Tanamedrove medicinis winaSe kvlav mTeli simwvaviT … · da tvinis sisxlis mimoqcevis mwvave darRvevbi, romlebsac safuZvlad udevs progresirebadi aTerosklerozi. ... gulsisxlZarRvTa

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

3

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.

6

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;

7

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

8

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.

9

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

10

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).

11

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).

12

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).

13

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

14

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,

15

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

16

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



ganviTarebis riski 70 wlamde 15 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)


histologiuri

formebi


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


urTierTkavSiri Suaxnis pacientebSi (45-59 ww)


histologiuri

formebi



karcinoma

55 19 7 13

arainvaziuri


6 2 3 6


karcinoma

140 45 32 60


karcinoma

17 5.4 11 21

invaziuri meduluri

karcinoma

38 12.3 _ _

invaziuri papiluri

karcinoma

_ _ _


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


urTierTkavSiri xandazmul pacientebSi (60-79 ww)


histologiuri

formebi



carcinoma

_ _ _ _

arainvaziuri


_ _ _ _


carcinoma

32 44,2 14 19


karcinoma

23 31,9 1 1.3

invaziuri meduluri

karcinoma

_ _ _ _

invaziuri papiluri

karcinoma

_ _ _ _


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


69


70


71


72


73


74


75

suraTi 10. skiri, estrogen-uaryofiTi. X 250

76

suraTi 11. wilakovani karcinoma, estrogen-uaryofiTi. X 200

77


78


79

suraTi 14. meduluri karcinoma, estrogen-dadebiTi. X 120

80

suraTi 15. sadinrovani karcinoma, estrogen-dadebiTi. X 300

81


82


83


84


85


86


87


88


89


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

Documents

Tanamedrove medicinis winaSe kvlav mTeli simwvaviT … · da tvinis sisxlis mimoqcevis mwvave darRvevbi, romlebsac safuZvlad udevs progresirebadi aTerosklerozi. ... gulsisxlZarRvTa