Chemotherapy

Here I want to talk about chemotherapy, its pros and cons. In this type of cancer treatment, we give drugs mostly intravenously. As you know, within seven seconds they are going to get to virtually every cell in the body. The good thing about chemotherapy is that we don’t need a target. This is why it has become so important in metastatic cancer. We don’t need to know where the cancer cells are hiding, the drugs will get there. However, it is very toxic and it isn’t good for handling tumor bulk.

There are a couple of things about this treatment that you need to know. There is something called the Goldie-Coldman hypothesis. This is a huge mathematical concept that I have no idea what is about. I know, however, what Doctors Goldie and Coldman found out. They found out that chemotherapy would fail even in very small numbers of cells unless you go the whole way and get all the possible metastatic cells. You cannot back off and get the same result.

If you’re getting a bad result with surgery or radiation you can always back off for the patient to rest and pick up again. In chemotherapy, however, if you don’t finish the course of treatment because of toxicity, then the patient is very likely to have a lot of resistant cells that escaped through natural selection. You’ll get the most resistant cells.

Goldie and Coldman also say that it’s very unlikely you’re going to be able to do the job with one drug. We usually don’t use one drug. We use multiple drugs so that we can lower the toxicity of each one. We try to get drugs with different toxicities. Maybe we use one that works maybe depressing the bone marrow, which is a bad thing. We may use another that has another toxicity and you get a synergistic effect that kills the cells you want to kill and not make the patient so sick.

Ideally we use eight or ten drugs, but we generally use two or three and try to get the patient to complete the whole cycle. Just about the time things are really getting bad for the patient we back off and pick up again later. These cycles are timed to try to get the cancer cells when they just caught their breath and started to multiply again. Meanwhile, normal cells have probably recovered pretty well.

It is very hard to measure the effectiveness of the treatment unless you have some tumor you can see. The most important type of chemotherapy is the category called adjuvant therapy. Adjuvant cancer therapy has a very specific definition. It means that it is given to a patient in whom we cannot prove that they have metastasis, but we highly suspect it.

What we found out is that if you wait until there are enough tumor cells to produce symptoms it is usually too late to get the best results from any treatment. If you move in to a patient who has microscopic metastasis, you’re going to get the best result. How do we know who that patient is?

Adjuvant therapy, therefore, is defined as drug therapy given to a patient without proven metastasis but who we think has a very high likelihood of having them. Doctors do all the studies they can and say to the patient: “Look, it is likely that you’re cured, but we’ve got a lot of bad biologic markers. We would do you a lot of good if we do the chemotherapy now, before this comes back three years down the road.”

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Radiation Therapy

A second kind of cancer treatment is radiation therapy. In this case we use high energy coming out of a radiation generator to create a release of energy within the patient’s DNA. Comparing this kind of treatment with surgery, radiation is going to give us excellent control of those microscopic margins, because we aim it in the area where the primary tumor is located, but also is going to have a wider spectrum. As opposed to surgery, radiation is not invasive and it has very few side effects and does kill cells. The problem is, though, you still need a target tumor, just as with surgery. We have to know where we are aiming it. You cannot radiate the whole body.

Also, you only get one lifetime anatomic dose. Once you have full therapeutic radiation, you can never have it again no matter how many years later. You’ve done enough damage to the blood vessels. If you radiate again on that area, probably you’ll cause death of any of the tissue you radiate.

Radiation doesn’t handle bulk very well. It needs a small amount of tumor cells, unlike surgery. It might be a good complement to surgery, however. Surgery handles the margins poorly, radiation handles them well.

The primary goal of radiation therapy is the injury to the cancer cells’ DNA. The wavelength used is such that radiation can cause a break in the DNA chain. The idea, however, is not to fry the cell. If you’re going to fry cells, you’re going to fry all the cells radiation goes through.

What we’re looking for with radiation therapy is to get the cancer cells to lose reproductive ability. We want the cell not to die because you boiled it up like an egg, but to make it so that when it tries to reproduce it just can’t. That may take several cell divisions before it falls apart, and that’s why radiation may take so long to show results. These cells have to go through a certain number of attempts to replicate before they finally die. Here we are making use of the fact that the fast-replicating cells are the cancer cells, so they are the ones dying. Most of our cells are resting, not replicating, so they are not going to feel the effect of radiation.

The dosages used are usually 5000 Rads or 50 Gray to a specific are, for example the whole breast. If you want to compare that with diagnostic radiation, a mammogram would be about 1 rad.

There are some cases of tumors induced by radiation therapy, but not nearly as many as other sources of radiation.

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Breast Cancer Surgery

Breast cancer surgery has always been the first line of treatment for this disease, and remains so today, even though is the most invasive one. Surgery is the tool with which we can remove the bulk of the tumor most easily. The good thing about surgery is that it removes the whole mass, whenever possible. A problem with it is that it requires a target. We have to know where the tumor is. This is often the case with breast cancer surgery.

Also, surgery is very invasive and we don’t get control of the microscopic margins. When we take out a cancer, it is very important that we leave no tumor cells behind at the edges. The way we do this is trying to go in and take normal tissue around the tumor as much as we can without causing destruction. In certain areas this is going to be easier than in others. For example, in breast cancer surgery we can usually take an area of normal breast tissue around the tumor, whereas in the brain everything you take will lead to destruction.

In breast cancer we have three operations we use to do. William Halsted, a very famous professor of surgery at John Hopkins, is considered the father of modern surgery. He invented rubber gloves for his girlfriend, who was a nurse allergic to disinfectants. He invented the radical mastectomy for breast cancer. With this, the entire breast was removed, and also all the pectoral muscles were removed, because he thought cancer spread through the pectoral muscles. We now know this isn’t often the case.

Around the 1960’s, doctors decided that that was too much surgery. We started removing the entire breast but leaving the pectoral muscles. After that, we moved into what is now called lumpectomy, where the tumor is removed with a little margin of normal tissue. Then, through a separate incision, we use to take out lymph nodes and do what is called a sentinel node biopsy. We inject either dye or radioactive material before the operation that will be picked up by the lymphatics and deposited in these lymph nodes. Then, we open up the axilla and we look for the dye. We take out the lymph nodes and we see if it contains metastasis. It is unusual for metastases to skip lymph nodes, so if it is clean, we consider that the tumor has not metastasized.

In order to see if this really works, surgical protocols were started about three decades ago. With many studies we found that lumpectomy with axillary dissection worked as well as the modified radical mastectomy, which worked also as well as Halsted’s radical mastectomy. Now, the lumpectomy with axillary dissection is the gold standard.

What we try to achieve surgery is to do less and less to patients in a surgical way, as it is so invasive. So far, however, we still have the need to do breast cancer surgery in a lot of cases.

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