Chapter 13: Additional Research Studies: HER2/neu Breast Cancer; Taxanes
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Description
Dr. Buzdar begins this chapter by talking about MD Anderson's contributions in the 1990s to therapy for HER2/neu breast cancer. He describes a trial with women with intact breast cancer, half of whom were given the best standard chemotherapy before surgery and half who were given the new anti-HER2/neu therapy. He describes the dramatic result when surgeons discovered that the tumors had disappeared, even microscopic tumors, resulting in this drug's approval as standard of care. Dr. Buzdar notes that the MD Anderson breast group has been on the forefront of research. He gives the example of Dr. David Hohn, who conducted the first studies of taxames in humans. He describes the randomized trial that resulted in Taxol becoming standard of care. He notes that now the challenge is to determine which patients will respond to which treatments.
Identifier
BuzdarA_02_20170216_C13
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; Research; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Devices, Drugs, Procedures
Transcript
Tacey A. Rosolowski, PhD:
Now, within the span of your career, there was this changing, understanding, that cancer was not one disease but in fact it was many diseases. How did that affect you as an intellect, you know getting your head around that concept? How did that change your perspective, change your work?
Aman Buzdar, MD:
I think it makes the life -- in the beginning, it becomes a challenge, because the thing is, when we started, breast cancer was breast cancer. Some of them were premenopausal, some were postmenopausal. Now we understand that breast cancer is a whole bunch of diseases. One aspect which we didn't talk about, the newest thing is the15 to 20 percent or 25 percent of the tumors, breast cancer tumors, what we call HER2/neu positive. These tumors --before the current technology and the treatments which are available-- these patients will have very poor prognoses. Previous treatments were very, either modestly effectively or totally ineffective, until anti-HER2/neu therapies were developed. Another amazing thing is that --we were not at the forefront. Those studies were carried out in California, by Dr. Dennis Slamon, where he took the patients, measured around the tumor, to see if they are HER2/neu positive or HER2/neu negative tumors. HER2/neu positive tumors, when he gave these antibody treatment, some of the patients went dramatically into remission, and it was amazing that when you combined with chemotherapy, that you were able to change the history of the disease. Our contribution into that was that this was in patients who had disseminated widespread cancer. You were able to control their disease for a longer period of time, but you were not able to cure many patients. So what we did was in the late '90s, we took those women who came to us with intact breast cancer, but it was HER2/neu positive. We knew that the current therapies were suboptimal in this patient. So what we did was before surgery, we gave them --half of the patients-- our best standard chemotherapy, which we talked about it earlier. In other half of the patients, we give this anti-HER2/neu therapy for 24 weeks, and then we did the surgery. We were going to do a fairly large study. It became absolutely clear to me and Dr. Hortobagyi --we had not even treated about maybe a handful of patients-- that the patients who are receiving anti-HER2/neu therapy, when the surgeon went in there, there was no cancer left in a number of patients, not even microscope cancer left, and some of these patients had had cancers which you could put your hand around it [gesturing].
Tacey A. Rosolowski, PhD:
Huge, yeah, oh my gosh.
Aman Buzdar, MD:
So after we became aware of it, that we had treated about maybe 42 patients, half of them were getting standard best chemotherapy and the other half were getting this chemotherapy with anti-HER2/neu therapy. In patients who are getting anti-HER2/neu therapy with chemotherapy, in more than half of the patients, at the time of surgery, there was not a single microscopic cancer cell left in the breast or in the lymph node. [00:512:03]
Tacey A. Rosolowski, PhD:
That's amazing.
Aman Buzdar, MD:
We had to stop the study, and drug company was very paranoid. They said, Why did you stop the study, was there unusual toxicity? The drug company came and looked at every chart. We had to show them that, yes, this is not because of the failure. It is because of unexpected extreme success that we stopped the control arm. The patients who were just getting chemotherapy, we started to offer the chemotherapy with anti-HER2/neu therapy to everybody, and that became the standard of care. One of the other major achievements of MD Anderson; we published those 40 patients' experience, and that was, I think it was maybe 2005 or something like that, and that paper has been cited more than a thousand times in the literature.
Tacey A. Rosolowski, PhD:
Wow, that's amazing.
Aman Buzdar, MD:
And now those therapies are established. At that point, it was not even -- studies were done, that were ongoing, that after surgery, you gave chemotherapy or chemotherapy with this anti-HER2/neu therapy. There were several trials ongoing. It was a couple of years before we had already shown this, then the data of those studies became available and the FDA approved the drug for those early stage disease. That was another area which MD Anderson played a very pivotal role.
Tacey A. Rosolowski, PhD:
It must have been so exciting.
Aman Buzdar, MD:
Oh, it was amazing. The thing is, even -- the thing which I heard, that one of our -- this was when the word had gotten out, because it's small. MD Anderson is a big place but it is a small place, because you consider --if the surgeon, a few times they operated and there is nothing left, the word gets around. One day, there was one of our MD Anderson employees getting an unfortunate diagnosis of breast cancer, and she said, "I hope that my tumor is HER2/neu positive." The thing is, that's how things can change quickly. We were able to show the efficacy of this drug with less than 50 patients. Why were we able to show it? Because the cancer was still there, whereas the other studies, surgery was done first, then they gave the chemotherapy or chemotherapy with the anti-HER2/neu. Those were close to seven, eight, nine thousand patient studies, and they showed the same thing. The patients who got chemotherapy alone had a poor outcome, whereas when you added this anti-HER2/neu therapy, it dramatically kept a large number of patients alive free of disease. That is now the standard of care.
Tacey A. Rosolowski, PhD:
Do you have cases of champagne, you know, on hand, to keep celebrating all these successes? There have been a lot of them.
Aman Buzdar, MD:
There are a lot of these successes. These are not just my successes.
Tacey A. Rosolowski, PhD:
Oh, sure.
Aman Buzdar, MD:
But I think I feel that this is -- it is a group effort and subsequently, this concept was tested in cooperative group studies and it is valid, that this is -- but this was the first cohort, handful of patients randomized. Actually, we asked the NCI to support us early, they didn't want to do it.
Tacey A. Rosolowski, PhD:
Why?
Aman Buzdar, MD:
They said oh, it's far too short in [metastatic?], I said [metastatic?], already they have shown it, that patients live longer. They said oh, the safety is not known, they said that. Again, we went ahead and did it, after getting the IRB approval.
Tacey A. Rosolowski, PhD:
That's an amazing story, it really is. I can only imagine the satisfaction that you must feel, you know to have participated in this.
Aman Buzdar, MD:
Oh, it is amazing. These are the things, because the thing is, there is MD Anderson breast group has been on the forefront, defining some of the newer therapies which are today considered standard, but when we started, these things, these were totally investigational.
Tacey A. Rosolowski, PhD:
Aren't you glad that you and your wife decided not to go to Newark?
Aman Buzdar, MD:
That's right. (both laugh) Now I know, that area has improved a lot. I have gone back and even given some talks there.
Tacey A. Rosolowski, PhD:
I don't mean to dis Newark, but I mean that was sort of the pivotal moment, when you decided all right, we're going to --
Aman Buzdar, MD:
Oh, yeah, I think it was destiny.
Tacey A. Rosolowski, PhD:
Really? Yeah, amazing, amazing career. Are there any other pieces in this kind of research arena, that you want to talk about?
Aman Buzdar, MD:
I think the other thing, which we talked about, and here we played some also, to some degree, pivotal role, was in taxanes, which was not me, but Dr. Holmes. She's a practicing physician. She used to be in our group, where paclitaxel --which was the drug—actually, we did the first study in humans. She was the principal investigator. It was the NCI sponsored study and it showed a very high response rate in patients with disseminated cancer. She took all the x-rays of patients who responded, took it to NCI, because NCI wanted to look at it themselves. They looked at it. Then she submitted the abstract to ASCO. The abstract was not even accepted for publication in that presentation.
Tacey A. Rosolowski, PhD:
Wow.
Aman Buzdar, MD:
They thought well, this is too early and it shouldn't be presented. Now it is, actually it is one of the backbones of the treatment in disseminated breast cancer and in early breast cancer. Beside the anthracyclines, doxorubicin, epirubicin, and the taxanes, these are now standards. Patients have to receive those both therapies to get maximum benefit from chemotherapy. That was discovered over here.
Tacey A. Rosolowski, PhD:
That's amazing. Now, you've used the word disseminated cancer a number of times and is that a synonym for metastatic disease?
Aman Buzdar, MD:
Yeah, disseminated, yeah.
Tacey A. Rosolowski, PhD:
So why is there a new term now? I'd never heard that term, disseminated cancer.
Aman Buzdar, MD:
Well, I am just using it, the term, which is if somebody listens to it down the line, they might not understand metastatic breast cancer.
Tacey A. Rosolowski, PhD:
Oh, okay, I just wasn't clear if there was a change in the terminology.
Aman Buzdar, MD:
No, no. It's stage four on metastatic breast cancer.
Tacey A. Rosolowski, PhD:
Right, right. Any other areas of research that you feel you want to acknowledge?
Aman Buzdar, MD:
So the same thing when -- so, this, didn't publish it, they didn't want her to publish it, so we put it in the adjuvant setting. In the new adjuvant setting, we showed again the same thing. The patients, if you just continue giving the same three-drug combination with fluorouracil, doxorubicin and cyclophosphamide, for say a longer period of time, which was eight cycles of chemotherapy --whereas the randomized study we did actually at that time, half of the patients we gave only four cycles of the three-drug combination, and the other four cycles were given Taxol-- and it showed that there was fewer recurrences in the patient population who received the Taxol in sequence with the anthracycline. Now that is considered standard. But we were again, the first ones to show, from our group, not only in metastatic breast cancer, but in early stage breast cancer two.
Tacey A. Rosolowski, PhD:
This proliferation of drugs is really pretty amazing. I mean suddenly, the availability of these drugs.
Aman Buzdar, MD:
Oh yeah, there are so many. The anti-HER2/neu therapies, there are a whole bunch of anti-HER2/neu therapies which are available. Now the challenge is what -- to identify the patients in which current therapies, --if you give it in the new adjuvant setting before surgery, more than half of the patients go into complete remission. There is no residual disease left. The question is to identify who are the patients for whom the current therapy can cure the disease. The thing is we know already now, that the patients who have no residual disease left at the time of surgery, you look at the natural history, at ten, fifteen, twenty years later, over 90 to 95 percent of these patients will never have cancer again. So they are cured. So the thing is, you can't cure somebody twice. We need to identify where the current therapies are effective, and you don't want to add more therapies on top of it because you don't need to cure them twice. Find those patients in which current therapies are ineffective and offer them the newer therapies and newer drugs which we are evaluating.
Tacey A. Rosolowski, PhD:
I hadn't realized that that was now something that could be said. Because it used to be if you had cancer once, you were always waiting for it to come back, and now that's not the case.
Aman Buzdar, MD:
No, it's not. Actually, we can say, with reasonable certainty, that if a patient has a pathological complete remission with any systemic therapy, you will remain alive, free of disease, the rest of your life. There is less than 10 percent chance of cancer coming back.
Tacey A. Rosolowski, PhD:
Wow, that's really something. Any other areas of research we need to acknowledge?
Aman Buzdar, MD:
I think we talked about ity. Any other things which are on your list?  
Recommended Citation
Buzdar, Aman U. MD and Rosolowski, Tacey A. PhD, "Chapter 13: Additional Research Studies: HER2/neu Breast Cancer; Taxanes" (2017). Interview Chapters. 574.
https://openworks.mdanderson.org/mchv_interviewchapters/574
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