Hair loss Treatment Center

PARTICIPANTS Hyman B. Muss, MD Associate Director for Cancer Research, Vermont Cancer Center Hope S. Rugo, MD Medical Oncologist and Hematologist Associate Clinical Professor of Medicine, UCSF

Doctor, breast cancer is a very diverse disease. Can you review the main stages?

HOPE RUGO, MD: Stage I is small cancer that is confined to the breast, and it hasn't spread through the lymph circulation or blood circulation to the nodes under the arm. Those lymph nodes are where the blood flow and lymph flow go to apparently first from the breast.

Stage II breast cancer, that's when either the tumor is a little bit larger, or it's also spread to nodes under the arm.

Stage III breast cancer is a little more advanced. These are larger tumors, probably larger than a small apple, and in that situation, sometimes the tumor is large enough or growing fast enough that there's redness over the surface of the breast, or the tumor actually has invaded in the skin of the breast, and that's called stage III, or inflammatory breast cancer.

Stage IV breast cancer is a very heterogeneous disease. This is breast cancer that has spread outside of the breast and the draining lymph nodes under the arm to somewhere else in the body. The cancer spreads, again, by the bloodstream or by the lymph circulation to the lungs, the liver, bone, sometimes the lymph nodes in other parts of the body, sometimes even the brain.

The stages are really divided I through III, and IV into disease that is potentially curable and disease which we consider incurable. So much of what we understand and use for decisions about treatment have to do with what stage you are and what we understand the curability to be.

CATHY CONLEY: So how does the treatment approach differ from early stage disease and metastatic disease?

HOPE RUGO, MD: Metastatic breast cancer, or stage IV breast cancer, where breast cancer cells -- they look just like the breast, cancer cells that are from breast tissue -- are in other organs, like liver, lung or bone. In that situation, we currently don't appear to be curing that disease. That doesn't mean that we can't help people to live longer and have better quality of life. So our goal needs to be very clear for metastatic, advanced stage, stage IV breast cancer -- all those terms are used -- that what we're doing is preserving quality of life and quantity of life.

In contrast, when we're treating early stage breast cancer, our goal, of course, is to prevent the cancer from ever growing back, to cure the woman of the breast cancer so she doesn't recur and die of breast cancer someday. So for that goal we're willing to give a little bit more intensive treatment. As long as we can keep people relatively well, we're willing to have side effects such as hair loss or low blood counts, or even other side effects, such as nausea and vomiting, if we can control them and it's for a short period of time, like three to six months. We're gaining so much on the other end, that it appears worthwhile when you do those risk versus benefit analyses.

CATHY CONLEY: Dr. Muss, what's the role of anthracyclines in both the adjuvant and metastatic settings?

HYMAN B. MUSS, MD: Well, anthracyclines in the adjuvant setting -- by which we mean giving them to women with early stage breast cancer, hopefully many of whom are cured, but we're adding a little insurance with chemotherapy -- in that setting, anthracyclines have been shown overall to be superior to chemotherapy treatments that don't contain these drugs.

In the metastatic setting, it's a little bit different. For those patients, unfortunately, cure is a rare thing. In those patients, anthracyclines can be very effective in shrinking cancer, and in so doing, improve a patient's quality of life, making it easier for them to get around, to enjoy their lives.

CATHY CONLEY: What is the difference between the two anthracyclines on the market, the epirubicin and the doxorubicin?

HOPE RUGO, MD: There is a difference in the structure of epirubicin compared to doxorubicin, the prior standard, and what that ended up resulting in is that you can actually give more epirubicin than doxorubicin without the same problems that we see with doxorubicin, and those problems are primarily heart toxicity.

What that means for the treatment programs that we've devised, which have been used both for early stage and late stage breast cancer, is that once you've given what we consider a standard course of anthracycline, if you use epirubicin, you haven't reached your lifetime maximum dose of anthracycline. If you use doxorubicin in that same setting, you're at your maximum.

CATHY CONLEY: Are there differences in the way the epirubicin and the doxorubicin are used, and does it vary in the different stages of the disease?

HYMAN B. MUSS, MD: Well, I think historically they've been very similar in the way they've been used. Initially, both were used in women with metastatic breast cancer, which is where we learn how effective treatments are. Now, and for many years, adriamycin or doxorubicin, which was an earlier developed drug, was tested in the early setting and very promising. More recently, epirubicin, which has actually been around for a long time, has been rediscovered, in a sense, and put into several very high-quality adjuvant therapy trials, where it's shown to be superior to some of the other standards of care.

CATHY CONLEY: Can you talk about the difference in toxicity between the two agents?

HYMAN B. MUSS, MD: The anthracyclines cause heart damage by damaging heart muscle. It's not like a coronary, like a heart attack. They don't cause heart attacks. What they cause your heart to do is not pump well and lead to heart failure.

Fortunately, with all the agents, and when given appropriately, and when patients are closely followed by their physicians and nurses, it's usually not a major problem, but it can be. In women with metastatic breast cancer, where their breast cancer is a major problem and it's not going to be a curable event, heart failure is of concern, but unfortunately most of those women don't live many, many years, and so your goal of treatment is to do the best for the breast cancer at that time.

In the adjuvant setting, where many women hopefully are never going to have a problem with breast cancer again, you're concerned what's going to happen at five and ten years, so it's very important up front that we minimize damage to the heart. There's some evidence that epirubicin, when given at a dosage that has a similar effect on cancer cells as doxorubicin, may be a little less cardiotoxic, and perhaps that is an advantage.

CATHY CONLEY: Are there any head-to-head comparisons?

HOPE RUGO, MD: There has not been a prospective -- in other words, starting a trial, randomizing women like the flip of a coin to one drug or the other -- but there has actually been a retrospective look at collected studies, randomized studies that used either doxorubicin or epirubicin. That data hasn't been published yet, but it does suggest that the studies that used epirubicin had a better outcome than the studies that used doxorubicin. I think we need to take a very critical look at those studies. It doesn't prove that one drug is better than another, but it's very suggestive, and it's helped us to design studies that can hopefully answer that question.

CATHY CONLEY: Are the treatment regimens involving anthracyclines changing in any way?

HYMAN B. MUSS, MD: I think that there has been a resurgent interest in, for instance, the use of epirubicin in clinical trials. Several major trials, specifically one large Canadian trial in younger women, premenopausal women -- women still having menstrual function -- who have positive lymph nodes, comparing an epirubicin-containing chemotherapy regimen with a similar regimen that lacked epirubicin showed some convincing survival benefit for the epirubicin.

CATHY CONLEY: Well, doctor, how do you think the use of anthracyclines will change over the next few years with all the information, all the breast cancer therapies and how it is incorporated into the practice?

HYMAN B. MUSS, MD: I think we're trying to learn who benefits most by various drugs. For instance, we know that anthracyclines as a group of drugs are superior to non-anthracycline regimens. But we'd like to identify which of the patients are most likely to benefit. We're going to look for the targets. We're interested in looking at our patients as they come into the clinic and saying, "We've tested your breast cancer, and you have chemical X, and we know, by having chemical X, you should get an anthracycline-containing treatment, because it's going to do better."

CATHY CONLEY: Dr. Rugo, your final comments?

HOPE RUGO, MD: I do think that the use of anthracyclines is going to change, to use a longer treatment program. So instead of a three-month course of four cycles, we may be using a four-and-a-half month course of six cycles. If that's the case, I think there's going to be increasing use of epirubicin rather than doxorubicin, because we can use those six cycles without reaching the lifetime maximum dose of anthracycline.

CATHY CONLEY: Well, Dr. Hope Rugo, thanks so much for your time. We appreciate you being with us.

HOPE RUGO, MD: Thank you very much.

CATHY CONLEY: Dr. Hyman Muss, thank you for joining us.