Decisions in Breast Cancer

While more than 200,000 North American women are diagnosed with breast cancer every year, most of the time the disease is found in its early, most curable stages. This bodes well for the long-term survival of these women, but there are often many treatment decisions to make in a relative short and stressful span of time. Once the benefits of a particular treatment for a particular patient are assessed, women and their medical teams must weigh the risks and benefits in order to design the best treatment plan.

Tools for better decision-making are now in the works. A study published the July 28th issue of the Journal of the American Medical Association evaluated a decision aid, called a decision board, which includes pictures and text, that physicians can use when presenting information about surgery, which is one of the first breast cancer treatment decisions. Researchers found that the decision board helped patients make a more informed choice when deciding whether to have a mastectomy or a lumpectomy; the women were also more satisfied with their decision six and 12 months later.

Below, Clifford Hudis, MD, chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center in New York City, talks about the goals of breast cancer therapy and how treatment decisions are best approached.

What is the goal of treatment for early-stage breast cancer?
The goal of therapy for early-stage breast cancer is cure, and there are many ways to get there. Different treatment choices will often be associated with different side effect profiles, and that's where we have to have a long discussion weighing the risks and benefits of different approaches.

For early-stage breast cancer, most people will say they're willing to put up with fairly substantial side effects in the short run because their hope is that they will never hear from the cancer again. If we're going to think of a scale, it will be tipped towards more toxicity for more benefit. When we're treating advanced cancer, however, the scale may be tipped the other way. People may not want to deal with a whole lot of toxicity or give up quality of life for very marginal benefits. So these are the kinds of decisions that come into play.

What's the goal of surgery for a woman who has early-stage disease?
For early-stage disease, the goal of surgery is to remove all of the cancer with clear margins around it and to determine the risk of spread by looking at the status of the lymph nodes under the armpit.

In the early days of breast cancer surgery, the procedure of choice was a mastectomy. But the National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted a series of randomized studies that showed that just as many women could be cured with a lumpectomy and radiation therapy as could be cured with mastectomy. Women who choose lumpectomy need the radiation because it lowers the risk of local recurrence in the breast.

Does everyone require radiation therapy after lumpectomy?
There is a movement afoot to look very carefully at some subgroups of people who may not need radiation after a lumpectomy. For example, researchers are looking at women with DCIS (ductal carcinoma in situ), which is a precancer that remains confined to the ducts, so we don't call it an invasive cancer. It does not have the potential, that we know of, to spread distantly beyond the breast.

As the degree of invasiveness of the cancer goes down and as the age of the patient goes up, the risk of recurrence is lower. Hence, the potential gains from radiation may be smaller.

How do women decide between mastectomy and lumpectomy?
The choice of mastectomy vs. lumpectomy is a fairly difficult one for some people. On the one hand, the mastectomy is over with quickly. You can choose to do reconstruction right away or at a later date. On the other hand, the lumpectomy allows you to preserve the breast, but generally requires four to six weeks of postoperative radiation therapy five days a week.

Some variables are technical. For example, if there is a large cancer in a small breast and the cosmetic result of a lumpectomy will be unacceptable, doctors and patients may select mastectomy. But there can be a large cancer in a woman with a very large breast that's amenable to lumpectomy.

In addition, patients who live far from a radiation center, who have economic issues with coming for treatment every day, may elect to have a mastectomy simply so they're not having to come to the hospital for six weeks for daily treatments. So there are many factors that can influence this decision and not all of them are medical.

Do women have a lot of anxiety over local recurrence following a lumpectomy?
I think there is a lot of anxiety over recurrence in the breast, although we try to counsel people that that's not the major issue. In the end, what matters is whether the cancer spreads throughout the body or not. In the rare case of a local recurrence in the preserved breast, one can treat that with mastectomy.

Let's talk about the numbers for a minute. Say about 5 percent of the people with a lumpectomy and radiation therapy ultimately end up with an in-breast local recurrence, which is 1 in 20. That means 1 in 20 ends up with a mastectomy because of a recurrence and that 19 in 20 get to avoid mastectomy. So it really comes down to a question of what matters to the individual patient.

Still, there are many patients for whom the yearly mammogram and maybe MRI and physical exam is anxiety provoking, and some of those people will elect bilateral mastectomy instead. But for most patients, preserving the breast seems to be the priority, and they're willing to put up with this small risk of local recurrence in exchange for the benefits of keeping their breast.

What is the goal of adjuvant (post-surgical) therapy?
The goal of adjuvant therapy is to kill cancer cells that might have spread beyond the breast and lymph nodes before the surgery took place. They're out and about in the body, and we don't have a way of identifying exactly where they are so we have to treat with medicines that circulate throughout the body and kill cancer cells wherever they may be.

How much does chemotherapy reduce risk of recurrence?
Chemotherapy across the board lowers the annual rate of recurrence by about 24 percent. And this adds up, depending on the absolute risk of a patient, to roughly a one-fifth to one-quarter or slightly better reduction in risk at five years. That's the average for old chemotherapy regimens like CMF (Cytoxan, methotrexate and fluorouracil). Most modern chemotherapy regimens that work better than CMF will obviously offer even greater advantage.

How is someone's personal benefit from chemotherapy assessed?
Chemotherapy decision-making is really challenging for everybody involved. We first have to ask ourselves what's the benefit of chemotherapy generally. Then we have to apply that to the individual patient, which means calculating her individual risk of recurrence.

Once we get into that discussion, adjuvant chemotherapy is not generally recommended unless women will likely reduce their risk of recurrence with chemotherapy by at least 1 percent. Some people will set it even higher. Clinicians often set it at 2 or 3 percent, but patients surveyed after treatment typically set it at 1 percent.

When we talk about these small benefits of 1, 2 or 3 percent, we're talking about prevention of recurrence at five years. That's the threshold that most people are focused on. If you took 10 years, of course, the benefits would be larger because risk reduction with chemotherapy improves each year. So it's often a question of how young you are. A woman who's 85 years old, and facing a very high risk of breast cancer recurrence, might decide chemotherapy is not worth it because her overall probability of living much beyond 90 is limited. Her chance of dying of another disease is high. But a 30-year-old, even looking at a very small difference at five years, might decide it's easily worth it, because she can extrapolate out to 10 years and 15 years and 20 years.

How do you balance the benefits of chemotherapy with the side effects?
People are very worried about the side effects of chemotherapy. In fact, often they're more focused on the side effects than the potential benefits. The side effects traditionally included hair loss, nausea and vomiting, risk of infection, fatigue.

But the last 10 years have been exciting, not only because of better therapies, but also because of better ways of treating the side effects and supporting people through their therapy. We have much better anti-nausea medicines, for example, so vomiting has now become relatively rare. One of the things we still struggle with is fatigue. We don't have a direct way to deal with the fatigue that's common with chemotherapy. And we don't have a way to deal with the hair loss that occurs.

Then there are the life-threatening side effects that are long term, such as leukemia or heart failure. They are, thankfully, very rare. They are in many cases associated with specific drugs, and we may reserve the use of those drugs for very high-risk situations where the benefits of therapy dramatically outweigh those risks.

In the last few years, we've developed chemotherapy regimens that have fewer of these side effects and are, in many cases, shorter than traditional therapy, so the duration of these side effects can be shortened, as well.

What are the hormone therapy choices?
If a breast cancer has estrogen and progesterone receptors, which means that these hormones may fuel the growth of these cancers, the treatment options are broader. Tamoxifen, of course, is the gold standard, and this drug is given to women with hormone-responsive breast cancer. It attaches to the estrogen receptor and deprives the cancer of a needed hormone. It thereby starves the cancer cell of a needed nutrient, if you will. The aromatase inhibitors do this by shutting off the residual production of estrogen at sites outside the ovaries. But they're in a sense doing the same thing as tamoxifen.

How much risk reduction is associated with hormone therapy?
Tamoxifen given for five years to women with hormone-responsive breast cancer lowers the risk of recurrence by 40 percent per year, and the overall benefit will be close to a one-third reduction in risk. There is no consistent evidence of benefit with tamoxifen beyond five years. In addition, the risk of developing uterine cancer increases with more exposure, so after five years you get no additional benefit, but you keep adding risk.

The last few years have given us new options in adjuvant hormone therapy for postmenopausal women. It now looks increasingly like substituting or switching to or following that tamoxifen with an aromatase inhibitor further improves outcome.

We have three large randomized trials as of May of 2004, all of which show the same thing: The risk of a recurrence of breast cancer in the breast or a recurrence of breast cancer outside the breast is more greatly reduced when a woman is on a aromatase inhibitor compared to tamoxifen.

How could a postmenopausal woman decide between hormone therapies?
Choosing between tamoxifen, the standard therapy, and one of the newer aromatase inhibitors still remains somewhat tricky. On the one hand, there is no question that the likelihood of events is reduced when you take one of these new drugs over the short run. The big question is what do they do to bone density because aromatase inhibitors significantly lower estrogen, and that decreases bone density.

On the other hand, tamoxifen has some fairly well-described short-term side effects like an increased risk of uterine cancer and aside from that, an increased risk of vaginal complaints like bleeding or discharge. And these things seem to be less of an issue with the aromatase inhibitors. There is also an increased risk of blood clots with tamoxifen, and maybe stroke and even heart attacks. So we have to consider all these issues carefully. Obviously a woman, for example, who has had her uterus removed, has taken away one of the concerns with tamoxifen.

We simply don't know what the very best strategy is, so I think we have to say that doctors and their patients will have to individualize treatment.