As I wrote in Daily Health News,
October 25, 2004, tamoxifen (Nolvadex) has been a
very effective part of postsurgery breast cancer
treatment. Its benefits were confirmed in the 1998
Breast Cancer Prevention Trial, with results
showing 49% fewer diagnoses of invasive cancer
in the group of women taking tamoxifen. Given
this success rate, researchers in 1998 began to
look at its use for women considered to be at high
risk for breast cancer -- those with a family history,
problematic breast biopsies and other factors. But
a recent study published in Neurology clouded the
picture for women who were considering taking
tamoxifen prophylactically. It showed that tamoxifen
increased risk for strokes -- in particular, ischemic
strokes (those caused by clots).
The study, from Duke University
Medical Center, analyzed nine prior studies and
found that seven strokes had occured per 1,000
patients taking the drug. Study coauthor Cheryl D.
Bushnell, MD, called the findings statistically
significant.
The reason for the connection with
stroke is that one side effect of tamoxifen is increased
clotting. According to Maura N. Dickler, MD, a specialist
in breast cancer treatment at Memorial Sloan-Kettering Cancer
Center in New York City, doctors were aware of the risk long
before this study. The Duke University study is simply confirming
the clotting risk. Dr. Dickler told me that earlier studies showed
increased risk for clots in the legs (deep vein thrombosis) with
the potential consequence of pulmonary embolism (a clot breaking
loose and going to the lungs, often with fatal consequences).
Earlier studies also showed increased risk for endometrial cancer,
a rare form of uterine cancer and strokes. However, those earlier
studies did not show ischemic strokes to be as great a risk as the
most recent study does.
However, she says it's important to remember
that this study is a different type than previous ones that
reach different risk/benefit conclusions. The new study is a
meta-analysis, which is to say it analyzes earlier data and
draws a conclusion, a process that typically reflects bias
and other selection problems that can affect outcome.
Clinical trials, on the other hand, test prospectively by
having one group take a drug over time while a second group
takes a placebo -- with neither group knowing which is which.
At the end, study authors collect data and evaluate the
performance of the drug in question. The 1998 prevention
study was a clinical trial that took place over a five-year
period with more than 13,000 women participating. Although
this study did show an increased risk for the tamoxifen group,
it was not as high as in the Duke study.
DECISION TREE
Most importantly, all studies ultimately
lead to the same implications for women seeking to take
tamoxifen for prophylactic reasons, says Dr. Dickler. The
therapy requires taking the drug for five years -- the women
in this group will have to decide if the benefits strongly
outweigh the risks. Women must not take the drug if they have
risk factors for clotting or strokes, heart disease, diabetes
or have had a prior stroke -- these are greater medical risks
than breast cancer. But even for women without such risk factors,
there are other considerations. Tamoxifen has quality-of-life
side effects that include headaches, nausea, loss of libido,
painful intercourse and vaginal discharge. A woman must ask
herself if she is willing to endure this kind of discomfort
for the sake of possibly preventing cancer in the future.
Women who do opt for tamoxifen should
see their oncologist every six months, says Dr. Dickler,
at which time the doctor should review all side effects
with her and arrange for a liver function test. In particular,
be alert to leg pain -- it may be a manifestation of disrupted
calcium metabolism and perhaps a clot in your legs. Because
the danger of clotting is particularly high after surgery,
it's critical to suspend use of tamoxifen for at least two
weeks prior to any surgical procedure.
In the not-too-distant future, it is
possible that the risk/benefit of tamoxifen therapy will
become a moot point for many women -- including even
some who are being treated to prevent a recurrence of
breast cancer. Dr. Dickler says that the medical world
is increasingly moving toward a type of drug called aromatase
inhibitors for women with early-stage breast cancer to prevent
recurrence after surgery. These drugs do not appear to increase
the risk for stroke, and if testing bears out their safety,
it is possible that they might be the new drugs of choice
for high-risk women as well. Aromatase inhibitors block the
creation of the estrogen metabolites thought to be the true
inducers of cancer in some, whereas tamoxifen blocks estradiol
(estrogen).
According to Daily Health News contributing
editor Andrew L. Rubman, ND, natural aromatase inhibitors
(in particular, di-indole methionine, or DIM, derived from
cruciferous vegetables) are currently available in health-food
stores and might be worth considering if a woman is at
increased risk for breast cancer.
Sources.
Maura N. Dickler, MD, Memorial
Sloan-Kettering Cancer Center, New York City.
