Doberluv
10-31-2005, 03:21 PM
Can We Neuter Cancer in Dogs?
Kevin Hahn, HVM, Ph.D., Dipl. ACVIM
Director of Oncology Services – Gulf Coast Veterinary
Oncology
I spent this past month reviewing studies reported
over the past 30
years regarding the role of hormones and cancer in
dogs.
Do neutering and spaying increase or decrease the risk
of cancer?
Do the procedures alter the prognosis once a pet
develops cancer? How
do hormones cause or prevent cancer?
Uncertainty Factor
I'm still not sure what to recommend to my clients.
There are reports showing that spayed females have
four-time greater
risk for developing cardiac hemangiosarcomas compared
to intact
females. Neutered males also show a significant
increase in risk for
these tumors compared to intact males.
Many of us are familiar with the data that show that
female dogs
spayed before the first heat cycle have half the risk
of mammary
carcinoma of those spayed after the first cycle but
before the second
heat cycle. Dogs spayed after the fifth heat cycle,
or never spayed,
have the highest risk.
Testicular carcinomas in dogs are common, but
neutering eliminates
that risk.
But prostate cancer is actually more common in
castrated dogs then
intact ones. Prostate cancer in dogs is hormonally
independent and
castrated dogs have up to a four-time greater risk of
developing
prostate cancer then intact dogs.
Neutered or spayed dogs have a one-half to threefold
higher risk for
developing bladder tumors and twice the risk of
developing
osteosarcoma as compared to intact dogs.
In on study, males were four times more likely then
females to die
within two years of diagnosis. Male and female dogs
that underwent
gonadectomy before 1 year of age had an approximate
one in four
lifetime risk for osteosarcoma and were significantly
more likely to
develop a tumor then dogs that were sexually intact.
Hormones' Role in Cancer
The possible mechanism by which gonadal hormone
exposure might protect
against or cause the development of tumors in both
males and females
is not known.
Endogenous sex steroids such as estrogen and
testosterone may serve as
prodifferentiation agents that inhibit the malignant
transformation of
cells.
Alternatively, gonadectomized female and male dogs
live longer then
sexually intact dogs, which might be expected to
contribute to a
higher overall cancer incidence associated with
gonadectomy reported
by others.
There are substantial and convincing bodies of
experimental, clinical
and epidemilogic evidence indicating that hormones
play a major role
in the etiology of many cancers.
The underlying mechanism proposed is that neoplasia is
the consequence
of prolonged hormonal stimulation of the particular
target organ, the
normal growth and function of which is controlled by
one or more
steroid or polypeptide hormones.
Genetic Controls
Evidence is mounting to show that the amount of
hormone to which a
tissue is effectively exposed is under strong genetic
control.
Therefore, in addition to external factors such as
diet or exogenous
hormone use, which may modify hormone profiles,
polymorphisms in genes
encoding proteins involved in steroid-hormone
biosynthesis, metabolism
or extra- and intracellular transport and DNA binding
are important
determinants of individual cancer risk.
The major carcinogenic consequence of this hormonal
exposure and the
end organ is cellular proliferation.
The emergence of a malignant phenotype depends on a
series of somatic
mutations that occur during cell division, but the
entire sequence of
genes involved in progression from normal cell to a
particular
malignant phenotype are not known.
Candidate genes include those in the endocrine pathway
as well as DNA
repair genes, tumor suppressor genes and oncogenes.
One explanation of why hormones may initiate cancer
but then the
cancer progresses in a hormone-independent environment
is discussed in
the June issue of Nature Medicine.
Dr. David Feldman found that, because of a mutation,
the stress
hormones cortisone and cortisol can trigger the growth
of later-stage
cancer cells. Feldman and colleagues report that an
androgen-receptor
gene in metastatic cancer cells contains two mutations
that transform
its activity.
Androgens are no longer bound tightly to the receptor.
Instead,
cortisol and cortisone bind and act like
pseudo-androgens, activating
the same metabolic pathways that androgens normally
would trigger.
This means that cancer cells are deluged with signals
to divide, which
could account for their rapid multiplication in
high-grade metastatic
or later-stage cancers.
So do we neuter dogs at an early age to prevent breast
and testicular
cancer but place them at risk for hemangiosarcomas,
osteosarcoma,
bladder or prostate cancer?
Do we monitor cortisol levels in dogs with cancer and
attempt to
reduce these levels in order to improve prognosis?
Unfortunately the answers are not known, but are close
at hand.
With the development of the canine genome map,
investigators are able
to identify loci that predispose dogs to cancer.
My hope is that this will lead to an understanding of
gene regulation
and the role of hormones in cancer initiation and
promotion. Then,
and only then, will we know when it is time to neuter
cancer.
Kevin Hahn, HVM, Ph.D., Dipl. ACVIM
Director of Oncology Services – Gulf Coast Veterinary
Oncology
Kevin Hahn, HVM, Ph.D., Dipl. ACVIM
Director of Oncology Services – Gulf Coast Veterinary
Oncology
I spent this past month reviewing studies reported
over the past 30
years regarding the role of hormones and cancer in
dogs.
Do neutering and spaying increase or decrease the risk
of cancer?
Do the procedures alter the prognosis once a pet
develops cancer? How
do hormones cause or prevent cancer?
Uncertainty Factor
I'm still not sure what to recommend to my clients.
There are reports showing that spayed females have
four-time greater
risk for developing cardiac hemangiosarcomas compared
to intact
females. Neutered males also show a significant
increase in risk for
these tumors compared to intact males.
Many of us are familiar with the data that show that
female dogs
spayed before the first heat cycle have half the risk
of mammary
carcinoma of those spayed after the first cycle but
before the second
heat cycle. Dogs spayed after the fifth heat cycle,
or never spayed,
have the highest risk.
Testicular carcinomas in dogs are common, but
neutering eliminates
that risk.
But prostate cancer is actually more common in
castrated dogs then
intact ones. Prostate cancer in dogs is hormonally
independent and
castrated dogs have up to a four-time greater risk of
developing
prostate cancer then intact dogs.
Neutered or spayed dogs have a one-half to threefold
higher risk for
developing bladder tumors and twice the risk of
developing
osteosarcoma as compared to intact dogs.
In on study, males were four times more likely then
females to die
within two years of diagnosis. Male and female dogs
that underwent
gonadectomy before 1 year of age had an approximate
one in four
lifetime risk for osteosarcoma and were significantly
more likely to
develop a tumor then dogs that were sexually intact.
Hormones' Role in Cancer
The possible mechanism by which gonadal hormone
exposure might protect
against or cause the development of tumors in both
males and females
is not known.
Endogenous sex steroids such as estrogen and
testosterone may serve as
prodifferentiation agents that inhibit the malignant
transformation of
cells.
Alternatively, gonadectomized female and male dogs
live longer then
sexually intact dogs, which might be expected to
contribute to a
higher overall cancer incidence associated with
gonadectomy reported
by others.
There are substantial and convincing bodies of
experimental, clinical
and epidemilogic evidence indicating that hormones
play a major role
in the etiology of many cancers.
The underlying mechanism proposed is that neoplasia is
the consequence
of prolonged hormonal stimulation of the particular
target organ, the
normal growth and function of which is controlled by
one or more
steroid or polypeptide hormones.
Genetic Controls
Evidence is mounting to show that the amount of
hormone to which a
tissue is effectively exposed is under strong genetic
control.
Therefore, in addition to external factors such as
diet or exogenous
hormone use, which may modify hormone profiles,
polymorphisms in genes
encoding proteins involved in steroid-hormone
biosynthesis, metabolism
or extra- and intracellular transport and DNA binding
are important
determinants of individual cancer risk.
The major carcinogenic consequence of this hormonal
exposure and the
end organ is cellular proliferation.
The emergence of a malignant phenotype depends on a
series of somatic
mutations that occur during cell division, but the
entire sequence of
genes involved in progression from normal cell to a
particular
malignant phenotype are not known.
Candidate genes include those in the endocrine pathway
as well as DNA
repair genes, tumor suppressor genes and oncogenes.
One explanation of why hormones may initiate cancer
but then the
cancer progresses in a hormone-independent environment
is discussed in
the June issue of Nature Medicine.
Dr. David Feldman found that, because of a mutation,
the stress
hormones cortisone and cortisol can trigger the growth
of later-stage
cancer cells. Feldman and colleagues report that an
androgen-receptor
gene in metastatic cancer cells contains two mutations
that transform
its activity.
Androgens are no longer bound tightly to the receptor.
Instead,
cortisol and cortisone bind and act like
pseudo-androgens, activating
the same metabolic pathways that androgens normally
would trigger.
This means that cancer cells are deluged with signals
to divide, which
could account for their rapid multiplication in
high-grade metastatic
or later-stage cancers.
So do we neuter dogs at an early age to prevent breast
and testicular
cancer but place them at risk for hemangiosarcomas,
osteosarcoma,
bladder or prostate cancer?
Do we monitor cortisol levels in dogs with cancer and
attempt to
reduce these levels in order to improve prognosis?
Unfortunately the answers are not known, but are close
at hand.
With the development of the canine genome map,
investigators are able
to identify loci that predispose dogs to cancer.
My hope is that this will lead to an understanding of
gene regulation
and the role of hormones in cancer initiation and
promotion. Then,
and only then, will we know when it is time to neuter
cancer.
Kevin Hahn, HVM, Ph.D., Dipl. ACVIM
Director of Oncology Services – Gulf Coast Veterinary
Oncology