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
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
Susan
G. Komen Breast Cancer Foundation |
November 2003
In
This Issue:
Medication Halts
Breast Cancer Recurrence In Many Women
Tamoxifen
First, Letrozole Follows
Tamoxifen
Compared with Letrozole
What
Are Aromatase Inhibitors?
New
Study Looks at Limited-Field Radiation after Breast Cancer Surgery
Treatment
Shorter, and Fewer Side Effects
Experts
Want More Study
Online
Resources
Other
Resources:
St.
John's Mercy Cancer Services
Find
a St. John's Mercy Physician
Breast
Health Information
Women's
Health Information
St.
John's Mercy Classes and Programs
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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