From Endocrinology to Oncology: The Pioneering Journey of Dr. Marc Lippman

Table of Contents

• Key Points
• About the Podcast Series
• The People Behind the Conversation
• Early Life and Education
• An Unusual Path to Cancer Medicine
• The Science Revolution: Measuring Hormones
• Elwood Jensen and the Estrogen Receptor
• Building Breast Cancer Research at the NCI
• The Lab Work: Cell Lines and Controversy
• Mentoring the Next Generation of Leaders
• Moving From Lab to Clinic: Key Trials
• What This Means for Patients Today
• Limitations and Lessons Learned
• Recommendations for Patients and Families
• Frequently Asked Questions
• Source Information

Key Points

• Estrogen receptor testing guides whether hormone therapy will be effective for breast cancer.
• A randomized trial of about 350 women showed lumpectomy with radiation can equal mastectomy.
• Hormone therapy drugs like tamoxifen became available after receptor research linked them to response.
• Translational science—applying lab discoveries to patient care—is now standard in cancer research.
• Multidisciplinary teams of specialists are recommended to coordinate comprehensive breast cancer care.

About the Podcast Series

The Cancer Stories: The Art of Oncology podcast is part of the ASCO Podcast Network, which offers nine different programs covering educational and scientific content in cancer care. The series features author interviews and readings from a section of the Journal of Clinical Oncology called Art of Oncology, which publishes personal essays, reflections, and opinions on cancer care.

This particular episode, released on February 28, 2020, is part of a special series called "Conversations with the Pioneers of Oncology," where Dr. Hayes interviews the founders who shaped cancer clinical care over the last 70 years. The goal is to help listeners understand the courage, vision, and scientific background of these leaders, and to use that history to build a better future for patients and their families during and after cancer treatment.

The People Behind the Conversation

Dr. Daniel F. Hayes is the host of this episode. He serves as the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center. His research focuses on experimental therapeutics (new treatments) and cancer biomarkers (biological signs of disease), especially in breast cancer. He has chaired the SWOG Breast Cancer Translational Medicine Committee and was an inaugural member and chair of the American Society of Clinical Oncology (ASCO) Tumor Marker Guidelines Committee. Dr. Hayes also served on the ASCO Board of Directors and served a three-year term as President of ASCO from 2016 to 2018.

Dr. Marc Lippman is the guest. According to Dr. Hayes, Dr. Lippman was instrumental in the early studies of the role of the estrogen receptor (a protein inside breast cells that binds to the hormone estrogen and can fuel cancer growth) in breast cancer. Dr. Hayes considers him and his former colleague Dr. William McGuire to be the first investigators to perform what we now call "translational" science in solid tumors — meaning they took discoveries from the laboratory and applied them directly to patient care.

Early Life and Education

Dr. Lippman grew up in Brooklyn, New York, in what he describes as a "very, very intellectually rich family." He notes there was never any question that he would pursue science — he was certain from an early age that science was where he was headed.

His educational journey included:

• Undergraduate degree at Cornell University, where he played on the varsity tennis team
• Medical degree at Yale University
• Residency at Johns Hopkins
• Fellowship in endocrinology (the study of hormones) at Yale

During his medical school years, Dr. Lippman had to complete a thesis and worked with a hematologist (a specialist in blood disorders) who studied leukemia. He enjoyed that work greatly, and it planted a seed that would later connect his two passions: endocrinology and cancer.

An Unusual Path to Cancer Medicine

Dr. Lippman's route to becoming a cancer doctor was anything but traditional. In fact, he never formally trained in oncology at all.

His path was shaped by a historical event: the Vietnam War. Many physicians and would-be physicians, including Dr. Lippman, were not eager to serve in Vietnam. One alternative route was to become an officer in the Public Health Service at the National Institutes of Health (NIH) and complete military service there. This appealed to him greatly.

At the NIH, the selection process was unusual — scientists and administrators personally chose researchers for their labs. Because Dr. Lippman had worked in a hematology lab, a scientist and administrator at the NCI named Saul Perry invited him to join his group, which ran the leukemia service. Dr. Lippman accepted the offer, thinking it was his only alternative.

"I had to spend a year on the wards taking care of extremely sick people, most of whom died during that year." — Dr. Lippman

Despite the intensity of that clinical year, Dr. Lippman continued studying endocrinology on the side, taking courses in molecular endocrinology. There he met a mentor named Brad Thompson, and his first project was an attempt to combine his two interests: leukemia and endocrinology. He began measuring glucocorticoid receptors (proteins that bind to steroid hormones like cortisol) in leukemia cells. The team showed that these receptors existed, that they were true receptors, and that they predicted how patients would respond to treatment.

"I mean, we did in leukemia what people were doing in breast cancer," Dr. Lippman recalls. "I thought that was pretty interesting. And there was always this tension in my mind between the science of endocrinology and the almost complete lack thereof, at that time, in oncology."

After completing his clinical year at the NIH and two years in the laboratory with Brad Thompson, he returned to Yale for formal endocrinology training, believing that is where he would complete his career. But after about a year, Dr. Paul Carbone called and asked if he would like to come back to the NCI to join the breast cancer service.

"I have to tell you candidly, I had never treated a case of breast cancer in my life when I went to join the breast cancer program at the NCI," Dr. Lippman admits. "And I completely learned everything I learned about breast cancer absolutely on the fly."

The move was remarkably fast-tracked. Shortly after Dr. Lippman arrived, Dr. Carbone left for Wisconsin, and the nominal head of the breast group, Doug Tormey, also departed. At about age 30 or 31, Dr. Lippman was suddenly running a program caring for breast cancer patients — just two years after he had never treated a single one.

The Science Revolution: Measuring Hormones

To understand why Dr. Lippman's work was so transformative, it helps to understand the state of medicine in the 1960s and 1970s. As Dr. Lippman observes, much of what we now consider evidence-based medicine "was completely mysterious" during his medical school years.

At that time, he says, the only fully scientific field was infectious disease, because the scientific framework known as Koch's postulates allowed doctors to know what germs caused what diseases and what drugs killed what bugs. Endocrinology, by contrast, was based on "completely functional assays" — methods that looked at whole-body effects, such as whether a rabbit ovulated, rather than measuring the actual hormones themselves.

That all changed with Nobel Prize-winning research that developed the radioimmunoassay and radioreceptor assay. These techniques allowed scientists to measure minuscule (tiny) amounts of hormones in the body with unprecedented precision.

"Within about one year, virtually every endocrine disease, the pathophysiology of Addison's, thyroid disease, you name it, was worked out based on being able to measure minuscule amounts of hormones," Dr. Lippman says. "And to me, this was fabulous. I was going to be an endocrinologist. I had no doubt about it. This was real science."

This scientific revolution is a reminder of how technology can open up entire fields of medicine. Just as these measurement techniques transformed endocrinology, Dr. Lippman recognized they could transform cancer care too.

Elwood Jensen and the Estrogen Receptor

Dr. Jensen, whom Dr. Lippman describes as "a tremendous scientist and basically a chemist," was the real pioneer of the estrogen receptor field. His work shows how a technical breakthrough can change everything.

Dr. Jensen succeeded in creating radiolabeled steroids — hormones tagged with radioactive markers that could be tracked and measured. Without such high-specific-activity compounds, it was impossible to measure hormone binding at the very low concentrations (picomolar and nanomolar ranges) where receptors operate.

Specifically, Dr. Jensen manufactured hexestrol, a compound similar to estradiol (the main estrogen hormone). With this tool, he could separate bound hormone from free hormone and prove that receptors exist. This was critical research that opened up the entire field of hormone dependency in breast cancer, which, until then, had been based entirely on clinical criteria for response.

Almost simultaneously, another breakthrough occurred: the invention of serious drugs that could interfere with hormone action. Most notable among these was tamoxifen, along with several other drugs synthesized around the same time. For the first time, doctors had an oral therapy that could be easily given to patients, rather than having to remove hormone-producing organs (such as the ovaries) or give very toxic, super-pharmacological doses of steroids.

This created an urgent need to understand how and why these drugs worked. Many researchers entered the field, including Bill McGuire, James Whitless, and Dr. Lippman himself. Early in the 1970s, researchers found a very strong correlation between the presence of hormone receptors and patient response to therapy. This launched an entire field of study into how receptors work, where they bind, what they do, and what genes they activate. "That became a lifetime exercise for many," Dr. Lippman reflects.

Building Breast Cancer Research at the NCI

The NCI in those days was primarily focused on leukemia and lymphoma — the so-called "gang of five" studies involving the chemotherapy regimens known as MOPP and CHOP, led by pioneers like Drs. Frei and others. Breast cancer research was not a major priority.

But several forces were converging to change that. Cooperative groups were developing the first multi-drug combinations for breast cancer, including CMF (cyclophosphamide, methotrexate, and fluorouracil, referred to by one colleague as "Johnny's regimen") and the MD Anderson regimens known as FAC (fluorouracil, doxorubicin, and cyclophosphamide), as well as regimens including vinca alkaloids and prednisone.

For the first time, reasonably active regimens were available for metastatic (spread) disease, whereas in years past, doctors had only a handful of single agents: vinca, methotrexate, and 5-FU. This was an important turning point for patients with advanced breast cancer.

Dr. Lippman also credits the extraordinary organizational skills of Dr. Bernie Fisher, whom he calls a "tremendous scientist" and a "tremendous surgeon." Fisher created and led the NSABP (National Surgical Adjuvant Breast and Bowel Project), a cooperative group that, from its very inception, conducted some of the most groundbreaking studies in breast cancer — not just in hormone therapy, but also in surgical approaches.

Later, extraordinary data emerged showing that adjuvant therapy (treatment given after surgery to reduce the risk of cancer returning) was successful. The early NSABP studies used single agents, and then the CMF studies from Milan were "extraordinary," Dr. Lippman says. He notes that breast cancer "was and remains the most tractable of the solid tumors with the possible exception of testicular cancer."

The Lab Work: Cell Lines and Controversy

When Dr. Lippman arrived at the NCI, he was given laboratory space and told to pursue his interests. He had been working on models of gluconeogenesis (a process of glucose production) in liver cells at Yale — work unrelated to cancer. Now, he had to figure out what to do next.

One major advance that had been building from the late 1950s to the mid-1960s was the ability to grow cancer cells in culture. Pioneers like Harry Eagle, Hamm, and Dulbecco had figured out how to maintain cells outside the body. Today, this is taken for granted, but at the time, it was revolutionary.

Dr. Lippman had an idea: since someone had described a breast cancer cell line that had estrogen receptors, why not use cell culture as a model to understand how hormones manipulate breast cancer cells? He set about developing this model, and after about six months, he succeeded.

The downside? Nobody else could reproduce his results — including Dr. Dale McGuire. Many researchers dismissed the work as garbage, suggesting he was making it up. Dr. Lippman published his findings in Nature and other serious journals, but skepticism followed him.

"I remember giving a lecture at Harvard. And somebody at the end at the questions said, we just can't reproduce this data. We don't think you're telling the truth."

This period was very upsetting for the young researcher. But ultimately, time proved him right. "What turned out to be very fortuitous was that we were right," he says. "And so eventually, that made things even easier for me in terms of my career."

Mentoring the Next Generation of Leaders

During this era, the NIH held a unique appeal for young scientists. The tail end of the Vietnam War meant some of the best and brightest were still finding their way to the NIH. Additionally, in those days, there were only a handful of comprehensive cancer centers — compared to more than three dozen today — and most of them, like Stanford, focused on leukemia and lymphoma and had almost no breast cancer program.

For both reasons, researchers who wanted to work in breast cancer came to Dr. Lippman. He says he was also fortunate to have outstanding people from Europe and Asia come to participate in his work, noting that many sought what he jokingly calls "a BTA degree" — "Been to America."

The list of his mentees is remarkable. It includes:

• Neil Rosen
• Ed Gellman
• Doug Yee
• George Wilding

All of these individuals went on to become cancer center directors. Dr. Lippman has authored nearly 500 peer-reviewed papers and co-edits Diseases of the Breast, a textbook considered by many to be "the Bible of breast cancer," with Dr. Jay Harris, Monica Morrow, and Kent Osborne.

Moving From Lab to Clinic: Key Trials

Dr. Lippman's first translational study — meaning a study that connects laboratory science to patient care — actually happened during his fellowship, when he tried to correlate responses to glucocorticoid steroids in leukemia patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). He was used to going back and forth between the bench and the bedside.

His love of caring for patients is a recurring theme. "I found that the main appeal of oncology was dealing with people at times of enormous obvious stress and disturbance in their lives," he says. "And I found that that brought out some of my best skill sets." He notes that he was always involved with patients and did not just stay in the laboratory.

One of the major trials Dr. Lippman worked on involved a collaboration with Dr. Allen Lichter. The two doctors endlessly discussed the right therapy for localized breast cancer. At that time, some prominent researchers, like Dr. Sam Hellman of the Joint Center, refused to participate in clinical trials comparing lumpectomy with radiation, because he was convinced — correctly, it would later turn out — that this approach was equivalent to mastectomy (complete removal of the breast).

Dr. Lippman and Dr. Lichter decided, perhaps "arrogantly" as Dr. Lippman puts it, that they could conduct a single-institution trial on their own. They ran a prospective randomized trial of about 350 women at the NCI comparing lumpectomy with radiation against an alternative — and all these patients also became part of advanced disease trials and other research. Dr. Lippman describes working side by side with Dr. Lichter as "some of the happiest days of my life," in what may have been the first multidisciplinary clinic in breast cancer — a clinic where multiple types of specialists work together as a team.

For context, Dr. Hayes interjects that Dr. Lichter later started the Department of Radiation Oncology at the University of Michigan, served as its dean, became President of ASCO, and was the CEO of ASCO for many years.

What This Means for Patients Today

For patients reading this today, it's hard to overstate how much of modern breast cancer care traces back to the work described in this conversation. When a patient with breast cancer has their tumor tested for estrogen receptors, they are benefiting directly from the receptor science pioneered by Dr. Jensen, Dr. McGuire, and Dr. Lippman.

When a patient is prescribed tamoxifen or an aromatase inhibitor, they are taking a drug created in the era that Dr. Lippman helped build. The knowledge that hormone receptor status predicts treatment response remains a cornerstone of breast cancer management to this day.

The randomized trial that Dr. Lippman and Dr. Lichter ran — helping establish that breast-conserving therapy (lumpectomy with radiation) could be equivalent to mastectomy — also transformed surgical practice. Many women today who are diagnosed with early-stage breast cancer can choose less disfiguring surgery, in no small part because of this pioneering work.

Dr. Lippman's insistence on combining laboratory research with patient care also helped establish the model of "translational science" that is now standard in cancer research. The idea that a researcher should also see patients — and that insights from one side should inform the other — is now woven into the fabric of academic medicine. For patients, this means faster movement of scientific discoveries from the lab to the clinic.

Limitations and Lessons Learned

As with any historical account, there are important limitations and lessons to note:

• One person's story: This podcast captures Dr. Lippman's personal reflections, which are subject to memory and perspective. It is not a comprehensive history of breast cancer research.
• Difficulty of early work: Dr. Lippman's initial results were not reproducible by other labs, a common challenge in early-stage science. This highlights that groundbreaking findings take time to validate.
• Context of the era: The rapid advancement described in this interview occurred in a specific historical moment (the Vietnam War era, the early days of cell culture, the development of radioimmunoassays). Some career pathways described — such as being handed a major program at age 30 — may not reflect today's more structured training requirements.
• Changing times: Dr. Lippman notes with concern that researchers today often receive their first major research grants (R01s) at much older ages, a problem he believes "people need to address."

Recommendations for Patients and Families

While this article is not a substitute for medical advice, Dr. Lippman's story offers valuable lessons that patients and their families may find meaningful:

1. Ask about your tumor's hormone receptor status. If you or a loved one is diagnosed with breast cancer, knowing whether the tumor has estrogen or progesterone receptors is essential. This information helps guide treatment decisions and is a direct result of the pioneering research described in this conversation.
2. Understand that cancer research is a long journey. The path from laboratory discovery to everyday treatment took decades. New treatments you may hear about in the news are built on years of painstaking research.
3. Seek multidisciplinary care. Dr. Lippman described his work with Dr. Lichter in what may have been the first multidisciplinary breast cancer clinic. Today, patients are best served when surgeons, medical oncologists, radiation oncologists, and other specialists work together as a team.
4. Value the patient-physician relationship. Dr. Lippman's love for dealing with people "at times of enormous obvious stress" was central to his practice. Having a doctor who genuinely cares and communicates openly can make a real difference in your experience.
5. Be cautious in interpreting preliminary research. Even Dr. Lippman's celebrated work was initially doubted by peers. If you read about a new study, remember that scientific findings must be replicated, peer-reviewed, and validated before they change clinical practice.

Frequently Asked Questions

What is estrogen receptor testing and why does it matter for my breast cancer treatment?

Estrogen receptor testing checks whether breast cancer cells have proteins that bind to estrogen and can fuel cancer growth. Knowing your tumor's hormone receptor status helps guide treatment decisions. If receptors are present, hormone therapy like tamoxifen or aromatase inhibitors may be recommended. This testing is a direct result of early research described in this conversation.

What are the treatment options for early-stage breast cancer?

For early-stage breast cancer, two main surgical approaches are mastectomy, which removes the whole breast, or breast-conserving therapy, which is lumpectomy followed by radiation. A randomized trial of about 350 women at the NCI helped establish that breast-conserving therapy could be equivalent to mastectomy. Many women today can choose less disfiguring surgery based on this evidence.

What is hormone therapy for breast cancer and how does it work?

Hormone therapy uses drugs like tamoxifen or aromatase inhibitors to block or lower estrogen, which can fuel breast cancer growth. This oral therapy became available after research showed a strong link between hormone receptors and patient response. It is now a cornerstone of treatment for hormone-receptor-positive breast cancer, offering a less toxic alternative to surgery or high-dose steroids.

Why was the development of the estrogen receptor discovery important?

Research on the estrogen receptor showed that doctors could predict whether a patient would respond to hormone therapy by measuring receptors in tumor tissue. This launched a new field of study and transformed breast cancer care. Today, testing for estrogen and progesterone receptors is standard, and hormone therapy based on those results is routine for many patients.

What does 'translational science' mean in cancer care?

Translational science means taking discoveries from the laboratory and applying them directly to patient care. Dr. Lippman and a colleague were among the first to do this in solid tumors. This model, where researchers also see patients, helps move scientific findings into clinical use faster, which can mean quicker access to new treatments and more personalized care.

Should I ask about my tumor's hormone receptor status if I'm diagnosed with breast cancer?

Yes. Knowing whether your tumor has estrogen or progesterone receptors is essential because it helps guide treatment decisions. If receptors are present, hormone therapy may be effective. This information comes from pioneering research described in this conversation. Talk to your doctor about your receptor status and what it means for your individualized treatment plan.

Should a breast cancer patient get a second opinion on whether lumpectomy with radiation is a safe alternative to mastectomy?

For a woman diagnosed with early-stage breast cancer, a second opinion can help confirm that breast-conserving therapy (lumpectomy with radiation) is a safe alternative to mastectomy, since a randomized trial of about 350 women at the NCI showed these approaches are equivalent. A second opinion can also ensure your tumor is tested for estrogen and progesterone receptors, which guides whether hormone therapy like tamoxifen may benefit you. Multidisciplinary review, with surgeons, medical oncologists, and radiation oncologists working together, can help you weigh your options. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original Title: Cancer Stories: The Art of Oncology: Conversations with the Pioneers of Oncology: Dr. Marc Lippman

Format: JCO (Journal of Clinical Oncology) Cancer Stories podcast, published by the ASCO Podcast Network

Original Air Date: February 28, 2020

Host: Dr. Daniel F. Hayes, MD (Stuart B. Padnos Professor of Breast Cancer Research, University of Michigan Rogel Cancer Center; Past President, ASCO)

Guest: Dr. Marc Lippman, MD (Professor, researcher, and co-editor of Diseases of the Breast)

Series Editor Note: The Cancer Stories: The Art of Oncology series is hosted by Dr. Lidia Schapira, MD, FASCO, Associate Editor for JCO's Art of Oncology, Associate Professor of Medicine at Stanford University School of Medicine, and Director of the Cancer Survivorship Program. She also serves as Editor-in-Chief of ASCO's Cancer.Net, a website providing expert-reviewed cancer information for patients and caregivers.

Disclaimers: The purpose of this podcast is to educate and inform. It is not a substitute for professional medical care and is not intended for diagnosing or treating individual conditions. Guests on the podcast express their own opinions, experiences, and conclusions, which do not necessarily reflect the views of ASCO. The mention of any product, service, organization, activity, or therapy is not an ASCO endorsement.

This patient-friendly article is based on peer-reviewed research and an educational podcast published through the American Society of Clinical Oncology.