is going to be important.
Chris Riback: There is so much there, and from questions of …
Dr. Storniolo: Let me just finish that.
Chris Riback: Yes, please.
Dr. Storniolo: So for example, African-Americans. We’re learning so much about triple negative breast cancer, or basal-like cancer. Very, very aggressive form of breast cancer. Much more common in women of African descent. Well women of African descent in this country is, in and of itself, a huge span people. I mean that can be anywhere from 10 to 15 percent African to 90 percent African or more, and so does that impact your risk? Some of it, like in my cases, just interesting, but some of it, in terms of risk for breast cancer is much more than interesting. It could potentially impact your breast cancer risk.
Chris Riback: Yeah, there is so much there from the questions and impacts of ethnicity to pregnancy to just the ways that tissue changes at the very beginning, and that’s among the many things that you look at, and that incredible tissue bank that you run and get to do research off of.
Dr. Anna Maria Storniolo is professor of clinical medicine at the Indiana University School of Medicine. She’s also the director of the Catherine Peachey Breast Cancer Prevention program and a BCRF grantee since 2007.
Dr. Storniolo, thank you so much for your time. I really appreciate it.
Dr. Storniolo: Thank you so much. This has been a joy.
Chris Riback: To learn more about breast cancer research, or to subscribe to our podcast, go to BCRFCure.org/podcasts.
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