The
information in this column is intended for informational
purposes only, and does not constitute medical advice or
recommendations by the author. Please consult with your
physician before making any lifestyle or medication changes, or if you
have any other concerns regarding your health.
BREAST
CANCER RECURRENCE
& HORMONE REPLACEMENT THERAPY (HRT)
Regular readers of this
column are already well informed about the known risks associated with
taking
hormone replacement therapy (HRT) to relieve the symptoms of menopause. With the results of the
landmark Women’s
Health Initiative Study (WHIS), and similar studies, clearly
implicating
combination HRT with an increased risk of breast cancer, heart disease,
stroke,
dementia, and other serious illnesses, physicians and their patients
are,
increasingly, taking a more conservative approach to dealing with the
unpleasant
symptoms that often accompany the onset of menopause.
Among
women who have
previously been diagnosed with breast cancer, the risk of developing a
recurrence of their cancer, and new breast cancers as well, is known to
be
higher than for women of otherwise average breast cancer risk, and with
no
prior history of breast cancer.
Up
until now, there has not
been a great deal of research data looking specifically at the added
risk, if
any, of taking HRT after a prior diagnosis of breast cancer, although
most
experts believe that HRT is almost certainly a risk factor for breast
cancer
recurrence (i.e., in addition to the development of new cancers in the
breast). Now, a new
study, from multiple
university medical centers in Europe,
looks at
the impact of HRT in breast cancer recurrence among women with a prior
history
of this form of cancer. This
new
research study, just published in the Journal
of the National Cancer Institute, is part of a prospective
study, called
the HABIT Study, which consisted of 442 Scandinavian breast cancer
survivors. A total
of 221 women were randomized to
receive HRT, while the remaining 221 women were randomized to no HRT at
all.
The
results of this study
were quite striking. Among
the 221 women
taking HRT, just over 22% of these women were estimated to develop
recurrent
breast cancer after an average of 5 years of follow-up. Among the 221 women who did
not take HRT, only
8% went on to develop a recurrence of their previous breast cancer at 5
years. This
represents a nearly two-and-a-half fold
increase in the risk of breast cancer associated with the use of HRT
and, with
respect to the natural history of breast cancer recurrence, within a
rather
short period of time as well. In
fact,
because the risk of recurrent breast cancer appeared to be so high in
the group
of women taking HRT, this research study was prematurely halted in 2004
(just
as the WHIS was prematurely terminated in 2002) , and the women taking
HRT were
warned about the apparent increased risk of breast cancer recurrence
associated
with taking HRT.
As
multiple other previous studies have shown, and as I and other breast
cancer
experts have warned for years, the use of HRT (and combination HRT in
particular) appears to have significantly contributed to the
decades-old
gradual rise in the annual number of breast cancer cases diagnosed in
the
United States since the mid-1960s, when HRT became especially popular
in the
U.S. and in other western countries around the world.
The striking and unprecedented recent decline
in the annual incidence of breast cancer in the United States,
and in other western
countries, following the publication of the preliminary results of the
WHIS in
2002, has paralleled the declining number of prescriptions written for
HRT
since this landmark study was published in the Journal
of the American Medical Association.
Ironically, I wrote a book on this very topic
(including the shameful history of misrepresentation, and the covert
financial
and marketing support provided to pro-HRT physicians, by the dominant
pharmaceutical manufacturer of HRT drugs in the mid-1960s, and
thereafter) in
2004. However, the
majority of senior publishing
house editors who reviewed the manuscript (most of whom were women, it
must be
said) dismissively accused me of being “biased” against HRT; and
several opined
that, as a man, I simply could not understand the ravages of menopause
and,
hence, the quality-of-life improvement brought about by HRT medications
(notwithstanding decades of clinical research showing that only 2-5% of
women
experience profoundly disabling symptoms associated with menopause, and
in the
majority of all women passing through menopause, these symptoms
significantly
and spontaneously abate within 3-5 years).
The
results of this new study are completely consistent with what we now
know about
the molecular biology of estrogen and progesterone (the primary female
sex
hormones), and their stimulatory effects on the proliferation of breast
cancer
cells (the overwhelming majority of breast cancers, especially in women
aged 50
and older, have chemical receptors for these sex hormones, which
stimulate
these cancer cells to grow and divide).
My advice to all women, and especially
to women with a prior history of breast cancer, is to avoid HRT drugs,
period. This has
been my consistent recommendation
for the past 20 years, based upon clinical research and observations
dating
back to the 1930s. With
the enormous
amount of confirmatory data that has been subsequently published since
2004, I don’t
appear to be the one with significant biases in this area….
CAROTID
ARTERY DISEASE: SURGERY
VS. STENTS?
A relatively common
manifestation of peripheral arterial atherosclerotic disease
(“hardening of the
arteries”) is carotid artery stenosis.
The
carotid arteries supply most of the blood to the brain, and when they
become
clogged with atherosclerotic plaque and blood clots, bits of these
materials
can break off (or embolize) and lodge in the smaller arteries that feed
the
brain, causing temporary or permanent damage to the brain. These embolic
complications of carotid artery
disease are referred to as, respectively, transient ischemic attacks
and strokes
(the same vascular disease process occurs in the coronary arteries, and
leads
to heart attacks, or myocardial infarctions).
Nearly
150,000 operations for
carotid artery stenosis are currently performed each year in the United States,
as there is abundant research evidence supporting surgical over medical
treatment
in patients with significant narrowing of their carotid arteries (the
primary
risk of untreated carotid artery stenosis is stroke).
In this operation, the clogged-up, narrowed
artery is surgically opened, and the surgeon then carefully peels the
thickened, diseased lining away from the wall of the artery, leaving a
clean
surface behind. The
artery is then sewn
shut (often, a synthetic patch is also used to reconstruct the artery,
to
prevent narrowing of the artery).
This
operation, referred to as carotid endarterectomy, is not without risk
(as with
any operation), however, and is associated with a 0.5-2% risk of
postoperative
stroke, as well as a small risk of bleeding, infection and death.
A
relatively recent
innovation in the management of arterial atherosclerotic disease has
involved
the use of shunts, most of which can be placed through small,
superficial
incisions in the groin or arm, much as cardiologists and interventional
radiologists
have been doing for decades in order to perform x-rays studies of the
arterial
system (“angiography”), and more recently, to treat diseased coronary
arteries
with balloon catheters and stents.
This
minimally-invasive approach to atherosclerotic vascular disease has
revolutionized the management of not only coronary artery disease, but
also for
aneurysms (abnormal dilation of atherosclerotic arteries) of the aorta
(the
largest artery in the body), and the large branch arteries that arise
from the
aorta to supply the lower extremities (the iliac and femoral arteries). However, given the
potentially catastrophic
complications (including death) associated with strokes, the use of
balloon
catheters and stents to treat narrowed areas of the carotid arteries
has not
advanced as rapidly as it has for other diseased arteries in the body.
A
new study from Harvard
University, and several other collaborating U.S. medical centers, and
just
published in this week’s New England
Journal of Medicine, provides important clinical data to
suggest that
minimally invasive carotid artery stenting may finally have become at
least the
equal of carotid endarterectomy, at least in highly selected patients. In this prospective
randomized clinical
study, a total of 334 patients with narrowed carotid arteries were
randomized
to either standard surgical treatment (i.e., carotid endarterectomy)
vs.
carotid artery stenting. The
average
follow-up of these patients was 3 years.
Altogether,
almost 80% of the
patients participating in this clinical trial were available for
follow-up
evaluation after 3 years. The
bottom
line: patients in both treatment groups experienced a statistically
equivalent
incidence of stroke, myocardial infarction and death (the average
incidence of any
of these three complications in both groups of patients, at 3 years,
was
27%).
This
study will likely be
considered a landmark research trial regarding the optimal management
of severe
carotid artery stenosis, especially in patients who are considered to
be at
very high risk of complications following traditional surgical
intervention. The
use, in this study, of
a special device designed to catch errant bits of clot and plaque that
might be
dislodged during placement of the stent very likely helped to achieve
the
excellent results reported in this high-quality research trial, and
sets this
study apart from some earlier studies that did not use such
“anti-embolization”
devices (and which often reported prohibitive stroke rates associated
with
carotid artery ballooning and stenting).
As
a reminder to my readers,
the risk factors most commonly associated with carotid artery
atherosclerosis
(and, indeed, with atherosclerosis throughout the body) include
smoking,
elevated cholesterol and fat levels in the blood, obesity, a sedentary
lifestyle and high blood pressure.
Given
that an ounce of prevention is worth far more than a pound of cure when
it
comes to your health, if you currently have any of these risk factors,
then
please see your physician soon, and modify your lifestyle to eliminate
(or
control) these risk factors.
STATIN
DRUGS & CANCER
PREVENTION
There
continues to be a great
deal of debate regarding the class of cholesterol-lowering drugs
referred to as
statins, and their effects (if any) on lowering the risk of developing
certain
cancers. In
addition to their potent
ability to reduce the levels of so-called “bad cholesterol” (LDL) in
the blood,
and to increase the levels of “good cholesterol” (HDL), most statins
appear to
have at least mild anti-inflammatory effects as well.
(Chronic inflammation in the body has been
linked both to the development of atherosclerotic narrowing of the
arteries in
our bodies as well as to the development of many cancers.) Multiple prior laboratory
and clinical
research trials have generated conflicting data regarding the effects
of statin
drugs on cancer risk, with some studies showing a reduction in the risk
of at
least certain types of cancer with prolonged statin use, and other
studies
showing no apparent cancer-prevention benefit at all.
A
newly published study, in The American
Journal of Medicine,
provides results that suggest, as other recent studies have, that there
may
actually be a small, but significant, cancer-prevention effect
associated with
at least some of the statin drugs.
This
study, from Quebec,
Canada,
was based upon a large public
health clinical data registry, and looked at patients aged 45 years and
greater, between 1998 and 2004, who had survived a heart attack, and
had been
prescribed a statin drug as a results of their heart attack. Four
statin drugs
within the so-called “lipophilic class” (atorvastatin, simvastatin,
lovastatin
and fluvastatin) were specifically included in this retrospective
research
study. More than
30,000 patient
histories were evaluated in this large public health study, including
more than
18,000 patients who were never prescribed a statin drug, 6,015 patients
who
received high-dose statin medications, and 5,323 patients who were
prescribed
low-dose statin medications.
After
an average of 7 years
of follow-up, this study determined that the high-dose statin users,
when
compared to patients not taking any statin drugs, experienced a 25%
reduction
in the likelihood of admission to a hospital with a new diagnosis of
cancer. The
low-dose statin users also
appeared to experience a reduction in hospital admissions related to
the
diagnosis of cancer, with a more modest 11% reduction in the incidence
of
admissions for cancer. Unlike
similar recent
clinical studies that have shown that only prolonged statin use may be
associated with a reduction in the risk of developing cancer, this
particular
study found that even relatively short durations of statin usage
appeared to be
associated with a reduced risk of being admitted to a hospital with a
new
diagnosis of cancer, especially among patients receiving higher doses
of these
medications.
This
study offers some
further encouragement to those who believe that at least some statin
drugs may
be associated with the incidental benefit of reducing the risk of
cancer. However, I
think that the jury is still out
on this one, for now anyway. As
with
most retrospective studies based upon public health databases, there
are many
potential sources of bias in retrospective epidemiological studies such
as this
one. Unlike
randomized, prospective
controlled studies, which seek to control as many potentially
confounding
variables as possible up front, retrospective studies are far more
prone to
bias, which can lead to erroneous conclusions.
At
this time, I would not
recommend that anyone take a statin drug primarily to reduce their risk
of
cancer. However, if
you are already
taking a lipophilic statin for elevated cholesterol levels, then there
is at
least the possibility that you may be receiving an additional health
benefit
from your statin drug. Obviously,
a
prospective, randomized, placebo-controlled study of statins would have
to be
done to definitively answer the question regarding statins and cancer
risk. Until such a
study is performed, we cannot be
completely certain that statins really do reduce the risk of cancer.
Disclaimer:
As always, my advice to readers is to seek the advice of your physician
before making any significant changes in
medications, diet, or level of physical activity.
