Shift in Treating Breast Cancer Is Under Debate
By GINA KOLATA
Published: May 12, 2006
Doctors who treat women with breast cancer are glimpsing the possibility of
a vastly different future. After years of adding more and more to the
regimen — more drugs, shorter intervals between chemotherapy sessions,
higher doses, longer periods of a harsh therapy — they are now wondering
whether many women could skip chemotherapy altogether.
If the new ideas, supported by a recent report, are validated by large
studies like two that are just beginning, the treatment of breast cancer
will markedly change.
Today, national guidelines call for giving chemotherapy to almost all of the
nearly 200,000 women a year whose illness is diagnosed as breast cancer. In
the new approach, chemotherapy would be mostly for the 30 percent of women
whose breast cancer is not fueled by estrogen.
So far the data are tantalizing, but the evidence is very new and still in
flux. And even if some women with hormone-dependent tumors can skip
chemotherapy, no one can yet say for sure which women they might be. Some
doctors have already cut back on chemotherapy, but the advice a woman gets
often depends on which doctor she sees.
It could be a decade before the new studies — one American, one European —
provide any answers.
"It's a slightly uncomfortable time," said Dr. Eric P. Winer, who directs
the breast oncology center at the Dana-Farber Cancer Institute in Boston.
"Some of us feel like we have enough information to start backing off on
chemotherapy in selected patients, and others are less convinced."
Among the less convinced is Dr. John H. Glick, director of the Abramson
Cancer Center of the University of Pennsylvania. Dr. Glick tells his
patients about the new data but does not suggest they skip chemotherapy.
After all, he notes, the national guidelines were based on results from
large randomized clinical trials. And the recent data indicating that some
women can skip chemotherapy are based on an after-the-fact analysis of
selected clinical trials.
"We're in an era where evidence-based medicine should govern practice," Dr.
For women with breast cancer, of course, the uncertainty is excruciating.
Faced with a disease that already causes indecision and anxiety, they are
now confronted with incomplete data, differing opinions from different
doctors and a choice that can seem almost impossible: Should they give up a
taxing treatment when all the answers are not in and they have what may be a
"If the medical profession is not even close to being of one mind, how is
the woman to know?" said Donald A. Berry, a statistician at the University
of Texas M. D. Anderson Cancer Center, the lead author of a recent paper
questioning chemotherapy's benefits in many women.
Barbara Brenner, who has had breast cancer and is executive director of the
advocacy group Breast Cancer Action, said, "There's a real problem," and
added, "We finally tell people at the end of the day: 'You're going to get a
lot of information. Trust your gut. Nobody has the answers.' "
"I'm really glad I was diagnosed 13 years ago," Ms. Brenner said, "when
there were fewer choices."
Doctors worry, too. It took two years before the National Cancer Institute
and its researchers could even agree on a design for the large new American
study that will test the idea that many women might safely forgo
The study, which starts enrolling patients at the end of this month, will
involve women whose cancers are fueled by estrogen and have not spread
beyond the breast. They will be randomly assigned to have the standard
treatment — chemotherapy followed by a drug like tamoxifen that starves
tumors of estrogen — or to skip chemotherapy and have treatment only with a
drug like tamoxifen.
Unlike the American study, the one now planned in Europe will also include
women whose cancer has spread beyond their breasts into nearby lymph nodes.
The American study may eventually add such women, said Sheila E. Taube, who
directs the cancer diagnosis program at the National Cancer Institute.
Dr. Taube said the debate reminded her of one a few decades ago, when the
question was whether all women with cancer needed mastectomies or whether
many could have a lumpectomy instead. "To me, the situations are analogous,"
The chemotherapy question starts with American and European guidelines that
say almost every woman with breast cancer that has gone beyond its earliest
stages, when it is confined to the milk duct, should have the treatment. And
for good reason, many cancer researchers say: a series of large studies has
shown that chemotherapy saves lives and that newer and more aggressive
regimens are improvements over older ones.
That has led doctors to feel most at ease giving very aggressive treatments
to almost everyone.
"Part of it is that this area of medicine we're practicing in is kind of a
high wire act," said Dr. Michael Lee, an oncologist in private practice in
Norfolk, Va. "It is more comfortable to adopt things that are aggressive."
But most of those studies were done at a time when doctors did not
distinguish between the 70 percent of women with breast cancers fueled by
estrogen and the 30 percent whose cancers were not.
Now Dr. Berry, the M. D. Anderson statistician, and a group of leading
cancer researchers have found that the chemotherapy benefits in those
clinical trials were concentrated almost exclusively in women whose cancers
were impervious to estrogen. For the others, with estrogen-sensitive tumors,
the lifesaving benefit came from hormonal therapy. The results of the
analysis, published recently in The Journal of the American Medical
Association, were the same even if the cancer had spread to the lymph nodes.
The drawback of that study, Dr. Glick notes, is that it was not a large
prospective randomized clinical trial, the gold standard in medicine.
There is also another issue. What if some women with estrogen-fed tumors do
benefit from chemotherapy? How can they be identified?
One possibility is new genetic tests, which are part of the two studies that
are about to begin. The cancer institute is using the Oncotype DX test,
which includes genes associated with response to chemotherapy, among them
genes involved with a cell's response to estrogen.
The study is ethical, said Dr. Larry Norton of Memorial Sloan-Kettering
Cancer Center in New York, because the only women whose treatment will be
decided at random are those in a kind of gray area, not women for whom
chemotherapy would be a clear benefit or clearly unnecessary.
"I think the clinical trial is really a superb one," Dr. Norton said. "I
would like to see it go so we have definitive data."
In the meantime, some physicians, like Dr. Winer, are taking their own best
shot at figuring out who really benefits from chemotherapy. He asks how
sensitive the tumor is to estrogen, how aggressive a pathologist believes it
is, how big it is, how much has spread to the lymph nodes and whether its
surface has a type of protein, HER2, that is associated with a better
response to chemotherapy. After talking through the decision with his
patients, he says, he is comfortable omitting chemotherapy in some who would
have had it not long ago.
Others, like Dr. Francisco J. Esteva of M. D. Anderson, use a computer
program to calculate a woman's risks of recurrence and give the option of no
chemotherapy only to women with low-risk cancers confined to their breasts.
Still others, like Dr. Glick, are starting to tell women with estrogen-fed
cancers that although they still need chemotherapy, they may not need the
most intense treatment.
And while some, including Dr. Winer, predict that the use of chemotherapy
will almost certainly decline in the years ahead, for now most doctors are
sticking with the current guidelines, waiting for expert advice from
national panels on what to do.
"I don't know that many doctors who are comfortable giving women an option
about chemotherapy," said Fran Visco, president of the National Breast
Cancer Coalition, an advocacy group. "A lot of physicians talk about the
data, but then they say, 'But, to be on the safe side. ...' "
Still, doctors say it is not simply that they are urging more and more
chemotherapy on patients. In many cases, it is patients who want the most
"A cancer diagnosis is earth-shattering," said Dr. Lee, who has had cancer
himself. "You stay up at night. You wonder. Even when you're doing well, you
don't know whether to trust it."
And so, he said, "a lot of people will take a treatment even if there is a
very low statistical chance that they will benefit."
That was what happened a few months ago, when Dr. Esteva told Janice Baty of
Sulphur, La., a 40-year-old mother of two, that she might not need
chemotherapy. After a long discussion with Ms. Baty and her husband, Dr.
Esteva left them so they could decide what to do.
"My husband said, 'Look, we have two little kids,' " Ms. Baty recalled. "I
called the doctor back in and said, 'We're doing the chemo.' "
Women who say they want the most aggressive treatment may not fully realize
what they are asking for, said Mary Peelen, 45, of San Francisco. Ms. Peelen
learned in January 2005 that she had cancer. It was small, was fed by
estrogen and had spread to just two of her lymph nodes. Her oncologist was
adamant: chemotherapy was her only option.
"I felt frightened and very coerced," she said. She had an aggressive
regimen, suffered terribly and was left with painful nerve damage in her
arms and hands that prevents movements like opening jars or using scissors
and frequently makes her drop things.
Ms. Peelen feels that in a way, she just missed the revolution, perhaps one
of the last women with her type of cancer who will have to suffer so much.
For now, the answers as to who should have chemotherapy are far from clear.
"I think practice should change, but it's very dicey," said Dr. Berry, of M.
His colleague Dr. Esteva says it is one thing for a statistician like Dr.
Berry to look at retrospective data, and another for a physician, like
himself, to sit down with a patient who has to make what may be a
"It's not a perfect science," Dr. Esteva said. "A statistically small
reduction in risk may be very important to some women, while for others
chemotherapy is not worth it."
And so, Dr. Esteva said, he is left asking many women with early-stage
breast cancer to decide what can seem like the undecidable: whether they
want "to take something potentially toxic when you have a 90 percent chance
of being cured without it."
"My experience ," he said, "is that more want to get chemo than not."