Many studies have shown that ladies with advanced
nsclc live longer than men. four, 86, 87 a population study examining
lung cancer presentation and survival in premenopausal
versus postmenopausal ladies revealed that the premenopausal
ladies presented with additional advanced disease together with poorly
differentiated tumors with less favorable histologies. 88 but,
during this study, there wasn't a major survival distinction between
premenopausal and postmenopausal ladies. in a very more
recent study, ladies older than the age of sixty had a statistically
significant survival advantage over each men and younger ladies ;
the distinction compared to younger ladies is potentially caused
by higher levels of circulating estrogens within the younger population.
89 men failed to show a survival distinction by age.
hormone replacement therapy ( hrt ) has conjointly been
examined in relation to lung cancer risk and survival and has
yielded conflicting results. ganti et al. ninety have reported that in
virtually 500 female lung cancer patients examined, a major
association between each a coffeeer median age at lung cancer
diagnosis and a shorter median survival time in ladies who
used hrt round the time of diagnosis versus those who did
not. this result was additional pronounced in smoking women
versus nonsmokers, suggesting an interaction between estrogens
and tobacco carcinogens. but, different reports counsel that
hrt use prior to diagnosis may really defend ladies from
developing lung cancer, particularly if they smoked. 91 an inverse
relationship was conjointly observed between hrt use and nsclc
risk in postmenopausal ladies with er-positive lung tumors,
however not er-negative lung tumors. 92 this might counsel that
there are completely different effects on the balance between induction
of cell differentiation and cell proliferation by estrogen in
normal lung epithelium compared to malignant epithelium.
as a result of lung tumors are conjointly known to provide aromatase ( see
discussion that follows ), it's potential that exogenous hormone
use reduced native estrogen production by inhibiting aromatase
expression. exact hrt used, duration peoplee and timing of
use, is important data required to elucidate the exact role of
hrt on lung cancer risk and survival of lung cancer patients
in future studies.
though epidemiologic studies evaluating the effects
of estrogen on lung cancer risk have yielded varying results,
preclinical proof clearly shows that estrogen acts to induce
cell proliferation of nsclc cells in vitro and that in vivo and might
modulate expression of genes in nsclc cell lines that are important
for inducing cell proliferation. 78, 83, 93 genomic estrogen
signaling has been demonstrated to occur mainly through
er in nsclc cells. 94 furthermore, fulvestrant, an er antagonist
with no agonist effects, inhibits cell proliferation in
vitro and lung tumor xenograft growth in severe combined
immunodeficient mice by 40%. 78 so, preclinical evidence
strongly suggests that targeting the estrogen signaling pathway
might have therapeutic value to treat or forestall lung cancer.
there are nowadays 3 on the market strategies to target the
estrogen signaling pathway in cancer cells : ( a ) antagonists of
er purpose through medication like tamoxifen and raloxifene ;
( b ) downregulation of er purpose through agents like fulvestrant ;
and ( c ) reduction of estrogen levels through aromatase
inhibitors, like the reversible nonsteroidal agents letrozole
and anastrozole and therefore the irreversible steroidal inactivator exemestane.
95, ninety six tamoxifen and raloxifene have partial agonist effects in
sure tissues, like endometrium. tamoxifen has been shown
to increase lung tumor xenograft growth and that is not an appropriate
alternative of therapy for nsclc. 94 additionally, results from the
tamoxifen breast cancer prevention trial as a part of the national
surgical adjuvant breast and bowel project failed to show any decreased
risk of lung cancer. 97 seventeen tumors of the lung, trachea,
and bronchus were reported among the placebo cluster and
twenty in the ladies who had received tamoxifen therapy. although
not statistically significant, these results counsel that tamoxifen
may have a few agonistic effects within the lung.
nsclc live longer than men. four, 86, 87 a population study examining
lung cancer presentation and survival in premenopausal
versus postmenopausal ladies revealed that the premenopausal
ladies presented with additional advanced disease together with poorly
differentiated tumors with less favorable histologies. 88 but,
during this study, there wasn't a major survival distinction between
premenopausal and postmenopausal ladies. in a very more
recent study, ladies older than the age of sixty had a statistically
significant survival advantage over each men and younger ladies ;
the distinction compared to younger ladies is potentially caused
by higher levels of circulating estrogens within the younger population.
89 men failed to show a survival distinction by age.
hormone replacement therapy ( hrt ) has conjointly been
examined in relation to lung cancer risk and survival and has
yielded conflicting results. ganti et al. ninety have reported that in
virtually 500 female lung cancer patients examined, a major
association between each a coffeeer median age at lung cancer
diagnosis and a shorter median survival time in ladies who
used hrt round the time of diagnosis versus those who did
not. this result was additional pronounced in smoking women
versus nonsmokers, suggesting an interaction between estrogens
and tobacco carcinogens. but, different reports counsel that
hrt use prior to diagnosis may really defend ladies from
developing lung cancer, particularly if they smoked. 91 an inverse
relationship was conjointly observed between hrt use and nsclc
risk in postmenopausal ladies with er-positive lung tumors,
however not er-negative lung tumors. 92 this might counsel that
there are completely different effects on the balance between induction
of cell differentiation and cell proliferation by estrogen in
normal lung epithelium compared to malignant epithelium.
as a result of lung tumors are conjointly known to provide aromatase ( see
discussion that follows ), it's potential that exogenous hormone
use reduced native estrogen production by inhibiting aromatase
expression. exact hrt used, duration peoplee and timing of
use, is important data required to elucidate the exact role of
hrt on lung cancer risk and survival of lung cancer patients
in future studies.
though epidemiologic studies evaluating the effects
of estrogen on lung cancer risk have yielded varying results,
preclinical proof clearly shows that estrogen acts to induce
cell proliferation of nsclc cells in vitro and that in vivo and might
modulate expression of genes in nsclc cell lines that are important
for inducing cell proliferation. 78, 83, 93 genomic estrogen
signaling has been demonstrated to occur mainly through
er in nsclc cells. 94 furthermore, fulvestrant, an er antagonist
with no agonist effects, inhibits cell proliferation in
vitro and lung tumor xenograft growth in severe combined
immunodeficient mice by 40%. 78 so, preclinical evidence
strongly suggests that targeting the estrogen signaling pathway
might have therapeutic value to treat or forestall lung cancer.
there are nowadays 3 on the market strategies to target the
estrogen signaling pathway in cancer cells : ( a ) antagonists of
er purpose through medication like tamoxifen and raloxifene ;
( b ) downregulation of er purpose through agents like fulvestrant ;
and ( c ) reduction of estrogen levels through aromatase
inhibitors, like the reversible nonsteroidal agents letrozole
and anastrozole and therefore the irreversible steroidal inactivator exemestane.
95, ninety six tamoxifen and raloxifene have partial agonist effects in
sure tissues, like endometrium. tamoxifen has been shown
to increase lung tumor xenograft growth and that is not an appropriate
alternative of therapy for nsclc. 94 additionally, results from the
tamoxifen breast cancer prevention trial as a part of the national
surgical adjuvant breast and bowel project failed to show any decreased
risk of lung cancer. 97 seventeen tumors of the lung, trachea,
and bronchus were reported among the placebo cluster and
twenty in the ladies who had received tamoxifen therapy. although
not statistically significant, these results counsel that tamoxifen
may have a few agonistic effects within the lung.
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