In this installment of The ASCO Post’s Living a Full Life series, guest editor Jame Abraham, MD, FACP, spoke with Seema A. Khan, MD, MPH, Professor of Breast Cancer Surgery at Northwestern Medicine, Feinberg School of Medicine. Along with her surgical and academic pursuits, Dr. Khan is an active researcher studying the molecular profiles of benign breast disease, both to aid in the identification of high-risk women and to find targets that can be manipulated for breast cancer prevention. She is also investigating new approaches to medical therapies for breast cancer risk reduction.

Dr. Khan was born in Quetta, one of the largest cities in Pakistan, surrounded by verdant hills and mountains. “When I was born, Quetta was a provincial sleepy place and very beautiful. It’s in a hilly area, and it almost was regarded as a resort town, but it had a military college; my father was in the Army and was posted there. My grandparents were in India, so my family ancestral home actually is in Uttar Pradesh, not too far from Delhi. In fact, I spent the first 2 years of my life in India with my grandmother, and we went back many times. I have fond memories of trips to India to visit my grandparents. They grew mangoes, which was the family business,” she related.

SEEMA A. KHAN, MD, MPH

On her surgical oncology fellowship at Roswell Park: “The surgeons treated primary disease, but they also did the adjuvant systemic therapy for primary disease. That was somewhat unusual, even at the time, but it was divided along organ site, so there was a colorectal service, an upper GI service, and so on.”

On risk of breast cancer: “At SUNY, I didn’t have a lot of access to breast cancer specimens; the thing that was most accessible was benign breast tissue. I started a bank of benign breast tissue and then did a few studies looking at indicators of risk in benign breast tissue and went on from there.”

On the clinical puzzle of ductal carcinoma in situ: “I don’t think we’ve figured out the optimal management for DCIS, but I’m also a little wary of backing off completely. These trials of observation, active monitoring, and active surveillance for DCIS are very interesting and necessary, and we learn a lot from them.”

Dr. Khan continued: “My father was in the Army and joined during the Second World War. He fought in Burma and acquired a fungal infection in his foot, which he called Burma rot, and it would flare up from time to time. My grandfather was in World War II, too, and went to Iran. We traveled from place to place because a military family moves around a lot; we spent time in Bangladesh as well before it was Bangladesh. I graduated from Dow Medical College in Karachi, one of the oldest medical colleges in Pakistan. I came to the United States in 1979.”

Not a Family Tradition

Asked if there were any family ties to medicine that might have influenced her decision to become a physician, Dr. Khan responded: “There were no doctors in my family. My closest relative who was a doctor was a second or third cousin, a woman, actually. Women who worked were either teachers, doctors, or broadcasters; in fact, my mother was a broadcaster. Although my mother would freelance on the radio and actually had quite a good radio career telling stories and doing narration, the opportunities for women were relatively limited. I liked science at school, so that seemed like a good thing to do. Two of my very close friends were also interested in medicine, so we traveled together as a trio.”

A Serendipitous Turn

According to Dr. Khan, her road to a career in surgery took a serendipitous turn. “The fact that I did surgery was pretty accidental. When I was at Dow Medical College as a medical student, which is a low-resource environment, things were pretty chaotic in many of the wards. However, one ward—the urology ward—was run on a very tight leash; it was extremely efficient and clean and provided great training. The urologist who was professor there is now an internationally known transplant surgeon. Although there was no transplant at the time, they did dialysis for kidney failure; it got me interested in nephrology, but I didn’t realize there was an internal medicine specialty in nephrology in other countries.”

Guest Editor

Jame Abraham, MD, FACP

Dr. Abraham is Chairman of the Department of Hematology and Medical Oncology at Cleveland Clinic and Professor of Medicine at Lerner College of Medicine.

Dr. Khan continued: “When I came to the United States looking for a job, I was intending to go into urology. However, the experience of urology I had in my training was not that positive, so I decided to stay in general surgery, which I also liked. It was challenging on many levels: for one, I was the only female resident in my program, and for a while afterward, I was often the only woman in the group. Even when I was doing my fellowship, there was only one other woman; we were definitely not represented in surgery the way we are now. For instance, our resident class, the recent intern class, we took seven residents, six of whom are women,” she explained.

Early Days as a Woman in Surgical Oncology

Asked to elaborate on her experience as a woman in surgical oncology, Dr Khan replied: “Things have certainly changed quite a bit since my early days in surgical oncology. In fact, I tell my younger colleagues now that when I was interviewing for a surgical residency position, I was asked things like, ‘Was I going to have children? Did I plan to be pregnant anytime soon?’ They were not being out of line for the times; in fact, it was the business-as-usual approach in a male-dominated specialty. For example, one of my attendings who was a very nice man, asked me with a straight face, ‘What exactly are you doing here? Why aren’t you at home having babies?’ That sort of thing happened not infrequently, but I didn’t realize at the time, being fresh from Pakistan where these attitudes are prevalent, that these questions were totally inappropriate.”

Arriving at Roswell Park

After Dr. Khan finished her surgical residency in a community hospital in Baltimore, Saint Agnes, she did a fellowship in surgical oncology at Roswell Park. Asked to shed light on her fellowship, Dr. Khan commented: “As you probably know, ‘Roswell Park’ was the name of a surgeon, so the surgeons treated primary disease, of course, but they also did the adjuvant systemic therapy for primary disease. So, in our breast service, for instance, we would have patients coming for weekly methotrexate in the office; we would mix doxorubicin, and patients would receive adjuvant therapy on the surgical service. That was somewhat unusual, even at the time, but it was divided along organ site, so there was a colorectal service, an upper GI service, and so on.”

Dr. Khan continued: “I ended up on the breast service because I had a very close friend who was intensely interested in research, and she got me interested in it. Since I trained in a community setting, I didn’t have any research experience during my residency training, but during my fellowship, I was introduced to it by my friend, Dr. Azra Raza, who was already at Roswell Park, thought it was the most wonderful thing in the world, and helped me design my first project. The next influential person was the surgeon who ran the breast service, Dr. Thomas Dao. He was also a successful researcher, and had done part of his training with Dr. Charles Huggins at the University of Chicago. If you remember, Dr. Huggins was the first surgeon to receive a Nobel Prize, and he did so for his work on endocrine therapy of breast and prostate cancers.”

For 3 years, Dr. Khan also worked on investigative projects with Dr. Dao, which kick-started her career as a researcher. “During that time, I decided I should get better informed about statistical methods and also about public health. I got very interested in the epidemiology of breast cancer, so I went to Harvard School of Public Health and got a master’s in epidemiology in 1990. After that, I went to SUNY Health Science Center in Syracuse, mainly because I had developed a relationship with my future husband, who was working there. He’s a researcher, so I moved to Syracuse mainly for that reason,” said Dr. Khan.

A Good Start

According to Dr. Khan, SUNY offered a propitious starting point for her surgical career, as she was mentored by Dr. Patricia J. Numann, Distinguished Professor of Surgery at SUNY Upstate Medical University, who is recognized nationally as a role model for female physicians. “Dr. Numann started the Association for Women’s Surgeons, and it was a friendly environment to start working in. They had some intramural funding that I applied for and received. Then I got an ASCO Young Investigators Award based on work I had done with Dr. Raza at Roswell Park. It was a very constructive and rewarding way to build a career for me and a lot of other women in the field. Surgery for breast cancer has a very honorable tradition, of course, but it is a relatively narrow area to practice in, so having a parallel interest in research really makes it even more rewarding.”

A Fruitful Decade in Syracuse

Dr. Khan noted that her 10 years in Syracuse proved to be foundational for her career. “It was a time of multiple activities. Among other things, I ran a lab project that I started based on my interest then in public health and risk factors for breast cancer. SUNY wasn’t a high-volume center for breast cancer surgery, so I didn’t have a lot of access to breast cancer specimens; the thing that was most accessible was benign breast tissue. In those days, we used to do mainly surgical biopsies, and the trend for core-needle biopsies was just starting in the early 1990s. I started a bank of benign breast tissue and then did a few studies looking at indicators of risk in benign breast tissue and went on from there.”

A Career Move

In 2000, after 10 years at SUNY, Dr. Khan moved to Northwestern University, where she is currently Professor of Surgery in the Feinberg School of Medicine and the Bluhm Family Professor of Cancer Research. Her current studies include examination of the effects of progesterone antagonists in women with breast cancer and breast cancer risk biomarkers in benign breast biopsy samples.

Asked to reflect on her journey to Northwestern and her research focus on ductal carcinoma in situ (DCIS), Dr. Khan replied: “I had just received my first NCI [National Cancer Institute] grant, which actually was a small R03 grant; it addressed aspects of measuring biomarkers in benign breasts. I’ve really been interested in breast tissue–based biomarkers for breast cancer risk, and DCIS is the final stop in that spectrum before invasive cancer. Through the years, I’ve worked on benign breast biomarkers as well as DCIS, because in some ways, the role of surgeons is still critical. Although surgery is critical in other aspects of breast cancer care, too, for DCIS, the main treatment is local treatment. When we give systemic therapy, it’s only for prevention of future events, so that was a very logical thing.”

Dr. Khan continued: “In Syracuse, I started going to CALGB meetings. CALGB had a committee for surgeons, I think, which was not true for all groups at the time. Bill Wood was a key player in CALBG, and he instigated this need to form a specific group of surgeons who were paying attention to the surgical aspects of cancer clinical trials, quality control of surgery, and so on. I started attending that group and actually developed some very, very good relationships within that group. That further fostered my interest in clinical research as well.”

A Still-Evolving Treatment Model

We asked Dr. Khan whether over the course of her career, she thinks the clinical puzzle of DCIS has been solved. She replied: “No. I don’t think we’ve figured out the optimal management for DCIS, but I’m also a little wary of backing off completely. These trials of observation, active monitoring, and active surveillance for low-risk DCIS are very interesting and necessary, and we learn a lot from them. However, when we start also considering the patient perspectives and the cost of monitoring, I think we will actually find there are still women who want to be treated. There’s a lot of room for de-escalating radiation therapy, for instance, but for smaller high-risk DCIS lesions that don’t require mastectomy, surgical intervention alone is actually not that effective. The way I see it evolving is that most women will still have surgery, but they’ll have limited surgery.”

Dr. Khan continued: “I don’t think anyone would consider not treating women who truly need mastectomy—such as those who have a breast full of calcifications of grade 3 DCIS. Then the smaller DCIS tumors, I assume, will be excised, but a good proportion of women will not need radiotherapy. And all of these choices will be based on a far better characterization of risk than is possible now. Then hopefully for the endocrine agents, we will have less toxic ways of delivering them. Also, we will have other endocrine agents that prevent the whole spectrum of DCIS biology, not just hormone receptor–positive disease.”

Although Dr. Khan believes there is a lot more work to be done, she considers it a very exciting phase in breast cancer research. “For one, there is the Cancer Moonshot in the United States and the Grand Challenge in Europe. Both of them are going to generate an enormous amount of data to sort through, make sense of, and apply clinically; I hope we do that with some perspective and some sensitivity for the burdens of both treatment and surveillance for patients with DCIS. It’s a powerful period in cancer research and treatment.”

Family Life: Finding a Balance

Dr. Abraham noted the issue of physician burnout, and asked Dr. Khan to share a bit about her family life and how she balances her demanding career. “I’ve been married for almost 35 years now,” she said. “My husband is a neuroscientist, working mainly on understanding the various aspects of chronic pain. He’s also at Northwestern, so we moved together from Syracuse to Chicago. We have two children, and I’ve learned a lot about gender identity issues because my older child is gender-fluid. They are working in Chicago at a community health center for women. My younger child is in Los Angeles and is working on a writing career. When we get together as a family, we travel to culturally rich places we all want to see. Actually, Italy is a favorite place to go. We’ve done several hiking trips and try to do so regularly. Then, of course, we are by Lake Michigan, so that’s a beautiful area to explore as well. Family and the outdoors are the ways I find a good work-life balance. Plus, I love my work, so that’s a huge benefit.”

Progress Over the Arc of an Esteemed Career

Dr. Abraham asked Dr. Khan whether she has seen the discipline of surgical oncology or surgery change over the course of her career. “Yes, it certainly has changed,” Dr. Khan replied. “Oncology, as you know, has undergone tremendous transformations, and surgical oncology has changed with oncology. Surgical oncologists are molecularly oriented. I joke sometimes that breast surgeons are a unique breed, as they are intent on researching themselves out of a job; pretty much all the advances that have happened in breast surgery relate to less surgery, not more, and I think that trend is going to continue. Breast surgeons will still be needed, obviously, because there are many situations where the three modalities of cancer treatment are synergistic, so we will still have a contribution to make, but the contribution of surgery has really been changing.”

Over the past decade or so, Dr. Khan has been very interested in the treatment of women with stage IV breast cancer and an intact primary tumor. “The results of the clinical trial we did, of course, were very disappointing,” she revealed, “so now most of the time when I talk about that issue, I’m trying to persuade audiences to pay attention to all the developments in medical oncology; from the time we start a surgical trial nowadays to the time we end it, systemic therapy has changed, and that’s a common theme.”

Dr. Khan continued: “We predicted the 3-year survival rate would be 40% in the local regional treatment group in the intervention group. It turned out the 3-year survival was almost 70%, which is indeed significant. The same theme is echoed in the BR002 trial presented at the 2022 ASCO Annual Meeting on a metastasis-directed local therapy. In that study, they projected a disease-free interval or time to disease progression of 10 months in the group that received systemic therapy alone. In fact, it was 20 months. In addition, we need to recognize the toxicities of medical therapy as well. Local treatment, if it supplements the benefit of medical treatment, or lessens its burden, should be considered; it is not a lifelong endeavor, which medical treatment sometimes can be. So, yes, I’ve seen a dramatic change in surgical oncology over the course of my career, and the advances have been tremendous.”

Stand Up and Be Counted

When asked to provide words of advice for a woman pursuing a career as a surgeon, Dr. Khan replied: “I think women surgeons are changing the field because they are aware of human needs in many ways that are different than the awareness of men. Many women entering the field want to have families and bring up their children, and an important message for society overall at the local, national, and international levels is that the responsibility for bringing up and nurturing childrens’ lives is not predominantly a female responsibility. It’s a societal responsibility in which men should partake equally. Also, remember that half the children are male … so equal participation of men in childcare benefits everybody; it benefits men and women,” she stated.

Dr. Khan added: “Even though we have made great progress in gender equality, the path for female surgeons can be quite difficult, particularly during residency. For that reason, many women put off childbearing until they have established their career. That’s true in other professions as well, but it’s particularly an issue for surgeons, who have such a demanding schedule. It’s wonderful to see the kinds of innovations that are also being brought into medicine by women leaders and scientists. So, I would say to young women entering the field—stand up and be counted and have your voice heard.”