Chapter 09: Early Research: Changing the Natural History of Breast Cancer
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Description
In this chapter, Dr. Buzdar talks about his first studies of combination chemotherapy that he conducted with Dr. Gabriel Hortobagyi and that successfully "changed the natural history of breast cancer." He discusses a first study of patients with recurring breast cancer in one or two places, noting that 25%-30% of the patients treated in the seventies are still alive today. He explains that the success of the treatment meant that the research team never conducted a randomized trial. He discusses the next study of combination chemotherapy given to patients with inflammatory carcinoma of the breast. He explains how skeptical individuals were of the success of the trail, both within and outside the institution. He talks about the controversy surrounding aggressive chemotherapeutic treatments.
Identifier
BuzdarA_02_20170216_C09
Publication Date
2-16-2017
Publisher
The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The Researcher; Discovery and Success; The Researcher; MD Anderson Impact; MD Anderson Impact; Devices, Drugs, Procedures; Multi-disciplinary Approaches; Controversy; Controversies; Research; Survivors, Survivorship; Patients, Treatment, Survivors; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Ethics
Transcript
Tacey A. Rosolowski, PhD:
Well, we strategized a little bit before we turned the recorder on, and you had wanted to address a subject related to research activities, which I wanted to return to that story. You wanted to speak about the impact that you and team members had on the natural history of the disease of breast cancer, so if you could talk to me about that.
Aman Buzdar, MD:
I think there are several areas which we feel very proud that we were on the frontline to change the biology of the disease. The first example, I think we briefly talked about it the other day, that combination chemotherapy with Dr. Hortobagyi and his team initiated in patients with advanced disseminated cancer, that not only you were able to control the disease in 70-plus percent of the patients, but 15-plus percent of patients went into completely remission. The thing which was amazing is that some of those patients who went into remission, they are still alive in unmaintained remission now.
Tacey A. Rosolowski, PhD:
And that's since the '70s.
Aman Buzdar, MD:
Since the '70s.
Tacey A. Rosolowski, PhD:
Oh my heavens, wow.
Aman Buzdar, MD:
So I think that is one thing. At that point, when we tried to publish this information, there was quite a bit of healthy skepticism, because it was not feasible, they thought oh, these patients didn't have cancer, but it is reality that there are patients in which we had biopsy proven evidence of disseminated disease and they, with treatment, went into remission and remain in remission. Even though it is a small subset of patient population, but it was the first time that we could show that. So the next step which we did was, that there are patients in which cancer, after initial treatment, recurs at one place or at two places, and in those one or two places, you may be able to remove the cancer and do even radiation therapy to that area. But the natural history is that in spite of removing that spot of cancer or doing the radiation on top of it, 80 to 90 percent of these patients recur within a year, somewhere else, and they will eventually die of the disease. Since we're sure that the chemotherapy worked in patients with disseminated cancer, we wanted to test, in this subset of patients, which had very limited, one or two sites of recurrence, that after removing these sites of recurrence, giving the same therapy, whether we could keep these patients alive free of disease. To our amazement, that about 25 to 30 percent of these patients are alive, free of cancer, 20, 30 years later, which was another subset of patients, the natural history of the disease was dramatically changed. It was again, because we did not do a randomized trial. We did just a single phase two study, that it took like 40 years for cooperative groups to do the randomized trial, to show what we had shown 30-plus years ago, that you could keep certain patients in unmaintained remission if they have very limited disease burden.
Tacey A. Rosolowski, PhD:
Now, why didn't your teams do a randomized trial at the time?
Aman Buzdar, MD:
Because, the thing is, at that point, we looked at our own data. Consecutive series of patients, I looked at it and showed it to other colleagues, that within a year, 80-plus percent of patients have recurring disease somewhere else, in spite of surgery, radiation therapy and everything. We felt that it was inappropriate to offer no therapy to these patients, because the outcome, we know from our experience. So this is what we call historical controls. We had historical control information from our own institution, patients who were treated at MD Anderson. That's why we thought that it was not appropriate, in the best interests of the patient, to just not offer therapy.
Tacey A. Rosolowski, PhD:
Absolutely, absolutely. Now, these results were published?
Aman Buzdar, MD:
Well, they were published. These are now considered standard.
Tacey A. Rosolowski, PhD:
Standard, right.
Aman Buzdar, MD:
But it was us, and I wrote those protocols, and we got it out of those studies.
Tacey A. Rosolowski, PhD:
Yeah, that's amazing.
Aman Buzdar, MD:
That was in the mid-'70s.
Tacey A. Rosolowski, PhD:
In the mid-'70s, that's amazing. I know Gabriel Hortobagyi had mentioned that the work that you were doing was really -- I mean that all of you were doing was really on the forefront, and for some reason it didn't coalesce in my mind, you know a kind of way in which one study proceeded to the other and continued to reinforce.
Aman Buzdar, MD:
These things actually changed the same day. There was a subset of patients, what we call inflammatory carcinoma of the breast. Inflammatory carcinoma of the breast, it was a long time ago. If you picked up the textbooks which were written in the '60s or '70s, the textbook authors will say you should not do surgery on these patients because they cannot be cured, and just offer them palliative care. Since we have this chemotherapy available, surgeons did mind to operate on them, our radiotherapists were willing to radiate them, but still, over 90 percent of these patients were dead within a year to 18 months. So what we did was, that instead of doing surgery or radiation therapy, these are the patients with inflammatory carcinoma, we gave the same combination chemotherapy to these patients and to our amazement, a lot of patients, the cancer shrunk. Then, still, our surgeon didn't want to operate on it, and the first cohort of patients, we convinced our radiotherapy colleague to radiate the breast, and some of those patients are still alive, free of cancer 30, 40 years later.
Tacey A. Rosolowski, PhD:
That's amazing.
Aman Buzdar, MD:
That was another subgroup of patients in which the natural history was changed, and what is the fraction which can remain alive, free of disease? It's about 25 to 30 percent of the patients. The natural history, without the systemic therapy upfront, is less than 1 to 2 percent of these patients will be even alive at two years.
Tacey A. Rosolowski, PhD:
That's amazing, that's amazing.
Aman Buzdar, MD:
So that was when we showed this, again, it was from our historical experience. We knew that you -- but, when we initially did this study, I was the one. I had to sit down and convince our radiotherapy colleagues. We sat down and went, chart by chart, Dr. Montague, Eleanor Montague was at that point the breast radiotherapist. I said Eleanor, here is the data, that these are the patients who are alive, free of cancer. Initially, she was very skeptical. They wrote a paper, they said oh, chemotherapy does not help. I had to sit down and go over all this data with her, and then we republished the same patient information in Cancer. A year later, after discussing with the editor, that here is a subset of patients which we treated and there are, a sizeable fraction of these patients are alive, free of disease. That was published in Cancer.
Tacey A. Rosolowski, PhD:
And that was in the mid-'70s, late '70s?
Aman Buzdar, MD:
It was in the late '70s.
Tacey A. Rosolowski, PhD:
The late '70s. So even Eleanor Montague was skeptical.  
Recommended Citation
Buzdar, Aman U. MD and Rosolowski, Tacey A. PhD, "Chapter 09: Early Research: Changing the Natural History of Breast Cancer" (2017). Interview Chapters. 570.
https://openworks.mdanderson.org/mchv_interviewchapters/570
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