George Sledge, MD: How to Channel Your Inner McGuire

Kathy D. Miller, MD; George W. Sledge, Jr., MD


December 17, 2010

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Kathy D. Miller, MD: Hello. I'm Dr. Kathy Miller, Associate Professor of Medicine at the Indiana University School of Medicine in Indianapolis. This is the Medscape Oncology Highlights on Breast Cancer coming to you from the 2010 San Antonio Breast Cancer Symposium in San Antonio. Joining me today is Dr. George Sledge, Professor of Medicine and Pathology at the Indiana University Simon Cancer Center and also current president of the American Society of Clinical Oncology (ASCO). George is also this year's William L. McGuire Memorial Lecture award winner, and we've asked George to join us today to talk specifically about some of the issues that you raised in that lecture.

The Clinic Is the Final Laboratory

George W. Sledge, Jr., MD: Thank you, Kathy. I'm delighted to be here. Well, the McGuire award is given out once a year at the San Antonio Breast Cancer Symposium and this year I was honored to receive it. It's particularly an honor for me because I trained with Bill McGuire so it gave me the chance to give what I call McGuire rules about how we should be approaching translational research in breast cancer.

Dr. Miller: So what are the McGuire rules, because I think those are really lessons for all of us in the field.

Dr. Sledge: Let's hope I can remember all of them, but let's start with the simplest one which is always "Get tissue." One of the problems we still run into today regularly in Phase 3 trials is that we don't collect tissue and we lose an enormous chance to understand the biology of the disease and an enormous chance to move forward by coming up with new therapies based on what we've learned from that biology. The second lesson from Bill McGuire was don't just collect tissue, but collect annotated tissue. Tissue is worthwhile to the extent that it's associated with other data bits about the patient, what the patient receives, what's the patient's family history, what's the patient's follow-up, and all too often we don't do that.

Dr. Miller: That makes it particularly relevant to collecting tissues as part of clinical trials because the annotation is essentially already done.

Dr. Sledge: Absolutely and indeed one wonders about large efforts to collect tissues outside of trials that are ongoing. I suspect the money would be far better spent collecting tissues within the trial and making good use of it. Bill also believed that biomarkers were hard -- that they required real care, that they required high order mathematics and they required the same care that we put into phase 3 trials in terms of doing power calculations, and I think he grew progressively frustrated with his colleagues who didn't put the same degree of care into it that he did, so I would say that's another important McGuire rule. Bill also believed as a card-carrying lab rat (as someone who started his life studying the mysteries of the chicken oviduct) that the clinic is the final laboratory, that what we learn in the laboratory is only valuable to the extent that it's tested in the clinic. One will often hear the differentiation of the laboratory vs the clinic is what you do in the laboratory is science and what you do in the clinic is something else. I think Bill would have found that preposterous. The laboratory doesn't end at the laboratory's walls; it ends when you finish the clinical trial and you prove the hypothesis.

The Power of Normal

Now I have added a McGuire rule and it's one that Bill thought about but was never able to carry off. It's what I call the power of normal. We have for many years collected these tissues, collected tumor vs tumor, or studied tumor vs tumor and we've done very little about collecting normal tissues. In recent years at the Indiana University Simon Cancer Center with support from the Komen for the Cure Foundation, we have begun to collect normal tissues from women who have never had breast cancer, normal breast tissue from core biopsies, serum, plasma, and DNA, and these now represent a base against which we can measure cancer. This is incredibly important as we go forward and are looking at neoplasia and prevention models. We have to know what normal is before we can intervene in the first steps on the road to curing cancer.

Dr. Miller: I think our patients find that interesting and disturbing because it seems so intuitive. How can we say to a patient "we don't really understand normal." Having said that a few times, they look at me and think, well how silly is that; how can you not understand normal?

Dr. Sledge: For a long time the issue has been that doctors assumed that women would not be willing to give normal breast biopsy tissue outside of the context of their care of their cancer. Well, what we've discovered is that that certainly is not the case. There are deep wells of altruism that we can draw on in terms of our study of breast cancer biology.

Smart People Make You Look Smarter

Dr. Miller: You mentioned one other Bill McGuire rule, which was to surround yourself with smart people.

Dr. Sledge: Yes.

Dr. Miller: Why is that important?

Dr. Sledge: Well, first off smart people make you look smarter or at least sound smarter, but I think that there is something special about bringing together creative people that allows you to do wonderful things in the sciences and, indeed, in medicine as well. Bill McGuire did that in a very special way at San Antonio. He brought together clinical leaders such as Chuck Coltman, who is the head of the Southwest Oncology Group, junior faculty members such as Kent Osborne and Dan Von Hoff, who went on to fabulous careers. If you look at the very small hematology/oncology division that Bill McGuire had back when I started as a fellow, it included future presidents of the American Society of Clinical Oncology, of the American Association for Cancer Research, Karnofsky Award winners, Rosenthal Award winners -- I think there is something magical and special about bringing together a collection of really smart people who are able to work together toward a common goal.

Oncology Is a Math Problem

Dr. Miller: One other thing that I picked up on in a more profound way in your talk, was how really dependent Bill McGuire was on Gary Clark who is a statistician and that was a very profound partnership and really influenced a lot of his work and perhaps many of us have been a bit guilty of not making friends in that same way with our statistical and bioinformatics colleagues.

Dr. Sledge: We've always intended to bring in the biostatistician or bioinformatician at the end of things to help explain the data you generated, but I think Bill's genius was to bring a superb biostatistician, Gary Clark, in very early in the process actually to even help in terms of how you collected the tissue that you were going to use later for analysis and I think that's part of what made him so productive. It's clear to me that looking as we move into this era of genomics where data become very, very cheap that cancer is now basically a math problem. We used to think of it as a biology problem but it's now basically a math problem and the world in the future I suspect is going to belong to those who are able to do complex mathematical analyses of large and complex gene array datasets in breast cancer.

Dr. Miller: So we lost Bill McGuire way too early when he was still in the midst of a very productive career. You knew Bill well for years. If Bill were here today, what would he be doing?

Dr. Sledge: Bill died about 6 or 7 years before our first genomic studies in breast cancer and event before the Internet was available to us on a broad basis. I would be astonished, if he had lived, if Bill had not dived deeply into the waters of genomics. I would be astonished if he had not used his tissue bank to plumb the depths of all the big genomic issues that we're still wrestling with and, indeed, I would be astonished if he hadn't been the first one to do it simply because Bill was superb at acquiring and bringing new technology to the breast cancer problem.

Dr. Miller: I remember your quote about him saying when space got short he just bought more freezers to keep accumulating tissue.

Dr. Sledge: That's correct. Just buy more freezers.

Dr. Miller: I suspect now he would buying more servers to be able to store and keep all the data that would be generated.

Dr. Sledge: Bill loved numbers. He loved the power of numbers. He believed that nature spoke to us through mathematics and through the power of large numbers and he would have made excellent use of the genomic data that we have pouring in on us today.

Closing Remarks

Dr. Miller: George, thank you for joining us.

Dr. Sledge: Thank you, Kathy.

Dr. Miller: Thank you to our audience for joining us for this edition of Medscape Oncology Insights. This is Dr. Kathy Miller at the 2010 San Antonio Breast Cancer Symposium Meeting in San Antonio.


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