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Dr. Hayes interviews Dr. Bloomfield on her role as one of the first physician-scientists to investigate treatment for acute myeloid leukemia (AML).

Dr. Daniel F. Hayes is the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center. Dr. Hayes’ research interests are in the field of experimental therapeutics and cancer biomarkers, especially in breast cancer. He has served as chair of the SWOG Breast Cancer Translational Medicine Committee, and he was an inaugural member and chaired the American Society of Clinical Oncology (ASCO) Tumor Marker Guidelines Committee. Dr. Hayes served on the ASCO Board of Directors, and served a 3 year term as President of ASCO from 2016-2018.

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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Welcome to JCO's Cancer Stories-- The art of Oncology brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the role of cancer care. You can find all of the shows, including this one, at podcast.asco.org.

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Welcome to today's version of the ASCO Cancer Stories podcast. Today, my guest on the podcast is Dr. Clara Bloomfield. Dr. Bloomfield was instrumental in the early studies investigating the biology of leukemias and lymphomas, and also the interaction between various molecular markers and treatment.

She founded the Correlative Science Committee of The Cancer and Leukemia Group B, which is now designated the Alliance in the 1980s. And I believe that was probably the first such committee in the cooperative groups, and she chaired it for at least 25 years. Her work resulted in numerous groundbreaking insights that led to changes in practice. Personally, and having worked with her for several of those years in CALGB, I really consider her one of the first investigators to perform what we now blithely called, quote, "translational," end of quote, science in cancer.

Dr. Bloomfield was born in New York City, but her father, who was an expert in labor and industrial relations, moved the family to Washington, DC during World War II. And after the war, he then took a position at the University of Illinois, leading Dr. Bloomfield to have a nearly lifelong association with the Midwest. She attended undergraduate school at the University of Wisconsin, but then graduated from San Diego State College during a brief foray to the West Coast.

She returned to the Midwest to attend medical school at the University of Chicago, and then completed her internal medicine residency and her medical oncology fellowship at the University of Minnesota, where she stayed on faculty until 1989. She then became chair of the Department of Medicine at Roswell Park Cancer Institute in Buffalo for the next eight years, and then moved to the Ohio State University, where she accepted the position as director of the comprehensive and now designated the James Cancer Center.

She's remained at OSU and is currently a distinguished university professor and the William G. Pace II professor of cancer research and a senior advisor at the OSU James Cancer Center. Dr. Bloomfield has authored hundreds of peer-reviewed papers. She is an elected member of the National Academy of Medicine and the National Academy of Sciences. She's, frankly, won just too many awards that I can name here. But importantly, she served on the ASCO board of directors, and in 2009, she gave the David A. Karnofsky Memorial Lecture, the highest honor our society can bestow.

Clara, welcome to our program.

Thank you.

You know, I have a lot of questions for you, many of which I thought about that I should have asked you 30 years ago or so when we first started working together in CALGB. But I think the biggest one is, how did you get interested in leukemia in the first place? Were any particular personal insights that resulted in the basis of your career? Or was it just happenstance?

I think it happened because in grade school, I had a number of classmates who developed leukemia. And they were sent to the National Cancer Institute because people in those days didn't treat leukemia. And they returned with steroid-bloated faces and soon died. And I thought, well, wouldn't it be cool to develop medicine that could save kids from dying? I'd already decided to become a doctor, so seeing the real-life effects of cancer helped shape my early desire to become an oncologist.

So that must have been about the same time, a little bit after, that Drs. Frei, and Freireich, and Holland started combination therapy for leukemia. They must have had a big impact on your career then.

I don't remember. [? No, ?] I'm kidding.

Actually, the other question-- I know that you spent some time at Stanford and ran into Henry Kaplan. And there was a cute anecdote, I think, about how you presented with his backing at one of the conferences. Can you tell us a little bit about Dr. Kaplan and your work with him?

Sure. During my junior and senior years in medical school, I did a sub-internship at the University of California at San Francisco. And I saw a patient with Hodgkin's disease who was not being treated with curative intent. And I said to the attending, you're not giving this patient modern therapy. And the attending replied, well, if you're so smart, we'll have you do grand rounds on how to treat Hodgkin's disease.

Remember, I was a medical student. So I called Professor Henry Kaplan at Stanford for advice. And he was great, and he said, well, they never want me to come. I'd be happy to come and help you give grand rounds. So to the surprise of my attending and awe as a medical student, I conducted grand rounds at the University of California at San Francisco with Professor Kaplan.

That must have been a big surprise.

Yes, I think it was.

Actually, one of my interviews has been with Saul Rosenberg, and he also had some great stories about Dr. Kaplan when they first started giving chemotherapy at Stanford. And Kaplan was apparently quite supportive of doing this. So--

Yes, he was.

--I never got to meet him. Yeah. Another question, again, about the time you entered the field, I referred to what I consider the big three, Frei, Freireich, and Holland, but their therapy was really pretty empiric for leukemia. It was just hoping that giving more drugs would be better than one drug.

But you really got us into genetics. What made you do that? I mean, what made you think that we could treat people, really, with precision medicine better than we did in those days?

Well, my second research project I had as a fellow, which was presented at ACR in May of 1972 and published in April of 1973, involved daunorubicin-prednisone therapy for AML. And in that, the question was raised in patients without Auer rods, the question were these of CML in blast crisis was raised, so chromosome studies were done. And this got me started studying cytogenetics in leukemia, and subsequently molecular genetics. And also, you asked if I had a role model, and the answer is no. I did not have a role model.

I know that very early on in your career, you published a very controversial paper suggesting that the Philadelphia chromosome could be found in acute lymphocytic leukemia, which at the time, I think, was probably heresy, since it had been associated with CML. I understand that you interacted with Avery Sandberg, the [? tube ?] giant. I remember hearing about Avery Sandberg when I was a freshman in college in genetics, and he supported you. What was the background behind that?

At the 1975 ASH meeting, I presented an abstract, I gave a talk on the Philadelphia chromosome-- on Philadelphia chromosome positive acute leukemia. And after that talk, many prominent cytogeneticists raised questions about the validity of my findings. However, Avery Sandberg, while surprised by the findings, said, she may be right. Sometimes these youngsters get things that we've missed.

And did you walk out beating your chest? That must have been quite a moment.

I was happy that he-- I was happy that he supported me.

Well, I want to go on to some of your other work, but I'm going to tell you that in our fellows clinical conference here a couple of weeks ago, which I attend every week, one of the fellows started talking about FLT3 leukemia. But his comment was leukemia is described as the most genomically defined cancer. And I didn't bring it up at that meeting, but I thought, you owe Clara Bloomfield for that statement.

You should be really proud of your work. I almost picked up the phone to call you to tell you that our fellows don't know that you did the work. They should, and that's why we're doing these podcasts.

So the only thing-- I know you challenged dogma was the treatment of older patients with leukemia. And as you and I both get older, I think it becomes more near and dear to our heart. Can you give some insight into that? I mean, my impression, when I was a fellow, was we just kind of said, oh, you're over 60, it's not worth treating you. But I think you really challenged that and changed that dogma.

So ASH [INAUDIBLE] the third paper I published and project that I started on when I started as a fellow, because I was asked to do this by one of my attendings, was to look at treating older patients with acute leukemia. In the early 1970s, which we're talking about, it was considered that standard intensive treatment of patients with acute leukemia over the age of 40 or 50 years of age was malpractice or at least wrong. So when I was asked to look at this, we had a few patients over the age of 60 with AML treated with what was then standard intensive chemotherapy.

So I compared the outcome of patients aged 21 to 40, 41 to 60, and 61 to 86 years. And what I found was that patients aged 41 to 60 and greater than 60 responded equally well. As a result, we said that patients over 60 should be treated.

This meant that what we did was told major researchers in leukemia that they were wrong. This caused quite a stir, as you might imagine. And interestingly, within the next five to 10 years, they all came back to me and said they had been wrong.

In that regard, I watched you in CALGB. I was on the solid tumor side, obviously, but you were really a pioneer in organizing and conducting translational research and correlative research in leukemia in the cooperative groups. When you started, I don't think there was any of that, was there?

Were there a lot of obstacles to doing that? I think everybody just takes it for granted now, especially with so-called precision medicine. But what did you have to do to get that started at CALGB?

From 1982 on, I was chair of the Correlative Science Committee in Cancer and Leukemia Group B. In 1984, I actually started to have NIH grant to support correlative science in the CALGB cooperative group. In 1984, we already had a trial in Cancer and Leukemia Group B to do cytogenetics in acute leukemia.

I mean, a lot of this work was based on my work in cytogenetics. And while there may have been clinicians who were opposed, I had the support of important people like Professor Janet Rowley and the cytogeneticists at the CALGB institutions. And there really were not significant obstacles that I can remember. Of course, if there were people who tried to block me, I probably didn't care and worked around them.

I'm sure that's true.

I am too. This is part of what-- when you're one of the few women, as I was when I started in the field, I mean, I suppose I was always getting blocked about things, I just don't think much about it. I didn't then and I don't now.

That segues into my final question, actually. And these days, more than half of our medical students are women. More than half of our residents are women at the University of Michigan. More than half of our fellows in hem-onc are women. Increasingly, the faculty is there.

But when you started, you were really a pioneer, I think, in introducing women into clinical and laboratory research in oncology and academic medical leadership. And I just want to list the things, because I don't think you will, that I think you've done. First, I understand you were the first woman chief resident at the University of Minnesota, the first woman full professor in medicine at the University of Minnesota, one of the first women chairs of medicine in the United States when you were at Roswell Park, the third woman to be director of an NCI-designated Cancer Center.

And frankly, as I was preparing this, I was on an airplane and I was watching A Matter of Sex about Ruth Bader Ginsburg, and I thought, this is a really familiar story. Do you have any war stories that you thought were particularly telling when you began? And especially, for example, I know you have a story about what the dean told you when you were considering becoming an academic professor. Do you have anything to inspire the people listening to this podcast?

I'm sure there were some probably pretty aggressive war stories that I don't remember. And as I said, I don't tend to think about what happened in the past since I'm trying to keep up with the present. But I guess there are a couple of stories.

Unbelievably, when I was a medical student, I always sat in the front row in class because that was the only way I could see the slides. And the dean, medical school dean, called me into his office and said it was not ladylike to sit in the front row. And I told him-- it's unbelievable really-- I told him that when he became a lady, he could tell me how to act like one, and walked out on him.

But the more important story, I suppose-- that I can remember-- is that when I was appointed an associate professor, which occurred three years after I became an assistant professor, so the head of medicine called me in and said, congratulations, Clara. This is a great accomplishment. He went on to say, however, that since your husband is on the faculty and gets a good salary, we are not going to increase your salary. So when I came home, I told my husband, where upon he called the dean, who called the University president, who said, you be sure she gets the same salary or higher than the highest one you've ever given a new associate professor in medicine. Thus, my pay issue was immediately resolved.

It's hard to believe that's a true story, except I saw similar things myself as I was going up, and they were getting corrected, at least. Well, anyway, we're running out of time. And I just want to thank you for all the things you've done, the contributions you've made to the field. Your legacy is incredible, in my opinion.

And I think people will long remember what Clara Bloomfield has done in terms of changing how we treat leukemia, changing the treatment of leukemia into groups of patients who traditionally weren't treated, like older folks, and probably the pioneering work you did in bringing women into science and medicine, especially in oncology. So thanks for taking time to speak with me today. And I think people are going to be really thrilled to listen to your story as they drive to work and say, wow, I didn't realize that that's what it was like back in the old days. So thanks so much. And I think, especially, our young and translational scientists, particularly women, and also, most importantly, our patients deserve to give you credit for all of the things you've done and [? thanks ?] you've done.

Until next time, thank you for listening to this JCO's Cancer Stories-- The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories-- The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org.

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