Clifford Hudis on Breast Cancer Prevention

Well, as a group, that is to say globally, we can do something about the breast cancer risk but I am very quick to say that I don’t know whether individual women can directly and certainly prevent their own breast cancer. I have to expand a little bit to explain why. To prevent breast cancer you have to understand the risks for breast cancer. The first risk that we clearly understand is the inheritance of a mutated gene from a parent. If you inherit that gene, there is an overwhelming likelihood that you’ll develop breast and maybe ovary cancer and for that subset of breast cancers prevention is pretty difficult short of risk-reducing surgery, meaning removal of the breasts. The second thing that one has to recognize is that the single most common risk factor for breast cancer is aging and none of us are seeking to prevent aging. So now you get in to more subtle things like diet, lifestyle and similar, and we probably can prevent breast cancer in that reign-- in that domain but it takes a little bit of work to show it. For example, people who are more sedentary and obese or overweight have a higher risk of breast cancer but-- so those are things you can modify. There  are even some drugs that you can take that lower the risk of breast cancer though they’re not wildly popular. The anti-breast cancer drug tamoxifen and other drugs like that have been shown to reduce the risk but most people seeking to prevent breast cancer aren’t looking for a medical intervention; they’re looking for something more generally applicable and presumably less toxic.

Question: What is tamoxifen?

Clifford Hudis: It is a very old drug actually. It’s one of the earliest effective treatments for breast cancer. To tell you about tamoxifen I feel like I have to back up to the beginning of breast cancer medicine. The very first effective medical treatment for cancer as opposed to surgical removal of the cancer was removal of a woman’s ovaries. It was reported by a Scottish surgeon in 1896. His name was Beatson and what he was fundamentally doing was depriving the tumors of estrogen. So tamoxifen leapfrogs as many generations ahead. Tamoxifen can be thought of as a modified estrogen. It attaches to something called the estrogen receptor the same way that estrogen does except when it attaches to the estrogen receptor different things happen in the cell. If estrogen tells a cell to grow, tamoxifen tells a cell stop growing and die. I’m being very simplistic but that’s a simple way to think about it. So tamoxifen is an oral drug. It’s broadly available. It has some side effects that can be attributed to an antiestrogen effect. Interestingly, it has some side effects that are consistent with those of estrogen itself so it’s a very complicated drug. It’s generic, it’s inexpensive, so around the world it may be the most broadly available anti-breast cancer medicine and because it’s inexpensive it’s really cost effective. It has a tremendous worldwide impact. In most parts of the world it’s used to treat established breast cancer. In most parts of the world it’s used to prevent recurrence of early-stage breast cancer, meaning after an operation, and in some parts of the world it’s actually used to prevent breast cancer, which is what we’re talking about right now.

Question: What are other popular drugs?

Clifford Hudis:  Well, popular is a different question. I’m not sure what is the most popular drug. Tamoxifen is a broadly available drug. In order to answer that question, one has to start to talk about the biology of breast cancer. Breast cancer is not just one disease. It is better thought of as a collection of diseases and in the same way that you don’t lump pancreas cancer, breast cancer and leukemia together, you say they are different kinds of cancers with different treatments, the same is true within breast cancer. So there’s one kind of breast cancer that’s hormone responsive. It’s described microscopically by the pathologist clearly because it has the estrogen receptor. For breast cancers that have the estrogen receptor there are a collection of hormone therapies that interfere with it as I described for tamoxifen, and after tamoxifen the most commonly used drugs certainly have to be the aromatase inhibitors with the caveat that those drugs are really only useful after menopause. Tamoxifen is useful regardless of menopausal status. For the estrogen receptor-negative breast cancers there’s a very exciting subgroup that have something called HER2. That stands for H-E-R-2, the human epidermal growth factor receptor. Those cancers are targeted with a very exciting antibody called trastuzumab. You may know it by its brand name, Herceptin. They’re also targetable by other exciting new drugs as well not having to do directly with chemotherapy, and for the cancers that don’t have any of these receptors chemotherapy treatments remain the mainstay.

Question: What are the latest advances in breast cancer prevention?

Clifford Hudis:  Well, there are tremendous advances. It’s never been more exciting in terms of the molecular biology of breast cancer and cancer in general and the translation of that understanding in to medications. So one of the things we’ve been trying to do is find better, safer drugs than tamoxifen. A class of drugs called aromatase inhibitors is widely available. They offer marginal advantages over tamoxifen in terms of efficacy and also safety, and right now in early looks at data they appear to have the same or better prevention effect as does tamoxifen and they may represent just the next step but there are many more yet to come.

Memorial Sloan-Kettering's Clifford Hudis on what is known about breast cancer prevention and treatment.

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