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.
BRCA
BREAST CANCER
MUTATIONS & MRI SCANS
An estimated 5-10%
of all breast cancer cases are associated with an inherited mutation in
either
the BRCA1 or BRCA2 genes. In
addition to
conferring a 50-85% lifetime risk of breast cancer, inherited mutations
in
either of these genes are also associated with a 20-60% lifetime risk
of
ovarian and peritoneal cancer as well.
(As
this gene mutation can be passed down to both men and women, men can
also be
affected by BRCA gene mutations, and they may experience an increased
risk of
breast and prostate cancer.) Current
breast cancer screening guidelines for women with BRCA1 and BRCA2 gene
mutations include the early use of annual mammograms (starting between
25 and
30 years of age, instead of age 40, as is the case for the general
public) and frequent
clinical breast exams.
Recently,
the
American Cancer Society and other breast cancer advocacy groups have
suggested
that MRI scans of the breast should also be added to annual mammograms,
in an
effort to detect breast cancers at an even earlier stage than is
usually
possible with mammography alone.
However, MRI scans, like mammography, have their
limitations and
drawbacks. First of
all, MRI scans are
far more expensive than mammograms, and many healthcare analysts have
rightly
asked how our already grossly under-funded healthcare system will be
able to
absorb the added cost of expensive breast MRI screening exams. Secondly, breast MRI, like
all clinical tests,
is not perfect. Current
generation MRI
machines and computerized imaging software can accurately detect
pre-invasive
and invasive breast cancer in more than 90% of cases (as opposed to
mammography’s 80-85% overall accuracy, and its even poorer sensitivity
in young
women with dense breast tissue).
However, MRI’s higher degree of sensitivity and overall
accuracy is
achieved at the expense of specificity.
MRI is currently associated with a “false negative” rate
of 10-30%
percent, unfortunately. This
means that
for every 100 women who have an abnormal breast MRI test, somewhere
between 10
and 30 of these breast abnormalities will ultimately be determined to
be benign
lesions of the breast, rather than cancer.
Additive to the economic costs of MRI as a breast cancer
screening tool,
therefore, are the economic, physical and emotional costs associated
with the
many women who must undergo biopsies of breast abnormalities identified
by MRI that
turn out, in the end, not to be cancer after all.
A
new Canadian
study, from Toronto,
just published in the journal Cancer
Epidemiology Biomarkers & Prevention, takes a closer
look at the
diagnostic value of mammography in younger women with BRCA1 and BRCA2
gene
mutations, and the role of both mammography and MRI scans in screening
young women
with these hereditary breast cancer syndromes.
In this small study, 42 women with a recent diagnosis of
pre-invasive or
invasive breast cancer, and with known BRCA gene mutations, underwent
computer-assisted measurements of their breast tissue density. The average age of these
participating women
was 48. The women
were then grouped
according to their breast density measurements, and were then subjected
to both
mammography and breast MRI imaging.
The
findings of
this study were in general agreement with similar previous studies, and
confirmed that women with denser breasts (as is common in young,
premenopausal
women) are less accurately screened for breast cancer by mammography
alone. Overall, the
sensitivity of
mammography alone in the women participating in this study was a rather
dismal
20% for pre-invasive breast cancer (ductal carcinoma in situ, or DCIS)
versus
87% for MRI alone. Among
patients
diagnosed with invasive breast cancer, the sensitivity of mammography
alone
wasn’t much better, only 26%, while the sensitivity of MRI in detecting
invasive breast cancer was 90%. Importantly,
this small study determined that even among women with less dense
breasts,
mammography was still significantly less sensitive in detecting DCIS
and
invasive breast cancer than MRI.
Several
recent
studies have confirmed that MRI is more sensitive in detecting breast
cancer,
and at an earlier stage, than mammography alone.
Given the complex and still unclear clinical
and economic “risk-to-benefit” associations involved with breast MRI,
the
indications for breast MRI screening will continue to be debated for
some
time. At some
point, given the enormous
cost associated with the more routine use of breast MRI, there will
have to be
some solid clinical data showing that the added sensitivity of MRI in
detecting
early breast cancers translates into meaningful clinical and societal
benefits. However,
increasingly, screening
MRI of the breast is becoming the de
facto imaging standard of care for women with BRCA gene
mutations (and the
few other gene mutations that have been associated with familial breast
cancer,
as well), and for women with a personal history of breast cancer or a
strong
family history of breast cancer. It
remains to be seen, however, whether or not the current indications for
screening
breast MRI will someday be expanded to include the general public. I predict that,
eventually, the indications
for routine annual MRI breast cancer screening will indeed be expanded
to
include the general public, but not before more substantial
high-quality
clinical research data comes along to prove that, despite the high cost
of MRI,
it is still a cost-effective public health screening tool from both
clinical
and economic perspectives.
BLADDER
CANCER PREVENTION WITH BROCCOLI?
An
estimated 75-80% of all
cancers in the United States
can probably be prevented by lifestyle changes alone, according to many
public
health experts (this is a major theme of a new book that I am currently
writing). Given the
enormous potential
of achievable cancer prevention strategies to reduce the incidence of
cancer in
our society (i.e., relative to the important but very incremental
survival
gains that we are making with improved screening and treatment
interventions),
cancer prevention is an area of great interest to me.
Along these lines, a new study in the journal
Cancer Research looks at the effects
of broccoli sprouts on the development of cancer of the bladder in
laboratory
rats.
According
to the American Cancer
Society, nearly 70,000 new cases of bladder cancer will be diagnosed in
this
country in 2008, and an estimated 14,000 people will die of the disease. When discovered early,
bladder cancer is
highly treatable and often curable.
In
its later stages, bladder cancer often requires radical surgery for
treatment,
and as with most cancers, cure rates decline with advancing stages of
disease.
The
so-called cruciferous
vegetables (e.g., watercress,
Brussels
sprouts, broccoli, cabbage, bok choi, kale, horseradish, radish and
turnips) contain high
concentrations of isothiocyanates, which have
been shown, in numerous research studies, to have potential anti-cancer
properties. Broccoli
sprouts, in
particular, have very high concentrations of isothiocyanates.
Previous
research, relying mostly
upon cell cultures and laboratory animals, have suggested that
isothiocyanates
may be capable of shutting down important biochemical pathways
associated with
cancer cell development and growth, as well as activating other
biochemical
pathways that are associated with cancer cell “suicide” (apoptosis). Some research studies have
also suggested
that isothiocyanates might also increase the activity of enzymes in the
body
that “detoxify” many of the cancer-causing substances that we commonly
ingest
or inhale.
This
study was jointly carried
out by researchers from the Roswell Park Cancer Institute in Buffalo,
the Johns Hopkins
University
in Baltimore,
and Massey
University
in New
Zealand.
Using an established rat model for bladder
cancer, feeding the animals a freeze-dried extract of broccoli sprouts
was
observed to significantly inhibit the development of bladder cancer. Additionally, levels of
enzymes known to
detoxify cancer-causing substances increased with increasing doses of
broccoli
sprout dietary supplementation. More
than 70% of the ingested isothiocyanates were also found to be excreted
into
the urine of these animals, and high levels of isothiocyanates were
also found
within cells lining the bladder as well.
This
study shows that, at least
in one animal model of bladder cancer, broccoli sprouts appear to have
significant and potent cancer prevention properties.
Other studies have shown similar anti-cancer
properties as well. Unfortunately,
while
there are a couple of ongoing human clinical research trials looking at
the
effects of dietary isothiocyanates on the prevention and treatment of
prostate
and lung cancer, there has been very little in the way of prospective,
randomized human clinical trials with dietary isothiocyanates. Therefore, it remains
unclear if the
anti-cancer properties of dietary isothiocyanates seen in a Petri dish
or in
laboratory animals will actually translate to humans as well. However, given the lack of
apparent side
effects associated with naturally-occurring sources of isothiocyanates,
it
seems reasonable to include them within a well-balanced low-fat,
high-fiber
diet for now, and until high quality prospective clinical trials
definitively
assess their risks and benefits in humans.
DIABETES:
RISK OF DEATH DUE TO HEART ATTACK &
STROKE
It
has long been known that
diabetes is associated with an increased risk of cardiovascular
disease, and
that diabetic patients often develop coronary artery disease, heart
attacks,
strokes and peripheral vascular disease at a younger age than people
without
diabetes. However,
the true extent to
which diabetes alters the risk of cardiovascular disease has not been
consistently evident from prior research trials.
A new, very large Danish public health study
in the journal Circulation provides
new information regarding the degree of cardiovascular disease risk
associated
with diabetes, especially among younger adult patients.
In
this study from
Copenhagen, 5 years of data from a national public health registry was
used to
assess all residents from Denmark who were 30 years of age or older. This study specifically
compared death rates
due to cardiovascular disease between patients receiving medications
for
diabetes and patients with and a history of heart attack (myocardial
infarction) but without a history of diabetes.
Both groups of patients were then compared with otherwise
healthy,
age-matched patients without a history of diabetes or myocardial
infarction. Nearly
72,000 patients with
diabetes were included, as well as almost 80,000 patients with a prior
history
of myocardial infarction (but without a history of diabetes).
When
men with diabetes were
compared with men without diabetes (but with a prior history of
myocardial
infarction), the risk of death due to cardiovascular disease in each
group, as
compared to non-diabetic men without a history of myocardial
infarction, was
strikingly similar. During
the 5-year
course of this study, the diabetic men experienced 2.4 times the risk
of cardiovascular
death when compared to their same-age peers without diabetes or a
history of
myocardial infarction. Likewise,
the
non-diabetic men with a prior history of heart attack experienced a
2.4-fold
increased risk of cardiovascular death when compared to healthy
same-aged male peers.
When
women were studied, the
results were essentially the same.
Diabetic women had 2.5 times the risk of cardiovascular
death when
compared to non-diabetic women without a history of myocardial
infarction,
while non-diabetic women with a history of heart attack faced a
2.6-fold
increased risk of cardiovascular death when compared to their healthy
same-aged
female peers.
Taken
together, this
excellent and very large public health study really puts into
perspective the
additive risk of cardiovascular disease (and death due to
cardiovascular
causes) associated with diabetes, even in relatively young adult
patients. Essentially,
a diagnosis of diabetes, even
without a prior history of cardiovascular disease, appears to put such
patients
at an equivalent risk of death due to cardiovascular disease as is seen
in non-diabetic
patients with a documented prior history of coronary artery disease and
a heart
attack.
The
incidence of diabetes,
which is a systemic disease that often affects virtually every organ in
the body,
is dramatically rising in tandem with the exploding incidence of
obesity in our
society. In
addition to more aggressive
efforts at diabetes prevention, the results of this important study
suggest
that more aggressive cardiovascular disease prevention, screening and
treatment
efforts should be directed at patients with diabetes, including young
and
otherwise healthy patients with diabetes.
As with cancer, it appears that the majority of
adult-onset cases of
diabetes could probably be prevented with healthy lifestyle approaches,
including a healthy low-carbohydrate, low-fat, high-fiber diet; plenty
of
exercise; and the avoidance of obesity.
Prevention
remains a far more
effective intervention against the development of both diabetes and
cancer than
any “after the fact” treatment options available to us today….
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.
