Chapter 03: Undertaking Breast Cancer Research When the Field was Young

Chapter 03: Undertaking Breast Cancer Research When the Field was Young

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Description

In this chapter, Dr. Buzdar sketches his evolving research focus within the Breast Cancer Section. He explains that, at the time, there was little that could be done for breast cancer patients as oncology was in its infancy. He talks about the dramatic results achieved when he and Dr. Gabriel Hortobagyi [oral history interview] developed the 3-drug combination of 5-flourouracil, Adriamycin and cyclophosphamide for use in patients with metastatic breast cancer, resulting in cancers shrinking in 75% of patients. The combination was then used for adjuvant therapy. Dr. Buzdar talks about controversy over using aggressive chemo therapy with severe side effects, noting that the study was blocked by other disciplines when it came up for review in the IRB.

Identifier

BuzdarA_01_20170210_C03

Publication Date

2-10-2017

Publisher

The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; The Researcher; Research; Joining MD Anderson; Discovery and Success; Healing, Hope, and the Promise of Research; MD Anderson Impact; MD Anderson Impact; Overview; Definitions, Explanations, Translations; Building/Transforming the Institution; Multi-disciplinary Approaches; Obstacles, Challenges; Institutional Politics; Controversy; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care

Transcript

Tacey A. Rosolowski, PhD:

All right, well tell me about that experience, because you came in, you were in oncology during the fellowship year?

Aman Buzdar, MD:

Mm-hmm.

Tacey A. Rosolowski, PhD:

Okay. So, tell me, what was your research project, how did all that evolve? Who did you work with?

Aman Buzdar, MD:

Well, I worked, because of my area, and since my interest was, as I told you, what brought me to oncology was that woman with breast cancer. That was my area of interest, and so after spending one year, I wanted to work in the breast cancer area, and I was given the opportunity, by Dr. Blumenschein, who was at that time the section chief, George Blumenschein, who was actually, there is a doctor over here, Dr. Blumenschein, that is his son actually.

Tacey A. Rosolowski, PhD:

Oh, okay, I didn't realize that.

Aman Buzdar, MD:

I said,Okay, and then I had to tell my wife that I wanted to stay more than a year.

Tacey A. Rosolowski, PhD:

You had some stressful drives home.

Aman Buzdar, MD:

I know that. But it has been, since I've joined the department and there were so many opportunities, very shortly actually, as soon as I got into it, a number of research projects we started, under guidance of Dr. Blumenschein, and some of them got very goodly published.

Tacey A. Rosolowski, PhD:

Now, what were some of the areas you were working on, what were the specifics? I mean, I'd like to know about the evolution of your research areas.

Aman Buzdar, MD:

The evolution of the research which we did in the beginning --when I joined, at that time, was the earliest phase of oncology, especially for breast cancer. Besides surgery and radiation therapy, there was not a whole lot you could do, except maybe remove the ovaries of the women, give them estrogen, high doses, and it will help. Then there were some drugs which were coming. We started to use them in combination --a new compound, like anthracyclines, what we called doxorubicin, and we developed a combination over here which was actually even until today, it is one of the standard treatments for treatment of breast cancer.

Tacey A. Rosolowski, PhD:

And what is that combination?

Aman Buzdar, MD:

It's called three drug combination. Abbreviation is FAC.

Tacey A. Rosolowski, PhD:

Oh, FAC. Now, did you work on that with Gabriel Hortobagyi [oral history interview]? Am I remembering that correctly?

Aman Buzdar, MD:

Yes.

Tacey A. Rosolowski, PhD:

Yeah, okay.

Aman Buzdar, MD:

Actually, I was the PI, the principal investigator, and I wrote the protocol. We published that information, and that is still one of the standard backbone of the therapy.

Tacey A. Rosolowski, PhD:

Now, tell me about your rationale for combining the three drugs, and this was -- what does the F, A, and C stand for?

Aman Buzdar, MD:

Fluorouracil, it is fluorouracil, which is one of the oldest drugs, and cyclophosphamide, they were around. But anthracycline or doxorubicin, or Adriamycin was the newest drug. Because when it was combined -- Hortobagyi did the first study in patients with metastatic breast cancer, and at that point, when you gave, say, cyclophosphamide alone, or fluorouracil alone, or methotrexate --that was another drug-- they will cause improvement in 10, 15 percent of the patients. But when you combine these three drugs, in combination, when we gave it to the patients with metastatic breast cancer --with Dr. Hortobagyi, and we did the studies together with Dr. Blumenschein-- in more than seventy-five percent of the time, the cancer shrunk.

Tacey A. Rosolowski, PhD:

Wow.

Aman Buzdar, MD:

The other impressive thing was that in about fifteen to twenty percent of the time, the cancer completely disappeared in patients who had widespread metastatic disease.

Tacey A. Rosolowski, PhD:

Amazing.

Aman Buzdar, MD:

So, once we established that in metastatic patients, patients with widespread cancer, we said, Why not test it in patients who have cancer, and they are going to, in spite of surgery and radiation, they have a very high risk of recurrence of cancer very shortly. Test this combination in those patients, to see if it will keep more patients alive, free of disease.

Tacey A. Rosolowski, PhD:

So this was the adjuvant.

Aman Buzdar, MD:

Adjuvant, yes. Of course, at that time, this is again, in the early '70s, and our surgeons, our medical oncologists, they were very much against it.

Tacey A. Rosolowski, PhD:

I was just going to ask you about this. Tell me, what were their rationales? What was the controversy about?

Aman Buzdar, MD:

Controversy was because, at that time --this is in the '70s-- you don't have good nausea medication. You don't have drugs which will -- because these drugs are, you know cytotoxic drugs that cause nausea, vomiting, a lot of side effects, and there was very little you could do to control that. So the key thing o--ur surgeons, even some of the medical oncologists, like the protocol which I wrote, and for several months, it never made it to the review committees. It had to be reviewed by the committees, including the IRBs, and several months went by. Finally, I had to go to the top administration, Dr. Hickey, who is deceased --and the Hickey Auditorium is in his name. So I went to his office and I said, Dr. Hickey, I can understand people having reservations, but this is not --I am not treating the people by picking them up off the street. This is a research project, and it has to be reviewed and it has to be approved by the Ethics Committee, and I can do this, really. Our surgeons and our radiotherapists, they were blocking this thing. It had not even come up for review. It will be always deferred, deferred. So finally, it was put on the agenda, and I was able to treat a small number of patients on that treatment. Our surgeons -- some of our earlier surgeons, they were very reluctant because of the side effects, it causing nausea and vomiting, but they will not think, Oh, these patients are quite sure they are going to die. We treated a small number of patients and almost in '77, we had already, the data that the majority of the patients we gave this treatment, they are free, without any recurrence of cancer. "ƒ

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Chapter 03: Undertaking Breast Cancer Research When the Field was Young

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