tanamedrove medicinis winase kvlav mteli simwvavit … · da tvinis sisxlis mimoqcevis mwvave...
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1
ivane javaxiSvilis saxelobis Tbilisis saxelmwifo universiteti
al. naTiSvilis saxelobis morfologiis
instituti
xelnaweris uflebiT
natalia qebaZe
estrogen-receptorebi da aTerogenuli statusi –
ZuZus kibos morfologiuri Taviseburebebisa da
prognozis biomarkerebi
medicinaSi doqtoris akademiuri xarisxis mosapoveblad
warmodgenili
d i s e r t a c i a
samecniero xelmZRvanelebi: uCa gabunia _ medicinis mecnierebaTa
doqtori, profesori
nona kakauriZe _ medicinis mecnierebaTa
doqtori, profesori
Tbilisi
2010
avtoris stili daculia
2
sarCevi
Temis aqtualoba ................................................................................................................. 3
kvlevis mizani da amocanebi ................................................................................. 5
naSromis mecnieruli siaxle .................................................................................. 6
naSromis praqtikuli Rirebuleba ....................................................................... 8
literaturis mimoxilva ............................................................................................…… 9
gamoyenebuli masala da kvlevis meTodebi .......................................... 36
danarTi – sakuTari masala ................................................................................... 39
sakuTar gamokvlevaTa Sedegebi ..................................................................... 44
miRebuli monacemebis analizi …................................................................. 55
ilustraciebi ....................................................................................................................... 65
daskvnebi ................................................................................................................................. 92
praqtikuli rekomendaciebi .................................................................................. 94
literaturis saZiebeli .............................................................................................. 96
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Temis aqtualoba
gulsisxlZarRvTa daavadebebi da avTvisebiani simsivneebi
warmoadgens Tanamedrove medicinis erT-erT urTules problemas da,
rogorc sikvdilobisa da invalidobis mizezi, ikavebs pirvel da
meore adgils yvela industriulad ganviTarebul qveyanaSi.
Pproblebis maRali socialuri mniSvneloba amarTlebs mkurnalobis
Ziebis nebismier axal variants. mkurnalobisa da pacientebis
cxovrebis donis amaRlebis erT-erT rezervs warmoadgens im
sakiTxebis gadawyveta, romlebic imyofeba onkologiisa da
angiologiis mijnaze.
cnobilia, rom organizmis makroparametrebidan, romlebic
moqmedeben ZuZus kibos ganviTarebaze, didi mniSvneloba eniWeba wonasa
da lipidur statuss. isini miekuTvnebian faqtorebs, romlebic
zemoqmedeben imunur sistemaze da estrogenebis produqciaze. xolo
estrogenebis produqciis moSla iwvevs ZuZus kibos ganviTarebas.
ZuZus kibos gavrcelebaze agreTve moqmedebs sisxlis SratSi
lipiduri fraqciebis disbalansi (hiper- da dislipoproteinemia).
lipidebi da lipoproteinebi monawileoben imunomaregulirebeli
efeqtebis formirebaSi, awarmoeben estrogenebis receptoruli
SekavSirebis modulirebas samizne qsovilebSi. amitom pacientis
organizmis lipiduri statusis codnam, gansakuTrebiT daavadebis
sawyis etapze, SesaZlebelia garkveuli wvlili Seitanos ZuZus kibos
mkurnalobis strategiaSi.
saqarTveloSi sikvdiloba gulsisxlZarRvTa daavadebebisgan
wamyvani pozicia ukavia. uxSiresad sikvdilis mizezs warmoadgens
iSemiuri daavadebis garTulebebi, maT Soris miokardiumis infarqti
da tvinis sisxlis mimoqcevis mwvave darRvevbi, romlebsac safuZvlad
udevs progresirebadi aTerosklerozi. rogorc cnobilia,
aTerosklerozis wamyvan paTogenur faqtors warmoadgens lipiduri
cvlis moSla, amitom lipiduri profilis codna warmoadgens
aTerosklerozisa da misi garTulebebis riskis gansazRvris
aucilebel komponents.
4
qalebs klimaqterul periodamde aReniSnebaT aTerosklerozis
ganviTarebis mcire riski, gamomdinare iqidan, rom estrogenebi
dadebiTad moqmedeben lipidur cvlaze.
wlebis ganmavlobaSi ginekologebi did imedebs amyarebdnen
hormonul CanacvlebiT Terapiaze. arsebobda azri, rom qalis
sasqeso hormonebis gamoyeneba sakvercxeebis endokrinuli funqciis
regresis periodSi xels SeuSlis aTerosklerozis ganviTarebis
process. magram Catarebulma kvlevebma ar gaamarTla molodini.
rogorc adrindeli gamokvlevebidan iyo cnobili, kvlav dadasturda
is faqti, rom ChT zrdis hormondamokidebuli avTvisebiani
simsivneebis ganviTarebis risks (mag., ZuZus kibos), rac TavisTavad iyo
hormonuli Terapiis prognozirebadi gverdiTi movlena. garda amisa
aRmoCnda, rom hormonuli CanacvlebiTi Terapia ara marto ar
amcirebs gulsisxlZarRvTa daavadebebis warmoqmnis risks, aramed
pacientebis zogierT jgufSi xels uwyobs maT ganviTarebas. bolo
wlebis am kvlevebis Sedegebi gvafiqrebs, rom saWiroa
aTerosklerozisa da ZuZus kibos profilaqtikis axali meTodebis
SemuSaveba.
5
kvlevis mizani da amocanebi
kvlevis mizans warmoadgens ZuZus kibos invaziurobisa da
avTvisebianobis individualizacia biomarkerebis originaluri
kompleqsis (asaki, estrogen-receptorebis statusi, lipiduri speqtri)
safuZvelze.
amocanebi:
1. ZuZus kiboTi daavadebul qalTa postoperaciuli istoriebis
Seswavla retrospeqtulad da hospitalizebul pacientebSi;
2. Seswavlil masalaSi estrogen-receptorebis (er) statusisa da
morfologiuri formebis dadgena;
3. amonarCev pacientebSi gulis iSemiuro daavadebisa (gid) da misi
risk-faqtorebis (lipiduri statusi) dadgena;
4. sakontrolo jgufis pacientebSi lipiduri speqtris dadgena;
5. er-is statuss, ZuZus kibos avTvisebianobis maxasiaTeblebs
(morfologiuri formebis, invaziurobis da stadiurobis
safuZvelze) da lipidur maCveneblebs Soris kavSiris dadgena
sxvadasxva asakobriv jgufebSi;
6. masalis statistikuri damuSavebis safuZvelze kompleqsuri
biomarkerebis dadgena invaziurobisa da stadiurobis
prognozirebis mizniT asakis faqtoris gaTvaliswinebiT;
7. miRebuli Sedegebis safuZvelze praqtikuli rekomendaciebis
SemuSaveba da danergva.
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naSromis mecnieruli siaxle
naSromis mecnieruli siaxlea lipiduri speqtris maCveneblebis
rogorc biomarkerebis gamoyeneba ZuZus kibos sxvadasxva formebisa da
er-is statusis gaTvaliswinebiT asakovan aspeqtSi, anu estrogeniT
regulaciis TandaTanobiTi regresis pirobebSi.
dadginda, rom:
1. estrogen-dadebiTi (er `+”) kibos SemTxvevebi matulobs Suaxnis
asakSi aTerogenuli lipidebis dabali maCveneblebis fonze,
estrogenebis Semcirebis miuxedavad;
2. estrogen-uaryofiTi (er `_”) simsivneebis dros ar xdeba
estrogenebis SekavSireba samizne qsovilebis er-Tan (ZuZu,
gulsisxlZarRvTa sistema, RviZli), ris Sedegad periferiul
sisxlSi aRiniSneba estrogenebis normaluri, an momatebuli
done, da mimdinareobs aTerogenuli lipoproteinebis fonze da,
amdenad, dislipidemia da normaluri, an maRali raodenobis
estrogenis maCveneblebi warmoadgens samizne populacias
aTerosklerozuli daavadebis da er `_” ZuZus kibos
profilaqtikisTvis;
3. er `_” simsivneebis ujredebi proliferaciisa da
gavrcelebisTvis moixmars qolesterins, rac gamoixateba saerTo
qolesterinisa da maRali simkvrivis lipoproteinebis
qolesterinis daqveiTebaSi. trigliceridebis momateba am dros
gamowveulia maRali simkvrivis lipoproteinebis qolesterinis
SemcirebiT, romelic warmoadgens am maCveneblis erT-erT
regulators;
4. er `+” simsivneebis gavrcelebis maCvenebelia saerTo
qolesterinis, dabali simkvrivis lipoproteinebis
qolesterinisa da trigliceridebis mniSvnelovani momateba I
stadiisgan gansxvavebiT, maRali simkvrivis lipoproteinebis
qolesterinis igive maCveneblebis dros;
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5. sadinrovani karcinomis (ZuZus kibos yvelaze gavrcelebuli
forma) avTvisebianobas axasiaTebs saerTo qolesterinis
daqveiTeba danarCeni aTerogenuli lipidebis momatebis fonze.
Tanamedrove medicinaSi qalis premenopauzisa da menopauzis
periodi gamoirCeva estrogen/progesteronis disbalansiT, razec
didadaa damokidebuli Semdegi sakvanZo sakiTxebi:
• klimaqteruli sindromis ganviTareba, romlis
dasaregulureblad xSirad gamoiyeneba estrogenebi;
• am periods Tanxvdeba gulis iSemiuri daavdebis (gid)
incindentebis mateba pikur donemde, dislipidemiis farTo
gavrceleba am populaciaSi, rac am kategorias gamoyofs gid-is
maRali riskis kategoriad. am dros dislipidemiis
koreqciisTvis farTod gamoiyeneba estrogenebi;
• estrogenebis disbalansi iwvevs hipoqolesterinemias, dabali
simkvrivis lipoproteinebis qolesterinis, trigliceridebis,
Semadedebeli sistemis gaaqtivebas, Trombozebs, ZuZus kibos
ganviTarebis maRal risks;
• amdenad, es aris maRali riskis populacia (50-70ww) rogorc
gid-is, agreTve ZuZus kibos ganviTarebis TvalsazrisiT. A
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naSromis praqtikuli GRirebuleba
ZuZus kibos morfologiisa da lipiduri cvlis safuZvelze
gamoiyo gid-is riskis mqone pacientTa jgufi. amitom mniSvnelovania
Seiqmnas pacientTa kontingenti individualuri usafrTxo
mkurnalobisTvis, sadac gaTvaliswinebul iqneba rogorc gid-is, aseve
ZuZus kibos risk-faqtorebi, raTa ar moxdes am ori paTologiis
progresirebis provocireba. mkurnalobis daniSvnisas
gaTvaliswinebul iqneba risk-faqtorebis koreqcia.
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literaturis mimoxilva
Tanamedrove medicinis winaSe mTeli simwvaviT dgas sikvdilobis da
invalidobis ganmapirobebeli ori uxSiresi avadmyofobis
avTvisebiani simsivneebisa da aTerosklerozis sakiTxi. orive
avadmyofoba upiratesad asakovan qalTa xvedria da amitom
mniSvnelovania am or daavadebas Soris arsebuli urTierTobis
garkveva.
gansakuTrebiT mniSvnelovania am urTierTobis garkveva menopauzis
mdgomareobaSi myof qalebSi, radgan swored am periodSi xSiria
rogorc aTerosklerozi, ise ZuZus epiTeluri genezis simsivneebi, maT
Soris ZuZus kiboc, romlis sixSirec saqarTveloSi metad maRalia
(sixaruliZe a., madiCi k., nemsaZe g., 2000).
statistikuri monacemebiT dadgenilia, rom avTvisebiani
simsivneebiT daavadebis saerTo struqturaSi ZuZus kibos pirveli
adgili ukavia, gansakuTrebiT xSiria igi ekonomiurad ganviTarebul
qveynebSi (sixaruliZe a., madiCi k., nemsaZe g, 2000).
msoflios masStabiT qalTa populaciaSi daavadebis yovel milion
axal SemTxvevaze ZuZus kiboze modis SemTxvevaTa 18% (McPherson K.,
Steel C. M., Dixon J. M., 2000).
did britaneTSi 40-50 wlis qalebSi sikvdilobis yvelaze
gavrcelebul mizezs ZuZus kibo warmoadgens, rac Seadgens
sikdilobis 1/5 am asakobriv jgufSi (Grodstein F., Stampfer M., 1997).
yovelwliurad aRiniSneba 14 000 meti letaluri SemTxveva da igi
gansakuTrebiT xSiria 50-64 wlis asakis qalebs Soris (Beral V., Banks E.,
Reeves G., 2002).
50 wlis asakSi yovel 1000 qalze 2 aReniSneba axlad
diagnostirebuli ZuZus kibo, rac niSnavs, rom ZuZus kibos
gavrceleba Seadgens TiTqmis 2% (Manson J. E., Bassuk S. S., Harman M., et al.,
2006).
yovelwliurad mTel msoflioSi ZuZus kibos 540 000 axali
SemTxveva vlindeba. YjanmrTelobis dacvis msoflio organizaciis
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eqspertTa monacemebiT, 2000 wlisTvis gamovlinda ZuZus kibos 800000-
1000000 axali SemTxveva (sixaruliZe a., madiCi k., nemsaZe g., 2000).
saqarTveloSi sakmaod mZime viTarebaa ZuZus kiboTi avadobis
mxriv. zogadad aRiniSneba avTvisebiani simsivneebis zrdis tendencia
(janmrTelobis dacva, saqarTvelo 2005) (ix. sur. 1).
Tu, magaliTad, saqarTveloSi 1998 wels ZuZus kiboTi avadobis
maCvenebelma 100 000 mosaxleze Seadgenda 34,5 (anu, meti iyo iaponiis
avadobis maCvenebelze), 2002 wels igi gaxda 44,6 (TiTqmis gautolda
braziliis maCvenebels), xolo 2005 wlisTvis man miaRwia 50,0 (Svid
weliwadSi gaxSirda 1,7-jer) (janmrTelobis dacva, saqarTvelo, 2005)
(ix. sur. 2).
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ZuZus avTvisebiani simsivneebiT avadoba qalebSi asakobrivi
jgufebis mixedviT gadanawilda Semdegnairad: yvelaze xSirad igi
gvxvdeba 55-59 wlis asakobriv jgufSi da Seadgens 203,9 SemTxvevas 100
000 mosaxleze; meore adgilzea 65-69 wlis asakobrivi jgufi (136,6
SemTxveva 100 000 mosaxleze), xolo mesame adgilzea 50-54 wlis
asakobrivi jgufi (124,3 SemTxveva 100 000 mosaxleze) (janmrTelobis
dacva, saqarTvelo, 2005) (ix. sur. 3).
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onkologiur pacientebs Soris sikvdilobis yvelaze xSir mizezs
ZuZus kibo warmoadgens da misi sixSire matulobs im regionebSic,
sadac aqamde aRiniSneboda am daavadebis SedarebiT dabali
gavrceleba (Key T. J., Verkasalo P. K., Banks E., 2001).
mniSvnlovania ZuZus kibosa da aTerosklerozis
urTierTmimarTebis sakiTxi. qalebs vidre ar SeusruldebaT 50 weli
aReniSnebaT saerTo qolesterinis (sq), trigliceridebisa (tg) da
dabali simkvrivis lipoproteinebis qolesterinis (dslq) dabali,
xolo maRali simkvrivis lipoproteinebis qolesterinis (mslq)
maRali done (heisi j., tamiri i., tiroleri h., rivkini b., 1980).
CanacvlebiTi Terapia estrogenebiT amcirebs qolesterinis dones da
dslq matebas klimaqterul periodSi da iwvevs mslq stabilizacias
(volSi b., Sifi i., rozneri b., 1991).
gamokvlevebma, romlebic tardeboda 24 wlis manZilze, aCvena, rom
arcerTi qali menopauzamde ar daavadebula miokardiumis infarqtiT
da ar momkvdara koronaruli sisxlZarRvebis paTologiiT (Stout R. W.,
1985).
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A amasTan dakavSirebiT inglisSi Caatares gamokvleva, ramac cxadyo,
rom im pacientebs, visac naadrevad CamouyalibdaT koronaruli
sisxlZarRvebis dazianeba, ZiriTadad Seadgendnen postmenopauzur
periodSi myofi qalebi (Stout R.W., 1985).
msoflio masStabiT Catarebulia didi raodenobiT gamokvleva,
ramac gviCvena, rom estrogenebis gamoyeneba postmenopauzur periodSi
amcirebs gulsisxlZarRvTa daavadebebis risks 30%-iT (Mendelsohn M. E.,
Karas R., 1999, Akhrass F., Evans A. T., Wang Y., et al., 2003), Tumca paralelurad
matulobs ZuZus kibos ganviTarebis riski (Speroff L., Glass R. H., Kase N.,
1994; Willett W. C., Rockhill B., Hankinson S. E., et al., 2000).
kvlevebis Sedegebis mixedviT, avTvisebiani simsivneebiT daavadebis
saerTo struqturaSi ZuZus kibos sixSirem moimata ukanaskneli 10
wlis ganmavlobaSi saerTod da kerZod saqarTveloSic. Tu 1995 wels
100 000 qalze modioda ZuZus kibos 44,4 SemTxveva, grZelvadiani
prognozirebis monacemebiT, 2000 wlisTvis misma sixSirem miaRwia
48,8±1,4 SemTxvevas (Stout R.W., 1985). gamomdinare aqedan, ZuZus
simsivneebis profilaqtikis, diagnostikisa da mkurnalobis sakiTxebs
uaRresad didi mniSvneloba eniWeba.
rac Seexeba gulis iSemiur daavadebas (gid), rogorc
aTerosklerozis garTulebas, igi mamakacebSi ufro xSiria, vidre
qalebSi (Stout R.W., 1985), Tumca bolo aTwleulebSi qalebSi SeimCneva
matebis tendencia. ase, magaliTad, inglisSi da uelsSi 1973 wels
dafiqsirda 763 gid-iT sikvdiliT SemTxveva qalebSi 30-34 wlis
farglebSi, maSin roca imave periodSi mamakacebSi dafiqsirda 10692
SemTxveva (Kagan A., Dawber T. R., Kannel W. B., Revotskie N., 1977). magram 50
wlis Semdeg gid-iT dasnebovnebis sixSire mamakacebSi da qalebSi
erTmaneTs uaxlovdeba da 70 wlis Semdeg TiTqmis identuri xdeba
(Stout R.W., 1985). aRniSnul faqtSi wamyvani mniSvneloba eniWeba
estrogenebs (Akhrass F., Evans A. T., Wang Y., et al., 2003).
ZuZus normaluri ujredebi Seicavs specifiur SemakavSirebel
proteinebs estrogenebisTvis, proJestinisTvis,
glukokortikoidebisTvis da androgenebisTvis. maTi raodenoba
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damokidebulia sarZeve jirkvlis diferenciaciis stadiaze
(Moudgil V., 1985, Nerukar A. A., Desal S. B., Baraniya J., Yadav J., Chinoy R. F., 1997).
rogorc aCvena eqsperimentulma kvlevebma estrogen-receptoris
(er) koncentracia ZuZus normalur qsovilSi aranamSobiareb an
fexmZime mRrRnelebSi mciredia da matulobs laqtaciis periodSi
(Kelly P. et al., 1983).
J.Wittliff-ma (1975) janmrTel ZuZus qsovilSi aRmoaCina er-is Zalian
mcire raodenobiT. es movlena avtorma daukavSira ZuZus qsovilSi
arsebul mcire raodenobiT epiTelur ujredebs da meti raodenobiT
cximovan ujredebs (Wittliff J., 1975; Leclercq G., Heuson J., 1977).
er agreTve aRmoCenil iqna ZuZus kibos SemTxvevaSi (Allegra J. C.,
Lippman M. E., Thompson B., et al., 1979; Lesser M. L., Rosen P. P., Senei R. T. et al.,
1981).
sarZeve jirkvlis normaluri qsovili malignizirebulisgan
gansxvavebiT Seicavs cota er (Stout R.W., 1985, Koenders P. G., Beex L. V.,
Langens R., Kloppenborg P. W. C., Smals A.G. H., Benraad Th. J., and the breast cancer
study group, 1991).
hormonuli receptorebis donis gansazRvrisas yuradsaRebia
klinikuri da fiziologiuri faqtorebi: sqesi, asaki, rasa, organos
lokalizacia, simsivnis ujredovneba da histologiuri
diferenciacia, menopauza, fexmZimoba da laqtacia, wamlebis miReba
(Wittliff J. L., Pasic R., Bland K. I., 1991; Ownby H. E., Frederick J., Russo J., et al., 1995,
Hill A. D., Doyle J. M., McDermon E. W., et al., 1997).
infiltraciuli sadinrovani karcinomis bioptatebSi aRmoCenil
iqna steroiduli hormonebi, romelTa koncentracia varirebda
nulidan TiTqmis 6000 fmol/mg (Wittliff J. L., Pasic R., Bland K. I., 1991).
ganisazRvra ara mxolod histologiuri daxasiTeba, rac xsnis er
donis variabelobas ZuZus kiboSi (Blanco G., Alavaikko M., Ohala A., et al.,
1984).
Anthony N. Roberts, R. Hähnel (1981) gamoikvlies asociaciebi er-s, ZuZus
kibos morfologiur Taviseburebebsa da prognozs Soris pirveladi
karcinomis 53 SemTxvevaSi. aranairi arsebiTi asociacia er-sa da
morfologiur Taviseburebebs Soris (stadia, ujredovneba, fibrozi,
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elastozi, nekrozi, limfuri penetracia, folikuluri hiperplazia,
vaskuluri invazia, histocitozi, limfocituri ujredebis
infiltracia, invazirebuli limfuri ujredebis raodenoba, simsivnis
zoma, recidivebis adgili) ar iqna aRmoCenili.
ZuZus kibos dros naTeli periodi da sicocxlis meti
xangrZlivoba er `+” pacientebs aReniSnaT.
Tumca sxva kvlevebis Tanaxmad (Thomas C. Putti, Dalia M. Abd El-Rehim,
Emad A. Rakha, Claire E. Paish, Andrew H.S. Lee, Sarah E. Pinder and Ian O. Ellis, 2005),
er `_” simsivneebi atareben gansakuTrebul morfologiur Tvisebebs.
maT wamyvan morfologiur Tvisebebs miekuTvneba intensiuri
gavrceleba (gamoxatuli invaziuroba), komedo-tipis nekrozi da
centraluri fibrozi/nekrozi. am jgufs miekuTvneba iseTi subtipebi,
rogoric aris metaplaziuri karcinoma, adenoidur-cisturi karcinoma,
apokrinuri karcinoma da wilakovani karcinoma.
er-is, rogorc recidivis da sicocxlis xangrZlivobis
mniSvneloba, Seswavlil iqna 121 qalSi, romelTa SemTxvevaSi
masteqtomiidan gasuli iyo 5_12 weli (Parl F. F., Schmidt B. P., Dupont W. D.,
Wagner R. K., 1984). er-is statusis prognostuli mniSvneloba
gansazRvrul iqna damoukideblad da simsivnis stadiis, iRliis
metastazebis da histopaTologiuri stadiis gaTvaliswinebiT (Howell
A., Harland R. N. L., Branwell V. H. C., et al., 1984). kvlevis Sedegad gairkva, rom
er `_” da er `+” simsivneebs Soris prognozis TvalsazrisiT
mniSvnelovani statistikuri gansxvaveba ar iyo aRmoCenili, Tumca
ukanasknel jgufSi SeiniSneboda recidivebis ufro gviani warmoqmna
da ufro grZelvadiani sicocxlis xangrZlivoba. monacemebis
multivariaciulma analizma aCvena, er-is statusis sinergiuli
moqmedeba iRliis metastazebis warmoqmnis riskze. pacientebs
iRliis metastazebiT aReniSnebodaT 2.8-jer momatebuli
recidivebis riski, im pacientebTan SedarebiT, visac metastazebi
ar gamouvlinda. qalebSi iRliis metastazebiT, visi pirveladi
ZuZus kibo iyo er `_” es riski matulobda 4.6-jer, SedarebiT im
qalebTan, visac aReniSnebodaT er `+” simsivneebi metastazebis
gareSe (p=0.0003). kiboTi gamowveuli sikvdilianobis riski 5.6-jer
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iyo momatebuli mcired diferencirebuli simsivneebis
SemTxvevaSi, maRal diferencirebul simsivneebTan SedarebiT. mcired
diferencirebuli er `_” simsivneebis dros dafiqsirda sikvdilobis
maRali riski, SedarebiT maRal diferencirebul er `+” karcinomis
mqone pacientebTan (P=0.009). er-is statusis gansazRvra simsivnis
stadiis, iRliis metastazebis da histopaTologiuri stadiis
gaTvaliswinebiT informatulia simsivnis recidivisa da sikvdilobis
momatebuli riskis identificirebisTvis (Howell A., Harland R. N. L.,
Branwell V. H. C., et al., 1984, Stanford J. L., Szklo M., Brinton L. A., 1986).
estrogeni es aris hormoni, romelic aucilebelia sarZeve jirkvlis
normaluri zrdisTvis da ganviTarebisTvis. mas udidesi mniSvneloba
eniWeba reproduqciul procesebSi da aregulirebs menstrualur
cikls (Moudgil V. K., 1985). igi agreTve xels uwyobs gulisa da Zvlis
qsovilis normalur funqcionirebas. Tumca mis xangrZliv
zemoqmedebas SeuZlia ziani miayenos qalis organizms, kerZod,
matulobs ZuZus kibos ganviTarebis riski (Clark R. A., 2002, Yager J. D.,
Davidson N. E., 2006).
1940 wels ZuZus kiboTi dasnebovnebis riski Seadgenda 5%, rac
niSnavs, rom yovel 20 qalze modioda ZuZus kiboTi dasnebovnebis 1
SemTxveva. amerikis kanceris sazogadoebis kvlevis Tanaxmad 2009 wels
riskma Sedagina 13%, anu ukve 9 qalidan 1 avaddeba ZuZus kiboTi.
Tumca sainteresoa is faqti, rom pacientebis 75% ar gaaCniaT ZuZus
kibos ganvTarebis raime risk-faqtori.
arsebobs sxvadasxva saxis risk-faqtorebi. zogierTi maTganis,
magaliTad sqesis da asakis, Secvla SeuZlebelia. zogi
dakavSirebulia garemo faqtorebTan, an adamianis cxovrebis stilis
individualur TvisebebTan (sigaretis moweva, alkoholi, araswori
kveba). sxvadasxva risk-faqtorebs sxvadasxva zegavlena aqvT da, aqedan
gamomdinare, ZuZus kiboTi dasnebovnebis albaToba cvalebadobs
cxovrebis manZilze (Dupont W. D., Page D. L., 1985).
qvemoT moyvanil cxrilSi CamoTvlilia ZuZus kibos sarwmuno da
savaraudo risk-faqtorebi (McPherson K., Steel C. M., Dixon J. M., 2000), Cven
aqedan ganvixilavT mxolod ramdenimes (ix. cx. 1).
17
cxrili 1. ZuZus kibos ganviTarebis risk-faqtorebi
risk-faqtori SedarebiTi riski maRali riskis jgufi
asaki >10 xandazmulebi
geografiuli
mdebareoba
5 ganviTarebuli
qveynebi
menarqes asaki 3 menarqe 11 wlamde
menopauzis asaki 2 menopauza 54 wlis
mere
pirveli mSobiaroba 3 pirveli bavSvi 40
wlis zeviT
genetikuri faqtori ≥2 ZuZus kibo pirveli
xarisxis naTesavebSi
winamorbedi
keTilTvisebiani
simsivne
4-5 atipiuri hiperplazia
erT-erTi ZuZus kibo >4
socioekonomiuri
jgufi
2
kveba 1.5 najeri cximebis Warbi
miReba
wona:
menopaizamde 0.7 sxeulis masis indeqsi
>35
menopauzis Semdeg 2 sxeulis masis indeqsi
>35
alkoholi 1.3 Warbi miReba
ionizirebuli
radiacia
3 axalgazrda qalebis
radiaciuli dasxiveba
hormonebis miReba
egzogenurad:
18
oraluri
kontraceptivebi
1.24 xangrZlivi miReba
hormonuli
CanacvlebiTi Terapia
1.35 grZelvadiani miReba
≥10 weli
dieTilstilbestroli 2 gamoyeneba fexmZimobis
periodSi
inglisSi ZuZus kibos ganviTarebis riski gadanawilda Semdegnairad
(Perkins E. A., Small B. J., Balducci L., 2007) (ix. cx. 2):
cxrili 2. ZuZus kibos ganviTarebis riski asakis mixedviT
25 wlamde 15,000 SemTxvevaze 1
30 wlamde 1,900 SemTxvevaze 1
40 wlamde 200 SemTxvevaze 1
50 wlamde 50 SemTxvevaze 1
60 wlamde 23 SemTxvevaze 1
ganviTarebis riski 70 wlamde 15 SemTxvevaze 1
ganviTarebis riski 80 wlamde 11 SemTxvevaze 1
ganviTarebis riski 85 wlamde 10 SemTxvevaze 1
ZuZus kibos ganviTarebis erT-erT mniSvnelovan risk-faqtors
warmoadgens asaki (Brinton L. A., Devesa S. S, 1996; Key T. J., Verkasalo P. K., Banks
E., 2001).
rogorc cxrilidan Cans, asakis matebasTan erTad matulobs ZuZus
kibos ganviTarebis riskic.
mamakacebs aReniSnebaT ZuZus kibos ganviTarebis gacilebiT dabali
riski (daaxloebiT 1,08 mamakaci 100 000 SemTxvevaze), magram aqac
aRiniSneba SemTxvevaTa matebis tendencia (Giordano L., Sharon H., Cohen D.
19
S., Buzdar A. U., Perkins G,, Hortobagyi G. N., 2004). prognozi mamkacebSi, I
stadiis SemTxvevaSic ki, ufro mZimea qalebTan SedarebiT (Armando E.
Giuliano, 2006).
estrogenebis maRali done sisxlSi asocirebulia ZuZus kibos
ganviTarebis maRal riskTan. garkveuli movlenebi, romlebic zrdian
endogenuri estrognebis eqspozicias (uSviloba, gviani pirveli
mSobiaroba, ZuZuTi kvebaze uaris Tqma, naadrevi menarqe da gviani
menopauza), ganapirobeben ZuZus kibos ganviTarebis maRal risks mTeli
cxovrebis manZilze (Yager J. D., Davidson N. E., 2006).
mravalricxovanma kvlevebma cxadyo, rom pirveli mSobiaroba
naadrev asakSi, bevri Svili (daaxloebiT 7%-iT Semcirebuli riski
yovel Svilze) da ZuZuTi kveba (4%-iT Semcirebuli riski ZuZuTi
kvebiT yovel welze) korelirebs ZuZus kibos Semcirebul riskTan
(Byers T., Graham S., Rzepka T., Marshall J., 1985).
did britaneTSi Catarebuli mravalricxovani gamokvlevebis meta-
analizis Sedegad gamovlinda, rom qalebs, romlebic Rebulobdnen
hormonul CanacvlebiT Terapias menopauzis Semdeg 5 wlis
ganmavlobaSi, aReniSnebodaT ZuZus kibos ganviTarebis garkveuli
riski (Rebbeck T., Timothy R., Kauff N. D., Domchek S. M., 2009). Tumca
menopauzuri simptomebis samkurnalod hormonebis moklevadianma
miRebam ZuZus kibos ganviTarebis riskze zegavlena ar iqonia, an
imoqmeda mcired (Rebbeck T., Timothy R., Kauff N. D., Domchek S. M., 2009).
ZuZus keTilTvisebian simsivneebSi naadrev etapebze pacientebis
mcire jgufSi aRmoCenil iqna mcire raodenobiT er.
Semdgom May-Levin F. da Tanaavtorebma (1977) 47-dan 6 SemTxvevaSi
aRmoaCines er ZuZus keTilTvisebian simsivneSi. mkvlevarebi
varaudoben, rom maproliferebeli keTilTvisebiani er `+” simsivneebi
potenciurad avTvisebiani arian.
ZuZus kibos mimdinareobaSi Mmenopauzas eniWeba mniSvnelovani roli.
Martin P. da Tanaavtorebma (1978), gamoikvlies ra premenopauzis
periodSi myofi 84 pacientis fibroadenoma, daadgines 11 SemTxvevaSi
intensiuri ujredovani proliferacia, er-is maRali SemcvelobiT (20
fmol-ze meti 1 mg cilaze), xolo 49 simsivneSi _ dabali SemcvelobiT
20
(<7 fmol/mg). 24 SemTxvevaSi er-is Semcvelobam fibroadenomebSi
Seadgina 7_20 fmol/mg. Allegra J. da Tanaavtorebma (1979) aRmoaCines er
(>10 fmol/mg) keTilTvisebian simsivneebSi, ZiriTadad
fibroadenomebSi, 55 pacientidan 21-Si (38%), 46 pacientidan 20-Si (43%).
premenopauzaSi simsivneebi er `+” iyo, maSin rodesac 9-dan 8
pacients menopauzaSi aRmoaCndaT er `_” simsivne (<10 fmol/mg).
Ll. s. basaliki da Tanaavtorebis Tanaxmad (1982), er-is
Semcveloba ZuZus keTilTvisebian simsivneebSi (>10 fmol/mg) 41-dan 21
pacients aReniSna (51%). YyuradRebas iqcevs pacientebis jgufi
proliferaciuli fibfrozul-kistozuri mastopatiiT, romlebTac er-
is done ufro maRali aRmoaCndaT (34,4±10,8 fmol/mg), vidre
fibroadenomiT (27,3±3,7 fmol/mg) da araproliferaciuli fibfrozul-
kistozuri mastopaTiiT (19,5±3,2 fmol/mg) dasnebovnebul pirebs.
Lippman M. (1980) aRniSnavs, rom fibroadenomebi Seicavs er-is ufro
maRal koncetracias, vidre ZuZus keTilTvisebiani simsivneebis
fibrozul-kistozuri tipebi. Jacquimier J. da Tanaavtorebma (1982)
fibrozul-kistozuri mastopaTiis nimuSebSi 27-dan 17-Si (63%)
aRmoaCines er koncetraciiT >5 fmol/mg. Eer saSualod Seadgenda
14,5±14 fmol/mg fibroadenomebSi da epiTelur-hiperplastiur
simsivneebSi izrdeboda 31,5±23 fmol/mg-de.
Kutten F. da Tanaavtorebi (1981) gansazRvravdnen er-is koncetracias
46 premenopauzaSi myofi pacientis fibroadenomis citoplazmaSi da
birTvebSi menstualuri ciklis sxvadasxva fazaSi da aRniSnes er-is
koncentraciis garkveuli zrda folikulur fazaSi, aseve sagrZnobi
zrda preovulatorul da Semcireba luTeinur fazaSi.
KkeTilTvisebiani simsivneebi ufro xSirad gvxvdeba premenopauzaSi
myof qalebSi, sadac endogenur estrogenebs SeuZliaT daikavon
estrogen-receptorTan SemakavSirebeli adgilebi (Byrne C., Connolly J. L.,
et al., 2000).
avTvisebiani simsivneebi Seicaven er-s koncentraciiT 0_2500
fmol/mg (McGuire W. et al., 1975; Leclercq G., Heuson J., 1977]) xolo sxva
gamokvlevebis Tanaxmad _ 5000 fmol/mg-de (Wittliff J., 1984). aseTi
diapazoni ganpirobebulia simsivnis ujredovani Semcvelobis
21
morfologiuri da biologiuri heterogenurobiT da garkveuli tipis
ujredebis sxvadasxva estrogen SemakavSirebeli sididiT.
er-is done SeiZleba varirebdes erTidaigive simsivnis sxvadasxva
lokusSi. er-is yvelaze maRali koncentraciebi aRmoCenil iqna
simsivnis periferiul nawilSi, SedarebiT centralur nawilTan
(Allegra J. et al., 1980). zogi mkvlevaris Tanaxmad didi zomis simsivneebi
ufri xSirad er `_” arian da er-is done Seadgens M<10 fmol/mg (King
D. et al., 1980), xolo sxvebi am korelacias ar aRniSnaven (Leake R. et al.,
1981). aseve ar iqna aRmoCenili kavSiri receptorul statussa da
simsivnis lokalizacias Soris (McGuire W. et al., 1975).
er-is raodenoba ZuZus kibos simsivneebSi damokidebulia simsivnis
proliferaciis SedarebiT siCqaresTan da ujreduli ciklis
fazasTan. Meyer J. da Lee J. (1980) monacemebiT, simsivneebs er-is maRali
koncentraciiT gaaCniaT gacilebiT naklebi ujredebi S-fazaSi,
vidre er `_” simsivneebs an simsivneebi er-is mcire SemcvelobiT.
dabalmaprolifirebel ujredebSi 2-jer meti er iqna aRmoCenili,
vidre swrafadmaprolifirebel ijredebSi (Nerukar A. A., Desal S. B.,
Baraniya J., Yadav J., Chinoy R. F., 1997).
bolo wlebis gamokvlevebis Tanaxmad, er-is arseboba ZuZus kibos
ujredebSi kavSirSia simsivnis histologiur tipTan da mis
diferenciaciis xarisxTan (Sterner H. et al., 1980; Rasmussen B. et al., 1981),
amitom er SeiZleba gamoiyenebul iqnes, rogorc ZuZus simsivneebis
diferencirebis xarisxis bioqimiuri markeri.
zogi avtoris Tanaxmad ZuZus infiltraciuli karcinomebi
(wilakovani da tubuluri) Seicaven ufro met er-s, vidre
sadinrovani da meduluri karcinomebi (Rasmussen B. et al., 1981;
Skinner J. et al., 1982).
Lesser M. da Tanaavtorebma (1981), gamoikvlies ra 784 pacientis
simsivne, daadgines, rom sadinrovani infiltaciuli simsivneebis 57%
Seicavda er-s, wilakovani _ 49%, xolo meduluri tipis simsivneebi
mxolod 9%. Sterner H. da Tanaavtorebma (1980) invaziuri kibos 342
nimuSSi aRmoaCines korelacia er-is statussa da simsivnis
diferencirebas Soris (maRaldiferencirebul simsivneebSi er-is
22
koncentraciis mateba da ararseboba, an er-is umniSvnelo doneebi
dabaldiferencirebul simsivneebSi). Hanselman R. da Genton C.
aRmoaCines er-is koncentraciis Semcireba simsivnis avTvisebianobis
xarisxis zrdasTan erTad.
er-is Sejereba simsivnis histologiur aRnagobasTan da ZuZus kibos
diferencirebis xarisxTan Cautarda 153 pacients. simsivneebis 80%
klasificirebul iqna rogorc sadinrovani infiltraciuli kibo
avTvisebianobis sxvadasxva xarisxiT. simsivneebi avTvisebianobis III
xarisxiT xasiaTdebodnen er-is dabali koncentraciiT da er-is
Semcveli simsivneebis procentulobis SemcirebiT (McKeown-Eyssen G. E.,
Rogers-Melamed I., Clarke E. A.m, 1985; Elledge R. M., Osborne C. K., 1997).
MmiRebuli monacemebi metyvelebs ZuZus er-is statusis da ujredebis
diferencirebis xarisxis urTierTkavSirze, ramac aCvena, rom er `_”
simsivneebi xasiaTdebian ufro maRali proliferatiuli indeqsiT,
vidre er `+”.
mravalricxovan gamokvlevebSi naCvenebia, rom menopauzaSi myofi
pacientebis ZuZus pirveladi simsivneebi Seicaven er-is ufro maRal
koncentraciebs da ufro xSirad arian er `+”, vidre menopauzis
periodamde arsebuli simsivneebi (Бассалык Л. С. и др., 1982; Цырлина Е.Ф. и
др., 1984; McGuire W. et al., 1978; Seibert K., Lippman M., 1982 ).
Seibert K. da Tanaavtorebma (1982) gamoavlines, rom premenopauzaSi
myofi 775 pacientis simsivnidan 425 er `+” iyo, xolo menopauzaSi
myofi pacientebis 70% Seicavda er-s (1464 pacientidan 1032-s). er-is
koncentracia simsivneebSi premenopauzisas gacilebiT naklebia, vidre
menopauzis periodSi. Saez S. da Chouvet C. (1984) monacemebis mixedviT er-
is koncentracia Seadgens 40±10 fmol 1 mg cilaze premenopauzis
periodSi myof pacientebSi (108 adamiani) da 148±22 fmol/mg _
menopauzis periodSi myof pacientebSi (289 adamiani).
menopauzaSi myofi pacientebis simsivneebi ufro xSirad er `+” iyo
da maTSi er-is done ufro maRalia, vidre premenopauzis periodSi
myofi pacientebis simsivneebSi (ix. cx. 3).
23
Ecxrili 3. er-is Semcveloba sarZeve jirkvlis simsivneebSi
pacientebis menopauzis statusis gaTvaliswinebiT
E er-is raodenoba
statusi
pacientebis
raodemoba % fmol1 mgcilaze
(M+m)
premenopauza
klimaqsi da
menopauza <5
welze
menopauza >5
welze
626
285
485
59
71
69
38,9±2,1
60,5±5,1
65,2±5,2
Elwood E. da Godolphin W. (1980) gansazRvres 735 pacientis sarZeve
jirkvlis pirveladi simsivneebis er-is statusi menopauzis dros da
menopauzis periodis dawyebamde da aRmoaCines kavSiri er-is statussa
da asaks Soris. 25-35 wlis pacientebis 43% aReniSnebodaT er `+”
simsivne, xolo 60-74 wlis pacientebis 80% _ er ”+” simsivne. 40-45
wlis asakSi er `+” simsivneebis raodenoba menopauzis periodSi da mis
dawyebamde ar gansxvavdeboda (70% da 68% Sesabamisad). Osborn C. da
Tanaavtorebi (1980) aseve aRniSnavdnen er `+” simsivneebis procentis
matebas pacientebis asakis Sesabanisad. Saez S. da Chouvet C. (1984)
aRniSnes Eer-is koncentraciis zrda asakis matebasTan erTad im
pacientebis simsivneebSi, romlebic imyofebian menopauzaSi: 148±84
fmol/mg-dan (50-59 wlis 84 pacienti) 179±48 fmol/mg-de (60-69 wlis 113
pacienti) da 230±100 fmol/mg-de (70-79 wlis 62 pacienti).
24
Clark G. da Tanaavtorebi (1984) gansazRvravdnen er-is koncentracias
ZuZus simsivnis 2977 bioptatSi menopauzis statusTan, asakTan da
limfur kvanZebSi metastazebis arsebobasTan damokidebulebiT.
maTemaTikuri analizis Sedegad avtorebma aRmoaCines, rom er-is
koncentracia da er `+” simsivneebis procenti pacientebis asakze
ufro aris damokidebuli, vidre menopauzis statusze da sxva
kriteriumebze.
ase da amgvarad, bolo wlebSi bevrma mkvlevarma aCvena, rom er-is
koncentraciis mateba ZuZus simsivneebSi da er `+” simsivneebis
raodenoba ZiriTadaT dakavSirebulia pacientebis asakTan menopauzis
periodSi da mis dawyebamde. varaudoben, rom am simsivneebis er-is
statusis Secvla sxvadasxva asakis pacientebSi ara marto
cirkulirebadi, aramed qsovilovani estradiolis koncentraciis
sxvaobis Sedegia.
arsebobs monacemebi sisxlSi mocirkulire steroiduli
hormonebis, estrogenebis, zegavlenis Sesaxeb er-is Semcvelobaze
samizne qsovilebSi (Pollow K. et al., 1977) da ZuZus simsivneebSi (Maass H. et
al., 1975; Vihko R at al., 1980; Heise E., Gorlich M., 1982; Saez S., Chouvet C., 1984).
erTiani azri simsivneebSi er-is donis Secvlis mizezebis Sesaxeb
menstrualur funqciasTan dakavSirebiT ar arsebobs. mkvlevarebis
umetesoba varaudobs, rom estrogenebis raodenobis cikluri
cvlileba premenopauzaSi myof pacientebSi moqmedebs simsivneebSi er-
is Semcvelobaze (Saez S., Chouvet C., 1984).
Heise E. da Gorlich M. (1982) aRniSnaven er-is yvelaze maRal dones ZuZus
simsivneebSi menstrualuri ciklis folikulinis fazaSi. Saez S. da
Chouvet C. (1984) naSromebSi aRiniSneba simsivneebSi er-is Semcvelobis
da sisxlSi estrogenebis koncentraciis umniSvnelo korelacia
menstrualuri ciklis ganmavlobaSi. premenopauzaSi myof pacientebis
Eer `+” simsivneebis raodenoba ciklis samive fazaSi mcired
gansxvavdeboda, rac Seadgenda Sesabamisad 60, 51 da 52%. Vihko R. da
Tanaavtorebis (1980) monacemebis Tanaxmad er-is yvelaze didi
koncentracia ZuZus simsivneebSi (>100 fmol/mg) aRiniSneboda sisxlSi
25
estrogenebis dabali donis mqone pacientebSi menstrualuri ciklis
damoukideblad.
sisxlSi estradiolis sxvadasxva koncentraciebis gavlena ZuZus
simsivneebSi er-is Semcvelobaze gamokvleul iqna premenopauzaSi myof
54 pacientze da ZuZus kiboTi daavadebul menopauzaSi myof 72
pacientze (Beral V., Banks E., Reeves G., 2002; Chen C. L., Weiss N. S., Newcomb P.,
Barlow W., White E., 2002). estradiolis koncentracias sisxlSi
sazRvravdnen er-is gamokvlevasTan erTad simsivneebis bioptatebSi.
estradiolis yvelaze maRali donis fonze premenopauzaSi myof
pacientebSi (ovulatoruli faza_106,9±18,8 pg/ml) er-is done
simsivneebSi dabali iyo (21,4±5,2 fmol/mg) folikulinur fazasTan
SedarebiT (45,7±7,6 fmol/mg). er `+” simsivneebiT dasnebovnebul 22
premenopauzur pacientSi estradiolis koncentracia sisxlSi iyo
dabali, vidre 32 pacientSi er `_” simsivneebiT (81,5±14,6 da 138±15,4
pg/ml Sesabamisad) ciklis fazis miuxedavad. igive kanonzomiereba
aRiniSneboda menopauzaSi myof pacientebSi: er `+’’ somsivneebisas _
45,8±9,2 pg/ml (38 pacienti), xolo er `_” simsivneebis dros _ 84,5±19
pg/ml (23 pacienti) estradioli sisxlSi. reproduqciuli asakis
pacientebSi er `+” simsivneebi gamovlinda 40,7%_Si, xolo menopauzaSi
myof pacientebSi _ 62,3%-Si.
estrogenebi da er avlenen mniSvnelovan fiziologiur gavlenas
sisxlZarRvTa tonusze (Stevenson J. C., Crook D., Godsland I. F., Collins P.,
Whitehead M. I., 1994). adamianSi hipertenziis dros gamovlenilia er-is
anormaloba. mravali kvlevis mixedviT dadgenilia estrogenebis
fiziologiuri roli organoebze, romelsac SeiZleba ewodos
“sasqeso hormonebis pasuxi” (Stevenson J. C., Crook D., Godsland I. F., Collins P.,
Whitehead M. I., 1994). er gamovlenilia ara mxolod ZuZuSi, ZvlebSi da
qalis reproduqciul sistemaSi, aramed RviZlSi, tvinSi da
gulsxisxlZarRvTa sistemaSi (Desai S. B., Moonim M. T., Gill A. K., Punia R. S.,
Naresh K. N., Chinoy R. F., 2000).
estrogenebis gulsxisxlZarRvTa sistemaze zemoqmedebis
meqanizmebis aRqma bolo dros gafarTovda da gaxda gasagebi, rom
estrogenebis biologiuri efeqtebis sirTule warmoadgens maTi
26
moqmedebis meqanizmis Sedegs (Stevenson J. C., Crook D., Godsland I. F., Collins P.,
Whitehead M. I., 1994).
estrogenebi aregulireben saxvadasxva sistemur da cirkulatorul
faqtorebs, rac moicavs lipidebs, anTebiT faqtorebs, sisxlis
Sededebis da antiSededebis sistemebs. estrogenebs SeuZliaT
imoqmedon uSualod gulze da sisxlZarRvebze er-is meSveobiT,
romlebic ganapirobeben moqmedbas gulsisxlZarRvTa sistemis
ujredebsa da qsovilebze (Ouyang P., Michosl E., Karas R.,2009).
klasikur variantSi er warmodgenilia rogorc transkripciis
ligandaqtivirebuli faqtori, romelic mdebareobs ujredis birTvSi
da aregulirebs genis eqspresias hormonebTan SekavSirebis sapasuxod.
mocemuli meqanizmi, romelsac xSirad uwodeben genomur gzas,
SesaZlebelia, safuZvlad udevs estrogenis grZelvadian efeqtebs,
iseTebs, rogoric aris lipidebis doneze da koagulaciur faqtorebze
zemoqmedeba (Stierer M., Rosen H., Weber R., Hanak H., Spona J., Tuchler H., 1993).
mogvianebiT gaxda gasagebi, rom er awarmoeben xanmokle, ramdenime
wuTis ganmavlobaSi mimdinare efeqtebs, da miekuTvnebian aragenomur
gzas, radgan ar arian damokiebuli genis eqspresiis cvalebadobaze
(Ouyang P., Michosl E., Karas R., 2009).
estrogenebis es efeqtebi ganpirobebulia er-is subpopulaciiT,
romelic mdebareobs ujredis membranaze. estrogenis aseTi
aragenomuri moqmedebis yvelaze Seswavlil gzas warmoadgens
endoTeliumis ujredis aqtivacia azotis Jangis sinTetaziT, rac
iwvevs arteriul vazodilatacias estrogenis gamoyenebis sapasuxod
(Anderson E. 2002).
simsivnis er-is statusis Secvlis meqanizmi estradiolis
zemoqmedebis Sedegad SeiZleba aixsnas imiT, rom estradioli, romlis
koncentracia reproduqciuli asakis pacientebSi sakmaod maRalia,
“ikavebs” er-is dakavSirebis adgilebs, rac xels uwyobs er-is
kompleqsebis translokacias birTvSi, ris gamoc isini miuwvdomeli
xdebian. menopauzis dros, rodesac sakvercxe kargavs Tavis funqcias
da sisxlSi ecema estradiolis done, simsivneebSi izrdeba er-is
koncentracia. zogi mkvlevaris azriT, premenopauzaSi myofi
27
pacientebis estradiolis maRali koncentracia sisxlSi ufro
aqveiTebes receptoruli cilis sinTezs, radgan ikavebs
citoplazmaturi er-is SemakavSirebel adgilebs (Evans R. M., 1998).
ujredSida estradiolis koncentracias SeuZlia imoqmedos
rogorc citoplazmuri er-is raodenobaze, aseve birTvul estradiol-
receptorul kompleqsze. Fishman J. da Tanaavtorebma (1977),
gamoikvlies ra er-is, estronisa da estradiolis Semcveloba 129
ZuZus simsivnis citozolSi, aRmoaCines, rom estradiolis done er
`+” simsivneebSi ufro maRali iyo, vidre er ”_” simsivneebSi an ZuZus
normalur qsovilSi. Eestronis da estradiolis koncentraciebis
mateba er `+” simsivneebis citozolebSi menopauzamde da menopauzis
periodSi asevev aRniSnes Drafta D. da Tanaavtorebma (1983). Tumca Thorsen
T. da Tanaavtorebma (1982) er `+” da er `_” simsivneebSi ver aRmoaCines
citoplazmis estradiolis raodenobaSi sxvaoba. am avtorebs miaCniaT,
rom ara estradiolis done simsivnis ujredebSi, aramed sxva
faqtorebi moqmedeben citoplazmuri er-is koncentraciaze.
cnobilia, rom ujredSida estradiolis Semcveloba SeiZleba
gaizardos periferuli sisxliT transportirebadi estradiolis da
misi biosinTezis xarjze sxva steroidebidan simsivneSi (Stierer M., Rosen
H., Weber R., Hanak H., Spona J., Tuchler H., 1993). citozoluri er-is dabali
Semcveloba premenopauzaSi myof pacientebis simsivneebSi
estrogenebis maRali koncentraciiT sisxlis SratSi, savaraudod
SeiZleba aixsnas er-is blokirebiT endogenuri estrogenebiT. magram
rogor avxnaT er-is maRali da dabali koncentracia menopauzuri
pacientebis simsivneebSi sisxlSi er-is dabali donis fonze? SeiZleba
vivaraudoT, rom aseT SemTxvevebSi simsivneSi estradioli
warmoiqmneba estronis aRdgenis (romelic menopauzis dros
warmoadgens ZiriTad mocirkulire estrogens) an androgenebis AA
rgolis aromatizaciis Sedegad, agreTve estrogenebis koniugatebis
hidrolizis Sedegad (Rashid R. K., Gallager H. S., 1984).
ZuZus kiboTi daavadebul pacientTa hormono-metabolur statuss
didi mniSvneloba eniWeba simsivnis mkurnalobisa da prognozisTvis.
er-is Semcveloba da koncentracia simsivneSi matulobs asakTan
28
erTad da Tavis piks aRwevs postmenopauzur periodSi (Anaise D., 2007).
er-is arseboba miuTiTebs imaze, rom estrogenis warmoqmnis ujreduli
meqanizmebi SenarCunebulia malignizaciis miuxedavad (Anaise D., 2007).
pacientebs er `+” simsivneebiT, er ”_” simsivneebis mqone
pacientebTan SedarebiT, aReniSnebaT ufro grZeli naTeli periodi
pirveladi mkurnalobis Semdeg, SedarebiT didi cxovrebis
xangrZlivoba da recidivis Semdgomi ufro grZelvadian cxovrebis
xangrZlivoba, miuxedavad metastazebis gavrcelebisa iRliis fosoSi
(Anaise D., 2007).
cnobilia, rom organizmis makroparametrebidan, romlebic
moqmedeben ZuZus kibos ganviTarebaze, didi mniSvneloba eniWeba wonasa
da lipidur statuss. isini miekuTvnebian faqtorebs, romlebic
zemoqmedeben imunur sistemaze da estrogenebis produqciaze. xolo
estrogenebis produqciis moSla iwvevs ZuZus kibos ganviTarebas
(Цырлина Е. В., Гамаюнова В. Б., Порошина Т. Е., 1999; Longecker M. P., Bernstein L.,
Paganinihill A. et al., 1996). ZuZus kibos gavrcelebaze agreTve moqmedebs
sisxlis SratSi lipiduri fraqciebis disbalansi (hiper- da
dislipoproteinemia) (Howson C. P., Kinne D., Wynder E. L., 1986). lipidebi da
lipoproteinebi monawileoben imunomaregulirebeli efeqtebis
formirebaSi, awarmoeben estrogenebis receptoruli SekavSirebis
modulirebas samizne qsovilebSi (Lane D. M., Boatman K. K., McConathy W. J.,
1995). amitom pacientis organizmis lipiduri statusis codnam,
gansakuTrebiT daavadebis sawyis etapze, SesaZlebelia garkveuli
wvlili Seitanos ZuZus kibos mkurnalobis strategiaSi (Rashid R. K.,
Gallager H. S., 1984).
cnobilia, rom aqtiurad zrdadi avTviseviani simsivnis dros
sisxlSi SeiZleba aRiniSnos hipoqolesterinemia da msl-q da dsl-q
donis daweva (Fanelli F. R., Cangiano C., Muscaritolli M., et al., 1995; Kerber J.,
Pricelius S., Heidrich M., Miller M., 1999). es aixsneba simsivnis mier
qolesternis Semcveli metabolitebis aqtiuri STanTqmiT membranuli
struqturebis SenebisTvis aqtiurad zrdadi avTvisebiani ujredebis
mier. am fonze tg-is da maTi warmoebulebis (mono- da
digliceridebis) donem SeiZleba moimatos, radgan lipolizuri
29
simsivnuri substanciebi, Slian ra organizmis cximovan qsovils,
avseben maT fonds (Kerber J., Pricelius S., Heidrich M., Miller M., 1999; Allampallam
K., Dutt D., Nair C., et al., 2000).
erT-erTi kvlevis Tanaxmad sq-is da tg-is done sagrZnoblad
matulobda ZuZus avTvisebiani simsivneebis SemTxvevaSi,
keTilTvisebian simsivneebTan SedarebiT (P<0.05, P<0.005) (Essam A. Mady,
2000).
magram ZuZus kiboTi dasnebovnebuli pacientebis lipiduri
profili gamoirCeva garkveuli TaviseburebebiT. kerZod, aseTi
pacientebisaTvis damaxasiaTebelia α-qolesterinis anu mslq-is donis
mateba (Boyd N. F., McGuire V., 1990; Moorman P. G., Hulka B. S., Hiatt R. A., et al.,
1998). nawilobriv es aixsneba imiT, rom α-lipoproteini SeiZleba
sinTezirdes ZuZus karcinomis ujredebis mier (Hurlimann J., Van Melle G.,
1991). literaturuli monacemebis Tanaxmad, mslq-is fraqciis done
mizanSewonilia gaTvaliswinebul iqnes simsivnis sawinaaRmdego
Terapiis dros rogorc misi efeqturobis erT-erTi maCvenebeli, xolo
mslq-is donis mateba ganixilos rogorc arasasurveli prognostuli
faqtori (Zorilla E., Hulse M., Hernandez A., Gershberg H., 1988; American Society of
Clinical Oncology, 1996).
Essam A. Mady (2001) Tanaxmad, sq-is da tg-is done mkveTrad
matulobda ZuZus kibos SemTxvevaSi, ZuZus keTilTvisebian
simsivnesTan SedarebiT (P<0.005, P<0.05) da korelirebda estradiolis
donesTan. amis safuZvelze gamoiTqva varaudi, rom simsivnuri
qsovilis mier lipidebis STanTqma plazmidan korelirebs
estradiolTan da lipidebi warmoadgenen ZuZus kibos ganviTarebis
risk-fators.
Ggid-iT gamowveuli sikvdiloba Warbobs ZuZus kiboTi gamowveul
sikvdilobaze yvela asakis qalebSi (Bernstein L., 1998; Ouyang P., Michol E.,
Karas R.,2009). kardiovaskuluri SemTxvevebis umetesoba viTardeba
postmenopauzis periodSi, saSualod 10 wliT ufro gvian, vidre
mamakacebSi, da es aixsneba menopauzamde qalis sasqeso horrmonebis
damacavi meqanizmiT (Wingo P. A., Calle E. E., McTiernan A.; 2000, Kannel W. B.,
Wilson P. W., 1995).
30
cnobilia, rom 50-60 wlamde sqesobrivi sxvaoba isaxeba
gansakuTrebiT intensiurad da avadoba aTeroskleroziT mkveTrad
prevalirebs mamakacTa populaciaSi (Akhrass F., Evans A. T., Wang Y., et al.,
2003). Aaman miipyro mkvlevarTa yuradReba sasqeso hormonebis rolze
aTerosklerozuli procesis paTogenezSi. miRebuli monacemebiT,
qalis sasqeso hormonebi – estrogenebi – aferxebeben aTerosklerozis
ganviTarebas, rac dakavSirebulia plazmaSi mslq-is Semcvelobis
matebasTan (Victor G., Cannon R. O., 1996; Hozumi Y., Kawano M., Miyata M., 1997).
menopauzis periodSi ganviTarebul hipoestrogenemiisas aRiniSneba
qolesterinis, qolesterini/fosfolipidebis koeficientisa da β-
lopoproteinebis donis mateba da, Sesabamisad, izrdeba
aTerosklerozis ganviTarebis riski (Victor G., Cannon R. O., 1996). qalebs
koronaruli arteriebis aTeroskleroziT an naadrevi cerebruli
aTerosklerozis movlenebiT sarwmunod aReniSnebaT estrogenebis da
maTi fraqciis eqskreciis Semcireba (Akhrass F., Evans A. T., Wang Y. et al.,
2003).
estrogens SeuZlia moaxdinos rogorc dadebiTi, ise uaryofiTi
zegavlena gulsisxlZarRvTa sistemaze. erTis mxriv, mas gaaCnia
potenciurad dadebiT zemoqmedeba lipidebze: amcirebs dslq, zrdis
mslq, azotis oqsidis meSveobiT ganapirobebs vazodilatacias da
xels uSlis sisxlZarRvebis aTerogenul dazianebas (Victor G., Cannon R.
O., 1996). amave dros, estrogenebi xasiaTdebian mravali Trombuli
efeqtebiT: zrdian proTrombinis da amcireben antiTrombin III-is
dones, riTac xels uwyoben venozuri Tromboemboliebis ganviTarebis
riskis zrdas (Ouyang P., Michosl E., Karas R., 2009).
menopauza ganisazRvreba rogorc menstrualuri periodis finali
da gulisxmobs menstruaciis sabolood Sewyvetas 1 wlis Semdeg 1
wliani amenoreisa da sakvercxeebis folikulebis funqciis Sewyvetis
Semdeg (Pasqualini C., Leviel V., Guibert B., Faucon-Biguet N., 1991; Rio G. D., Velardo
A., Zizzo G., Avogaro A., Casa L. D., Marrama P., Macdonald I. A., 1994). bunebrivi
menopauzis mediana aris 51 weli (Lindheim S. R., Legro R.S., Bernstein L.,
Stanczyk F. Z., Vijod M. A., Presser S. C., Lobo R. A., 1992).
31
perimenopauza aris periodi tranziciisa reproduqciuli fazis
damTavrebis menopauzis 1 wlis Semdeg, grZeldeba 2_8 wlis manZilze
da dakavSirebuia menstrualur iregulaciasTan, klimaqterul
sindromTan, rogorebicaa alebi, oflianoba, Zilis darRveva,
vagialuri simSrale da hormonuli cvlileba (Zorilla E., Hulse M.,
Hernandez A., Gershberg H., 1998). postmenopauza ganisazRvreba rogorc
menopauzis dasawyisi (Fregly M. J., Thrasher T. N., 1977).
estrogenebi antiaTerosklerozuli moqmedebiT xasiaTdebian,
kerZod, zrdian mslq da amcireben dslq (tg-is done matulobs).
arsebobda azri, rom qalis sasqeso hormonebis gamoyeneba
sakvercxeebis endokrinuli funqciis regresis periodSi xels
SeuSlis aTerosklerozis ganviTarebis process (Сметник В. П. ,
Коновалова В. Н., 2009).
gansakuTrebulad mniSvnelovani roli eniWeba estrogenebs
menopauzis Semdeg, rodesac matulobs gulsisxlZarRvTa SemTxvevbis
raodenoba (Chae C. U,, Manson J. E., 2004; Ouyang P., Michosl E. D., Karas R. H,
2009).
lipoproteinebis cvlileba menopauzis periodSi Seswavlilia
xangrZlivi kvlevebis Sedegad, ris Tanaxmadac aRiniSneba dslq-is
momateba da mslq-is donis aramudmivoba (Proudler A. J., Ahmed A. H., Crook
D., Fogelman I., Rymer J. M., Stevenson J. C., 1995).
dRevandel dRes arsebobs hipoTeza, rom postmenopauzur Terapias
estrogenebiT, SeuZlia Seamciros gulsisxlZarRvTa daavadebebis
riski (Grodstein F., Stampfer M., 1995; Mendelsohn M. E., Karas R. H., 1999; Mikkola T.
S., Clarkson T. B., 2002).
estrogeni garkveul zegavlenas axdens kardiovaskulur riskze
da mas didi mniSvneloba eniWeba antiaTerogenuli Terapiis Catarebis
dros (Brinton E. A., 1996). aTerosklerozis cnobili modelis
gamoyenebiT maimunebSi Clarkson da Tanaavt. (1996) daadgines, rom
peroraluri koniugirebuli cxenis estrogenebis antiaTerogenuli
efeqti maimunebSi vlindeba mxolod minimalurad gamoxatuli
aTerosklerozuli procesis dros. igive Sedegebi miRebul iqna
32
bocvrebze da mRrRnelebze gamokvlevebis Catarebisas (Ouyang P., Michosl
E., Karas R., 2009).
kvlevaSi Women‘s Health Initiative (WHI) naCvenebi iyo, rom
estrogenebisa da placebos miRebis fonze mwvave infarqtis
ganviTarebis sixSire sakmaod SedarebiTia. amasTan erTad asakobrivi
jgufebis meoradma analizma aCvena, rom Sedegebi ufro axalgazrda
qalebSi gansxvavdeboda erTmanTisgan (Anderson G.L., Limacher M., Assaf A.
R., et al.; 2004, Hsia J., Langer R. D., Manson J. E., et al., 2006).
WHI kvlevis detaluri dizaini gamoqveynebuli iyo wina wlebSi
(Anderson G. L., Limacher M., Assaf A. R., et al., 2004; Stefanick M. L., Cochrane B. B.,
Hsia J., Barad D. H., Liu J. H., Johnson S. R., 2003). ZiriTadiAidea mdebareobda
imaSi, rom am randomizirebul kvlevaSi CarTuli iyvnen 50-79 wlis
qalebi histereqtomiiT. ZiriTad jgufSi pacientebi Rebulobdnen
cxenis koniugirebul estrogens, sakontroloSi _ placebos.
am kvlevis principialurad axal Sedegs warmoadgens is faqti,
rom estrogenebi 50-59 wlis qalebSi kardioproteqtuli moqmdebiT
xasiaTdebian. faqtiurad, estrogeni amcirebs miokardiumis infarqtis
ganviTarebis risks da acilebs Tavidan revaskularizaciis
aucileblobas. garda amisa, gaaCnia Tviseba gaaumjobesos sixlis
mimoqceva ara marto miokardiumSi, aramed sxva qsovilebSic (Manson J.
E., Bassuk S. S., Harman M., et al., 2006; Chae C. U., Manson J. E., 2004). Tumca am
problemis ufro mkafio gagebisTvis, aucilebelia Catardes mTeli
rigi gamokvlevebi didi raodenobis pacientis monawileobiT.
meios klinikis specialistebis azriT, estrogenebis miReba
postmenopauzis periodSi amcirebs aTerosklerozuli folaqebis
raodenobas da kalcifikacias koronarul sisxlZarRvebSi.
koronaruli sisxlZarRvebis autofsiurma gamokvlevam cxadyo, rom im
pacientebs, romlebic Rebulobdnen estrogenebs koronaruli
kalciumi, folaqebi da koeficienti kalciumi/folaqi iyo sarwmunod
dabali SedarebiT maTTan, vinc ar itarebda CanacvlebiT Terapias
estrogenebiT (Clin J., 2002).
freminhemis kvlevis Sedegad (1976) dadginda, rom kardiovaskulur
SemTxvevaTa ricxvi postmenopauzis periodSi myof qalebSi 2.6_jer
33
matulobs premenopauzasTan SedarebiT (Ouyang P., Michos E., Karas R., 2009,
2009).
arsebobda azri, rom sisxlis plazmis lipoproteinebi xels
uwyoben gulsisxlZarRvTa daavadebebis riskis zrdas, radgan
menopauzis Semdeg aRiniSneboda dslq-is da tg-is donis mateba.
aqedan gamomdinare, CanacvlebiT Terapias estrogenebiT unda Seemcira
lipidebis arasasurveli zemoqmedeba, Tumca kardioproteqtuli
Tvisebis mqone mslq-is donec mcirdeboda (Waters D. D., Alderman E. L., Hsia
J., et al., 2002).
kardiovaskuluri avadobis asakobrivi zrda pre- da
postmenopauzaSi aRiniSneba CanacvlebiTi Terapiis moqmedebis
miuxedavad (Godsland I. F., 2001). miRebuli monacemebi miuTiTeben
imaze, rom estrogenebis Semcireba menopauzis dros dakavSirebulia
gulsisxlZarRvTa avadobis momatebul riskTan da ufro metad
gamoxatulia premenopauzasTan SedarebiT (Robinson J. C., Folsom A. R.,
Nabulsi A. A., et al., 1996; Godsland I. F., 2001).
cxovelebze Catarebulma gamokvlevebma cxadyo, rom estrogenebi
avlenen vazodilataciur, anTebis sawinaaRmdego da antiaTerogenul
Tvisebebs, dadebiTad moqmedeben lipidur profilze (Anderson G. L.,
Manson J., Wallace R., et al., 2003). randomizirebul kvlevebSi, romlebic
Catarda bocvrebze ovarieqtomiis Semdgomi hiperqolesterinemiis
pirobebSi estradioli mniSvnelovnad amcirebda aTerosklerozis
progresirebas SedarebiT maTTan, visac aReniSnebodaT hormonebis
dabali done. Tagvebze Catarebulma kvlevebma aCvena, rom estradioli
mniSvnelovnad amcirebda sisxlZarRvTa kedlis dazianebas da zrdida
vazoproteqtorul efeqts (Anderson G. L., Manson J., Wallace R., et al., 2003).
maimunebSi ovarieqtomiis Semdgom 17-β-estradioli an cxenis
koniugirebuli estrogeni amcirebda koronaruli sisxlZarRvebis
aTerosklerozs 50_72%-iT sakontrolo cxovelebTan SedarebiT
(Anderson G. L., Limacher M., Assaf A. R., et al., 2004).
cxovelebze Catarebulma gamokvlevebma zogadad daamtkica
CanacvlebiTi Terapiis mniSvneloba menopauzis dadgomis Semdeg
(Anderson G. L., Manson J., Wallace R., et al., 2003). garda amisa, CanacvlebiTi
34
Terapiis mniSvneloba Cans mTeli rigi SerCeviTad kontrolirebadi
kvlevebis Sedegad (Akhrass F., Evans A. T., Wang Y., et al., 2003). maT
umetesobaSi SeiniSneba gulsisxlZarRvTa daavadebebis Semcirebis
tendencia (Beral V., Banks E., Reeves G., 2002). miuxedavad amisa, did
SerCeviTad kontrolirebad kvlevebSi hormonul Terapiasa da
miokardiumis infarqtis SemTxvevebis Semcirebas Soris arsebiTi
kavSiri ar gamovlenila (Ouyang P., Michosl E., Karas R., 2009].
kvlevaSi Cardiovascular Health Study monawileobdnen qalebi 65 wels
zemoT, romlebic Rebulobdnen estrogens. am kvlevis Sedegad
aRiniSna subklinikuri avadobis dabali sixSire (Mendelsohn M. E., Karas
R. H., 1999).
ufro masStaburi kvlevis, Nurses`s Health Study, Sedegad, sadac
monawileobda 70.000 asimptomuri qali, romlebic itarebdnen
CanacvlebiT Terapias, gamovlinda kardiovaskuluri SemTxvevebisa da
zogadi sikvdilobis Semcireba SedarebiT maTTan, vinc am mkurnalobas
ar itarebda (Anderson G. L., Limacher M., Assaf A. R., et al., 2004). magram
sayuradReboa is faqtic, rom qalebis umetesobas CanacvlebiTi
Terapia daewyo premenopauzis periodSi da kvlevis dasawyisSi maTi
gulsisxlZarRvTa daavadebebis Sesaxeb araferi iyo cnobili.
radgan aTerosklerozi progresirebs estrogenebis deficitis
fonze, logikuria, rom naadrevi CanacvlebiTi Terapia estrogenebiT
gamoiRebs Sedegs premenopauzis periodSi myof qalebSi (Anderson G. L.,
Limacher M., Assaf A. R., et al., 2004). qalTa umetesoba, romlebic
monawileobdnen iseT kvlevebSi, rogoricaa Nurses`s Health Study, sadac
estrogenis dacviTi moqmedeba gamovlenilia, CanacvlebiT Terapias
iwyebdnen menopuzis periodSi (Anderson G. L., Limacher M., Assaf A. R., et al.,
2004). kvleva WHI-Si monawileobas Rebulobda premenopauzis periodSi
myof qalTa arasakmarisi raodenoba imisTvis, rom nebismieri
kardiovaskuluri dacviTi meqanizmi yofiliyo TvalsaCino (Hulley S.,
Grady D., Bush T. et al., 2003). qalis saSualo asakma menopauzis Semdeg,
rodesac aTerosklerozuli procesebi iCens Tavs, Seadgina 10 weli.
cxovelebze Catarebuli kvlevebis Sedegad ar dadasturda is
faqti, rom Terapiis dawyebis dro aris kritikuli faqtori, agreTve
35
ar gamovlinda estrogenebis gamoyenebis efeqturoba im cxovelebSi,
romelTac aReniSnebodaT arteriebis dazianeba mkurnalobis
dawyebamde (Anderson G. L., Manson J., Wallace R., et al., 2003). cxovelebze am
gamokvlevebis Sedegebi Seesabameba kvleva Heart and Estrogen/Progestin
replacement study miRebuli meoradi profilaqtikis monacemebs.
kvleva Cardiovascular Health Study-s Tanaxmad estrogenebiT
CanacvlebiTma Terapiam postmenopauzis periodSi myof qalebSi
gulsisxlZarRvTa daavadebebis klinikuri an subklinikuri
gamovlinebebiT axalgazrda pacientebTan SedarebiT gamoiwvia mxris
arteriis vazodilatacia. am monacemebma gviCvena, rom estrogenebis
dadebiTi zemoqmedeba SesaZlebelia gamovlindes mxolod im
sisxlZarRvebSi, sadac ar aRiniSneba aTerosklerozuli procesi
(Ouyang P., Michosl E., Karas R., 2009).
arsebobda azri grZelvadiani CanacvlebiTi Terapiis efqturobis
Sesaxeb, magram es ar iqna dadasturebuli Svidwliani kvlevis Sedegad
(Ouyang P., Michosl E., Karas R., 2009)..
did randomizirebul kvleva WHI-Si Rebulobda monawileobas 16608
pacienti intaqturi saSvilosnoTi, romlebic daarandomizires cxenis
koniugirebuli estrogenis da medoqsiproJesteron acetatis an
placebos misaRebad 5-6 wlis manZilze (Hulley S., Grady D., Bush T. et al.,
2003). kvleva naadrevad iqna Sewyvetili CanacvlebiTi Terapiis fonze
ZuZus kibos ganviTarebis riskis zrdis gamo. agreTve ar gamovlenila
aranairi dadebiTi efqti gulsisxlZarRvTa sistemaze.
kvlevaSi, sadac 10739 qali histereqtomiiT randomizirebul iqna
cxenis koniugirebuli estrogenis an placebos misaRebad,
gulsisxlZarRvTa sistemis mxriv agreTve ar gamovlenila aranairi
dadebiTi efeqti (Ouyang P., Michosl E., Karas R., 2009).
mimdinare randomizirebuli klinikuri gamokvlevebi mxars uWeren
AHA (American Heart Association) da ACC (American Cardiovascular College)
rekomendaciebs, romlis Tanaxmad ar aris mizanSewonili CanacvlebiTi
Terapiis gamoyeneba gulsisxlZarRvTa daavadebebis
profilaqtikisTvis.
36
gamoyenebuli masala da kvlevis meTodebi
kvleva Catarda a. RvamiCavas sax. onkologiis nacionaluri
centris mamologiis ganyofilebaSi ZuZus kiboTi daavadebuli
kontingentis SerCevisaTvis, Tbilisis klinikuri da eqsperimentuli
Terapiis samecniero-kvleviT institutSi – „Terapiis erovnul
centrSi“ – amonarCevi pacientebis klinikuri SeswavlisTvis da al.
naTiSvilis sax. morfologiis institutSi histologiuri
gamokvlevisTvis.
a. RvamiCavas sax. onkologiis nacionalur centrSi
retrospeqtulad SeviswavleT ZuZus kiboTi daavadebuli mdedrobiTi
sqesis 1063 avadmyofobis istoria. istoriebis Seswavla xdeboda
1999_2001 ww. saarqivo masalidan.
al. naTiSvilis sax. morfologiis institutSi gamovikvlieT ZuZus
kibos gamo operaciulad mocilebuli 60 SemTxveva, romelTagan yvela
warmoadgenda postoperaciul masalas.
eqsperimentuli Terapiis samecniero-kvleviT institutSi –
„Terapiis erovnul centrSi“ – SerCeul iqna 18 pacienti sakontrolo
jgufisTvis.
pacientebis Seswavla asakobriv aspeqtSi xdeboda gerontologTa
saerTaSoriso asociaciis kievis klasifikaciis mixedviT: I jgufi _
axalgazrda da mowifuli asakis mqone pacientebi (20_44 ww); II jgufi
_ Suaxnis asakis pacientebi (45_59 ww); III jgufi _ xandazmuli asakis
pacientebi (60_79 ww).
ZuZus kibo dadasturebuli iyo anamneziT, klinikuri monacemebiT,
mamografiuli gamokvleviT, postoperaciuli histopaTologiuri
gamokvleviT, zog SemTxvevaSi birTvul-magnituri rezonansiTa da
kompiuteruli tomografiiT.
kibos histologiuri formebisa da avTvisebianobis xarisxis
dadgena xdeboda msoflios jandacvis organizaciis mier mowodebuli
ZuZus simsivneebis histologiuri klasifikaciis mixedviT (WHO- World
Health Organization Classification of Tumors, 2003).
37
avTvisebianobis xarisxis Sefasebisas mxedvelobaSi viRebdiT
simsivnur qsovilSi milakebis Camoyalibebis tendencias,
hiperqromatozsa da mitozebs, birTvebis araerTgvarovnebas zomis,
formis da SeRebvis intensivobis mixedviT (ix. cxr. 4).
cxrili 4. ZuZus kibo avTvisebianobis xarisxis mixedviT
qulebis raodenoba
1 2 3
milakebis Camoyalibebis tendencia
mkafio zomieri umniSvnelo, an ar aRiniSneba
hiperqromatozi da mitozebi
iSviaTi mxedvelobis
velSi
ori, sami hiperqromatuli
birTvi da mitozi
mxedvelobis velSi
ori, sami da meti
mxedvelobis velSi
birTvebis araerTgvarovneba zomis, formis da SeRebvis intensivobiT
erTgvarovani zomieri mravalferovneba
Ggamoxatuli pleomorfizmi
cxr. 1-dan gamomdinare, Tu samive kriteriumis jamuri maCvenebeli
Seadgens 3-5 qulas simsivne dabali avTvisebianobisaa (avTvisebianobis
I xarisxi – G1), 6-7 qula miuTiTebs avTvisebianobis saSualo doneze
(avTvisebianobis II xarisxi – G2), xolo 8-9 qula – maRal
avTvisebianobaze (avTvisebianobis III xarisxi – G3).
aseve saWiroa gaTvaliswinebul iyos fibrozis xarisxi,
limfoiduri da plazmocituri infiltracia, eqstramamarul qsovilSi
simsivnuri ujredebis invazia, maTi sisxlZarRvebSi da limfur
kvanZebSi SeWra, metastazebis ganviTareba.
masalis fiqsacia xdeboda 10% neitralur formalinSi da karnuas
safiqsacio narevSi. naWrebis nawilis Cayalibeba xdeboda parafinSi,
nawilis – celoidinSi. masala Cayalibebuli parafinSi, 4-5 mkm sisqis
seriuli anaTlebis misaRebad, iWreboda rotaciul mikrotomze,
38
celoidinSi Cayalibebuli masala iWreboda marxilian mikrotomze,
sisqiT 5-6 mkm.
yvela SemTxvevaSi anaTlebi iRebeboda Hhematoqsilini/eoziniTa da
pikrofuqsiniT van gizonis wesiT.
er-is statusi ganisazRvra l. s. basalikis modificirebuli
meTodiT. 100-700 mg gayinuli biofsiuri masala qucmacdeboda
faifuris WurWelSi, romelSic moTavsebuli iyo Txevadi azoti.
Semdeg emateboda buferi SefardebiT 1:6 (tris-HCl ph 7,4 –10, edta–1,5 mm,
ditiotreitol – 0,5mm+10% glicerini). 5–10 wT Semdeg eqstraqciis
Sedegad miRebul iqna homogenati, romlis centrifugirebiT 105000g 1
sT-Si miiReboda citozoli. louris meTodiT citozolis meSveobiT
ganisazRvreboda cila da mis meSveobiT receptorebi.
lipidebi gazomil iqna sisxlis SratSi Janway – 4500
speqtrofotometriT uzmod. saerTo qolesterini (sq) da
trigliceridebi (tg) – enzimuri meTodiT. maRali simkvrivis
lipoproteidebis qolesterini (mslq), dabali simkvrivis
lipoproteidebis qolesterini (dslq), Zalian dabali simkvrivis
lipoproteidebis qolesterini (Zdslq) – precipitaciis
SemdegBBIOLABO France reaqtivebis gamoyenebiT.
kvlevis Sedegebi Setanil iqna Microsoft Office–is Excell-is
statistikuri programis monacemTa bazaSi da damuSavda SPSS-11,5
programis statistikuri paketis gamoyenebiT.M monacemebi
warmodgenilia saSualo mniSvneloba ± standartuli gadaxra (M±SD)
saxiT. raodenobrivi uwyveti sidideebis SefasebisTvis gamoyenebul
iqna stiudentis t kriteriumi. sarwmunoebis koeficienti
ganisazRvreboda, rogorc p<0,05. korelacia testirdeboda Pearson-is
mixedviT. sarwmunoeba gamoiTvleboda t-statistikiTY or sxvadasxva
saSualosTvis da F-statistikisTvis.
39
danarTi – sakuTari masala
er `+” statusis mqone pacientTa jgufi
N gvari, saxeli er`+“ asaki sq dslq mslq Zdslq tg ai diagnozi
1 zaaliSvili ludmila 88.6 51 131.6 66.23 42.57 22.8 114 2.1 marj. Z. intraduqt. karc. T1N0M0
2 lipariaSvili nana 22.2 42 168.5 125.3 51 35.6 178 1.8 marj. Z. mainf. karc. T2N1M0
3 alaverdaSvili mzia 31.9 52 212 122.4 58 31.6 158 2.6
marcx. Z. mainf. fibroz. karc. T2N1M0
4 daviTaSvili dodo 48.6 49 158 51.5 64.4 42.1 210.5 3.6
marj. Z. mainf. fibroz. karc. TN1M0
5 RuduSauri liana 56.4 46 155 96 31 28 144 4
marcx. Z. mainf. fibroz. karc. T2N0M1
6 gogoberiSvili manana 11.6 56 166.4 97.4 46 23 115 2.6 marjv. Z. mainf. karc. T2N0M0
7 SalutaSvili laura 25.8 45 168 82 46.6 28.7 117 3.3 marjv. Z. karc. T2N0M0
8 gagua gulo 47.6 46 151 99 62 28 180 1.4 marj.Z. karc. T2N1M0
9 mindoraSvili manana 52.4 39 188 80 31 42.2 180 4.2 marc. Z. meduluri kibo T2N1M0
10 oganesiani luiza 20.5 45 136 102 53 33.1 155 2.6 marcx. Z. mainf. karc. T2N0M0
11 musaeva liana 12.2 51 131.6 66.23 42.57 22.8 114 2.1 marcx. Z. mainf. karc. T2N0M0
12 nadareiSvili n.v. 18.6 42 168.5 125.3 51 35.6 178 1.8 marcx. Z. mainf. karc. T2N1M0
13 mamedova sofia 46.7 52 212 122.4 58 31.6 158 2.6 marjv. Z. mainf. karc. T1N1M0
14 bibilaSvili 22.5 49 158 51.5 60.1 42.1 210.5 3.6 marcx. Z. mainf. karc. T2N0M0
40
nunu
15 bilixoZe Tina 18.2 46 155 96 31 28 144 4 sin; karc. T1N0M0
16 baziSvili nana 27.8 56 166.4 97.4 46 23 115 2.6 marjv. Z. pejetis daavadeba, T1N0M0
17 beriaSvili naTela 31.2 45 168 82 46.6 28.7 117 3.3 marcx. Z. fibroz. karc. T2N1M0
18 galstiani diana 38.4 40 160.3 100.7 55.3 33.7 137 2.2marcx. Z. intraduqt. karc. mastopaT. fonze T2N0M0
19 WikaiZe naTela 34.8 51 131.6 66.23 42.57 22.8 114 2.1 marcx.Z.mainf.fib.karc. T1N0M0 20 tatiSvili nana 36.4 42 168.5 125.3 51 35.6 178 1.8 marcx.Z.mainf. kibo T2N1M0
21 metoniZe nanuli 37.4 52 212 122.4 58 31.6 158 2.6 marjv.Z.mainf. karc. T2N1M0
22 cqifuriSvili irina 32.5 49 158 51.5 67 42.1 210.5 3.6 marjv. Z. pejetis daavadeba T2N0M0
23 gigauri irina 18.2 46 155 96 31 28 144 4 marjv.Z. mainf. karc. T2N1M0
24 inaSvili dali 17.8 56 166.4 97.4 46 23 115 2.6 marcx. Z. mainf. karc. T2N1M0
25 oqrojanaSvili lena 31.2 45 168 82 46.6 28.7 117 3.3 marcx.Z.mainf.fib.karc. T2N0M0
26 alieva naina 38.4 40 160.3 100.7 55.3 33.7 137 2.2 marj. Z. kibo T2N1M0
27 mumlaZe marine 20 39 193 79 43.6 22.5 162 2.6 marcx. Z. karc. T2N1M0
28 jiqia rusudani 45 46 151 99 62 28 180 1.4 marcx. Z. mainf. karc. T2N0M0
29 sadisova narina 28.6 39 188 80 31 42.2 180 4.2 marj.Z. mainf. karc. T1N0M0
30 kereseliZe manana 47.4 45 136 102 53 33.1 155 2.6 marcx. Z. mainf. karc. T2N0M0
31 SavguliZe nanuli 22.4 43 182 96 96 27.05 135.25 1.71 marcx.Z. mainf. Kkarc. T2N1Mo
32 lobJaniZe ekaterine 92.5 45 196 112.8 112.8 31.56 157.79 2.75 marcx. Z. mainf. karc.T2N1Mo
33 Sanava inga 54.6 42 186 176.7 176.7 32.25 161.26 4.5 marcx. Z. karcinoma. T2N0M0
41
er `–” statusis mqone pacientTa jgufi
N gvari, saxeli er`-“ asaki sq dslq mslq Zdslq tg ai diagnozi
1 tizlariSvili galia 8.2 63 298 191.5 64.4 42.1 210.5 5.4 marc. mainf. meduluri karc. T2N1M0
2 makaseeva marina 7.2 55 191 103 50 38 192 2.8 marj. Z. mainf. kibo T2N1M0
3 RvinianiZe gulnara 7.5 44 178 120.4 34.8 22.8 114 4.1 marcx. Z. mainf. karc. T1N0M0
4 rexviaSvili izolda 6.4 41 152 68 61 23 117 1.5 marjv. Z. karc. T2N0M0
5 xerxeuliZe irina 8.6 64 201 114.7 42.5 43.8 219 3.7 marcx. Z. mainf. karc.T2N1M0
6 gogiCaiSvili maia 9.6 40 200.2 95.3 60 29 145 2.7 marcx. Z. mainf. karc. T1N0M0
7 mayaSvili JuJuna 8.2 45 178 91.7 42.5 43.8 219 3.2 marjv. Z. karc. T2N1M0
8 karaxaniani marina 6.5 47 210 120.1 43.3 35 177 2.2 marj. Z. kibo T2N1M0
9 gamsaxurdia jilda 7.4 43 155 96 35 22.6 114 2.8 marjv. Z. karc. T2N1M0
10 metoniZe nanuli 5.8 52 212 123 58 31 157 2.6 marcx. Z. mainf. karc. T2N1M0
11 glurjiZe ekaterine 6.5 33 189 125.7 38.7 24.6 123 3.9 marjv. Z. mainf. karc. T 2N0M0
12 zoiZe TinaTini 9.1 48 155 183.2 44 23 114 3.6 mainf. Z. karc. T1N0Mo 13 akofiani lilia 8.4 50 214 140.3 57 28.6 123.6 3.3 marcx. Z. mainf. karc.T2N1M0
14 ZimceiSvili elza 8.5 38 147 81.6 42.6 22.8 114 2.5 marcx.Z. mainf. karc T2N1M0
15 nayofia lela 7.1 42 181.9 116.5 42.6 22.8 114 3.3 marjv. Z. mainf. karc. T1N0M0 16 cercvaZe nazi 5.4 55 177.7 128 42.2 35 110 3 marcx. Z. mainf. karc. T2N1M0 17 lobjaniZe cico 5.3 51 182 90.8 58 33.2 166 2.1 marcx. Z. mainf. intraduqt.
42
Kkarcinoma T1N1M0
18 beria manana 6.6 50 265 145 38.7 31.56 135.25 2.75marjv. Z. mainf. fibroz. karc. T1N1M0
19 grigoriani xaTuna 6.5 45 192 96 65 32.25 154.2 4.5 marjv. Z. mainf. fibroz. karc. T2N1M0
20 kakulia marina 8.3 40 200 130 70.3 40.2 161.26 2.06 marcx. Z. meduluri karc. T1N0M0.
21 nadimaSvili qristine 7.3 46 179 125 42.35 32.08 151.2 1.59
marcx. Z. aramainfiltr. wilakovani karc. T0N1M0
22 jiqia ana 8.9 49 220 106.7 114.9 30.35 160.4 5.3 marjv. Z. mainf. karc. T2N1M0
23 gurgeniZe nana 6.1 40 165 110 52.02 35 149 0.5 marcx. Z. mainf. Kkarc. T2N0M0
24 mamulaSvili qeTevan 4.8 42 210 88 46.44 42 61.39 1.4
infiltrac.. wilakovani karc. T1N0M0
25 nozaZe manana 5.5 52 188 176 65.7 38.6 155 2.9 marjv. Z. mainf. karc. T2N1M0
26 kobaxiZe qeTino 7.4 34 163 164 69.66 23.5 70 3.4
marjv. Z. mainf. (fibroz. soliduri Senebis) karc. T1N0M0
27 abramiSvili rusudani 9.2 37 179 103 40.2 48.6 78 3
marcx. Z. meduluri tipis karc. T2N1M0
43
sakontrolo jgufi
N gvari, saxeli asaki sq dslq mslq Zdslq tg ai
1 Zarqua manana 46 180.5 96 57.4 27.05 135.25 1.71
2 mdinaraZe lia 46 197.4 112.8 53.02 31.56 157.79 2.75
3 janeliZe marina 47 185.1 176.7 46.44 32.25 161.26 4.5
4 saxvaZe lela 48 190.2 105.9 65.79 29.48 147.39 2.06
5 jafariZe marina 48 181.9 80.16 69.66 32.08 160.4 1.59
6 manjaviZe ekaterine 49 185.8 174.8 38.7 30.35 151.73 5.3
7 giorgaZe sofo 45 150.93 78.394 42.35 30.186 61.39 0.925275
8 lekiSvili Tamari 46 162.54 68.432 61.6 32.508 154.35 1.375205
9 Todria lela 46 172 98.9 38.7 34.4 70.16 0.73913
10 CixlaZe nona 48 189.6 85.88 65.8 37.92 79 1.207732
11 aruTinova liana 46 150.93 47.214 73.53 30.186 119.27 2.196721
12 avaliani 45 189.63 109.354 42.35 37.926 78.93 0.734093
13 SanSiaSvili cisana 46 313.5 135.9 114.9 62.7 135.25 1.306843
14 kenWiaSvili lamara 46 197.4 104.9 53.02 39.48 157.79 0.881792
15 laRiZe lamara 47 255.4 157.88 46.44 51.08 161.26 0.617684
16 beriZe rusudani 48 201.2 95.17 65.79 40.24 147.39 1.114112
17 bezaraSvili mayvala 48 181.9 75.86 69.66 36.38 160.4 1.397838
18 rigiSvili venera 49 243.8 156.34 38.7 48.76 151.73 0.559422
44
sakuTar gamokvlevaTa Sedegebi
retrospeqtulad SeviswavleT ZuZus kiboTi daavadebuli
mdedrobiTi sqesis 1063 avadmyofobis istoria. Cveni masalis mixedviT
(ix. cxr. 5), I jgufSi – axalgazrda da mowifuli asakis pacientebi _
(20_44 ww) _ ganawilda 632 pacienti, II jgufSi – Suaxnis pacientebi –
(45_59 ww) _ 359 pacienti, da III jgufSi – xandazmuli pacientebi _
(60_79 ww) – 72 pacienti. I jgufidan er `+” simsivneebis mqone
pacientebis raodenobam Seadgina 429 pacienti (67,9%), xolo er `_”
simsivneebiT dasnebovnebuli pacientebis raodenobam Seadgina 203
SemTxveva (32,1%). II jgufSi pacientebis gadanawileba moxda
Semdegnairad: er `+” pacientebi – 306 SemTxveva (85,2%), er `_”
pacientebi – 53 (14,8%). III jgufis er `+” pacientebis raodenobam
Seadgina 57 SemTxveva (79,2%), xolo er `_” pacientebis raodenoba iyo 15
(20,8%).
cxrili 5. ZuZus kiboTi daavadebulTa er-is statusi asakobriv
aspeqtSi
Eer `+~ er `_“ jgufi Aasaki
raodenoba % raodenoba %
I _ 632 20-44 429 67.9 203 32,1
II _ 359 45-59 306 85,2 53 14,8
III _ 72 60-79 57 79,2 15 20,8
jandacvis msoflio organizaciis klasifikaciis mixedviT (WHO-
World Health Organization Classification of Tumors, 2003). ZuZus kibos formebi
Cvens masalaSi gadanawilda Semdegnairad (ix. cxr. 6)
45
cxrili 6. ZuZus kibos histologiuri formebis ganawileba er-is
statusisa da asakis mixedviT
er `+” er `_” ZuZus kibos
histologiuri
formebi
20-44 45-59
60-79
20-44
45-59 60-
79
arainvaziuri
sadinrovani
karcinoma
4.4 19 _ 10.7 13 _
arainvaziuri
wilakovani
karcinoma
2 2 _ 11.8 6 _
invaziuri
sadinrovani
karcinoma
65 45 44,2 56.5 60 19
invaziuri
wilakovani
karcinoma
12 5.4 31,9 21 21 1.3
invaziuri
meduluri
karcinoma
12 12.3 _ _ _ _
invaziuri
papiluri
karcinoma
0.9 _ _ _ _ _
invaziuri
adenokistozuri
karcinoma
0.9 _ _ _ _ _
skiri 2.6 12.3 _ _ _ _
komedokarcinoma _ _ 0,1 _ _ _
pejetis daavadeba _ 4 _ _ _ _
rogorc cxrili 6-dan vxedavT, er `+” arainvaziuri sadinrovani
karcinoma ufro xSirad gvxvdeba 45-59 wlis asakobriv jgufSi _
SemTxvevaTa 19%, 20-44 wlis asakobriv jgufSi man Seadgina 4,4%, xolo
60_79 wlis asakobriv jgufSi saerTod ar Segvxvedria. er `_”
arainvaziuri sadinrovani karcinomis gavrceleba kvlav Warbobda 45-59
46
wlis asakobriv jgufSi _ 13%, xolo 20-44 wlis asakobriv jgufSi man
Seadgina 10,7%. er `+” arainvaziuri wilakovani karcinomis gavrceleba
erTnairia 20-44 wlis da 45-59 wlis pacientebSi _ 2%. 60-74 wlis
asakobriv jgufSi igi ar Segvxvedria. er `_” arainvaziuri wilakovani
karcinomis SemTxvevaSi pacientTa 11,8% axalgazrda da mowifuli
pacientebi iyvnen. pacientTa 6% Suaxnis asakobrivi jgufis pacientebs
Seadgenda. iseve, rogorc er `+” somsivneebis SemTxvevaSi, er `_”
arainvaziuri wilakovani karcinoma xandazmul pacientebSi ar
Segvxvedria, 19% igi 60-74 wlis pacintebs aReniSnaT.
er `+” invaziuri wilakovani karcinomis yvelaze didi nawili (31,9%)
aRiniSna 60-74 wlis asakobriv jgufSi. meore adgilzea 20-44 wlis
asakobrivi jgufi (12%) da SedarebiT iSviaTia 45-59 wlis qalebSi _
5,4%. er `_” invaziuri wilakovani karcinomis erTnairi raodenoba
(21%) aRiniSna 20-44 da 45-59 wlis asakobriv jgufSi, xolo xandazmul
pacientebSi igi mxolod 1,3% Segvxvda.
er `+” invaziuri meduluri karcinoma 20-44 wlis asakobriv jgufSi
aRiniSna SemTxvevaTa 12%-Si, 45-59 wlis asakobriv jgufSi _ 12,3%
SemTxvevaSi da saerTod ar Segvxvedria 60-79 wlis pacientebSi. er `_”
invaziuri meduluri karcinomis SemTxvevebi saerTod ar aRniSnula.
er `+” invaziuri papiluri karcinoma vlindeba mxolod axalgazrda
da mowiful pacientebSi (0,9%), iseve rogorc er `+” invaziuri
adenokistozuri karcinoma (0,9%).
skiri umeteswilad warmoCinda 45-59 wlis asakobriv jgufSi (12,3%).
20-44 wlis asakobriv jgufSi igi aRiniSna 2,6% da yvela SemTxveva er
`+” statusTan iyo dakavSirebuli (4,6%).
komedokarcinoma Segvxvda mxolod 60-79 wlis asakSi (0,1%) da er
`+” statuss atarebda.
pejetis daavadeba aRiniSna mxolod Suaxnis asakis pacientebSi (4%)
da atarebda er `+” xasiaTs.
Cven agreTve SeviswavleT urTierTkavSiri er, asaksa da ZuZus kibos
histologiur formebs Soris (ix. cxr. 7). rogorc cx. 7-dan
warmoCindeba, er `+” statusis mqone axalgazrda da mowifuli
pacientebis asakobriv jgufSi (20-44 ww) yvelaze xSirad gvxvdeba
47
invaziuri sadinrovani karcinoma, sadac man Seadgina 65,5% (277
SemTxveva). am jgufSi ZuZus kibos sxva histologiuri formebi
Semdegnairad gadanawilda: arainvaziuri sadinrovani karcinoma _ 4,4%
(19 SemTxveva), arainvaziuri wilakovani karcinoma _ 2% (9 SemTxveva),
invaziuri wilakovani karcinoma _ 12% (52 SemTxveva), invaziuri
meduluri karcinoma _ 12% (52 SemTxveva), invaziuri papiluri karcinoma
_ 0,9% (4 SemTxveva), invaziuri adenokistozuri karcinoma _ 0,9% (4
SemTxveva), skiri _ 2,6% (12 SemTxveva), komedokarcinoma da pejetis
daavadeba ar Segvxvedria.
er `_” statusis mqone 20-44 wlis pacientebis asakobriv jgufSi
ZuZus kibos histologiuri formebis gadanawileba moxda Semdegnairad:
arainvaziuri sadinrovani karcinoma _ 10,7% (22 SemTxveva), arainvaziuri
wilakovani karcinoma _ 11,8% (24 SemTxveva), invaziuri sadinrovani
karcinoma _ 56,5% (115 SemTxveva), invaziuri wilakovani karcinoma _ 21%
(42 SemTxveva). invaziuri meduluri karcinomis, invaziuri papiluri
karcinomis, invaziuri adenokistozuri karcinomis, skiris,
komedokarcinomisa da pejetis daavadebis SemTxvevbi ar aRniSnula.
cxrili 7. er-is da ZuZus kibos histologiuri formebis
urTierTkavSiri axalgazrda da mowiful pacientebSi (20-44 ww)
er `+” er `_” ZuZus kibos
histologiuri
formebi
raodenoba % raodenoba %
arainvaziuri sadinrovani
karcinoma
19 4.4 22 10.7
arainvaziuri
wilakovani karcinoma
9 2 24 11.8
invaziuri sadinrovani
karcinoma
277 65 115 56.5
invaziuri wilakovani
karcinoma
52 12 42 21
invaziuri meduluri
karcinoma
52 12 _ _
invaziuri papiluri 4 0.9 _ _
48
karcinoma
invaziuri adenokistozuri
karcinoma
4 0.9 _ _
skiri 12 2.6 _ _
komedokarcinoma _ _ _ _
pejetis daavadeba _ _ _ _
Suaxnis asakis (45-59 ww) pacientebSi er `+” ZuZus kibos SemTxvevebi
gadanawilda Semdegnairad (ix. cxr. 8): arainvaziuri sadinrovani
karcinoma _ 19% (55 SemTxveva), arainvaziuri wilakovani karcinoma _ 2%
(6 SemTxveva), invaziuri sadinrovani karcinoma _ 45% (140 SemTxveva),
invaziuri wilakovani karcinoma _ 5,4% (17 SemTxveva), invaziuri
meduluri karcinoma _ 12,3% (38 SemTxveva), skiri _ 12,3% (38 SemTxveva),
pejetis daavadeba _ 4% (12 SemTxveva). invaziuri papiluri karcinomis,
invaziuri adenokistozuri karcinomisa da komedokarcinomis
SemTxvevebi ar dafiqsirebula.
er `_” statusis mqone 45-59 wlis pacientebis asakobrivi jgufis
SemTxvevaSi ZuZus kibos yvelaze gavrcelebul formas warmoadgenda
invaziuri sadinrovani karcinoma, sadac man Seadgina 60% (32 SemTxveva).
ZuZus kibos sxva formebis gadanawileba moxda Semdegnairad:
arainvaziuri sadinrovani karcinoma _ 13% (7 SemTxveva), arainvaziuri
wilakovani karcinoma _ 6% (3 SemTxveva), invaziuri wilakovani
karcinoma _ 21% (11 SemTxveva). invaziuri meduluri karcinomis,
invaziuri papiluri karcinomis, invaziuri adenokistozuri karcinomis,
skiris, komedokacinomisa da pejetis daavadebis SemTxvevbi ar
aRniSnula.
49
cxrili 8. er-is da ZuZus kibos histologiuri formebis
urTierTkavSiri Suaxnis pacientebSi (45-59 ww)
er `+” er `_” ZuZus kibos
histologiuri
formebi
raodenoba % raodenoba %
arainvaziuri sadinrovani
karcinoma
55 19 7 13
arainvaziuri
wilakovani karcinoma
6 2 3 6
invaziuri sadinrovani
karcinoma
140 45 32 60
invaziuri wilakovani
karcinoma
17 5.4 11 21
invaziuri meduluri
karcinoma
38 12.3 _ _
invaziuri papiluri
karcinoma
_ _ _
invaziuri adenokistozuri
karcinoma
_ _ _
skiri 38 12.3 _ _
komedokarcinoma _ _ _
pejetis daavadeba 12 4 _ _
50
er `+” statusis mqone xandazmuli pacientebis asakobriv jgufSi
(60-79 ww) (ix. cxr. 9) Segvxvda mxolod invaziuri sadinrovani karcinoma,
sadac man Seadgina 44,2% (32 SemTxveva), invaziuri wilakovani karcinoma
_ 31,9% (23 SemTxveva) da komedokarcinoma _ 0,1% (2 SemTxveva).
arainvaziuri sadinrovani karcinomis, arainvaziuri wilakovani
karcinomis, invaziuri meduluri karcinomis, invaziuri papiluri
karcinomis, invaziuri adenokistozuri karcinomis, skirisa da pejetis
daavadebis SemTxvevebi ar aRniSnula.
er `_” statusis mqone 60-79 wlis pacientebis asakobriv jgufSi
Segvxvda mxolod invaziuri sadinrovani karcinoma _ 19% (14 pacienti)
da invaziuri wilakovani karcinoma _ 1,3% (1 SemTxveva). ZuZus kibos
danarCeni histologiuri formebi _ arainvaziuri sadinrovani
karcinoma, arainvaziuri wilakovani karcinoma, invaziuri meduluri
karcinoma, invaziuri papiluri karcinoma, invaziuri adenokistozuri
karcinoma, skiri, komedokarcinoma da pejetis daavadeba ar aRniSnula.
51
cxrili 9. er-is da ZuZus kibos histologiuri formebis
urTierTkavSiri xandazmul pacientebSi (60-79 ww)
er `+” er `_” ZuZus kibos
histologiuri
formebi
raodenoba % raodenoba %
arainvaziuri sadinrovani
carcinoma
_ _ _ _
arainvaziuri
wilakovani karcinoma
_ _ _ _
invaziuri sadinrovani
carcinoma
32 44,2 14 19
invaziuri wilakovani
karcinoma
23 31,9 1 1.3
invaziuri meduluri
karcinoma
_ _ _ _
invaziuri papiluri
karcinoma
_ _ _ _
invaziuri adenokistozuri
karcinoma
_ _ _ _
skiri _ _ _ _ komedokarcinoma 2 0,1 _ _
pejetis daavadeba _ _ _ _
Cvens mier agreTve Seswavlil iqna ZuZus kiboTi daavadebul qalTa
lipiduri speqtris maCveneblebi er-is statusis gaTvaliswinebiT
(diagrama 1).
pacientebi gadanawilebul iyvnen er `+” (I jgufi) da er `_” (II
jgufi) jgufebSi. jgufebs Soris er-is statusis maCveneblebis
Sedarebisas aRiniSna statistikurad sarwmuno gansxvaveba: 32,1±15,2
fmol/mg da 7,9±3.2 fmol/mg Sesabamisad (p<0,001).
52
I da II jgufis maCveneblebis Sedarebisas gamovlinda: sq _ 169,±±21,6
mg/dl da 190,9±48,4 mg/dl (p<0.05); dslq _ 95, ±23,9 mg/dl da 118,7±33,9
mg/dl (p<0.03); Zdslq _ 28,0±5,9 mg/dl da 33,6±7,6 mg/dl (p<0.05), da
trigliceridebi (tg) _ 138,6±30,4 mg/dl da 164,3±38,2 mg/dl (p<0.05) Soris
statistikurad sarwmuno gansxvaveba (cx. #4), rac aTerogenuli
lipidebis maRali maCveneblebiTaa ganpirobebuli.
rac Seexeba mslq-is maCveneblebs, maT Soris statistikurad
sarwmuno sxvaoba ar dafiqsirebula: (48,2±10,6 mg/dl da 48,4±10,4 mg/dl).
statistikurad sarwmuno sxvaoba agreTve ar aRniSnula ai-is
Soris (3±0,9 da 3±1,25 Sesabamisad ).
gamokvlevis dros jgufebs Soris asakobrivi sxvaoba
statistikurad ar gamovlenila (44,8±6,0 da 49,2±7,8 Sesabamisad).
53
diagrama 1. ZuZus kiboTi daavadebul qalTa lipiduri speqtris
maCveneblebi er-is statusis gaTvaliswinebiT
ER AGE TC LDL-C HDL-C VLDL-C TG IA
S1S2
7,91
49,2
p<0,
05 1
90,9
p<0,
03 1
18,7
48,4
p<0,
03 3
3,6
p<0,
05 1
64,3
3,1
32,1
p<0,
001
44,8
169,
1
95,2
48,2
28,0
138,
6
2,81
0
50
100
150
200
250
S1_ er `+” simsivneebis mqone pacientTa jgufi;
S2 – er `_” simsivneebis mqone pacientTa jgufi;
ER _ estrogen receptorebi; AGE _ asaki; TC – saerTo qolesterini;
LDL -C – dabali simkvrivis lipoproteinebis qolesterini; HDL-C –
maRali simkvrivis lipoproteinebis qolesterini; TG – trigliceridebi;
IA – aTerogenobis indeqsi; p _ sarwmuno sxvaoba.
Seswavlili 60 SemTxvevidan histogenezis mixedviT 40 sadinrovani
karcinomaa, 6 _ wilakovani karcinoma, 4 _ meduluri karcinoma, 6 _
fibrozuli kibo (skiri), 2 _ pejetis daavdeba.
54
yvela pacienti gadavanawileT 2 jgufad jandacvis organizaciis
mier mowodebuli ZuZus simsivneebis histologiuri klasifikaciis
mixedviT (WHO- World Health Organization Classification of Tumors, 2003). I jgufSi
Sevida 28 pacienti avTvisebianobis I xarisxiT _ G1, II jgufSi _ 32
pacienti avTvisebianobis II xarisxiT _ G2.
garda amisa, Cvens mier Seswavlil iqna 60 pacientis lipiduri
speqtri ZuZus kibos stadiurobasTan mimarTebaSi (ix. cxr. 3).
cxrili 10. lipiduri cvlis maCveneblebi ZuZus kiboTi daavadebul
pacientebSi
jgufi asaki sq dslq mslq Zdslq
tg Aai
I 45,8±5,4 165,7±23,0 48,7±10,5 91,8±21,3 31±6,8 154,2±30,2 2,7±0,8 II 47,7±8,4
190±35,0
48,4±9,6 117±32.4
30,6±7,8
148,8±40,7
3,1±0,9
P >0,5 <0,05 >0,7 <0,02 >0,5 >0,5 >0,5 sq – saerTo qolesterini (mg/dl), dslq – dabali simkvrivis lipoproteinebis qolesterini (mg/dl), mslq _ maRali simkvrivis lipoproteinebis qolesterini (mg/dl), Zdslq _ Zalian dabali simkvrivis lipoproteinebis qolesterini (mg/dl), tg _ trigliceridebi (mg/dl), ai _ aTerogenobis indeqsi, p _ sarwmuno sxvaoba.
lipiduri speqtris maCveneblebs Soris statistikurad sarwmuno
sxvaoba aRiniSna sq (165,7±23,0 mg/dl da 190±35,0 mg/dl Sesabamisad
(p<0,05) da mslq (91,8±21,3 mg/dl da 117±32.4 mg/dl Sesabamisad (p<0,02)
Soris.
lipiduri speqtris danarCen maCveneblebs Soris (mslq _ 48,7±10,5 mg/dl
da 48,4±9,6 mg/dl, Zdslq _ 31±6,8 mg/dl da 30,6±7,8 mg/dl, tg _ 154,2±30,2
mg/dl da 148,8±40,7 mg/dl, ai _ 2,7±0,8 da 3,1±0,9) statistikuri sxvaoba ar
gamovlenila.
55
miRebuli monacemebis analizi
Tanamedrove medicinis ori didi problemis _ ZuZus kibosa da
aTerosklerozis _ urTierTmimarTebis sakiTxis kvleva warmoadgens
aqtualur sakiTxs am ori daavadebis mier gamowveuli maRali
invalidobisa da letalobis gamo (Bernstein L.,1998; Симонова Л. И., Гертман
В. З., Пушкарь С., 2002).
cnobilia am ori daavadebis saerTo risk-faqtorebis mniSvneloba
maT genezsa da ganviTarebaSi. am risk-faqtorebis struqturaSi
centraluri adgili ukavia asaks (Brinton L. A., Devesa S. S, 1996, Key T. J.,
Verkasalo P. K., Banks E., 2001).
asakis matebasTan erTad matulobs ZuZus kibos ganviTarebis riskic.
yovelwliurad aRiniSneba 14 000 meti letaluri SemTxveva da igi
gansakuTrebiT xSiria 50-64 wlis asakis qalebs Soris (Beral V., Banks E.,
Reeves G., 2002). rogorc aTerosklerozi, aseve ZuZus kibos riski maRalia
premenopauzisa da gansakuTrebiT menopauzis asakSi (Bain R. P., Greenberg R.
S., Whitaker J. P., 1986). aRniSnuli gapirobebulia estrogenebis raodenobis
cvlilebiT asakTan damokidebulebaSi (Dickson R. B., Stancel G. M., 2000).
miuxedavad mravalricxovani kvlevebisa mravali sakiTxi moiTxovs
dazustebas arsebuli urTierTgamomricxavi debulebebis gamo. saqme
exeba estrogenebisa da er-is urTierTkavSirs ZuZus kibos morfogenezsa
da prognozSi (Desai S. B., Moonim M. T., Gill A. K., Punia R. S., Naresh K. N., Chinoy
R. F., 2000). TviT estrogenebis raodenoba icvleba qalis organizmis
funqcionirebis periodebTan mimarTebaSi, iseve rogorc estrogen-
statusi (Desai S. B., Moonim M. T., Gill A. K., Punia R. S., Naresh K. N., Chinoy R. F.,
2000) erTis mxriv, xolo meores mxriv, lipiduri statusi (Симонова Л.
И., Гертман В. З., Пушкарь С. Н., 2002). Aam ukanaskneli risk-faqtorebisa da
ZuZus kibos morfogenezis kavSiri metad bundovania. garda erTeuli
arasruli gamokvlevisa, ar arsebobs mwyobri paTogenezuri rgolebis
mimdevroba am parametrebis kavSiris Sesaxeb, Tumca cnobilia
estrogenebis antiaTerogenuli efeqti (Цырлина Е. В., Гамаюнова В. Б.,
Порошина Т. Е., 1999), rac amasTanave ZuZus kibos maRali ganviTarebis
riskis matarebelia (Chen C. L., Weiss N. S., Newcomb P., Barlow W., White E.,
56
2002). Aamdenad, Zneli dasadgenia zRvari estrogenebis Terapiul da
morbidul statuss Soris. hormonuli receptorebis statuss
gansazRvravs rigi faqtorebi: sqesi, asaki, rasa, organos lokalizacia,
simsivnis ujredovneba da histologiuri diferenciacia, menopauza,
fexmZimoba, laqtacia, wamlebis miReba (Wittliff J. L., et al., 1995, Hill A. D.,
Doyle J. M., McDermon E. W. et al., 1997).
Eer-is statusi mniSvnelovnadaa damokidebuli estrogenebis
raodenobasTan. estrogeni es aris hormoni, romelic aucilebelia
sarZeve jirkvlis normaluri zrdisa da ganviTrebisTvis. estrogens
udidesi mniSvneloba aqvs reproduqciul procesebSi da aregulirebs
menstrualur cikls (Moudgil V. K , 1985).
sakiTxis gadaWraSi sinaTlis Setana SesaZlebelia retrospeqtuli
analiziT ZuZus kibos morfogenezis, lipiduri da er-is statuss Soris
asakobriv aspeqtSi, estrogenis regulaciis TandaTanobiTi regresis
pirobebSi.
Cveni kvlevis monacemebi ar asaxavs epidemiologiur monacemebs ZuZus
kibos askobrivi gavrcelebis mxriv. literaturis mixedviT ZuZus kibos
raodenoba metia xandazmul pacientebSi axalgazrda da mowiful
pacientabTan SedarebiT (Bernstein L., 1998; Bain R. P., Greenberg R. S., Whitaker J.
P., 1986). Tumca, amerikis kibos asociaciis monacemebis Tanaxmad, afro-
amerikel qalebs 40 wlis Semdeg aReniSnebaT ZuZus kibos SedarebiT
meti raodenoba, kavkasiel qalebTan SedarebiT, romlebSic ZuZus kibos
gavrceleba Warbobs 40 wlis asakamde.
Cveni varaudiT, onkocentrSi Catarebuli operaciebis struqturaSi
axalgazrda da mowifuli kontingentis raodenobis umetesoba
gamowveulia am kontingentis operaciisTvis momarTvianobis aqtivobiT
da warmoadgens jandacvis organizaciis problemas danarCeni asakis
populaciaSi saganmanaTleblo da profilaqtikuri RonisZiebebis
gaumjobesebis Sesaxeb.
Cvens mier Seswavlili 1063 pacientidan er `+” simsivneTa SemTxvevebi
(ix. cxr. 5) Warbobs er `_” simsivneebis raodenobas, rac emTxveva sxva
avtorebis mier Catarebul gamokvlevebis Sedegebs (Blanco G., Alavaikko M.,
57
Ohala A. et al., 1984, Barnes D. M., Millis R. R., 1995, McCarty K. S., Silva J. S., Cox E. B.,
Leight G. S., Wells S. A., 2000).
ZuZus kibos mimdinareobas didad gansazRvravs er-is statusi (Beverly
L. N., Flanders D., Go R. C. P., et al., 1987), romelic Tavis mxriv kanonzomier
damokidebulebaSia asakTan, e.i. estrogenebis raodenobasTan (Wittliff J. L.,
1984; Barnes D. M., Millis R. R., 1995).
K. Seibert da Tanaavtorebis (1982) mier dadginda, romEestrogenebis
raodenobis Semcirebis paralelurad matulobs er `+” simsivneebis
procentuli raodenoba, rasac adasturebs Cveni monacemebic (ix. cxr. 5).
kerZod, I jgufSi Tu er `+” simsivne aReniSnaT pacientTa 67,9%, II da III
jgufSi Sesabamisad 85,2% da 79,2%.
sxva suraTi iSleba er `_” simsivneebis SemTxvevaSi. Yyvelaze meti
procentuli raodenoba aRiniSna axalgazrda da mowifuli asakis
pacientebSi – im periodSi, rodesac estrogenebis raodenoba SedarebiT
stabiluri da normaluria. Tu gaviTvaliswinebT literaturis
monacemebs, rom er `_” simsivneebis genezi ar aris estrogenebis
regulaciiT gapirobebuli (Wishaft G. C., Harnett A. N., Purushotham A. D., 1998),
cxadi xdeba Cveni monacemebis mtkicebulebis marTebuloba.
mniSvnelovania is garemoeba, rom fiziologiurad, menopauzaSi myof
asakovan pacientebSi, estrogenis SemcirebasTan erTad, sisxlSi
matulobs aTerogenuli lipidebi (Stout R.W., 1985). Bbolo wlebis
samedicino periodikaSi gamoqveynda erTeuli naSromebi lipiduri da
er-is statusis mniSvnelobis Sesaxeb ZuZus kibos genezSi, Tumca
Sedegebi xSirad araerTgvarovania (Stevenson J. C., Crook D., Godsland I. F.,
Collins P., Whitehead M. I., 1994; Speroff L., Glass R. H., Kase N. G., 1994). A
Cveni masalis monacemebiT SeviswavleT da davadgineT lipiduri
speqtrisa da er-is statusis damokidebuleba (ix. diagrama 1) ZuZus
kibos dros. pacientebi gadanawilebul iyvnen er `+” (I jgufi) da er
`_” (II jgufi) jgufebSi. jgufebs Soris aRiniSna statistikurad
sarwmuno gansxvaveba er-is statusis maCveneblebis Sedarebisas: 32,1±15,2
fmol/mg da 7,9±3.2 fmol/mg Sesabamisad (p<0,001).
I da II jgufis maCveneblebis Sedarebisas gamovlinda: II jgufSi (er
`_”) statistikurad sarwmuno aTerogenuli lipidebis _ sq-is (190,9±48,4
58
mg/dl), dslq-is (118,7±33,9 mg/dl) da tg-is (164,3±38,2 mg/dl) _ maRali
cifrebi, romelic aWarbebs miRebul normebs II jgufisTvis (Климов А. Н.,
Никулчева Н. Г., 1998), sapirispirod, I jgufis Sesabamis maCveneblebTan (
sq _ 169,±±21,6 mg/dl dslq _ 95, ±23,9 mg/dl da tg _ 138,6±30,4 mg/dl) da
ganapirobebs er `_” simsivneebis dros sisxlis aTerogenul xasiaTs.
rac Seexeba mslq-is maCveneblebs, maT Soris statistikurad sarwmuno
sxvaoba ar dafiqsirebula: (48,2±10,6 mg/dl da 48,4±10,4 mg/dl). Cvens mier
miRebuli kvlevis Sedegebi msgavsia sxva mkvlevarTa Sedegebisa (Howson
C. P., Kinne D., Wynder E. L., 1986, Симонова Л. И., Гертман В. З., Пушкарь С. Н., 2002).
literaturidan cnobilia, rom er `+” simsivneebisgan gansxvavebiT,
er `_” simsivneebis dros ar xdeba estrogenebis samizne qsovilebTan
SekavSireba (Elledge R. M., Osborne C. K., 1997; Anderson E., 2002).
er `+” jgufisaTvis damaxasiaTebelia SedarebiT dabali maCveneblebi
aTerogenuli lipidebisa. Aamazeve metyvelebs I jgufSi gamovlenili
uaryofiTi korelaciuri kavSiri tg da mslq Soris (r=0.617, p<0.05).
miRebuli Sedegebi wamoWris metad mniSvnelovan sakiTxs: er `_”
simsivneebis dros estrogenebis done ar ganapirobebs ZuZus kibos
genezs, Tumca am dros sisxlSi matulobs aTerogenuli lipidebi, rac
SesaZlebelia iwvevdes er `_” kibos zrdas, ujredebis proliferaciasa
da gavrcelebas _ anu avTvisebianobis prognozuli maCvenebelia.
er-is raodenobaze damokidebulia malignizaciis procesi da ZuZus
kibos prognozi. Aam aspeqtSi kvlevis Sedegebi urTierTgamomricxavia.
rigi avtorebi miiCneven, rom sarZeve jirkvlis malignizaciis dros,
er-is raodenoba Semcirebulia (Koenders P.G., Beex L.V., et all,1991), zogis
monacemebiT ki aranairi arsebiTi kavSiri er-sa da morfologiur
Taviseburebebs Soris ar arsebobs (Roberts A. N., Hähnel R.,1981).
sxva kvlevebis Tanaxmad, er `_” simsivneebi atarebs gansakuTrebul
morfologiur Tvisebebs. maT wamyvan morfologiur Tvisebas
miekuTvneba intensiuri gavrceleba (gamoxatuli invaziuroba) (Thomas C.
et al., 2005).
Cveni monacemebiT davadgineT kavSirebi er-is statuss, morfologiur
formebsa da avTvisebianobas Soris, ris safuZvelzec SeiZleba
prognozze msjeloba.
59
mniSvnelovania er-is da ZuZus morfologiuri struqturis
literaturuli aspeqtebi. kerZod, ZuZus normaluri qsovilis
morfologia _ epiTeluri ujredebis simcire da cximovani ujredebis
siWarbe kavSirSia er-is mcire raodenobasTan (Wittliff J., 1975; Leclercq G.,
Heuson J., 1977).
rogorc er `+”, ise er `_” ZuZus kiboTi daavadebul pacientebs
aReniSnebaT sadinrovani karcinomis ufro meti SemTxvevebi sxva
morfologiur formebTan SedarebiT.
rogorc cxr. 6-dan Cans, samive asakobriv jgufSi ZuZus kibos
invaziuri formebis SemTxvevebi Warbobs arainvaziuri ZuZus kibos
SemTxvevebs, rac emTxveva sxva avtorebis mier Catarebul gamokvlevebis
Sedegebs (Gathani T., Bull D., Green J., Reeves G., Bera V., 2005; Краевский Н. А.,
Смольянникова А. В., Саркисова Д. С., 1993).
rogorc invaziuri, aseve arainvaziuri ZuZus kibos SemTxvevaSi, er-
is statusis miuxedavad, kibos morfologiis saerTo struqturaSi
Warbobs sadinrovani karcinomis SemTxvevebi, rac emTxveva sxva
kvlevebis Sedegebsac (McKeown-Eyssen G. E., Rogers-Melamed I., Clarke E. A., 1985,
Elledge R. M., Osborne C. K., 1997).
gaviTvaliswineT ra, rom Cvens mier Seswavlili masala ar
warmoadgens epidemiologiuri kvlevis masalas, morfologiuri
formebis struqturuli ganawileba gamovTvaleT procentulad
sakuTriv jgufebSi. dayofa saSualebas iZleva koreqturad moxdes
calkeuli morfologiuri formebis Sefaseba asakisa da er-is statusis
mixedviT (ix. Ddiagrama 2 da 3).
marTalia, Cvens SemTxvevaSi ar Segviswavlia estrogenis done
sisxlSi, magram unda aRiniSnos, rom I jgufis pacientebs ar
aReniSnebodaT menopauza. II jgufis yvela qali imyofeboda
premenopauzisa da menopauzis periodSi, xolo III jgufis pacientebi
menoepauzis mdgomareobaSi,Ee.i. Seiqmna estrogenebis TandaTanobiTi
regresis modelirebis pirobebi.
Ddiagrama 2 avlens er `+” simsivneebis dros morfologiuri formebis
procentul struqturas estrogenis regresis asakobriv aspeqtSi.
60
diagrama 2. asakisa da morfologiuri formebis kavSiris urTierToba
Eer `+“ pacientebSi
0
10
20
30
40
50
60
70
1 2 3 4 5 6
I jg II jg III jg
I jgufi _ 20-44 wlis pacientebi; II jgufi _ 45-59 wlis pacientebi; III jgufi _ 60-79 wlis pacientebi. 1 _ arainvaziuri sadinrovani karcinoma; 2 _ arainvaziuri wilakovani karcinoma; 3 _ invaziuri sadinrovani karcinoma; 4 _ invaziuri wilakovani karcinoma; 5 _ invaziuri meduluri karcinoma; 6 _ skiri Aaxalgazrda da mowiful asakSi _ estrogenebiT SedarebiTi
normaluri regulaciis pirobebSi _ Warbobs sadinrovani invaziuri
karcinoma (65%), invaziuri wilakovani da meduluri karcinoma (12-12%).
Eestrogenebis Semcirebis pirobebSi Suaxnis asakSi SedarebiT
mcirdeba sadinrovani invaziuri karcinomis procentuli raodenoba
(45%), Tumca matulobs arainvaziuri sadinrovani karcinomisa da
skiris procentuli raodenoba (19% sapirispirod 4,4% da skiris
SemTxvevaSi 12,3%, sapirispirod 2,6%) I jgufTan mimarTebaSi.
61
amerikis kibos asociaciis monacemebis Tanaxmad, invaziuri
sadinrovani karcinomis SemTxvevaTa 2/3 Suaxnis da xandazmul
pacientebze modis.E
Cveni monacemebiT er `+” kibos dros estrogenebis donis sxvaoba
(anu asakobrivi aspeqti) ar moqmedebs arainvaziuri wilakovani da
invaziuri meduluri karcinomis paTogenezze, orive jgufSi erTnairi
procentuli maCveneblebis arsebobis SedegiT.
Eer `_” simsivneebis SemTxvevebSi, estrogenebis done ar aregulirebs
invaziurobas sadinrovani karcinomis SemTxvevaSi (ix. Ddiagrama 3),
razec metyvelebs arainvaziuri da invaziuri sadinrovani karcinomis
procentuli struqtura. Aarainvaziuri wilakovani karcinomis
ganviTarebas xels uwyobs estrogenis Semcireba, xolo invaziurobas ar
ganapirobebs.
Ddiagrama 3. asakisa da morfologiuri formebis kavSiris urTierToba
Eer `_” pacientebSi
0
20
40
60
80
100
120
1 2 3 4
I jg II jg III jg
I jgufi _ 20-44 wlis pacientebi; II jgufi _ 45-59 wlis pacientebi; III jgufi _ 60-79 wlis pacientebi. 1 _ arainvaziuri sadinrovani karcinoma; 2 _ arainvaziuri wilakovani karcinoma; 3 _ invaziuri sadinrovani karcinoma; 4 _ invaziuri wilakovani karcinoma
62
Eestrogenebis raodenoba da er-is statusi gansazRvravs
invaziurobas, gavrcelebas, lipemiasa da dslq-is receptorebis
inicirebas kibos qsovilSi (Elwood J. M., Godolphin W., 1980; Victor G., Cannon R.
O., 1996). Mmeores mxriv, zogierTi kibos forma producirebs mslq-is
(Симонова Л. И., Гертман В. З., Пушкарь С. Н., 2002). Tumca aRniSnuli kvlevebi
sporadulia da ar asaxavs sakiTxis sisrules.
Aam sakiTxis gadawyvetisTvis SeviswavleT lipiduri speqtri ZuZus
kibos stadiurobasTan mimarTebaSi (ix. cxr. 10). Aasakis variacia 40-56
ww.
miRebuli Sedegidan gamomdinareobs, rom kibos avTvisebianobis
dros, sarwmunod matulobs sq (I da II stadia): 165,7±23,0 mg/dl da
190±35,0 mg/dl da dslq (I da II stadia): 91,8±21,3 mg/dl da 117±32.4
mg/dl.
lipiduri speqtris danarCen maCveneblebs Soris (mslq _ 48,7±10,5 mg/dl
da 48,4±9,6 mg/dl, Zdslq _ 31±6,8 mg/dl da 30,6±7,8 mg/dl, tg _ 154,2±30,2
mg/dl da 148,8±40,7 mg/dl, ai _ 2,7±0,8 da 3,1±0,9) statistikuri sxvaoba ar
gamovlenila.
sq-is donis mateba dakavSirebuli iyo dslq-is fraqciis sarwmuno
matebasTan. amgvari disbalansi axasiaTebs aTerogenulobas, radgan
dslq-is fraqcia warmoadgens qolesterinis ZiriTad gadamtans
periferul qsovilebSi. igi Seicavs sisixlis qolesterinis 80%. mslq
warmoadgens antiaTerogenul fraqcias da awarmoebs qolesterinis
sawinaaRmdego transportirebas organizmSi (Климов А. Н., Никулчева Н. Г.,
1995).
amgvarad, I-II stadiis ZuZus kiboTi daavadebul pacientebs daavadebis
da misi xangrZlivobis progresirebasTan erTad sisxlis Sratis
lipiduri speqtrSi aRiniSneboda sq-is da dslq-is Semcireba, tg-is
matebis umniSvnelo tendenciiT.
cnobilia, rom aqtiurad zrdadi avTvisebiani simsivis fonze
sisxlSi SeiZleba aRiniSnos hipoqolesterinemia da mslq-is da dslq-is
donis Semcireba (Fanelli F. R., Cangiano C., Muscaritolli M., et al., 1995, Kerber J.,
Pricelius S., Heidrich M. Miller M., 1999). es aixsneba simsivnis mier
qolesterinSemcveli metabolitebis aqtiuri SekavSirebiT membranuli
63
struqturebis CamoyalibebisTvis avTvisebiani ujredebis meSveobiT. am
fonze tg-is da maTi warmoebulebis (mono- da digliceridebis) done
SeiZleba matulobdes, radgan simsivnuri lipolizuri substanciebi
Slian organizmis cximovan qsovils da amiT amdidreben maT fonds
(Kerber J., Pricelius S., Heidrich M. Miller M., 1999, Allampallam K., Dutt D., Nair C., et al.,
2000).
Tumca ZuZus kiboTi daavadebul pacientTa lipidur profils gaaCnia
garkveuli Taviseburebebi. kerZod, aseTi pacientebisTvis
damaxasiaTebelia α-qolesterinisa an mslq-is donis mateba sisxlSi
(Boyd N. F., McGuire V., 1990, Moorman P. G., Hulka B. S., Hiatt R. A., et al., 1998). es
nawilobriv dakavSirebulia imasTan, rom α-qolesterini SesaZlebelia
sinTezirdes ZuZus simsivnuri ujredebidan (Hurlimann J., Van Melle G., 1991).
literaturis monacemebis Tanaxmad, mslq-is fraqciis done
mizanSewonilia gaTvaliswinebul iqnes avTvisebiani simsivnis
sawinaaRmdego Terapiis Catarebisas, rogorc misi efeqturobis erT-
erTi maCvenebeli (Clinical practice guidelines for use of tumor markers in breast and
colorectal cancer, 1996), xolo mslq-is donis mateba _ rogorc
arakeTilsasurveli prognostuli faqtori.
Eer `+ invaziuri simsivnis gavrceleba, anu metastazebis arseboba
mimdinareobs statistikurad sarwmunod momatebuli aTerogenuli
lipidebis (sq, dslq, tg) fonze (ix. cxr. 11), xolo mslq-is maCveneblebi
ar aris gansxvavebuli I stadiisgan. savaraudod, aTerogenuli
lipidebis momateba xmardeba simsivnis gavrcelebas, rogorc
axalwarmoqmnili ujredebis samSeneblo masala. Ees jgufi imyofeba
aTerosklerozuli daavadebebis riskis qveS.
64
cxrili 11. invaziuri da arainvaziuri karcinomis damokidebuleba
lipidur speqtrTan estrogen-statusis gaTvaliswinebiT
I sq dslq Mmslq tg invaz. er `+” I stadia 170,6± 23 88 ,5±21,4 50,6±10,7 134,5±21,1 invaz. er `+” II stadia 194,3±36,7 124,1±32,4 49.4±9.3 166,6±40 arainvaz. er `+” I stadia 164,4±6,4 100±18,1 43,6±8,7 138,5±29,4 arainv. er `_” I stadia 185±22,3 94±18,4 45,5±9,5 156,7±43,8 invaz. er `_” I stadia 208±33,8 99±18,5 53,7±8,3 124,3±17,6 invaz. er `_” II stadia 163,2±14 142,5±31,6 40±3,7 184±38,5 sadinr. karc. er`+” I stadia
197±16,8
89,7±19,6
48,6±12,3
145,2±26,5
sadinr. karc. er`+” II stadia 176,2±18,7 106,1±19,4 46,2±10,6
182,5±37,1
sakontrolo jgufi 196±40 109±37,2 58±18,5 155.7±17.2
sq – saerTo qolesterini (mg/dl), dslq – dabali simkvrivis lipoproteinebis qolesterini (mg/dl), mslq _ maRali simkvrivis lipoproteinebis qolesterini (mg/dl), Zdslq _ Zalian dabali simkvrivis lipoproteinebis qolesterini (mg/dl), tg _ trigliceridebi (mg/dl), ai _ aTerogenobis indeqsi, p _ sarwmuno sxvaoba.
E
Eer „–“ invaziuri simsivneebis II stadiis dros aRiniSneba sq-is da
mslq-is daqveiTebuli maCveneblebis fonze dslq-is da tg-is maRali
mniSvnelobebi I stadiisgan gansxvavebiT.
er `+“Aarainvaziuri I da er „_“ I stadia mxolod sq-is raodenobiTaa
gansxvavebuli, amdenad arainvaziuri er „_“ simsivneebi avTvisebianobiT
gamoirCeva.
sadinrovani er „+“ invaziuri karcinomis dros gavrceleba
mimdinareoba statistikurad dabali sq-is, maRali dslq-is da tg-is
fonze.
65
i l u s t r a c i e b i
66
suraTi 1. pejetis daavadeba, estrogen-uaryofiTi. X 250
67
suraTi 2. sadinrovani karcinoma, estrogen-uaryofiTi. X 320
68
suraTi 3. sadinrovani karcinoma, estrogen-uaryofiTi. X 120
69
suraTi 4. sadinrovani karcinoma, estrogen-uaryofiTi. X 200
70
suraTi 5. sadinrovani karcinoma, estrogen-uaryofiTi. X 120
71
suraTi 6. sadinrovani karcinoma, estrogen-uaryofiTi. X 200
72
suraTi 7. sadinrovani karcinoma, estrogen-uaryofiTi. X 250
73
suraTi 8. sadinrovani karcinoma, estrogen-uaryofiTi. X 320
74
suraTi 9. sadinrovani karcinoma, estrogen-uaryofiTi. X 250
75
suraTi 10. skiri, estrogen-uaryofiTi. X 250
76
suraTi 11. wilakovani karcinoma, estrogen-uaryofiTi. X 200
77
suraTi 12. wilakovani karcinoma, estrogen-uaryofiTi. X 250
78
suraTi 13. wilakovani karcinoma, estrogen-uaryofiTi. X 200
79
suraTi 14. meduluri karcinoma, estrogen-dadebiTi. X 120
80
suraTi 15. sadinrovani karcinoma, estrogen-dadebiTi. X 300
81
suraTi 16. sadinrovani karcinoma, estrogen-dadebiTi. X 350
82
suraTi 17. sadinrovani karcinoma, estrogen-dadebiTi. X 200
83
suraTi 18. sadinrovani karcinoma, estrogen-dadebiTi. X 320
84
suraTi 19. sadinrovani karcinoma, estrogen-dadebiTi. X 320
85
suraTi 20. sadinrovani karcinoma, estrogen-dadebiTi. X 250
86
suraTi 21. sadinrovani karcinoma, estrogen-dadebiTi. X 300
87
suraTi 22. sadinrovani karcinoma, estrogen-dadebiTi. X 300
88
suraTi 23. sadinrovani karcinoma, estrogen-dadebiTi. X 250
89
suraTi 24. sadinrovani karcinoma, estrogen-dadebiTi. X 400
90
suraTi 25. skiri, estrogen-dadebiTi. X 250
91
suraTi 26. skiri, estrogen-dadebiTi. X 250
92
daskvnebi
1. asakis matebasTan erTad matulobs er @`+“ kibos SemTxvevebi,
romelic mimdinareobs aTerogenuli lipidebis (sq, dslq, tg)
normaluri, an daqveiTebuli maCveneblebis fonze, miuxedavad
estrogenebis Semcirebisa;
2. er @`+“ kibos dros invaziuri kibos raodenoba metia arainvaziuri
kibos raodenobaze yvela asakobriv jgufSi, Tumca axalgazrda
da mowiful asakSi, estrogenebiT SedarebiTi normaluri
regulaciis pirobebSi, Warbobs sadinrovani invaziuri karcinoma
da invaziuri wilakovani karcinoma. invaziuri kibos gavrcelebis
markerebia sq-is, dslq-isa da tg-is mniSvnelovani momateba
ucvleli mslq-is fonze;
3. er @`_“ ZuZus kibo, er @`+“ ZuZus kibos maCveneblebisgan
gansxvavebiT, mimdinareobs aTerogenuli lipidebis (sq, dslq, tg)
mniSvnelovani momatebiT Mmslq-is ucvleli mniSvnelobis fonze.
aRniSnuli speqtri ganapirobebs am populaciis maRal
aTerogenul risks. Aam fonze invaziuri kibos raodenoba metia
arainvaziuri kibos raodenobaze yvela asakobriv jgufSi;
4. er @`_” invaziuri ZuZus kibos gavrcelebis markerebia dslq-isa
da tg-is momateba dabali sq-isa da mslq-is fonze;
5. er @`+“ ZuZus kibosgan gansxvavebiT arainvaziuri er@`_” ZuZus
kibos dros aRiniSneba mxolod sq-is momateba;
6. er `+” kibos dros estrogenebis Semcirebis pirobebSi Suaxnis
asakis pacientebSi SedarebiT mcirdeba invaziuri kibos
SemTxvevebi. er `–“ kibos dros asaki, anu estrogenebis raodenoba,
ar aregulirebs kibos invaziurobas, rac dgindeba axalgazrda da
93
mowiful da Suaxis asakis pacientebis jgufSi invaziuri kibos
erTnairi procentiT;
7. sadinrovani karcinomis SemTxvevebi sagrZnoblad maRalia yvela
danarCen formebze yvela asakobriv jgufSi estrogen-statusisgan
damoukideblad. Mmisi gavrcelebis markerebia sq-is SedarebiT
dabali maCveneblebi dslq-isa da tg-is momatebis fonze;
8. ZuZus kibosa da aTerosklerozuli daavadebebis diagnozisTvis,
profilaqtikisa da mkurnalobisTvis mizanSewonilia lipiduri
speqtrisa da er-is maCveneblebis dadgena.
94
praqtikuli rekomendaciebi
praqtikosi eqimebis winaSe ambulatoruli miRebisa da skriningis
dros xSirad dgas ZuZus kibos diagnostikisa da profilaqtikis, xolo
misi arsebobis dros, avTvisebianobis dadgenisa da mkurnalobis, aseve
aTerosklerozis profilaqtikisa da mkurnalobis sakiTxebi. Cvens mier
SemuSavebuli lipiduri biomarkerebi estrogenis maCveneblebTan da
obieqtur monacemebTan erTad saSualebas iZleva gamoiyos samizne risk-
jgufebi, xolo kibosa da aTerosklerozis arsebobis pirobebSi _
moaxdinos hormonuli, Tu statinebiT mkurnalobis individualizacia
asakobrivi aspeqtisa da er-is statusis gaTvaliswinebiT.
hormonuli da statinebiT mkurnalobis Catarebis win
mizanSewonilia moxdes lipiduri speqtris, estrogenebisa da er-is
kompleqsuri Sefaseba rogorc ZuZus kibos, aseve aTerosklerozis
profilaqtikisa da mkurnalobis dros ZuZus kibos riskis Tavidan
acilebis mizniT.
95
Conclusions
1. With age increases the number of estrogen-positive (ER "+") tumors that develop on a
background of normal or low levels of atherogenic lipids: total cholesterol (TC), low
density lipoprotein cholesterol (LDLC), triglyceride (TG).
2. In the case of positive tumors of invasive cancer exceeds the number of non-invasive
cancer in all age groups, although at a young age is prevalent invasive ductal carcinoma
and invasive tubular carcinoma. Markers of invasive cancer is a significant increase in
TC, LDL-C and TG with unmodified HDL-C.
3. Estrogen-negative tumors (ER "_"), in contrast to ER "+", develop on the background
of a significant increase in atherogenic lipids with unmodified HDL-C. This causes
high atherogenic risk of this population. On this background the number of invasive
cancer prevails over the number of non-invasive cancer in all age groups.
4. Markers for ER "_" invasive cancer are increased levels of LDL and TG in the low rate
of TC and HDL.
5. Unlike ER "+" tumors non-invasive ER "_" breast cancer develops on the background
of the high rate of TC.
6. At low levels of estrogen in patients of middle age reduces the number of ER "+"
invasive cancer. In the case of ER "-" cancer age (the number of estrogen) does not
affect the invasiveness which manifests the same percentage of invasive cancer.
7. Regardless of the status of ductal carcinoma still prevails over all other forms of breast
cancer in all age forms. Markers of proliferation are relatively low levels of TC and
increased levels of LDL and TG.
8. For prevention, diagnosis and treatment of atherosclerosis and breast cancer appropriate
lipid status and estrogen receptors.
96
literaturis saZiebeli
1. volSi b., Sifi i., rozneri b. estrogenebis CanacvlebiTi Terapiis
zemoqmedeba lipoproteidebis koncetraciaze da metabolizmze.
1991_ 307.
2. sixaruliZe a., madiCi k., nemsaZe g. “ZuZus simsivneebis
diagnostika”, 2000, 5.
3. heisi j., tamiri i., tiroleri h., rivkini b. lipiproteinis
gavrceleba Crdilo amerikul populaciebSi. 1980_270.
4. Бассалык Л. С. “Рецепторы стероидных гормонов в опухолях человека” Moсkвa.
1987-35.
5. Климов А. Н., Никулчева Н. Г. Обмен липидов и липопротеидов и его нарушения.
Санкт-Петербург: Питер, 1999, с. 500.
6. Краевский Н. А., Смольянникова А. В., Саркисова Д. С. Патолого-анатомическая
диагностика опухолей человека, 1993; Т2: 180.
7. Симонова Л. И., Гертман В. З., Пушкарь С. Н. Липидный статус у больных раком
молочной железы I-II стадии. Онкология, 2002; Т 4, № 3, 236-237.
8. Сметник В. П. , Коновалова В. Н. //Метаболизм эстрогенов и рак молочной
железы у женщин: диагностическая значимость определения
гидроксиметаболитов эстрогенов в моче. Российский вестник акушера-
гинеколога, 2009.
9. Цырлина Е. В., Гамаюнова В. Б., Порошина Т. Е. Гормонально-метаболический
статус больных раком молочной железы, подвергшихся сохранной операции:
97
сопоставление с иэвестными прогностическими критериями. Вопросы онкологии
1999; 45 (3): 265-72.
10. Abul-Haji Y. I. Relationship between estrogen receptors, 17 beta-hydroxysteroid
dehydrogenase and estrogen content in human breast cancer. Steroids. 1979;34 (2):217-
25.
11. Allain C. C., Poon L. S., Chan C. S., et al.: Enzymatic determination of total serum
cholesterol. Clin Chem 1974;20:470-475.
12. Anaise D. Histologic types of cancer. Am J Public Health 2007; 63: 251-253.
13. Allegra J. C., Lippman M. E., Thompson B. et al.: Distribution, frequency, and
quantitative analysis of estrogen, progesterone, androgen and glucocorticoid receptors
in human breast cancer. Cancer Res 1979;9:1447-1454
14. Armando E. Giuliano, MD (May 31 2006). "Carcinoma of the Male Breast - General
Considerations". Breast Cancer. Armenian Health Network, Health.am. Retrieved
2007-02-27.
15. Anderson G. L., Limacher M., Assaf A. R., et al. Effects of conjugated equine
estrogens in postmenopausal women with hysterectomy: the Women's Health Initiative
randomized controlled trial. JAMA 2004;291:1701–1712.
16. Akhrass F., Evans A. T., Wang Y., et al. Hormone replacement therapy is associated
with less coronary atherosclerosis in postmenopausal women. J Clin Endocrinol Metab
2003;88:5611–5614.
17. Anderson G. L., Manson J., Wallace R. , et al. Implementation of the Women's Health
Initiative study design. Ann Epidemiol 2003;13:Suppl:S5–S17.
18. Allampallam K., Dutt D., Nair C., et al. The clinical and biological significance of
abnormal lipid profiles in patients with myelodysplastic syndrome. J Hematother Stem
Cells Res 2000; 9 (2): 247-55.
98
19. American Society of Clinical Oncology. Clinical practice guidelines for the use of
tumor marcers in breast and colorectal cancer. Adopted of May 17, 1996 by
American Society of Clinical Oncology. J Clin Oncol 1996; 14: 2843–77.
20. Anderson E.: The role of oestrogen and progesterone receptors in human mammary
development and tumorigenesis. Breast Cancer Res 2002, 4:197-201.
21. Bernstein L. The epidemiology of breast cancer. Women Cancer 1998: 1S: 7–13
22. Blanco G., Alavaikko M., Ohala A. et al: Estrogen and progesterone receptors breast
cancer: relationships to tumor histopathology and survival of patients. Anticancer Res
1984;4:383-390.
23. Byers T., Graham S., Rzepka T., Marshall J.; "Lactation and breast cancer. Evidence
for a negative association in premenopausal women". Am. J. Epidemiol. 1985;121 (5):
664–74. PMID 4014158.
24. Boyd N. F., McGuire V. Evidence of association between plasma high-density
lipoprtotein cholesterol and risk factors for breast cancer. J nat Cancer Institute 1990;
82: 460-8.
25. Barnes D. M., Millis R. R. Oestrogen receptors: the history, the relevance and the
methods of evaluation. In Progress in Pathology Vol. 2, Kirkham N. Lemoine N. (eds)
London: Churchhill Livingston, 1995.
26. Beverly L. N., Flanders D., Go R. C. P., et al.: A copmarison of estrogen and
progesterone receptors Black and White breast cancer patients. Am J Public Health
1987; 77: 351-353.
27. Breslow N. E., Day N. E.: Statistical Methods in Cancer Research- The Analysis of
Case-control Studies. Lyon, France: IARC, 1980.
99
28. Bain R. P., Greenberg R. S., Whitaker J. P.: Racial differences in survival of women
with breast cancer. J Chronic Dis 1986; 39: 631-642.
29. Banks E. Hormone replacement therapy and the sensitivity and specificity of breast
cancer screening: a review. J Med Screen 2001; 8: 29-34.
30. Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study.
The Lancet 2003; 24: 419-427.
31. Beral V., Banks E., Reeves G. Evidence from randomized trials on the long-term
effects of hormone replacement therapy. Lancet 2002; 360: 942-944.
32. Byrne C., Connolly J. L., et al. Biopsy confirmed benign breast disease,
postmenopausal use of exogenous female hormones, and breast carcinoma risk. Cancer
2000; 89: 2046-2052.
33. Bilimoria M., Morrow M. The woman at increase risk for breast cancer: evaluation and
management strategies. Cancer J Clin 1995;45: 263-278.
34. Black D. M. The genetics of breast cancer. Eur J Cancer 1994; 30a: 1957-1961.
35. Brinton L. A., Devesa S. S. Etiology and pathogenesis of breast cancer: incidence,
demographics and environmental factors. In: Harris J. R., Lippman M. E., Morrow M.,
Hellman S., eds. Disease of the breast. Philadelphia: Lippincott-Raven, 1996: 159-68.
36. Brinton E. A. Oral estrogen replacement therapy in postmenopausal women selectively
raises levels and production rates of lipoprotein A-1 and lowers hepatic lipase activity
without lowering the fractional catabolic rate. Arterioscler Thromb Vasc Biol
1996;16:431-440.
37. Clin J. Endocrinol Metab, 2002,87.
100
38. Chae C. U,, Manson J. E. Postmenopausal hormone therapy. In: Manson JE, Buring JE,
Ridker PM, Gaziano JM, eds. Clinical trials in heart disease. Philadelphia:
Saunders/Elsevier, 2004:349–63.
39. Chariyalertstak S., Ruangvejvovachi P. Immunohistochemical detection of estrogen and
progesterone receptors in primary breast cancer. Asian Pac J Allegry Immunol 1998;
16: 161-166.
40. Chen C. L., Weiss N. S., Newcomb P., Barlow W., White E. Hormone replacement
therapy in relation to breast cancer. JAMA 2002; 287: 734–741
41. Clavel–Chapelon F. Differential effects of reproductive factors on the risk of pre- and
postmenopausal breast cancer. Results from a large cohort of French women. BR J
Cancer 2002; 86: 723-727.
42. Chlebowski R. T., Hendrix S. L., et al. Influence of estrogen plus progestin on breast
cancer and mammography in healthy postmenopausal women: the Women’s Health
Initiative Randomized Trial. JAMA 2003; 24: 3243-3253.
43. Clamp A., Danson S., Clemons M. Hormonal risk factors for breast cancer:
identification, chemoprevention, and other intervention strategies. Lancet Oncol 2002;
10: 611-619.
44. Chen Y., Thompson W., et al. Epiodemiology of contralateral breast cancer. Cancer
Epidemiol Biomarkers Prev 1999; 8: 855-861.
45. Clinical practice guidelines for use of tumor markers in breast and colorectal cancer.
Adopted of May 17,1996 by American Society of Clinical Oncology. J Clin Oncol
1996; 14: 2843-77.
46. Daling J. R., Malone K. E., Doody D. R., Voigt L. F., Bernstein L., Marchbanks P. A.,
Coates R. J., Norman S. A., Weiss L. K., Ursin G., Burkman R. T., Deapen D., Folger
S. G., McDonald J. A., Simon M. S., Strom B. L., Spirtas R. Association of regimens of
101
hormone replacement therapy to prognostic factors among women diagnosed with
breast cancer aged 50–64 years. Cancer Epidemiol Biomarkers 2003; 12: 1175–1181.
47. Davis R. P., Nora P. F., Kooy R. G., Hines J. R. Experience with lobular carcinoma of
the breast. Emphasis on recent aspects of management. Arch Surg 1979;114: 485–488.
48. Dickson R. B., Stancel G. M.: Estrogen receptor-mediated processes in normal and
cancer cells. J Natl Cancer Inst Monogr 2000, 27:135-145.
49. Dupont W. D., Page D. L.: Risk Factors of Breast Cancer in Women with Proliferative
Breast Disease. N Engl J Med; 312; 3; 146-51; 1985.
50. Dixon J. M. Hormone replacement therapy and the breast . MBJ 2001; 323: 1381-
1382.
51. Decker D. Prophylactic mastectomy for familial breast cancer. JAMA 1993; 269: 2608-
2609
52. Desai S. B., Moonim M. T., Gill A. K., Punia R. S., Naresh K. N., Chinoy R. F.
Hormone receptor status of breast cancer in India: a study of 798 tumours. Breast 2000;
9: 267–270
53. Dixon J. M., Anderson T. J., Page D. L., Lee D., Duffy S. W. Infiltrating lobular
carcinoma of the breast. Histopathology 1982; 6: 149–161.
54. Clark R . A.: Estrogen & Breast Cancer Risk: Factors of Exposure. Fact Sheet #10,
2002.
55. Elledge R. M., Osborne C. K. Oestrogen receptors and breast cancer, BMJ 1997; 314:
1843-1844.
56. Elwood J. M., Godolphin W.: Oestroge receptors in breast tumors: association with
age, menopausal status and epidemiological and clinical features in 735 patients. Br J
Cancer 1980; 42: 635-644.
102
57. Evans R. M.: The steroid and thyroid hormone receptor superfamily. Science 1988,
240:889-895.
58. Ewertz M., Duffy S. W., et al. Age a first birth, parity and risk of breast cancer: a meta-
analysis of 8 studies from the Nordic cointries. Int J Cancer 1990; 46: 597-603.
59. Fisher B., Redmond C., Brown A., Wickerham D. L., Wolmark N., Allegra J. C.,
Escher G., Lippman M., Savlov E., Wittlif J. L., Fisher E. R.: Influence of tumor
estrogen and progesterone receptor levels on respons to tamoxifen and chemotherapy in
primary breast cancer. J Clin Oncol 1:227-241,1983.
60. Fanelli F. R., Cangiano C., Muscaritolli M., et al. Tumor-induced changes in host
metabolism: a possible marker of neoplastic disease. Supplement to Nutrition 1995; 11
(5): 595-9.
61. Fregly M. J., Thrasher T. N. Response of heart rate to acute administraion of
isoproterenol in rats treated chronically with norethynodrel, athinyl estradiol, and boh
combined. Endocrinology. 1997; 100: 148-154.
62. Gathani T., Bull D., Green J., Reeves G., Bera V. Breast cancer histological
classification: agreement between the Office for National Statistics and the National
Health Service Breast Screening Programme. Breast Cancer Research 2005; Vol 7, 6:
1090-1096.
63. Giordano L., Sharon H., Cohen D. S., Buzdar A. U., Perkins G., Hortobagyi G. N.
(May 2004): "Breast carcinoma in men". Cancer (American Cancer Society) 101 (1):
51–57. doi:10.1002/cncr.20312.
64. Godsland I. F. Effects of postmenopausal hormone replacement therapy on lipid,
lipoprotein, and apolipoprotein (a) concentrations: analysis of studies published from
1974-2000. Fertil Steril 2001;75:898-915.
103
65. Grodstein F., Stampfer M. The epidemiology of coronary heart disease and estrogen
replacement in postmenopausal women. Prog Cardiovasc Dis 1995;38:199–210.
66. Victor G., Cannon R. O. Cardiovascular Effects of Estrogen and Lipid-Lowering
Therapies in in Postmenopausal Women. Circulation 1996;93:1928-1937.
67. Hsia J, Langer RD, Manson JE, et al. Conjugated equine estrogens and coronary heart
disease: the Women's Health Initiative. Arch Intern Med 2006;166:357–365.
68. Hulley S., Grady D., Bush T. et al. Heart and Estrogen/progestin Replacement Study
(HERS) Research Group Randomized trial of estrogen plus progestin for secondary
prevention of coronary heart disease in postmenopausal women. JAMA. 2003.
69. Howson C. P., Kinne D., Wynder E. L. Body weight, serum cholesterol and stage of
primary breast cancer. Cancer 1986; 58: 2372-81.
70. Hurlimann J., Van Melle G. Prognostic value of serum proteins synthesized by breast
carcinoma cells. Am J Clin Pathol 1991; 95: 835–43.
71. Hurlimann I., Gebhard S., Gomez F. Oestrogen receptor, progesterone receptor, pS2,
ERD5, HSP27 and cathepsin D in invasive ductal breast carcinomas. Histopathology
1993; 23: 239-248.
72. Harvey J. M., Clark J. M., Osborne C. K., Allred D. C. Estrogen receptor status by
immunohistichemistry in superior to the ligand binding assays for predicting response
to adjuvant therapy in breast cancer. J Clin Oncol 1999; 17: 1474-1485.
73. Hawkins R. A., Roberts M. M., Forrest A. P. M.: Oestrogen receptors and breast
cancer: current status. Br J Surg 1980; 67: 153-169.
74. Hildreth N. G., Kelsey J. L., Eisenfeld A. J., et al.: Differences in breast cancer risk
factors according to the estrogen receptors level of the tumor. JNCI 1983; 70: 1027-
1031.
104
75. Hulka B. S., Chambless L. E., Wilkinson W. E., et al.: Hormonal and personal effects
on estrogen receptors in breast cancer. Am J Epidemiol 1984; 119: 692-704.
76. Howell A., Harland R. N. L., Branwell V. H. C., et al.: Steroid-hormone receptors and
survival after first relapse in breast cancer. Lancet 1984; 1: 588-591.
77. Hill A. D., Doyle J. M., McDermon E. W., et al. Hereditary breast cancer. Br J Surg
1997; 84: 1334-1339.
78. Hozumi Y., Kawano M., Miyata M. Severe hypertriglyceridemia caused by tamoxifen-
treatment after breast cancer surgery. Endocr J 1997;44:745-9.
79. Isaacs C.J., Peshkin B. N., Lerman C. Evaluation and management of women with a
strong famili history of breast cancer. In: In: Harris J. R., Lippman M. E., Morrow M.,
Osborne C. K.eds. Disease of the breast. Philadelphia: Lippincott Williams & Wilkins,
2000: 237-254.
80. Johansson R., Vanharanta R., Söderholm J. Estrogen receptors in mammary cancer :
Correlation with Age, menopausal status and response to therapy. Journal of Cancer
Research and Clinical Oncology 1984; 107: 221-224.
81. Kagan A., Dawber T. R., Kannel W. B., Revotskie N.: Editorial Coronary Heart
Desease in Young Women // Lancet- 1977.
82. Kerber J., Pricelius S., Heidrich M. Miller M. Increased lipid utilization in weight
losing and weight stable cancer patients with normal body weigt. Eur J Clin Nutr 1999;
53 (9): 740-5.
83. Kannel W.B., Wilson P.W. Risk factors that attenuate the female coronary disease
advantage. – Arch Intern Med. – 1995; 155: 57-61.
84. Key T. J., Verkasalo P. K., Banks E.: Epidemiology of Breast Cancer. Lancet Oncol.
2001 Mar; 2(3): 133-40.
105
85. Koenders P. G., Beex L. V., Langens R., Kloppenborg P. W. C., Smals A.G. H.,
Benraad Th. J., and the breast cancer study group. Steroid hormone receptor activity of
primary human breast cancer and pattern of first metastasis. Breast Cancer Res Treat
1991; 18: 27-32.
86. Korhonen T., Huhtala H. , Holli K. A comparison of the biological and clinical
features of invasive lobular and ductal carcinomas of the breast. Breast Cancer Res
Treat 2004; 85: 23–29.
87. Kelsey J. L., Gammon M. D., John E. M. Reproductive factors and breast cancer.
Epidemiol Rev 1993; 15: 36-47.
88. Lesser M. L., Rosen P. P., Senei R. T. et al: Estrogen and progesterone receptors in
breast carcinoma: Correlation with epidemiology and pathology. Cancer 48:288-299,
1981.
89. Longecker M. P., Bernstein L., Paganinihill A. et al. Risk factors of in situ breast
cancer. Cancer Epidemiol. Biomarkers Prevent. 1996; 12: 961-5.
90. Lane D. M., Boatman K. K., McConathy W. J. Serum lipids and apolipoproteins in
women with breast masses. Breast Cancer Research and Treatment, 1995; 34: 161-9.
91. Li Liu. Histologic Classification of Breast Cancer. Onco Link. 2001
92. Li C. I., Anderson B. O., Daling J. R., Moe R. E. Trends in incidence rates of invasive
lobular and ductal breast carcinoma. JAMA 2003; 289: 1421–142.
93. Li C. I., Malone K. E., Porter P. L., Weiss N. S., Tang M. T., Cushing-Haugen K. L.,
Daling J. R. Relationship between long durations and different regimens of hormone
therapy and risk of breast cancer. JAMA 2003; 289: 3254–3263.
94. Lindheim S. R., Legro R.S., Bernstein L., Stanczyk F. Z., Vijod M. A., Presser S. C.,
Lobo R. A. Behavioral stress responses in premenopausal and postmenopausal women
and the effects of estrogen. Am J Obstet Gynecol. 1992; 167: 1831-1836.
106
95. Lu X., Chen S., Huang S. A study on methodology and the criteria for positive
immunohistostaining of estrogen and progesterone receptors in parrafin embedded
sections of breast cancer. Chung Hua Ping Li Hsueh Tsa Chin 1996; 25: 329-331.
96. Lyytinen H, Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women
using estrogen-only therapy. Obstet Gynecol. 2006 ;108(6):1352-3.
97. McCarty K. S., Silva J. S., Cox E. B., Leight G. S., Wells S. A., McCarty K. S.
Relationship of age and menopausal status to estrogen receptor content in primary
carcinoma of the breast. PMC 2003; 48:128-133
98. Moudgil V. K. (ed.): Molecular Mechanisms of Steroid Hormone Action. Berlin,
Walter de Gruiter and Co, 1985, p 376.
99. Moe R. E., Daling J. R. Risk of mortality by histologic type of breast cancer among
women aged 50 to 79 years. Arch Intern Med 2003;163: 2149–2153.
100. Morabia A , Flandre P. Misclassification bias related to definition of
menopausal status in case–control studies of breast cancer. Int J Epidemiol 1992; 21:
222–228.
101. McPherson K., Steel C. M., Dixon J. M.: ABC of Breast Cancer. BMJ 2000;
321:624-8.
102. Mendelsohn M. E., Karas R. H.: The protective effects of estrogen on the
cardiovascular system. N Engl J Med 1999;340:1801–1811.
103. Mikkola T. S., Clarkson T. B.: Estrogen replacement therapy, atherosclerosis,
and vascular function. Cardiovasc Res 2002;53:605–619.
104. Manson J. E., Bassuk S. S., Harman M., et al. Postmenopausal hormone
therapy: new questions and the case for new clinical trials. Menopause 2006;13:139–
147.
107
105. Moorman P. G., Hulka B. S., Hiatt R. A., et al. Association between High-
Density Lipoprotein Cholesterol and Breast Cancer Varies by Menopausal Status.
Cancer Epidemiol Biomarkers and Prevention 1998; 7: 483–8.
106. Essam A. Mady . Association between estradiol, estrogen receptors, total lipids,
triglycerides, and cholesterol in patients with benign and malignant breast tumors.
Department of Biochemistry, Faculty of Science, and Oncology Diagnostic Unit,
Faculty of Medicine, 2001, Ain Shams University, Cairo, Egypt.
107. Mohla S., Sampson C. C., Khan T., et al.: Estrogen and progesterone receptors
in breast cancer in Black Americans. Cancer 1982; 50: 552-559.
108. Miyoshi Y., Tanji Y., Taguchi T.,Tamaki Y., Noguchi S. Association of Serum
Estrone Levels with Estrogen Receptor-positive Breast Cancer Risk in Postmenopausal
Japanese Women. Department of Surgical Oncology. Osaka University Graduate
School of Medicine 1994
109. McTierman A., Thomas D. B., Johnson L. K., Roseman D.: Risk factors for
estrogen receptor-rich and estrogen receptor-poor breast cancer. JNCI 1986; 77: 849-
854.
110. McKeown-Eyssen G. E., Rogers-Melamed I., Clarke E. A.: Estrogen receptor
status of brest cancer in Ontario. Can Med Assoc J 1985; 133: 997-1000.
111. Nerukar A. A., Desal S. B., Baraniya J., Yadav J., Chinoy R. F. Expression of
steroid receptors in breast carcinoma. An immunohistochemical study using parrafin
section. Ind J Pathol Mocrobiol 1997; 40: 284.
112. Natarajan N., Nemoto T., Mettlin C., et al.: Race-related differences in breast
cancer patients. Cancer 1985; 56: 1704-1709.
108
113. Newcomb P. A., Titus-Ernstoff L., Egan K. M., Trentham-Dietz A., Baron J. A.,
Storer B. E., Willett W. C., Stampfer M.J. Postmenopausal estrogen and progestin use
in relation to breast cancer risk. Cancer Epidemiol Biomarkers Prev 2002; 11: 593–600.
114. Newcomer L. M., Newcomb P. A., Potter J. D., Yasui Y., Trentham-Dietz A.,
Storer B. E., Longnecker M. P., Baron J. A., Daling J. R. Postmenopausal hormone
therapy and risk of breast cancer by histologic type (United States). Cancer Causes
Control 2003; 14: 225–233.
115. Ouyang P., Michosl E. D., Karas R. H. Заместительная гормональная
терапия и сердечно-сосудистая система: уроки и вопросы, требующие ответов.
Практическая ангиология. 2009 .
116. Ownby H. E., Frederick J., Russo J., et al.: Racial differences in breast cancer
patients. JNCI 1985; 75: 55-60.
117. Perkins E. A., Small B. J., Balducci L., Extermann M., Robb C., Haley W. E.
"Individual differences in well-being in older breast cancer survivors". Crit. Rev.
Oncol. Hematol. 2007; 62 (1): 74–83.
118. Robinson J. C., Folsom A. R., Nabulsi A. A., et al.: Can postmenopausal
hormone replacement improve plasma lipids in women with diabetes? The
Atherosclerosis Risk in Communities Study Investigators. Diab Care 1996;19:480-5
119. Thomas C. Putti, Dalia M. Abd El-Rehim, Emad A. Rakha, Claire E. Paish,
Andrew H.S. Lee, Sarah E. Pinder and Ian O. Ellis: Estrogen receptor-negative breast
carcinomas: a review of morphology and immunophenotypical analysis. Modern
Pathology , 2005;18: 26–35.
120. Pasqualini C., Leviel V., Guibert B., Faucon-Biguet N. Inhibitory action of
acute estradiol treatment on the activity and quantity of tyrosine hydroxylase in the
median eminence of ovariectomized rats. J Neuroendocrinol. 1991; 3: 575-580.
109
121. Proudler A. J., Ahmed A. H., Crook D., Fogelman I., Rymer J. M., Stevenson J.
C. Hormone replacement therapy and serum angiotensin-enzyme activity in
postmenopausal women. Lancet. 1995; 346:89-90.
122. Punnonen R., Lammintausta R., Erkkola R., Rauramo L. Estradiol valerate
therapy and the renin-aldosterone system in castrated women. Maturitas. 1980; 2:91-94.
123. Powles T. J., Eeles R., Ashley S., et al. Interim analysis of the incident breast
cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial.
Lancet 1998; 362: 98.
124. Rashid R. K., Gallager H. S. Correlation of estrogen receptor level and lipid
staining in breast carcinoma. Arch Pathol Lab Med. 1984;108(9):707-9.
125. Rebbeck T., Timothy R..; Noah D. Kauff, Susan M. Domchek (January 13,
2009).; "Meta-analysis of Risk Reduction Estimates Associated With Risk-Reducing
Salpingo-oophorectomy in BRCA1 or BRCA2 Mutation Carriers". Journal of the
National Cancer Institute (Oxford, UK) 101 (2): 80–87.
126. Anthony N. Roberts, R. Hähnel: Oestrogen Receptor Assay and Morphology of
Breast Cancer. Vol. 13, No. 2, Pages 317-325, 1981.
127. Rio G. D., Velardo A., Zizzo G., Avogaro A., Casa L. D., Marrama P.,
Macdonald I. A. Effect of estradiol treatment on the sympathoadrenal response to
mental stress in normal men. J Clin Endocrinol Metab. 1994; 79: 836-840.
128. Redkar A. A., Kabre S. S., Mittra I. Estrogen and progesterone receptors
measurment in breast cancer with enzyme- immunoassay and correlation with other
prognostic factors. Ind J Med Res 1992; 96: 1-8.
129. Rosner D., Bedwani R. N., Vana J. Noninvasive Breast Carcinoma: Results of a
National Survey. American College of Surgeons 1978; 30: 379-391.
110
130. Sims A. H., Howell A., Howell S. J., Clarke R. B.: Origins of breast cancer
subtypes and therapeutic implications. Nat Clin Practice Oncol 2007, 4:516-525
131. Stout R.W. – Hormones and Atherosclerosis, 1985,30.
132. Silverstein M. J., Lewinsky B. S., Waisman J. R., Gierson E. D., Colburn W. J.,
Senofsky G. M., Gamagami P. Infiltrating lobular carcinoma. Is it different from
infiltrating duct carcinoma? Cancer 1994; 73: 1673–1677
133. Stalsberg H., Thomas D. B. Age distribution of histologic types of breast
carcinoma. Int J Cancer 1993; 54: 1–7
134. Stefanick ML, Cochrane BB, Hsia J, Barad DH, Liu JH, Johnson SR. The
Women's Health Initiative postmenopausal hormone trials: overview and baseline
characteristics of participants. Ann Epidemiol 2003;13:Suppl:S78–S86.
135. Stevenson J. C., Crook D., Godsland I. F., Collins P., Whitehead M. I. Hormone
replacement therapy and the cardiovascular system: nonlipid effects. Drugs. 1994; 47:
35-41.
136. Stierer M., Rosen H., Weber R., Hanak H., Spona J., Tuchler H.
Immunohistochemical and biochemical measurement of estrogen and progesterone
receptors in primary breast cancer. Correlation of histopathology and prognostic
factors. Ann Surg 1993; 218: 13–21.
137. Speroff L., Glass R. H., Kase N. G. Menopause and postmenopausal hormone
therapy. In: Speroff L., Glass R. H., Kase N. G., eds. Gynecologic Endocrinology nd
Infertility. Baltimore, Md: Williams & Wilkins 1994: 583-644.
138. Shousha S., Coady A. T., Stamp T., James K. R., Alaghband-Zaden J.
Oestrogen receptors in mucinous carcinoma of the breast: an immunohistological study
using parrafin wax sections. J Clin Pathol 1989; 42: 902-905.
111
139. Stanford J. L., Szklo M., Brinton L. A.: Estrogen receptors and breast cancer.
Epidemiol Rev 1986; 8: 42-59.
140. Stanford J. L., Szklo M., Boring C. C., et al.: A case-control study of breast
cancer receptor status. Am J Epidemiol 1987; 125: 184-194.
141. Tanner J. M. Trend toward earlier menarche in London, Oslo, Copenhagen, the
Netherlands and Hungary. Nature 1973; 243; 5402; 95-96
142. Van den Brandt P. A., Spiegelman D., et al. Pooled analysis of prospective
cohort studies on height, weight and breast cancer risk. Am J Epodemiol 2000; 6: 514-
527.
143. Wittliff J. L., Pasic R., Bland K. I.: Steroid and Peptide Hormone Receptors
Identified in Breast Tissue. Chapter 43: 909, 1991.
144. Waters D. D., Alderman E. L., Hsia J., et al. Effects of hormone replacement
therapy and antioxidant vitamin supplements on coronary atherosclerosis in
postmenopausal women: a randomized controlled trial. JAMA 2002;288:2432–2440.
145. Weiss N. S., Stanford J. L., Daling J. R. Hormone replacement therapy in
relation to risk of lobular and ductal breast carcinoma in middle-aged women. Cancer
2000; 88: 2570–2577
146. Wingo P.A., Calle E.E., McTiernan A. How does breast cancer mortality
compare with that of other cancers and selected cardiovascular diseases at different
ages in U.S. women – J Womens Health Gend Based Med. – 2000; 9: 999-1006.
147. Wishaft G. C., Harnett A. N., Purushotham A. D. Oestrogen receptor status: no
longer an optional extra. The Breast 1998; 7:154-155.
148. Wenger C. R., Beardslee S., Owens M. A., Pounds G., Oldaker T., Vendely P.,
Pandian M. R., Harrington D., Clark G. M., McGuire W. L. DNA ploidy S-phase, and
112
steroid receptors in more than 127,000 breast cancer patients. Breast Cancer Res Treat
1993; 28: 9-20.
149. Wittliff J. L. Steroid-hormone receptors in breast cancer. Cancer 1984; 53: 630-
643.
150. Willett W. C., Rockhill B., Hankinson S. E., et al. Epidemiology and nongenetic
causes o breast cancer. In: Harris J. R., Lippman M. E., Morrow M., Osborne C. K.eds.
Disease of the breast. Philadelphia: Lippincott Williams & Wilkins, 2000: 175-220.
151. Yager J.D., Davidson N. E.: "Estrogen carcinogenesis in breast cancer". New
Engl J Med 354 (3): 270–82. 2006.
152. Yeatman T. J., Cantor A. B., Smith T. J., Smith S. K., Reintgen D. S., Miller M.
S., Ku N. N., Baekey P. A., Cox C. E. Tumor biology of infiltrating lobular carcinoma.
Implications for management. Ann Surg 1995; 222: 549–559.
153. Young J. L., Percy C. L., Asire A. J. Surveillance, epidemiology, and end
results: incidence and mortality, 1973–77. Natl Cancer Inst Monogr 1981; 57: 1–1082.
154. Zorilla E., Hulse M., Hernandez A., Gershberg H. Severe endogenous
hypertriglyceridemia during treatment with estrogen and oral contraceptives. J Clin
Endocrinol Metab 1988;28:1793-6
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