Making Decisions in Early-stage 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
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
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
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
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.