Breast Cancer Chemotherapy: An Interview with N.S. Tchekmedyian, M.D.

Chemotherapy Advancements & Combining Drugs

How has chemotherapy changed in the last 10 years?

I have been in oncology now for about 20 years and since I started my fellowship back in the early 80's things have not changed all that much. We do have a few good new drugs that we can choose, particularly the taxanes like Taxol and Taxotere, important new drugs, but overall the side effect profile of the drugs [and] their mechanism of action are pretty much the same. We have not had a lot of advances in conventional chemotherapy over the last decade. I should say, however, that we have had major advances in some other areas of biologic therapy, including antibodies, gene therapy and a variety of other things.

Has the chemotherapy experience changed per patient in the last 10 years?

Although chemotherapy drugs still have a lot of side effects and we have not had great advances in terms of the drugs themselves, we have had major breakthroughs in terms of diminishing the side effects. We have much, much better treatments to prevent nausea now than we had 10 or 15 or 20 years ago; we have much better control of the immune effects of chemotherapy; we have ways of preventing and treating anemia associated with chemotherapy; we have ways of preventing the white cell counts from going down to dangerous levels.

We seldom if ever have to admit a patient to the hospital because of side effects of chemotherapy. We're able to control those side effects very well. The quality of life is better. Most of my patients who come here to be treated — come over, they read, they watch TV, they have a visit, they chat and joke with their nurses and their doctors, and then they go home, and most of the time they have very few acute side effects.

What is the most exciting new chemotherapy drug that's been developed in the last few years?

I would say the most exciting chemotherapy drug that has been developed for breast cancer over the last decade is Taxol and the taxanes, including Taxotere. These are drugs that have a different mechanism of action. They actually work by interfering with cell division because they bind to microtubules, small filaments that are involved in the process of cell division. That is a different mechanism than most of the drugs that actually bind to the genetic material of the cell. They were very toxic when they were first discovered and tested. In fact, the first few patients who were treated got so sick that the drugs were almost thrown away because they thought that they wouldn't be able to use them. ... Their efficacy is very high and we have learned how to use them and therefore they are very well tolerated.

Why do some drugs work for some patients and not for others?

It can be quite frustrating to try to control a cancer both for the patient and the doctor ... Some cancers are inherently very resistant to chemotherapy and some others become resistant after a period of treatment. The reason why the cancer cells become resistant has to do with mutations or changes in their genetic material. As they divide, cells become progressively more derailed in the way their genetic material works and the more this process takes place, the more these cells become oblivious to the presence of these drugs around.

These genes are important in terms of telling the cell what to do, telling the cell how to behave. When this gene changes because of so many divisions and so many mutations, then the behavior of the cell becomes completely abnormal and that leads to resistance to drugs that normally kill cells.

So what's your strategy when you're giving chemotherapy drugs to a patient and it doesn't work on that patient? How do you decide what other drugs to try?

Generally we use the drugs with the higher level of efficacy and the lower level of toxicity up front and then as the cancer becomes more progressive and more resistant we have to go into drugs that perhaps are more toxic but that still have a chance of working, or we go into drugs of the lower levels of efficacy but used in a lower dose to approach what we call palliation.

So you're juggling dosage with a mixture of different drugs?

The choice of chemotherapy drugs for breast cancer is somewhat empirical and based on our knowledge and experience, but we usually can have a fairly rational and sound approach as to the selection of different drugs as we manage the patient. Many years and many decades of experience with drugs and different patients have shown us what works best and what should be used first and what should be used second and so on.

There are some tests available where you can take fresh cancer tissue and test it to see what drugs work better — what's called chemosensitivity assays. Unfortunately so far the results with these tests have been sub-optimal and they cannot be trusted. Most oncologists do not do those tests because they have not proven to result in improved patient outcome results.

How do you decide when to give chemotherapy in conjunction with surgery at the moment?

A one centimeter small growth contains a billion cells. It takes, we think, approximately eight years for a growth that size to show up in the breast. During those eight years and before you've reached that level of one billion cells. Many of those cells have penetrated into the blood stream and have been circulating around. Some of those cells will be knocked down by the immune system or some other factors and disappear, but some of them may survive and find a new place to live— the bone marrow inside the bones, in the liver, in the lungs, in the lymph glands or somewhere else, so when the surgeon cuts the breast open and takes a lump out, what we're taking out is what we see, the lump that contains the billion cells with some normal tissue around it, so that we get rid of the primary illness.

The problem with breast cancer is not that lump. The problem with breast cancer is the cells that left that lump and have been circulating around that can grow later on into new cancers, so-called metastasis. By using the combination of primary surgery with chemotherapy we approach the local problem and the systemic problem of those cells that have escaped, so chemotherapy used together with surgery makes a lot of sense. We've been doing that for many years and the results clearly show that we can cure patients who otherwise would have died of breast cancer by using chemotherapy as an adjuvant to surgery.