Jewish World Review Nov. 10, 2003 / 15 Mar-Cheshvan, 5764
By Robert A. Wascher, M.D., F.A.C.S.
http://www.NewsAndOpinion.com |
For women who have breast cancer, Tamoxifen is an effective adjuvant
treatment option when the breast cancer cells are sensitive to the female
hormone estrogen, particularly in women who have already passed through
menopause. Tamoxifen acts by blocking the receptors that estrogen latches
onto, thus preventing a woman's own estrogen from stimulating the growth of
additional tumor cells. Based upon previous studies, taking Tamoxifen for
more than five years appears to confer no more benefit than a five-year
course, although the risks associated with the drug continue to increase.
These risks include an enhanced risk of blood clots in the veins and lungs,
uterine cancer, and cataracts. Although a five-year course of Tamoxifen
significantly reduces the risk of recurrent or new estrogen-responsive
breast tumors, many women (and their physicians) have been searching for
additional therapies that might benefit breast cancer patients after they've
completed Tamoxifen therapy.
A second class of drugs, know as "aromatase inhibitors," have recently been
developed. After menopause (or after total hysterectomy, during which a
woman's ovaries are also removed), a woman's ovaries are no longer the
primary source of estrogen and other female sex hormones. However, the
adrenal glands, as well as fatty tissue throughout the body, continue to
produce estrogen throughout a woman's life. The aromatase inhibitors block
a key enzyme, aromatase which converts steroid molecules into estrogen in
the adrenal glands and fatty tissues. Early clinical studies have suggested
that this new class of anti-hormonal drugs are likely to be at least as
efficacious as Tamoxifen in preventing the recurrence of estrogen-sensitive
breast tumors. However, one important caveat to the use of aromatase
inhibitors must be mentioned when comparing them to Tamoxifen and related
"selective estrogen receptor modulators." Tamoxifen and related drugs, such
as raloxifene, will block the effects of estrogen on breast cells in women
with or without functioning ovaries. However, the aromatase inhibitors only
act on the adrenal gland and fatty tissue sources of estrogen, and hence can
only be used in women who no longer have functioning ovaries.
A new study has just been published, and it evaluated the use of an
aromatase inhibitor, letrozole, in postmenopausal women who had completed
five years of Tamoxifen after being diagnosed with breast cancer. The study
enrolled 5,187 women, and was prematurely shutdown when it became evident
that the women taking the letrozole were experiencing significantly fewer
breast cancer recurrences than the women who were taking the placebo pills.
The results of this study are reported in the current issue of the New
England Journal of Medicine. The study found that, after an average of
little more than two years, the group of women taking letrozole experienced
75 recurrent or new breast cancers, while a similar sized group of women
taking the placebo pills experienced 132 such cancers. Following
statistical analysis, it was estimated that the disease-free survival rate
at four years of follow-up was 93% for the women taking letrozole, versus
87% for the women taking the placebo. This means that, despite the very
short duration of the study, the women who were taking the letrozole were
significantly more likely to be alive and free of new or recurrent breast
cancers when compared to the women who took the placebo pills. Due to the
short duration of the study, no significant differences in overall survival
rates were identified between the two groups of women in this study.
However, if the disease-free survival advantages seen in the women taking
letrozole persist over time, one would expect to see significant differences
in the overall survival rates within about 10 years, given the natural
biology of breast cancer. A slightly higher risk of osteoporosis was seen
among the women taking letrozole, which is not surprising in view of the
role of estrogen in maintaining bone density. Ironically, although
Tamoxifen blocks estrogen receptors in the breast and the uterus, it
actually stimulates estrogen receptors in the bone, and acts like an
estrogen to improve bone density.
Based upon this and other studies, it is beginning to appear that at least
certain aromatase inhibitors may have a significant role to play in the
prevention of breast cancer in women with a history of estrogen-sensitive
breast tumors, although these drugs can only be used in women without
functioning ovaries. Other studies have also shown that these drugs, when
given to women with recently diagnosed breast cancer, and in place of
Tamoxifen, may be as effective, if not more effective, than Tamoxifen in
preventing the recurrence of preexisting or new breast cancers.
EFFECTIVENESS OF HYPERTENSION TREATMENT REGIMENS
A new study in the current issue of the journal Lancet looked at the results
of 29 different randomized clinical studies, involving 162,341 patients with
high blood pressure. These diverse studies evaluated the health-sparing
effects of several classes of anti-hypertensive drugs on patients with high
blood pressure, including the angiotensin-converting enzyme ("ACE")
inhibitors, calcium channel blockers, angiotensin-receptor blockers
("ARBs"), diuretics, and beta-blockers. While there are some clinically
valid reasons why your physician might preferentially prescribe one class of
high blood pressure medications for you over others (i.e., due to one or
more specific health factors in your case), many if not most physicians
prescribe such drugs based upon their own personal knowledge and comfort
levels with certain classes of drugs.
The study in Lancet found that as long as the regimen in question targeted
patients to reach significant blood pressure reduction goals, the end
results, in terms of overall health, did not vary significantly from one
regimen to another. Specifically, there were no major or significant
differences in the incidence of heart attacks or strokes among the various
regimens, as long as similar reductions in blood pressure were obtained.
Indeed, the study found that the greater the reduction in blood pressure
achieved, the lower the risk of subsequent cardiovascular events,
irrespective of the drug or regimen used.
Once again, there may be good medical reasons why you should avoid one or
more classes of medications for your high blood pressure. However, this
study should reassure both you and your doctor that, whatever regimen you
are on, you will be receiving the maximum protection against the dangerous
effects of chronic hypertension as long as your treatment is adjusted to
provide you with the greatest possible reduction in blood pressure that can
be safely obtained by your regimen.
NEW APPROACH TO UNCLOGGING YOUR ARTERIES
Ten hospitals in the US participated in this study, and 47 patients with
known coronary artery atherosclerosis completed a series of 5 intravenous
injections of the ApoA-I Milano over a period of 5 weeks. Intravascular
ultrasound was used before and after the injections to measure the size of
atherosclerotic plaques in their coronary arteries. The study was performed
in a randomized and double-blinded manner, so that neither the patients nor
the physicians knew who was receiving the ApoA-I Milano particles and who
was receiving placebo injections.
The results were, frankly, quite dramatic after such a brief duration of
therapy. The patients who received the HDL particles experienced an average
3.17% reduction in the volume of coronary artery plaques versus a 0.14%
reduction observed in the patients who received the placebo injections.
Although this very small pilot study will require validation by additional
larger scale studies, this is the first study of its type to show that
established atheromatous plaques on the coronary arteries of patients with
heart disease can be significantly reduced following the injection of a
substance into the blood. In the best case, this approach might someday
allow patients to undergo periodic treatments in their doctors' offices to
melt away disease-causing plaques from their arteries. Let's hope that the
results of this pilot study hold-up upon further study!
JWR contributor Dr. Robert Wascher is an oncologic surgeon, professor of surgery, oncology research scientist, and author. He lives in Honolulu with his wife and two daughters.
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Post-tamoxifen treatment for breast cancer
There are literally dozens of different medications currently in use to
treat high blood pressure, and these drugs fall into various classifications
depending upon their mechanisms of action in the body. Many studies have
confirmed that the effective control of high blood pressure can prevent, or
at least reduce, damage to the body's vital organs, including the brain, the
heart and the kidneys. However, the proliferation of numerous different
treatment regimens has left both patients and their doctors confused about
the most efficacious approach to managing this insidious disease.
Based upon some very interesting research on Mediterranean families with an
exceptionally low risk of cardiovascular disease, it has recently been
discovered that bigger really is better! The so-called "good cholesterol,"
high-density lipoprotein, or HDL, is known to reduce the amount of
cholesterol-rich plaque that forms on your arteries. The HDL particles
essentially remove cholesterol deposits from the lining of your arteries,
and return the excess cholesterol to the liver for excretion. Certain
families in Mediterranean Europe who were found to have a very low incidence
of cardiovascular disease were subsequently found to have unusually large
HDL particles in their blood, which is thought to at least partially explain
their resistance to heart disease. A gene that codes for this jumbo HDL
particle was later identified and sequenced. Based upon this discovery,
scientists theorized that injecting this large HDL molecule into patients
with normal-sized HDL particles might help to reduce the size of cholesterol
plaques in their arteries.