There are many challenges in managing breast cancer. Top among them is the fact that initial breast-conserving surgeries (the standard treatment for early-stage disease also known as lumpectomies) often miss vestiges of a patient’s tumor. In fact, up to 40 percent of women require another procedure following lumpectomy. Not only can additional surgery, of course, increase a patient’s anxiety and be physically taxing, but it can cause delays in critical subsequent treatments like chemotherapy and radiation.
Why is that rate so high? Why is properly identifying the tumor so difficult? Most importantly: What can be done to reduce repeat surgeries?
Dr. Mehra Golshan is working to uncover answers to these questions. He is the principal investigator of several phase II trials aiming to reduce the need for additional operations. And he has pioneered imagery techniques that have reduced the need for repeat surgeries by a remarkable 70–80 percent. Among his next goals: Scaling that technology to make it widely available to all.
Dr. Golshan understands cancer not just from his experience with patients, but also his experience as a patient, after being treated for colorectal cancer about two years ago. He is now cancer-free and fully at work, and after decades treating cancer professionally, experiencing it personally left him with a stark realization: He realized he actually knew very little.
A BCRF investigator since 2014, Dr. Golshan is the deputy chief medical officer for surgical services and director of the Breast Cancer Program for the Yale Cancer Center, Smilow Cancer Hospital, and Smilow Cancer Hospital Care Centers.
Chris Riback: Dr. Golshan thank you for joining. I appreciate your time.
Dr. Mehra Golshan: Thank you for having me this afternoon.
Chris Riback: Of course, I have many questions about your approach to tailoring surgery and therapy for women with early-stage breast cancer. I realize you are globally renowned in this, but I wanted to start with an aspect of your medical and scientific approach that I confess we don’t often read about often in the medical journals, which is you once celebrated a patient’s three-year survival milestone by meeting her at the top of a mountain and skiing down. That’s a heck of a medical approach. We don’t read about that one very often.
Dr. Mehra Golshan: Yes. When a woman or any patient really comes to the operating room, you’re in a very vulnerable position, to say the least, and you’re waiting for anesthesia and nursing and the doctors to do their safety checks, you see the pain, the vulnerability, the fear in their eyes and no matter what they give beforehand to take that anxiety away, people are scared. And some will benefit from a gentle hand on their shoulder or holding their hand or just some casual banter. And in this case, it was a patient of mine.
I was practicing in Boston at the time and a patient of mine who came to us for care from Colorado and from a very avid skiing family, and she had a really tough course. She had a triple-negative breast cancer, had to get chemotherapy upfront and was preparing for a very major operation with reconstruction, six, seven, eight hours. [She had a] young family. And one of the first things she wanted to do when she recovered from all this was to get up back on the slopes and ski again.
I tinker around with skiing. I’m definitely not professional or great, but I said, “Let’s get you through this.” And then in the future, we’ll meet up at Vail Mountain where they ski all the time. And I was fortunate three years later to meet her and her family up on Vail Mountain. And we skied a couple of runs together, had lunch together, skied a little bit more. And basically, they were just playing with me keeping up on the green and blue trails. And then they took off on the double [black] diamond. It was a lot of fun and something I’ll never forget.
Chris Riback: Well, it was nice of them to humor you in that way a couple of times and obviously that example of your own humanity and connection. And as I’ve read about you, I confess I’m not surprised having now learned a little bit else about you, but it was nice to read about and nice to hear because that connection between the doctors and patients, we don’t always hear that. We know that the care is always there, but that certainly says something.
Dr. Mehra Golshan: Thank you. It’s great. And we’ve remained very close friends and with her family. More importantly, she’s gotten to see her kids and family grow and we’re just fortunate to be part of that team.
Chris Riback: That’s wonderful. So, let’s talk about the medical care, and let’s talk about the areas where you, in particular, specialize in and spend your energy and focus. Let’s start at the highest level, I think. And if maybe you would take me through the process, how does a lumpectomy work? How do you determine what needs to be done for each patient? This is a key step obviously so that the patient can then advance to the post-surgery stage. You also spend a lot of your time, I believe, trying not to reach a surgery stage. So, talk to me about both aspects of that place.
Dr. Mehra Golshan: So historically many decades ago, all women with breast cancer had to be treated with a mastectomy. And fortunately, several decades ago, really pioneering, thoughtful people like Bernard Fisher and Umberto Veronesi, and others started testing this concept of lumpectomy or partial mastectomy or basically just removing the tumor in what we hope is a rim or ridge of normal tissue usually followed by radiation and comparing that to mastectomy. And we’ve shown that overall survival is exactly the same. So one isn’t better than the other in terms of keeping a woman alive longer, there’s a slight and very slight difference in what’s called local recurrence. A chance of that coming back in the breast. It’s slightly higher with the lumpectomy and radiation. But again, it doesn’t affect the outcome of the woman.
The challenge with lumpectomy though, is we want to remove the tumor, we want to get it all out and get what’s called clear margins and leave her with a cosmetically acceptable result. So do as minimum damage and removal of tissue as possible. The challenge though is that we do that during surgery and then we have to wait about a week for the final pathology to come back. And it’s not uncommon where that final pathology will show that those edges or those margins around the tumor aren’t clear. Some people will say, “Well, why can’t you do it like dermatologists do with most surgery?” They will take little shaves and test them while they’re removing that lesion. In breast tissue, the primary component or a large component has a large fat component or adiposity. And so doing things like frozen section or testing it in real-time, really isn’t accurate and doesn’t work.
So, we have to wait a week, and historically anywhere between 10 and 40 percent of the time, a woman has to come back a second time for what’s called a reoperation for clear margins. And of course, making that phone call and saying, “You know what? We got most of it, but not all of it. We got to meet and discuss what the next steps are. I think we should go back in and try to clear those margins out.” That’s not only disconcerting disappointing news to give—it raises the anxiety of the patients. Certainly doing more surgery will reduce the cosmetic benefit because you’re going to take more tissue out. It’s going to lead to a delay in the other treatments that are often necessary whether it’s chemotherapy or radiation, leads to increased healthcare costs. So anyway no one’s been able to figure that out yet and that’s one area that I’ve spent a fair amount of time researching and maybe we can touch base a little bit later on what we’re pushing toward in terms of deescalating or trying to put myself out of business.
Chris Riback: We all would love to see you as a ski bum. That’s our goal is to put you out of business.
Dr. Mehra Golshan: It’d be nice. [Though my] tennis game is a lot better.
Chris Riback: There are two parts that I’d really like to understand. One is, why is it so darn hard to get the imaging right under current procedures? Why that 40 percent and why is the imaging so hard? And then two, to your point, what are you doing to try to ensure that you don’t have the privilege to work again?
Dr. Mehra Golshan: So, the challenge is that the tumors that we see sometimes we can feel them, but in the United States, in many parts for example, in Europe the population is what’s called well screened. So, women do mammography, ultrasound, and MRI and we’re catching these tumors that are pretty small sizes. They’re often not palpable, meaning I can’t feel them at the time of surgery. We then rely on our radiology colleagues to help us during the operation. Not only telling us the size and the location, but helping direct the surgery as well. And unfortunately, the targeting is not perfect. And when we’re trying to remove that tissue or the tumor is we’re always trying to balance the aesthetic cosmetic outcome with the main goal which is to get that tumor cancer out of her and to get her to heal and recover.
In the United States and then all over the world, the breast tissue is something that in terms of the surgery that we do, it’s balancing that cancer, our oncologic outcome, with that aesthetic outcome. Because the woman at the end of the day, she’s got to be comfortable with what she looks like afterwards. Whether she’s looking at herself in the shower or the mirror or with a significant other or a spouse. And we haven’t been able to figure that out in real time. And so, it’s not just my work, but there’s hundreds of thousands of others around the country and around the world who have tried to figure out how we can cost-effectively and during that first operation, reliably tell her that, “We got it all out. You’re cancer-free. Time to heal and move on to the next phase.” And we’re not quite there yet, although we’ve made some really exciting advances in that area.
Chris Riback: Yes, you have. Tell me please about the exciting advances. You are testing interoperative imaging and molecular technology to improve those surgery outcomes.
Dr. Mehra Golshan: So, one test that many women, not all, but many women with breast cancer get is a breast MRI. And if any woman who’s listening to this will know that they get that breast MRI in what’s called the prone position. Meaning they’re lying on their stomach. The breast goes through an aperture and then they do the imaging of both breasts, or the one side where the tumor is. Yet as a surgeon, I’ve never operated on a woman’s breast with her lying on her stomach. She’s always lying on her back of course. And the breast is not a fixed organ. So like the brain or other parts of the body where if you put someone on their stomach or back, it doesn’t move. But the breast moves quite a bit. And one thing that we noticed was that when we were actually imaging the woman in the position that we’re operating, there’s a lot of tumor change.
Meaning the cancer not only looks different, it’s positioned different than it is when we were imaging them lying on their stomach. So, one of the trials that we have underway is looking at imaging of a woman’s breasts in terms of with MRI in the actual position that we do in the operating room. And there are actually several other correlates or secondary studies that have come off of that as well. You would think that’s a pretty simple thing is just turning a patient 180 degrees, but no one had done that until I started looking at this in this fancy operating room. We had at the Brigham and Women’s Hospital and now doing it at Yale University.
Chris Riback: And what has it done in terms of rates and cases and re-excision, and that type of thing?
Dr. Mehra Golshan: It’s cut it by well over 70 to 80 percent, the re-excision rates in terms of reduction. The challenge though, is that building into the operating room that where we were able to test it is a very expensive operating room where we just can’t build a lot of those all over the United States. But the goal of the research was to test it in this particular operating room and then bring it out into the real world, real-life where every woman or most women would have access to this. And so, we’ve pushed this from this kind of testbed operative suite to a much more widespread utilization in real-time, in the real world. That second area that we were looking at is this thing called mass spectrometry.
So, when I started doing this research on MRI, it’s in the specialized operating room, it was called AMIGO at Brigham. It’s Advanced Multimodality Image Guided Operating suite. And it’s one operating room. There’s a lot of really smart people in many other disciplines that were working—so there’s brain cancer surgery that was being done there, lung cancer, and many other types of tumor. And I met a PhD that was working on brain cancer and tumor resection at that time with one of the neurosurgeons and she had told me that there’s this technique that they’re working on. And this is Dr. Nathalie Auger, who works with me on my project.
That looking at the difference between cancer and normal especially in breast cancer, she was finding that there was this interface or there was this border that looked very different under a test called mass spectrometry. So, we have developed a technique where we can test that tissue that I remove in real-time to tell if there’s a tumor left or is it clear at the time of surgery. Now, if we could do this in real-time, then the next step is to say we can develop a tool, a box, an object, a detection device that is cheap, that anyone or any hospital can afford and be able to utilize. And that’s where we’re working on next. And it’s an exciting area.
Chris Riback: Yes. That’s the real-time visual overlay device.
Dr. Mehra Golshan: Yes. Correct.
Chris Riback: And so, on the first part, two questions that I’m thinking of in turning the patient 180 degrees. First one is, you identified and particularly to a lay person, an outsider like myself. One would think, “Well, gosh, doctors, sometimes they do the imaging or do it on the stomach, sometimes they do it on the back and at some point, in history, they must’ve figured out like 60, 80 years ago which side was the best way to do it.” What inspired you to think about that and was there an “aha” moment and did you knock yourself on the forehead afterwards and say.
Dr. Mehra Golshan: Why didn’t we? Not only me, but so many of us could have figured this out long ago. So, one of the interesting things is that breast MRI is used for women that, for example, that have hereditary mutations like BRCA1 or 2 or the Angelina Jolies or Christina Applegates of the world. We know in that case that it can actually identify tumors that mammogram or ultrasound or MRI exams can’t. However, for women who are newly diagnosed with breast cancer, most they’ve done trials that looked at whether breast MRI would help the surgeon in terms of being able to reduce that re-excision rates or determine the true extent of the tumor. And interestingly, those trials, both done in the United States and the UK and around the world actually did not show MRI to be a benefit.
So, if you have a test that’s actually better than mammography or ultrasound, why wasn’t it working? And one of the “aha” moments was that when we were doing our trial and the woman would have the MRI done lying on her stomach and then I’d operate lying on her back and then look at the MRI when it’s done 180 degrees in the opposite direction and seeing that difference between what the tumor looked like before and after and its location, I don’t think any surgeon in their mind was looking at that image that was done when they were lying on their stomach and in their head that they were flipping the patient over on her back and trying to figure out what ended up happening to that tumor.
I think we almost just looked at that image and then we operated as if that was the position we were operating on. And it was only when I kept seeing those pictures lying on stomach then lying on her back, that it was so strikingly different that maybe this was one of the reasons why MRI didn’t work. And again, we should have figured this out potentially long ago. And it took something like this to be able to do it. And again, it was because of there’s no way that this would have worked without the funding and support from BCRF.
Chris Riback: And the data that you mentioned, the stats, the reduction of I think you said 70, 80 percent. It’s remarkable.
Dr. Mehra Golshan: It’s remarkable to be able to do that. So, our goal is then we’re testing it and maybe I can show that it works, but then how can I bring this specific operating room or a technique to something that any breast surgeon in the United States or around the world can do, and that’s the second phase of therapy.
Chris Riback: Which is interesting. It sounds like at both on that capability and on the real-time visual overlay device, two sets of challenges. One is, the initial discovery and hopefully which you have done showing indications that it works, but then secondly, how do you bring it out to scale? How do you make it affordable for any hospital and what’s kind of your prognosis on that? How long? How successful? How hopeful? How many obstacles?
Dr. Mehra Golshan: So I’m hopeful. I went and got my MBA at MIT to figure out how I can get this. It ends up being very helpful to get a business degree, especially as a healthcare provider, we may figure out something that looks and makes sense to us and should just be easy to do. But when you try to bring it out to the real world, it doesn’t get there. So, believe it or not, that was not the only reason. But one reason I did get an MBA and went to a pretty good place called MIT where math and numbers play a large role in sorting things out. So, I am hopeful.
The great news is though that there are so many other people that are working on this, not just me and certainly our group and our program, but there are so many others. And if it’s not my MRI or mass spec, there’s so many other possibilities. And I do hope that one day that it’s one and done. They go into the operating room, they have their surgery done, and nearly 100 percent of the time we tell them it’s out and then we move on. And again, that whole reducing that re-excision, or that second operation.
And sometimes when you tell a woman that they’re going to have to be operated on the second time, they’re going to say, “Well, I don’t want to go through this again.” And I completely understand. I’ll say, “Well, I’ll just do a mastectomy because you’re going to remove everything then and I don’t have to worry about [being] a third operator patient.” And it’s something that I completely understand and again, mastectomy is not a wrong operation. It’s certainly an option and a choice women have yet when we can give as good outcomes with a smaller operation with a much quicker recovery, many women will choose that route.
Chris Riback: In starting to close out the conversation. Could we talk about you for a moment? You of course, are not just a doctor and not just an MBA and a businessperson, but you’ve also been a patient and you experienced cancer yourself. You’ve written about it very, very powerfully. Well, you may have written more than one piece, but the piece that I saw in Medium, so much of it spoke to any human. And a couple of lines really stood out for me. One was, “Since receiving my own diagnosis and starting treatment, I’ve realized I actually knew very little.” And second one was, “When I get back to practicing again, I will ask patients what they want to know.”
Dr. Mehra Golshan: And what they want to know. Yes.
Chris Riback: What was that like to feel that you didn’t know as much as you had thought and what were the parts of cancer that you knew very little about?
Dr. Mehra Golshan: So, I’ll flip the question in terms of I’ll answer the second part first. What patients want to know. I researched breast cancer, operated on so many thousands of women from the United States and around the world and honestly, I thought I knew anything and everything about breast cancer. And I would come in, so the woman asks the questions, so them and their family and examine them and reviewed all their testing and imaging. And I came with a plan and I would like to tell them all the possibilities. The things we were just discussing now. That re-excision is a possibility, or the cancer may come back or may not come back. And I would give percentages and numbers.
And many patients love that. Meaning they want as much information as possible to make that decision. When it was me and it wasn’t breast cancer, but it was me dealing with my own diagnosis. My wife and I, our only concern at that time was that I’m going to be okay and that we can get through this and that there are options and there’s hope. And all those numbers that I was feeling out before just fell away. They were anticipating that I’d be asking, “What are the percentages and what are the odds and what are the outcomes?” And I wasn’t asking any of that. And then I thought, “For years, this is what I’ve been doing and why don’t I just ask the woman and their family or their spouse?” We have patients with male breast cancer, ask him what it is that they want to know.
I’m happy to go into excruciating detail and spend as much time as needed. And sometimes they just want to know, let’s just get the ball rolling, and move on to the next step. And they didn’t want to hear it. And when I say I knew so very little, I see a patient episodically. Meaning, they’re diagnosed. I meet with them in the office, maybe meet with them one more time before surgery. I see them that morning of surgery operates, see them a week later postoperatively. And then I may not see them for six months to a year. And then what happened or what’s going on? And the challenge is not only that the patient goes through or that I went through but that my wife, my children, my extended family, it affects everybody.
Every part of your life revolves around this diagnosis and the treatment and you almost forget that those things are happening while our patients are going through this. And then it really never ends: meaning, you’re done with the surgery, chemo, radiation, and then there’s always the follow-up and surveillance. And I’ve written a little bit about that is, especially in the era of COVID is, it’s somehow when I’m in my doctor’s hat, seeing patients operating in clinic doing research and I’m in the hospital in the midst of COVID, I’ve become used to it. We have protocols and systems and safety in place, but then when I come in for my own tests and exams, I had become completely used to that my wife and often my children would come in for my testing or for my chemotherapy or obviously during my surgery and things like that.
But we’re now often not allowing visitors to come in. Appropriately, so for safety concerns. But that fear and anxiety and not that crutch to lean on. It’s like you look around the exam rooms and people are alone and it’s frightening. And to me it’s horrible that many have to go through. And hopefully, as vaccines and the strategies around COVID get better, that people, family, friends, significant others can come back and be a part of that, every piece of that journey that they can be and not have to deal with those alone. So, that’s good.
Chris Riback: And how are you feeling now?
Dr. Mehra Golshan: Fortunately, I’m back. I operate, see patients, and every time I walk in now, I pause, and I say, “Don’t just go in thinking you know what the next step is.” I may know operatively what the next step is going to be and what plan I should be offering, but before I go and start telling them that, I really listen to them and in terms of what their goal is in all this and then help them navigate those next steps.
Chris Riback: Dr. Golshan, thank you. I should ask you just very quickly, your relationship with BCRF. Is there a way to characterize what role BCRF plays in your research?
Dr. Mehra Golshan: Yes. For sure there’s no way that the work that not only I’ve done, but others have been doing could have gotten to the point that it has without BCRF’s support and funding and whether it’s the Lauder family or Dr. Larry Norton or Dr. Judy Garber. These people that are in leadership positions in BCRF and the way they approach the disease and the cure, is exactly what this world needs and there’s no way that I would have been able to accomplish what I have without their support. And every dollar counts. It’s that critical to us. And with a lot of the things that have been cut because of COVID and the difficulty in obtaining dollars through the National Institutes of Health and other governmental organizations, everything that BCRF does keeps me working one more day. And now I know personally how important it is for us to find the cure and to do better in the work that we’re doing. And I’ll do it for as long as I’m allowed to.
Chris Riback: Well wonderful. And I know you will take this only in the best way. We hope that the effort only leads to your not working anymore and spending your time on those slopes.
Dr. Mehra Golshan: I want to go play tennis or do something else with [inaudible].
Chris Riback: Sounds terrific. Dr. Golshan, thank you so much for your time. And obviously, the work that you do with patients every day.
Dr. Mehra Golshan: Thank you. Have a great afternoon.
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