Medication Halts
Cancer Recurrence In Many Women
Letrozole Follows
Tamoxifen Therapy
Breast
cancer patients taking the medication letrozole, following five
years of tamoxifen therapy, had about half the rate of cancer
recurrences as women taking a placebo (inactive substance).
Letrozole
is one of a new class of medications called aromatase inhibitors.
While
tamoxifen works by occupying the estrogen receptor and preventing
the hormone from binding, letrozole goes further and actually
blocks production of the hormone.
Because
the results were so promising, investigators halted a major
international trial of the new medication early.
"The
results are absolute, confirmed, and credible," study investigator
Dr. Paul Goss said at news conference. "An independent monitoring
committee recommended that we stop the study by preset statistical
boundaries, which we exceeded by at least 10-fold."
Dr.
Goss is also the lead author of a special, early-release article
detailing the findings in the New England Journal of
Medicine.
Tamoxifen
First, Letrozole Follows
Tamoxifen
has been a great boon to women who have estrogen-receptor-positive
breast cancer, meaning cancer that is fueled by the hormone
estrogen. The medication reduces the risk of recurrence
by 47 percent and the risk of death by 26 percent for five years
after surgery.
Unfortunately,
tamoxifen stops working after that time and may even reverse
its action, promoting the growth of cancer cells.
"What
is unrecognized is that over 50 percent of recurrences unfortunately
occur beyond five years after diagnosis," Dr. Goss said. "Because
it continues to relapse almost indefinitely, there is no limit
to the disease."
The
letrozole trial started enrolling participants in 1998. At this
point in time the study has enrolled 5,187 women in Canada,
the US, and Europe who were postmenopausal, had hormone-receptor-positive
tumors, and had been on tamoxifen for about five years (the
range was four-and-a-half to six years).
All
of the women had to be within three months of stopping tamoxifen
and all were disease-free when enrolled. The trial was coordinated
by the National Cancer Institute of Canada.
The
participants were randomly assigned to receive either 2.5 milligrams
of letrozole or a placebo daily for five years. Letrozole reduced
the risk of recurrence by 43 percent.
The
median follow-up was only 2.4 years when the trial was stopped.
"This
is one more example of the ability of to interrupt the progression
of a cancer using a drug that blocks a crucial metabolic pathway
in the tumor cell," says Dr. Andrew von Eschenbach, director
of the National Cancer Institute (NCI).
Tamoxifen Compared
with Letrozole
Side
effects in the placebo and letrozole groups were roughly equivalent,
except the rate of bone thinning was slightly higher with letrozole.
Tamoxifen,
by contrast, provides protection against bone fractures, although
it may contribute to endometrial cancer and blood clots. Women
considering taking letrozole need to talk to their physicians
about ways to mitigate the risk of osteoporosis.
Letrozole
has already been approved by the US Food and Drug Administration
(FDA) for some forms of breast cancer.
"I
would think that there would be sufficient basis to use this
as a pivotal trial to justify an amendment to their indication,"
said Dr. James Ingle of the Mayo Clinic and another investigator
on the trial.
Ultimately,
getting another [FDA] approval would be up to the medication's
maker, Novartis, which provided letrozole for the new study.
There
are some drawbacks to stopping a trial early, namely the number
of unanswered questions about side effects and the continued
effectiveness of the drug over time.
Current
and future studies of aromatase inhibitors will look at a range
of issues, including whether letrozole could be used instead
of tamoxifen, whether it could be used if women had been off
for tamoxifen for longer than three months, whether it works
in an equivalent fashion, and whether the success of letrozole
will continue over longer time frames.
"This
large trial only began in 1998 and we already have important
results that will change clinical practice," says Dr. Jeffrey
Abrams, coordinator of the NCI Cooperative Group
breast cancer treatment trials. "This is a tribute to the patients
and physicians who participated since their efforts will now
have a positive impact on so many lives."
Always
consult your physician for more information.
What
Are Aromatase Inhibitors?
According to the American
Cancer Society (ACS), aromatase inhibitors include
three medications that stop estrogen production, and these
currently are approved for use in treating breast cancer.
These medications
are called letrozole (Femara®), anastrozole (Arimidex®),
and exemestane (Aromasin®). They work by blocking an enzyme
responsible for producing small amounts of estrogen in postmenopausal
women.
These breast cancer
treatments cannot stop the ovaries of premenopausal women from
producing estrogen. For this reason they can only be used in
postmenopausal women.
The ACS
states that "many physicians prefer these medications to
tamoxifen as the first hormonal treatment for postmenopausal
women whose breast cancer has come back, if the cancer is hormone
receptor positive."
Aromatase inhibitors
have been compared with tamoxifen as adjuvant hormone therapy.
ACS explains that these medications have fewer
side effects than tamoxifen because they do not cause endometrial
cancer and very rarely cause blood clots.
They can, however,
cause osteoporosis and bone fractures because they remove all
estrogens from a postmenopausal woman.
Always consult your
physician for more information.
Online
Resources
(Our Organization
is not responsible for the content of Internet sites.)
American
Cancer Society
American
Society for Clinical Oncology
Centers
for Disease Control and Prevention (CDC)
National
Cancer Institute (NCI)
National
Institutes of Health (NIH)
National
Women's Health Information Center
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November 2003
Medication Halts
Breast Cancer Recurrence In Many Women
Tamoxifen
First, Letrozole Follows
Tamoxifen
Compared with Letrozole
What
Are Aromatase Inhibitors?
Treatment
Shorter, and Fewer Side Effects
Experts
Want More Study
Online
Resources
New
Study Looks at Limited-Field Radiation after Breast Cancer Surgery
A
woman with breast cancer who undergoes limited-field radiation
after surgery has similar survival and recurrence rates as a
woman who receives whole-breast radiation, researchers report
in the Journal of the National Cancer Institute.
"For
about 10 years, we have been looking at whether limited-field
radiation, which limits radiation to the tumor site and a small
surrounding area, is as effective as treating the whole breast
in patients with early-stage breast cancer," says Dr. Frank
A. Vicini, the chief of oncology at William Beaumont Hospital
in Royal Oak, Mich.
The
findings from the current study represent five-year results
of 199 women with early-stage breast cancer who were treated
with limited-field radiation after breast-conserving surgery.
Dr.
Vicini and his colleagues compared these women with 199 similar
women who were treated with whole-breast radiation therapy.
Treatment
Shorter, and Fewer Side Effects
The
researchers found that for women in both groups there was no
difference in the median time to the recurrence of cancer or
to recurrence of cancer at the same location.
Dr.
Vicini's team also found that there was no difference between
the women in the spread of cancer beyond the breast or in survival.
The
advantages of limited-field radiation therapy include a shorter
treatment cycle - five days compared with six weeks for whole-breast
radiation - and fewer side effects, Dr. Vicini says.
"These
results look good," Dr. Vicini says. "But are they good enough
to say that this is the standard of care?"
While
randomized trials that compare both treatments are going on
in Europe, Dr. Vicini would like to see a randomized study done
in the US.
The
advantage of such a study is that it would identify the kind
of patients most likely to benefit from limited-field radiation
therapy.
The
disadvantage is that it will take many years to complete. In
the meantime, physicians are offering limited-field radiation
therapy now, Dr. Vicini says.
He
cautions that limited-field radiation therapy, like many other
therapies, may become the standard of care without proper study.
Dr.
Vicini says limited-field radiation is appropriate therapy in
a select group of patients, namely those women with an early-stage
cancer that has not spread to the lymph nodes and has a clearly
defined tumor.
The
treatment will be beneficial to most women with early-stage
cancer who undergo breast-conserving surgery, Dr. Vicini says.
Dr.
Vicini advises women currently considering limited-field radiation
to discuss the treatment with their physician.
Experts
Want More Study
In
an editorial in the journal accompanying the study, Dr. Paul
Wallner, the chief of radiation oncology at the National
Cancer Institute (NCI), and his colleagues recommend
randomized trials before limited-field radiation therapy is
widely used.
"But
we recognize that physicians will use this therapy now and trials
will take a long time," Dr. Wallner says.
"We
are raising a note of caution," Dr. Wallner says. "One of our
concerns is that people will think this therapy is applicable
to a different group of patients than it was tested on."
Dr.
Wallner says patients may elect to have the therapy, but they
need to have all the data, so they should ask their physicians.
"Physicians
should be sure to tell their patients that the results are based
on small studies among highly selected patients," he adds.
Always consult your
physician for more information.
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