Chapter 09: Treatment for Locally Advanced Breast Cancer

Chapter 09: Treatment for Locally Advanced Breast Cancer

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Dr. Hortobagyi explains that at the same time that he was working on the FAC regimen (Fluorouracil, Adriamycin, Cyclophosphamide), he was also influenced by one of his mentors, Jordan Gutterman, who was experimenting with immunotherapy. Dr. Hortobagyi added BCG (Bacillus Calmette-Guérin) to the FAC regiment. Though unsuccessful, this study opened a new path, as it revealed that a patient’s baseline immune status determined her responsiveness to chemotherapy. Dr. Hortobagyi explains how this observation led him to look at locally advanced breast cancer (LABC), a disease that required extensive surgery and radiation for little effect on patient survival. (MD Anderson was seeing 300-400 cases per year and still sees many more cases than other cancer institutes: Dr. Hortobagyi explains what causes this disease and why it is so much more prevalent in the South.) Dr. Hortobagyi also observes that medical oncology was not respected in the seventies, but in the case of LABC, they relented. Studies were begun using the FAC regimen for LABC and also inflammatory breast cancer. The multidisciplinary regimen involved the drug regimen, surgery, then chemotherapy. Dr. Hortobagyi explains that 90% of patients had an objective response, with 10% showing a complete response. Patients were less disfigured and showed a much greater survival rate.

Identifier

HortobagyiGN_02_20130107_C09

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

Topics Covered

The Interview Subject's Story - The ResearcherThe Researcher Discovery and Success Patients Cancer and Disease This is MD Anderson Understanding the Institution Institutional Mission and Values Healing, Hope, and the Promise of Research Overview Definitions, Explanations, Translations Understanding Cancer, the History of Science, Cancer Research The History of Health Care, Patient Care

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 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:

We also looked at a variety of other immunological agents like corynebacterium parvum, levamisole, the Coley’s vaccine, et cetera, and all of them were very nonspecific. And in retrospect, I think we were observing the same effect—that if you were more competent at baseline you would do better—but that the nonspecific stimulation of the immune system had limited success, certainly when applied to a large group of patients. But in the meantime, and based on the success in metastatic disease, then another door opened, and that was the situation with locally advanced breast cancer. In the early ’70s in this institution, we were seeing a lot of women with newly diagnosed locally advanced breast cancer.

Tacey Ann Rosolowski, PhD:

Can you explain to me what that means, “locally advanced?”

Gabriel Hortobagyi, MD:

Locally advanced breast cancer means that the tumor in the breast reaches very large size, sometimes spreading to several of the regional lymph nodes without necessarily spreading to other organs or metastasizing. To a large extent, that is the effect of late diagnosis, either because of neglect or denial or lack of access to medical care. Sometimes it is because some very aggressive breast cancers actually do not form a detectable mass. They just grow sort of sheet thin, and the patient or the woman doesn’t notice that there is a mass in her breasts. She just notices perhaps that her bra doesn’t fit well on one side, whereas previously it did. But most of the time, these used to be neglected tumors that had ulcerated. They were foul smelling and bleeding and whatnot, and you had to wonder what was going through the mind of that person or the minds of those who surround her because some of these—you could smell them from down the hallway. If you were to be the spouse of that person, it was impossible to imagine that you didn’t know that there was something wrong.

Be that as it may—and of course, this was before the establishment of mammographic screening and early detection of breast cancer, which changed the situation dramatically. But at that time, we were seeing probably 300-400 locally advanced breast cancers per year. And of course, it helped that we were a public hospital, that we were a state hospital, and women without other resources were able to find care here. But it also was a consequence of the southern part of Texas being less prosperous and having a greater degree of poverty.

Tacey Ann Rosolowski, PhD:



Was that 300-400 statistic higher than in other areas of the country? Gabriel Hortobagyi MD Oh, yes. Oh, yes, although locally advanced breast cancer has mostly been a phenomenon of the South. Our counterparts at Memorial Sloan-Kettering in New York—they haven’t seen one in decades, so when we talk about locally advanced breast cancer, it’s like what is that?

Tacey Ann Rosolowski, PhD:

And is that a lack of access? I mean, what’s the cause?

Gabriel Hortobagyi, MD:

It’s a combination of all those things. It’s lack of education, lack of access, lack of resources—all of those things. Those large tumors, as you might imagine, would require very extensive surgical procedures and very extensive radiation therapy procedures in order to try to get control of them. But despite heroic surgical interventions and very high doses of radiation therapy by some of the pioneers of both fields in this institution—and they were truly extraordinary, skilled people—it was an exercise in futility. Because despite these huge operations, the majority of these patients would die of their breast cancer within just a couple of years, and it was because—women don’t die of breast cancer from having a lump in the breast. Women die of breast cancer because some of the cancer cells develop the ability to spread to other organs and gain access to the general circulation—to the blood circulation—and they travel wherever that takes them. And once breast cancer reaches those dramatic dimensions, then there is a great preponderance of cells that have the ability to metastasize.

So, after dealing with this for a decade or two, our surgeons and radiation oncologists—who at the time I arrived still looked at medical oncology as what are these upstarts trying to accomplish here? They don't have anything to contribute. We are the ones who cure cancer. And they were not really referring patients to us, so finally they sort of relented with this group of patients, because they noticed themselves that they were not making any progress, and they were banging their heads against the wall. We started to see these patients, and it was very dramatic because we said, “Well, we’ve got this FAC regimen. Let’s use it in these patients. The majority of them are going to die, so there is no real safety issue here; and at the same time, they are dying of metastatic disease. This is like having metastatic disease except that now we have something that is very easily measurable.” We started to treat a number of these patients, including a subset of them that had what we call inflammatory breast cancer, which is a very specific subtype of locally advanced breast cancer where the skin of the breast becomes red and acquires, because of swelling, the appearance of orange skin, which at that time we called peau d’orange—probably because some French investigator described it some years earlier. Inflammatory breast cancer is the most lethal form of breast cancer. If you treat the inflammatory breast cancer with surgery alone or radiotherapy alone or the combination of those two, about ninety percent of those patients have metastases within two years, and ninety-five percent of them are dead by five years. It’s a horrible, horrible disease.

We started to treat all locally advanced breast cancers with chemotherapy first. We gave them three cycles of our new cocktail; and lo and behold, the great majority of them had a magnificent response. About ninety percent achieved an objective response with a greater than fifty percent reduction, and about ten percent of them had a complete response, and the majority actually became operable with much less extensive surgical resection. Then we came up with this multidisciplinary regimen in which we started with chemotherapy for three cycles. Then we did either surgery or radiation therapy, depending on what was feasible at that time, and then we continued chemotherapy afterwards until we figured out we had to stop. Then all of a sudden, these patients were not only less disfigured, but they started to live. And while it wasn’t a total cure rate, we went from a five-year survival of about ten percent to a five-year survival of about fifty percent, and that was a very substantial jump. And all of a sudden, the reigning pessimism about locally advanced breast cancer started to change.

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