Looking for a kinder, gentler way to treat the disease
When the Miami Breast Conference was founded in 1983, treatment for breast cancer was mostly limited to surgical interventions and radical mastectomies. With the development of immunotherapy and targeted agents, the treatment landscape has progressed immensely, sparing many patients from what was often a debilitating and disfiguring surgery.
Prior to the 37th Annual Miami Breast Cancer Conference, ONCOLOGY sat down with Patrick I. Borgen, MD, to discuss the latest trends in surgical and medical oncology, the transformation of breast cancer treatment over the course of his career, and the role he played within that evolution.
Q: You are delivering a commentary at the Miami Breast Conference. Can you give us just a little preview of what it is going to entail?
DR. BORGEN: So right now, on the preliminary schedule I am actually going to give 2 talks. On Friday morning at the plenary session, I am going to present some work that we have done on a totally unique group of patients who unfortunately had their breast cancers missed, sometimes on a series of imaging studies. And so, by the time we saw them you could look back over time and see 1, 2, 3, 4 years of growth of a breast cancer. What it represents, and it is a sad dataset, but it represents the natural history of untreated breast cancer in the modern era with modern diet and modern stresses. And what we show is that it is completely impossible to predict the growth rate of breast cancer. In the dataset I will be presenting, the tumors are all estrogen receptor (ER)-positive (ER+). They are all negative for the human epidermal growth factor receptor 2 (HER2) oncogene. So, there should be a very homogenous population, but what we show is that it takes a complete random scattershot of how breast cancers actually grow.
This has a lot of implications, for example, in the medical–legal world, where often when there is a delay in diagnosis, the parties in the action will make bold statements about how big the tumor might have been, or how big it was a year ago or 2 years ago. This falls under the head of what is called tumor doubling time, and what we show in this paper is that it is almost impossible to predict tumor doubling time.
So, I think it is important. It is a piece of work we have been laboring on for about 5 years, and I am very proud to be sharing it with the Miami audience.
Q: Can you tell us a little about the second presentation?
DR. BORGEN: My second presentation at Miami in March will be on what we have done to, frankly, eliminate opioids from breast cancer surgery. So, when I got to Maimonides, which is a very large, very storied urban hospital in Brooklyn, I discovered things like we deliver 9000 babies a year. That is way more than Sloan Kettering delivers.
We have a very busy emergency department (ED). Our ED saw 120,000 patients last year. But what I learned was that we had an amazing opioid problem, [with patients] coming into our ED every single day from our neighborhood, and that a study showed that approximately 80% of those addicts… and victims of overdose…started with…a [physician-]prescribed narcotic.
So, about 5 years ago we got heavily involved in trying to reverse this. And there were a number of advances along the way that helped us. It really was, directly addressing a need in our community. And now it is clearly a national need.
So, I am really happy with what we did [here] in Brooklyn…we have treated over 1000 consecutive patients with a breast-conserving approach without a single milligram of opioids—over 1000 patients! So, if the rest of the country [can] come close to that, we could really make a dent in the opioid epidemic in this country.
Q: What are you looking forward to seeing presented at the conference?
DR. BORGEN: It has been another banner year in breast cancer research. During [the] Miami 2019…conference, the FDA approved atezolizumab (Tecentriq) as the very first true immunotherapy for…breast cancer. And since that time, we’ve learned more and more about immunotherapy. I think that will be a feature of [this] meeting. We continue to refine our understanding and treatment of HER2-positive (HER2+) breast cancers, and within the past year we saw approval for an antibody–drug conjugate called T-DM1 in patients who received neoadjuvant therapy in the HER2+ setting and had residual tumor burden.
We have also seen at least 3 commercially available cell cycle checkpoint inhibitors in the ER+, HER2-negative space. And these drugs have set a new standard of care, particularly in the metastatic setting. So, part of what the story is this year continues to be a class prediction as a goal, matching the disease in front of you to the treatment you are recommending. And I think we are getting better and better at doing that. And so, the strong implication is that breast cancer is certainly more complicated to treat [now] than any time in history.
Staying current in breast cancer is more challenging than at any previous time in history. And I think it is the role that Miami plays. I think that at Miami we pride ourselves on the practical. Our motto of “hear it Friday, use it Monday” has never been truer than…right now. Virtually all of the lectures will be proceeded by a clinical case study similar to our tumor board’s back home that we do every week with very specific questions that we want the speaker to answer. And so, this is highly clinically applicable information designed for the practicing surgeon, oncologist, radiation oncologist, radiologist, and pathologist who is in the trenches diagnosing and treating breast cancer [patients] every day.
Q: You said that breast cancer is more complicated now and more difficult to treat than it has ever been. Why is that?
DR. BORGEN: I think that we have always had a sort of fundamental understanding that breast cancer was a family of diseases, not a single disease. And yet, as recently as 10 or 15 years ago, we were largely treating it as a single disease. As a deeper understanding of breast cancer has emerged, and as clearer subtypes have emerged, and as effective treatments targeting specific subtypes have emerged, it means that we have got to be much smarter in our choices.
I like to say that breast cancer is no longer about seeing the clinical star, it is about seeing the star team, and I really do think that [it is] unbelievably important. For so many years we did surgery first, and then chemotherapy, and then radiation, and then hormone treatment. And very often today we change that sequence with neoadjuvant chemotherapy or neoadjuvant estrogen blockade. So, something that is as fundamental as the sequence of the treatments has really changed dramatically over the last decade.
And, of course, the agents that we have available, the immunotherapy agents, the cell cycle checkpoint inhibitors, even the poly(ADP-ribose) polymerase inhibitors that we are using in patients with BRCA1 and BRCA2 pathogenic mutations, are proving to be incredibly effective in that unique subset of patients with metastatic breast cancer. So much so that virtually every patient who has metastatic breast cancer now gets tested routinely for BRCA1 and BRCA2. So, it’s a more complicated horizon. But the glass is clearly half full and not half empty, because patients are doing better than they have ever done before. Survival rates continue to increase, and that increase is accelerating. So, the future is incredibly bright.
Q: How has the Miami Breast Conference changed over the years?
DR. BORGEN: When Dr Dan Osmond founded the meeting in the early 1980s, there really was a single flavor, if you will, of chemotherapy that was not really commonly used at that point. Mastectomy was the most common operation. Estrogen blockade with tamoxifen was around but not popularized. It was 10 years before screening mammograms became popular. And so really it was almost purely a surgical meeting. And if you fast-forward to today, 34 [or] 35 years later, our audience is about 60% surgeons, but the other 40% is vitally important, and really rounds out the team, because today it is impossible to treat this disease without a true multimodal approach.
Q: What are the major trends in surgery and medical oncology right now?
DR. BORGEN: I think all of the exciting work that is being done is in the neoadjuvant space, whether it is neoadjuvant chemotherapy, or neoadjuvant hormonal therapy, or neoadjuvant endocrine therapy. And what is happening is…very often we are able to downsize the magnitude of surgery, the disfigurement of the surgery, the disability of the surgery, and I think that is the most exciting trend in breast cancer for the surgeon that is out there today. We are doing more, we are doing smaller yet more sophisticated operations because patients are receiving medical therapy first.
Q: How did you wind up in medicine?
DR. BORGEN: My father, interestingly enough, worked for the National Aeronautics and Space Administration. He was part of the team that built the very first stage of the Apollo Saturn V rocket. The massive rocket that lifted the whole thing off the ground was built in New Orleans, and so I grew up in New Orleans. My mom was a schoolteacher and my dad was literally a rocket scientist. I initially wanted to be an engineer, really wanted to follow in his footsteps. And so, I studied engineering as an undergraduate at Tulane University and did not love it. And my heart kept coming back to medicine. So, at the end of my engineering degree at Tulane I applied for medical school, and lo and behold I got in and attended Louisiana State University (LSU) School of Medicine. And I have never looked back.
I have always been extremely happy about my decision to purse medicine. The idea of being part of a decision-making process, an intervention process at a critical moment in another human’s life, was really attractive to me. I wanted to make a difference. I wanted to, on an individual basis, make a difference. And I love people. And I think I have always had above-average people skills. And so that was really the attraction to medicine.
Q: What attracted you specifically from medicine to oncology?
DR. BORGEN: When I was a resident in surgery in New Orleans, a lot of what we did was trauma. And I did a fantastic number of operations for gunshot wounds and knife wounds. It was a huge part of training in surgery in New Orleans at the time. And as exciting as it was, it was not really intellectually stimulating. So probably as a result of my, you know, kind of deep trauma experience, I wanted to be able to study a disease, I wanted a common disease. I wanted a disease [in which]…discoveries could make a difference in a big way.
There were only a few tumors that fit the bill, and breast cancer was by far the most common and by far the least well understood in the late 80s. We were still doing radical and modified radical mastectomies. A quarter of our patients were dying. There were huge side effects from the surgery, it was debilitating and disfiguring and defeminizing. And so, once I decided on surgical oncology, the choice for breast cancer for me was easy. It was the most interesting, least well-understood disease that was out there.
Q: You have talked about your mentor Murray Brennan and how much respect you have for him. His saying is always: adulation is soporific. And you have also talked about the importance of being self-critical. So, in all that, how do you find the way to celebrate your success?
DR. BORGEN: That is a great question. I believe that I have never accomplished anything by myself. I believe that I have assembled teams. I have motivated teams. I have supported teams. So, our victories have always been group celebrations. And that was true at Memorial Sloan Kettering; it is true here in Brooklyn. You assemble the right team, you give them the resources they need, and then you stay out of their way. But I do not feel as strongly as Murray did about adulation being soporific. I think that this new generation of what have been called millennial(s) that are coming into medicine are wonderful. But the truth is they respond really, really well to positive reinforcement, more so than my generation did.
And so I think I have had to change my style to fit the new generation of cancer surgeons and cancer researchers, and I am very comfortable in that, and I laugh now when I think about, you know, Dr Brennan and the wonderful…impression that he made on me. But it would have been nice every once in a while, [for him] to say, “that a boy!”
And you know I have stayed very close to Dr Brennan and we have dinner 3 or 4 times a year, and I bust his chops about this now that I am of a certain age and do not fear him. I give him a really hard time and he laughs. He is funny about it. I think he was the greatest cancer surgeon of the 20th century, and I think history will…reflect that. But he got there by being really tough on himself, so I have emulated that to an extent, but I think I have softened my act over the years. I do not think I am the tough SOB that…I used to be.
Q: What was it that initially brought you to New York?
DR. BORGEN: I went to Tulane [as an] undergraduate and I went to LSU medical school, and then I trained at a wonderful surgery program called the Ochsner Clinic in New Orleans. And really, I fully believed that I would practice as a surgeon in New Orleans. I wanted to do a little more training, so sort of through a friend of a friend I contacted a guy named Dr Michael Osborn who ran the Breast Cancer Research Laboratory at Memorial Sloan Kettering.
And I got him on the phone, he had a thick British accent and I said, “Look, you do not know me, but we have a mutual friend, and I will come work for free.” And he said, “When can you show up?” And so, I took out a $20,000 bank loan, and I went to New York, and I worked for free for 1 year. And they decided to keep me, and they actually paid me for my second year there, which was nice. And then the following year I was offered a spot on the faculty, the surgical faculty, on the breast service at Memorial Sloan Kettering. Then 2 years later [I] became the chief of the division. So, it was a very magical time for me.
Q: Was it just the opportunity to practice at Memorial Sloan Kettering that attracted you to New York?
DR. BORGEN: Yeah, I made one of the rare adult decisions of my life, which was, New Orleans had family, it had the culture, the music, the food, the hunting and the fishing that I grew up with. But Memorial offered a world-class laboratory, a world-class research team, thousands and thousands of patients, and a chance to really study breast cancer in a whole different way. Looking back, I am sometimes surprised that I was that smart back then, because it was a tough decision to leave New Orleans and to leave my and my wife’s family behind. But you know, in retrospect, the richness of my growth, the richness of what I think we accomplished in breast cancer was remarkable. That would not have happened in New Orleans.
So then at Sloan, it was the dawn of the discovery of the BRCA1 and the BRCA2 genes. And that revolutionized our thinking about breast cancer. Our group discovered one of the critical founder effect mutations, and the only one in BRCA2, and kind of put us on the map. And I think we taught the world about BRCA1 and [BRCA]2 at a very high level—at a time when, you know, you learn genetics in medical school thinking you will never use it again, and suddenly it is part of your day-to-day lexicon.
I was able to hire 10 breast surgeons—one per year for 10 years. We doubled the size of the division, from treating 900 women a year to 1800 women a year. And…really [made] a massive amount of contributions. So, it was incredibly rewarding, and you cannot say enough about it.
Q: When you started at Memorial Sloan Kettering, the institution was doing BRCA research. Were you a part of that?
DR. BORGEN: Yeah. I hit the 2 years in the breast cancer research laboratory under the direction of Dr Michael Osborne. And Dr Osborne left to pursue other career pathways. And when he left there was a gap. The institution asked me to take over…the leadership of the lab, which I certainly embraced. That played a strong role in me deciding not to go back to New Orleans and to stay in New York.
And so, we were deeply involved. The structure of BRCA1 was discovered about a year after I started as an attending [physician], and we had an enormous population of patients to begin studying, and a few years later we discovered the founder effect mutation on BRCA2. And that was really a clinically important, practical discovery, and that sort of launched us.
Q: And you personally, you were at the forefront of HER2 research, correct?
DR. BORGEN: Very much. We had one of the world’s first cell lines that had amplified HER2. And so, we were able to do experiments in vitro outside of the body, learning about the form and function of the HER2 oncogene. And so, we did a lot of the early work on HER2.
Q: So how does a surgeon wind up doing so much molecular research and genetic research?
DR. BORGEN: I think that as a young surgeon I was convinced that surgery would not be the long-term answer. When you think about those first patients who were found to have BRCA1 mutations, and they said, “Doc, what can I do about this?” and we said, “Well, we can remove those breasts,” and they looked at you like you were crazy. I think no one who really thought this through back then felt that the future of prophylaxis would be radical surgery. And so, the answer had to be medical, it had to be genetic, it had to be genomic. So, I think early in my career I was convinced that surgery would play an important but diminishing role into the future.
Q: Over time, breast cancer treatment has been moving towards less invasive therapy. But more and more high-risk women—women who are BRCA-positive—are choosing prophylactic mastectomy. How do you counsel your patients when they come to you and say they want a double mastectomy?
DR. BORGEN: First of all, I think that it is purely a patient choice, not a doctor choice. I’m not so sure—I do some consulting for a big healthcare system here in New York and they [have] data on tens of thousands of patients, and it really looks like double prophylactic mastectomy is maybe less common than it was 10 years ago. And part of that is the advent of better screening of breast magnetic resonance imaging [and] 3-dimensional mammography.
In the 90s when mammograms were analog, there was a 40% false-negative rate [in] mammography [for] BRCA1-associated breast cancer. And so those numbers just did not add up. If you had a 70% chance of getting breast cancer and a 50% chance that a mammogram would miss it, then clearly you were likely to choose what Angelina Jolie chose,...a double mastectomy. In today’s age of much better imaging, I think that we…see less patients selecting to undergo risk-reducing mastectomy.
But at the end of the day, I give my patients as much of the story as I think I can. [I] feel that my role is to develop a relationship with them, so that I can help them make the decision that is right for them. But the worst thing in the world for a breast surgeon would be to have a patient say, “I regret doing this operation. I regret, you know, that I removed both breasts.” So, I think our job is to provide the facts, to provide our best guess about where the field is going, and then help the patient find the solution that is right for them.
You know there are very, very anxious—understandably anxious—patients who have seen relatives die of breast cancer who come in and say, “Forget it, I want both breasts removed,” and of course we do the operation. And then there are patients that are less certain and decide to take other courses. So, I really think this is an era where we are offering, but not selling risk-reducing mastectomy. I think that is important.
Q: You have also done a fair amount of research in male breast cancer. What is the biggest difference in treating male versus female patients with breast cancer?
DR. BORGEN: You are right. I [have] published [results from] a number of studies. I recently [saw] the very first male who had synchronous bilateral breast cancer. And he presented with just a drop of blood from 1 nipple. A very astute internist saw it and said to me “we got a mammography,” and lo and behold he had bilateral breast cancer. And…we learned later he was a BRCA2 mutation carrier. The risk of it [breast cancer] is significantly increased in BRCA2 mutation carriers who are men.
So, we continue to treat male breast cancer very similarly to how we treat female breast cancer. Because of the rare nature of the disease, we have to extrapolate from trials of female breast cancer. And…that has been effective. Men do respond very, very similarly to the treatments that have been developed for women. So, the chemotherapy is really identical. The estrogen blockade with tamoxifen is identical. The role of radiation is identical. The biggest difference is that, I would say 98% of the time, male breast cancers are below the nipple. We are still doing a lot of mastectomies. Breast conservation [in men] is not nearly…as common as it is in female breast cancer. That is actually the biggest difference right now.
Q: Of all the research that you have done in your career, and obviously you have done a lot of it, what do you think has been the most important or the most impactful?
DR. BORGEN: In the surgical arena, I think working towards kinder, gentler approaches to breast cancer has been the theme of my entire career. I was there for [the] transition from mastectomy to lumpectomy, from mastectomy to breast conservation therapy. We played a significant role in the design, development, and popularization of sentinel node biopsy. At the time, the largest US trial had about 3000 patients. We had done 6000 of the procedures. The development of nipple-sparing mastectomy was reconstruction, [and] we were there at the very beginning of that. In patients who [chose] or choose a mastectomy, this is a way to soften the blow of a very, very disfiguring operation. And so, I think the theme of my career has…been looking for a kinder, gentler way to treat the disease.
Q: Let us talk about racial disparity in outcomes. Black women are 14% more likely to die from breast cancer. What can be done just to close that disparity?
DR. BORGEN: It is a great question and it is 100% true. In Brooklyn…where screening remains a challenge, we have had a number of outreach programs to schools, to churches, to congregations to encourage screening. Through various foundations we offer prescreenings.
But it is more than just screening. It is more than just early detection, and we know that both African Americans and Caribbean Americans have a higher likelihood of getting triple negative breast cancer. And more research needs to be done to fine-tune our understanding of different subsets of triple negative breast cancer. We have been treating triple negative breast cancer, particularly in African American and Caribbean American patients, as a single disease entity. And it is not. It is a small family of diseases in and of itself.
Now, I think the approval of atezolizumab as the very first immunotherapy in breast cancer, which is being used in metastatic, triple-negative breast cancer, will save hundreds of lives of African American women. And I think we will begin to see progress in that area.
Q: Is part of it getting more African-American women to participate in clinical trials?
DR. BORGEN: It definitely is. When I was at Memorial Sloan Kettering, we built a breast center, it was called BECH—Breast Evaluation Center of Harlem. And it was a screening facility on 125th Street in Harlem that offered low or no-cost mammograms. And a lot of the community did not always trust Memorial. Some women felt they were being [used as] guinea pigs in some experiment. Of the women who had a first mammogram, only about [one-]third ever came back for a second mammogram. So clearly there were cultural impediments that we did not understand. And when the National Surgical Adjuvant Breast and Bowel Project started the world’s first breast cancer prevention trial, we offered participation in that trial at the Breast Evaluation Center of Harlem.
But the community leaders cautioned us that it might further decrease some behaviors of women seeking treatment, that it might further make women feel that they were being guinea pigs. Those differences persist today, and we have to have more broad-scale representation in our clinical trials.
Now, I am in Brooklyn, which is a real melting pot. Our Patient Bill of Rights is in 43 languages. And…we have extremely broad participation in clinical studies that we are doing. So, …one of the joys of working in Brooklyn right now is that we really are able to offer clinical trial participation across a more normal slice of America if you will. I think Brooklyn is a great microcosm of what America is about today. And so that has been exciting.
Q: You mentioned that you are in Brooklyn now. It is a very diverse area. How do those cultural differences play out in sort of the day-to-day treatment at Maimonides?
DR. BORGEN: What lured me away from Sloan after 20 years was to become part of a group to build the very first cancer center in the history of Brooklyn. And even though…our center is about…10 miles from where Sloan Kettering is, we have a largely underinsured and uninsured population. And [many] of those patients can not really go to the Sloans of the world, and so you had this amazing giant, the fourth largest city in America, in the shadow of Manhattan, literally, lacking cancer services.
So, the challenges have been many. Language. There are times [when] we have to use 2 interpreters; for example, Fukienese, to Mandarin, Mandarin to English. So, you are in a room with a patient with 2 different interpreters. So, transmitting complex information is a challenge. It is also the joy of the job. It is also providing…services to a group that 10 years ago did not have these services.
Q: Memorial Sloan Kettering is the top 1%, the pinnacle of cancer research. So, what was it about getting to work in Brooklyn that drew you out of that gilded tower?
DR. BORGEN: Yeah, I did not grow up in a gilded tower. My parents combined income in 1968 was $25,000. They were both happy. They both loved their jobs. And they were both very fulfilled [with] their jobs. And so, I knew having started at Sloan at a very young age that I really wanted to finish my career going back to an underserved area. And I looked in Louisiana, and I looked in Appalachia, and looked all across the country. And someone said, “Have you ever been to Brooklyn before?” And I said, “Yeah. I’ve been to Peter Luger’s Steak House twice in Brooklyn.”
And of course, as I started to research Brooklyn, I understood that it was 3 million people with no cancer services. In fact, there were no members of cancer societies living in Brooklyn. So, I really had a chance to go back to my roots, which is how I see this Brooklyn experiment, [and it] was just an unbelievably wonderful opportunity for me.
One of my friends told me that I went from doing well to doing good. And maybe that is true. But I love what we are doing here in Brooklyn, and I may have changed Sloan Kettering a little bit over my 20 years. I like to think I changed it a little bit. But I know I have changed Brooklyn an enormous amount, and that really feels…very satisfying.
Q: You lead a training program in Brooklyn. Tell me a little about that. What you are looking for, and what do you want your trainees to take away?
DR. BORGEN: We have over 500 residents and interns in our hospital. We have about 50 or 60 in surgery. And as we recruit trainees, we are looking for…empathy, community service, diversity. We want physicians and athletes and authors and painters. We want as diverse a person as we can find, cause frankly those diverse individuals by far make the best surgeons. So, it has been an evolution.
I have actually run this training program for 10 years now, and I am really proud of the surgeons that we are graduating. They are doing extremely well, and I think they are going out and emulating this program across the country, really. Surgeons have a bad reputation of being butt holes, and sometimes it is true. And we do not think surgeons need to be. We think surgeons who are, often in breast cancer, the quarterback of the team. [They] need to be kind and gentle, and really smart, and really empathetic, and I think that is what we are achieving.
Q: You have also taken a bit of a different approach to recruiting your team at Maimonides. Can you tell me a little about that and what you are looking for in a physician?
DR. BORGEN: I think that academic medicine almost universally puts a premium on academic productivity, how many publications, how many presentations, what is your national reputation? And certainly, I did that when I was recruiting at Sloan. But as I matured, I sort of realized that smart was relatively easy; nice was not always so easy. And as I was building my team here in Brooklyn, we recruited for values first, for emotional IQ first, empathy first, and then looked at somebody’s credentials. And what we found was that it was really difficult.
It was hard to find, but they were out there. But you had to look, you had to start with values and then once you established what you believed someone’s values were, then look at their ability, and that has made all the difference. I recruited about 80 surgeons to Brooklyn in my role as the chairman of surgery. And it has created a culture that doctors want to practice in. I get calls every day from physicians saying, “Gee, I hear you’re doing something really interesting in Brooklyn, I’d like to come take a look.” And, of course we say, “Come take a look.”
So, what we have created is a work environment that is very different than most academic institutions, where there is comradery, there is collegiality, there is mutual support, there is professionalism, there is transparency. People are self-critical. Murray Brenner would be so proud because people are self-critical. We have our morbidity and mortality conferences and the first thing the surgeon says is, “Let me tell you what I did and what I would do different next time,” and that makes all the difference.
And so, I think that whole fundamental concept of,…in medicine, insisting on nice and excellence is a game changer. There is a lot of institutions that take good care of patients. And,…our country is blessed to have thousands of those frankly. But the number of institutions that do that and make a patient feel well cared for is pretty rare, and that is what I think we do in Brooklyn.
Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.