Chapter 11: Adapting LABC Treatment for Stages 2 and 3 Breast Cancers

Authors

Gabriel N. Hortobagyi MD, The University of Texas MD Anderson Cancer Center
Tacey A. Rosolowski PhD, The University of Texas MD Anderson Cancer Center

Files

Description

Dr. Hortobagyi begins by explaining that the LABC (Locally Advanced Breast Cancer) treatment involved six months of chemotherapy, surgery, radiation, and treatment with hormonal Herceptin. His group then decided to expand the regimen to stage two, and stage three tumors and they designed a national clinical trial comparing the regimen with a protocol that performed the surgery first. Dr. Hortobagyi explains that new regimen offered advantages even though the effects on the tumor were not statistically greater than with surgery first. He points out that it was not possible to do a randomized trial at MD Anderson in the seventies, and so the process of clearly demonstrating the regimen’s value was greatly prolonged. To explain why surgery was the last to participate in randomized trials, Dr. Hortobagyi mentions that a 1980 conference in Tuscon brought the discussion to a head when Dr. Chuck [Charles] Moertel (a proponent) debated the issue with Dr. J Freireich (an opponent). It was clear that most of the oncology community in the country supported randomized trials and that MD Anderson had to evolve. The NCI became involved and spoke to institution leadership about the need to initiate such trials and the culture of the institution changed accordingly.

Identifier

HortobagyiGN_02_20130107_C11

Publication Date

1-7-2013

Publisher

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

City

Houston, Texas

Interview Session

Gabriel Hortobagyi, MD, Oral History Interview, January 07, 2013

Topics Covered

The Interview Subject's Story - The Researcher The Researcher Discovery and Success Professional Practice The Professional at Work Cancer and Disease Understanding the Institution Controversy Overview Definitions, Explanations, Translations Understanding Cancer, the History of Science, Cancer Research The History of Health Care, Patient Care

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Disciplines

History of Science, Technology, and Medicine | Oncology | Oral History

Transcript

Gabriel Hortobagyi, MD:

So, we developed then this process, and the process became sort of the classical approach to locally advanced breast cancer. It was chemotherapy. Eventually we increased it to six months then a surgical resection, which initially was a mastectomy. It later became a mastectomy for some, breast-conserving surgery for some others, and then radiation therapy. And then for patients with certain subtypes of breast cancer, hormonal therapy, and for certain other subtypes of breast cancer, Herceptin, and that is today the standard of care for all locally advanced breast cancers. And in the process of doing that, we became so encouraged by the results that we said, “We don’t have to limit this to these horrendously large tumors. But we could probably do this in patients with earlier—still large—but earlier tumors.” And so, then we moved to the large, operable stage III tumors and eventually to stage II tumors. And then secondarily, I was invited to help design a national clinical trial that compared my strategy with the traditional strategy of surgery first followed by adjuvant chemotherapy for clearly operable, earlier breast cancer. And that demonstrated that the two approaches were clearly interchangeable in terms of survival and that there were some advantages for doing chemotherapy first.

Tacey Ann Rosolowski, PhD:

And those advantages were?

Gabriel Hortobagyi, MD:

That in many cases patients who were only candidates for mastectomy after chemotherapy could be offered breast reconstructive surgery, that by not removing the tumor upfront you were actually able to watch what your chemotherapy was doing. Was it working or was it not? Because once you remove the tumor, you are sailing blindly. You have no idea whether your treatment works or not, and when you're talking about six months of chemotherapy, doing that condemns that patient to receiving that treatment whether she’s benefiting from it or not. And I think that is not acceptable because you can tell within a month or two if things are not working, and at the very least you can stop something that is not working from producing toxicities and side effects. And in the best of cases, you can also change to a different chemotherapy regimen that might work better, so that’s another aspect of it. By doing that and by taking some intermediate outcomes—like how much residual disease is there after chemotherapy at the time of surgery—you can make up your mind about the value of that initial treatment much faster than if you remove the tumor and you have to watch for years, sometimes decades, to figure out who benefited and who didn’t. And fourth because you can—from the point of view of pure science—you can sample the tumor as you go along with treatment and figure out what are the biological consequences of administering chemotherapy or Herceptin or a vaccine or whatever you’re administering before surgery. All of those are advantages are very, very important; and as a result of that, forty years later most of the national trials that are looking at new drugs or new procedures are using the new adjuvant chemotherapy or adjuvant systemic therapy model. And I think that’s very gratifying, because for many years, people didn’t believe that that was a good idea or that that was possible or that that was wise.

Tacey Ann Rosolowski, PhD:

What was the reason for the lag time in accepting that?

Gabriel Hortobagyi, MD:

Well, physicians are fairly conservative, and to some extent it was because in the early years we didn’t do what in retrospect would have helped very much, which was to do a randomized trial in the early ’70s. We would have shortcut the process certainly by a decade, perhaps two. It was the NSABP’s national trial that was started in 1988 and was reported about seven years later that actually helped make the transition, and then people looked back and said, “Ah, yes. MD Anderson has been saying that since the mid ’70s. Maybe they were right.”

Tacey Ann Rosolowski, PhD:

So why wasn’t this particular process taken through randomized trials?

Gabriel Hortobagyi, MD:

It was not possible to run a randomized trial at MD Anderson at that time.

Tacey Ann Rosolowski, PhD:

Okay, so that’s where that cultural—

Gabriel Hortobagyi, MD:

Yes, that’s where that cultural thing was a problem. In fact, if I look back at the 1970s, we had I believe four breast surgeons, each of them very accomplished, very well known. Each of them knew that he treated breast cancer better than the other three, and each of them did something different, which in retrospect didn’t make any difference. But it was their surgical procedure, and anyone who tried to talk to them about the other guy’s surgical procedure had to be totally wrong. Radiation Oncology was much more disciplined, and they had sort of a team. Surgery was the last to come on board in terms of trying to do the same thing. And even today, if you look around the surgical community around the country, it is a cottage industry, and it is a highly operator-dependent—no pun intended—discipline where, depending on where you train, you learn a different technique. And it is very hard to get surgeons to do a clinical trial where all of them are asked to do the same procedure the same way. And in fact, one of the greatest accomplishments of Bernie Fisher—who was a surgeon who was the leader or the chairman of the National Surgical Adjuvant Breast Project—was not necessarily the outcome of protocols, although he contributed much to that, but to convince about 2000 surgeons about the country or around North America to do the same things, to comply with the protocol requirements and therefore test certain procedures—the radical mastectomy, the modified radical mastectomy, lumpectomy and radiation, axillary dissection and then later sentinel lymph node biopsy. That was inconceivable even in the small microcosm of our institution to ask those four surgeons to do that. All of them are gone or dead so I don’t want to name names, but that was the situation at that time. Under those circumstances, to do a trial which requires everyone to do the same thing would not have been possible. But two of my most senior mentors would have opposed it with everything they had because that was just the wrong thing to do in their minds.

Tacey Ann Rosolowski, PhD:

When at MD Anderson did that particular mentality open up, loosen?

Gabriel Hortobagyi, MD:

In 1988-1990.

Tacey Ann Rosolowski, PhD:

Very slow in coming then.

Gabriel Hortobagyi, MD:

Yeah. Yes, it was very slow. It was very slow, and of course in the interval, I myself and my colleagues at my level—Dr. Buzdar and our peers in Radiation Oncology and Surgery—we were all evolving, too, because we had been taught this thing of thou shalt not do a randomized trial, or it is fine to do an empiric observation. I remember in the late 1970s and early 1980s there was a very important annual meeting in Tucson, Arizona, and it was organized every year by an oncologist by the name of Sydney Salmon, who was the head of the cancer center in Tucson, and it was called the Adjuvant Therapy of Cancer. It started with breast cancer because that’s where the initial clinical trials were done to demonstrate that adjuvant therapy—meaning postoperative chemotherapy—improved disease-free and overall survival. But eventually it included other tumor types. It included some hematological malignancies and colon cancer, et cetera. About the fourth or fifth meeting—so I think I'm talking about the early 1980s—they organized a debate in which Chuck Moertel, who was I believe the head of oncology at the Mayo Clinic and a passionate proponent of randomized trials, and J Freireich, who was of course the VP here and a passionate opponent of randomized trials—they put them up to debate the issue. It was a pretty dramatic discussion, and it brought to a point the difference. And by that time, most of the country was on the side of randomized trials, and we were still opposing it tooth and nail. And I think after that we pretty much had to evolve because the NCI got into the game, too, and I think behind the scenes indicated to MD Anderson leadership that we have to change. Because the field was evolving, we evolved, and eventually many of the national trials were led by MD Anderson faculty members, so we have come a long way in that sense.

Recommended Citation

Hortobagyi, Gabriel N. MD and Rosolowski, Tacey A. PhD, "Chapter 11: Adapting LABC Treatment for Stages 2 and 3 Breast Cancers" (2013). Interview Chapters. 1116.
https://openworks.mdanderson.org/mchv_interviewchapters/1116

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Open