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1 대한임상건강증진학회지제 8 권제 4 호 2008 Korean J Health Promot Dis Prev Vol. 8, No. 4, 2008 [ 원저 ] 한국여성에서체질량지수 (Body Mass Index) 에따른유방치밀도의차이 고유라, 신기원, 서윤영, 고정아, 박민선, 조비룡, 배우경 서울대학교의과대학가정의학교실 - 요약 - 연구배경 유방촬영술상치밀유방은유방암의위험요소일뿐아니라검사의민감도를감소시켜위음성의중요한요소가된다. 한국여성 에서비만도와유방치밀도와의관계는알려진바가적다. 본연구에서는한국여성에서체질량지수와치밀유방과의연관성을파악하고이를바탕으로적절한유방암검진방법을모색해보고자하였다. 방 법 2000년 2월부터 2006년 3월까지건강검진센터에서유방촬영술을시행한무증상의여성 16482명을대상으로연령과체질량지수에따른유방실질의밀도분포를분석하였으며추가적인유방초음파촬영을권유받은경우를분석하였다. 유방촬영술상유방실질의밀도는 ACR BI-RADS의유방실질분류를따랐다. 결 과 치밀유방의빈도는 4275명으로 25.9% 였으며연령과체질량지수가증가할수록각각감소하는경향을보였다. 연령으로보정한후의치밀유방의위험도는정상체중에비하여저체중의경우 1.381배높았고과체중의경우 0.792배, 비만의경우 0.540배, 고도비만의경우 0.298배로감소하는경향을보였다. 결 론 한국여성에서체질량지수는연령으로보정한후에도치밀유방과음의상관관계를갖는다. ( 대한임상건강증진학회지 2008;8(4): ) 중심단어 유방촬영술, 치밀유방, 체질량지수, 유방암검진 15 서론 우리나라에서유방암은위암에이어두번째로흔한암이며 1999년에 10만명당 16.7명이던것이 2000년도에는 10만명당 27.8명으로집계되었다. 1) 서양의유방암연령곡선은 40 대이후부터연령증가에따라지속적인상승곡선을나타내나한국인의유방암연령곡선은 2002년자료에의하면서구와는달리 20대이전의경우 2.4%, 30대의경우 18.3%, 40대의경우급격히증가하여 38.9%, 50대는 23.6%, 60대이후에는 16.9% 로서구인에비해 3~40대가차지하는분율이상대적으로높은것이특징이다. 1) 또한이연령대의암은보다높은연령대의암에비해치명률과사망률이높아상대적으로 교신저자 : 배우경서울대학교의과대학가정의학교실 주소 : 서울시종로구연건동 28번지서울대학교병원가정의학과교실 전화 : naslig@hanmail.net 접수일 : 2008년 11월 29일 채택일 : 2008년 12월 20일 서구에비해우리나라의경우 40대이전여성에대한검진의중요성이부각된다. 2),3) 유방암선별검사에대한가이드라인은여러가지로제시되고있으나일반적으로 50대이후매년선별유방촬영술 (screening mammography) 이권장되고있으며연구에따라차이가있으나 40대에서도사망률의감소를가져올수있다는연구결과에따라 40대이상에서유방촬영술이권장되고있다. 3,4) 이러한유방촬영술의민감도에영향을끼치는중요한인자중하나로유방의치밀도 (breast density) 가있다. 일반적으로유방의치밀도가높을수록유방암의발생위험도가높을것으로알려져있을뿐아니라유방촬영술에서검사의민감도 (sensitivity) 를낮추어위음성결과의원인이되며재검사율 (re-examination) 을높이는요소로작용하게된다. 5-8) 이러한유방의치밀도에영향을주는요소로는인종, 연령, 비만도, 여성호르몬수준등이관련된것으로알려져있으며 9) 이중비만도는유방의치밀도와음의상관관계를가질뿐아니라유방촬영술의민감도를떨어뜨리는요소로작용하는 281

2 [ 한국여성에서체질량지수 (Body Mass Index) 에따른유방치밀도의차이 ] 것이알려져있다. 10,11) 따라서, 결과적으로마른여성에서는낮은체질량지수 (Body Mass Index, BMI) 에의해유방촬영술의민감도가낮아지고치밀유방으로인해유방촬영술의민감도가낮아지게된다. 또한유방의치밀도는인종간차이가있어아프리카미국인에서가장밀도가낮으며아시아인에서밀도가높은것으로조사되며같은아시아인중에서도일본인과중국인에따라밀도차이가있는것으로나타나 12) 한국인에서의유방의치밀도또한다른분포를보일것으로예상된다. 이에대한국내연구로는김승형등 (2000) 이한국여성의연령에따른유방밀도의분포를서양여성과비교한바가있으며조정진 (2006) 등이유방밀도에영향을미치는유방암위험요인에대한연구가있었으나체질량지수에따른유방밀도에관해서는한국인을대상으로이루어진바가없었다. 13,14) 이에본연구에서는무증상의한국여성에서연령및체질량지수에따른유방밀도의분포양상을분석하고연령으로보정한체질량지수와치밀유방과의연관성을파악하고자하였다. Table 1. Breast density grade according to ACR BI-RADS classification Grade ACR BI-RADS*/Breast Composition 1 The breast is almost entirely fat 2 There are scattered fibroglandular densities 3 The breast tissue id heterogeneously dense. This may lower the sensitivity of mammography The breast tissue is extremely dense, which could 4 obscure a lesion on mammography * ACR BI-RADS : American college of radiology, Breast imaging reporting and data system 1>). 지방형유방 (fatty breast) 와치밀유방 (dense breast) 을나누는기준은연구마다차이가있으나본연구에는 2002년 Korb 의연구방법에따라 grade 1을지방형유방으로, grade 2, 3, 4에해당되는경우를치밀유방으로나누어분석하였다. 15) 3. 통계분석 연구방법 1. 연구대상 2000년 2월부터 2006년 3월까지건강검진센터에서유방촬영술을시행한무증상의여성 16495명을대상으로하였고설문지를통한조사에서유방암의과거력이있거나수술을받은여성은제외하였다. 결측값을제외하고 16482명의자료를분석하였다. 2. 연구방법연령은 40세미만, 70세이상, 40세에서 70세까지는 5년단위로나누어 8개의그룹으로나누었다. 체질량지수는아시아인에서의분류기준에따라저체중 (18.5미만) 정상체중 (18.5이상 23미만 ), 과체중 (23이상 25미만 ), 비만 (25이상 30미만 ), 고도비만 (30이상) 으로나누어분석하였다. 유방촬영술은 senographe 600T (GE Healthcare, U.S.A.) 을이용하여내사위촬영과상하촬영을시행하였고숙련된방사선과전문의일인에의해판독되었다. 유방촬영술상유방실질의밀도는 ACR BI-RADS(American College of Radiology, Breast Imaging Reporting And Data System) category에따라 almost entire fat 은 Grade 1으로, fibroglandular densities 는 Grade 2, extremely dense 는 Grade 4로판독하였다 (< 표 연령과유방밀도, 체질량지수와유방밀도의관계를알아보기위하여각각교차분석하였으며범주형자료의경향성을살펴보기위하여선형대선형결합의값을살펴보았다. 연령으로보정한뒤의체질량지수와유방밀도의관계를알아보기위해로지스틱회귀분석을시행하였으며 P for trend 를구하였다. 통계적유의성의기준은 P < 0.05로하였으며통계프로그램은 SPSS 12.0K for windows (ver.12.0) 프로그램을사용하였다. 결과 1. 일반인구학적분포및치밀유방의분포 (< 표 2>) 대상자들의연령의평균은 54 ± 세였으며, 체질량지수의평균은 23.6 ± 3.02였으며유방치밀도는 Grade 1에해당하는지방형유방 (fatty breast) 이 12207명으로 74.1% 였으며Grade 2, 3, 4에해당하는치밀유방 (dense breast) 이 4275명으로 25.9% 에해당하였다. 2. 연령에따른유방밀도의분포 (< 표 3>) 단변량분석에서치밀유방의빈도는 40대이하에서 49% 로가장높았으며연령이증가함에따라점차로감소하는경향성을보였다 (P trend <0.001 by linear by linear association). 치 282

3 [Breast Density in Mammography According to Body Mass Index(BMI) in Korean Women] Table 2. Baseline characteristics Variables N (%) (n=16482) mean ± S.D. Age 54±10.06 < (7.2) (8.8) (14.8) (17.3) (18.2) (16.4) (11.0) (6.4) BMI(kg/m 2 ) 23.6±3.02 BMI<18.5(underweight) 521 (3.2) 18.5 BMI<23(normal weight) 6815(41.3) 23 BMI<25(overweight) 4343(26.3) 25 BMI<30(obesity) 4361(26.5) 30 BMI(severe obesity) 444 (2.7) Breast density grade 1 Fatty breast 12207(74.1) 2 fibroglandular dense 1240 (7.5) 3 heterogeneously dense 1972(12.0) 4 extremely dense 1063 (6.4) 밀유방의위험도는 40세미만인군에비하여연령군이 5세씩증가함에따라 0.798, 0.793, 0.468, 0.238, 0.143, 0.110, 0.076배로감소하는것으로나타났으며체질량지수의영향성을보정한후에도이러한경향성은유지되었다 (P trend <0.001 by Likelihood ratio test for trend). 3. 체질량지수에따른유방밀도의분포 (< 표 4>) 체질량지수에따른치밀유방의비율은저체중군에서 46.6% 로가장높았으며점차로감소하여정상체중군에서는 33.3%, 과체중군에서는 23.5%, 비만군에서는 15.9%, 고도비만군에서는 10.4% 로관찰되었다. 치밀유방의위험도는정상체중군에비하여저체중군에서 1.8배높았으며과체중군에서 0.6배, 비만군에서 0.4배, 고도비만군에서는 0.2배로위험도가점차로감소하는경향성을보였다 (P trend < by linear by linear association). 연령으로보정한후의체질량지수에따른치밀유방의위험도는정상체중군에비하여저체중의경우 1.381(95% CI : ) 로증가하였고과체중의경우0.792(95% CI : ), 비만의경우 0.540(95% CI : ), 고도비만의 Table 3. Age and breast density in Korean women Age Dense Breast (n=4275) Table 4. BMI and breast density in Korean women BMI Dense Breast (n=4275) Fatty Breast (n=12207) Fatty Breast (n=12207) crude OR crude OR adjusted OR* <40 579(49.0) 603(51.0) (43.4) 817(56.6) 0.798( ) 0.857( ) (43.2) 1384(56.8) 0.793( ) 0.891( ) (31.0) 1972(69.0) 0.468( ) 0.551( ) (18.6) 2446(81.4) 0.238( ) 0.292( ) (12.1) 2377(87.9) 0.143( ) 0.178( ) (9.6) 1632(90.4) 0.110( ) 0.138( ) (6.8) 978(93.2) 0.076( ) 0.096( ) P for trend <0.001 <0.001 * adjusted for BMI Pfor trend were calculated with linear by linear association P for trend were calculated with Likelihood ratio test for trend adjusted OR* Underweight 243(46.6) 278(53.4) 1.750( ) ( ) Normal weight 2270(33.3) 4545(66.7) Overweight 1022(23.5) 3321(76.5) 0.616( ) 0.792( ) Obesity 694(15.9) 3667(84.1) 0.379( ) 0.540( ) Severe obesity 46(10.4) 398(89.6) 0.231( ) 0.298( ) P for trend <0.001 <0.001 * adjusted for age (by Logistic Regression) BMI : Body Mass Index (kg/m 2 ) : underweight (BMI<18.5), normal weight (18.5 BMI<23), overweight(23 BMI<25), obesity(25 BMI<30), severe obesity(30 BMI) P for trend were calculated with linear by linear association P for trend were calculated with Likelihood ratio test for trend 경우 0.298(95% CI : ) 로감소하여연령으로보정한후에도체질량지수가낮아질수록치밀유방의위험도가큰것이확인되었다 (P trend <0.001 by Likelihood ratio test for trend). 고찰 유방촬영술이현재까지알려진유방암으로인한사망률의감소를가져올수있는유일한스크리닝방법이라는데에는이견의여지가없다. 그러나이러한스크리닝검사로서의유방촬영술의민감도는유방의치밀도가높아지는치밀유방에 283

4 [ 한국여성에서체질량지수 (Body Mass Index) 에따른유방치밀도의차이 ] 서문제가된다. 특히젊은여성에서이러한치밀유방이많이발견되게되는데 Stomper 등의연구에따르면 30대의 62%, 40대의 56%, 50대의 37%, 60대의 27% 의여성이유방촬영술상에서치밀유방을나타내었다. 16) 한국여성을대상으로한김승형등의연구에서이러한경향은더욱두드러져 30에서 34세의여성의 88%, 35세에서 39세의여성의 91%, 40에서 44세의여성의 78% 가치밀유방에해당하였으며서구여성에비해치밀유방의비율이상대적으로높은양상을보였다. 13) 본연구의연령별치밀유방의비율및분포는이전연구결과와일치하였으나이전연구와달리전반적으로치밀유방의비율이낮은분포가관찰되었는데이는판독자간의차이이거나혹은두연구대상집단의비만도등의인구학적분포의차이에기인한것으로생각되어지나이전연구결과에서인구학적분포에대한정보가없어정확한분석은어려웠다. 체질량지수역시서양여성을대상으로한연구에서유방의치밀도에영향을주는주요한인자중하나로널리알려져있다. 10,11) 본연구에따르면연령을보정하고도비만도가낮을때치밀유방의밀도가높은것으로나타났으며 40대이하의저체중여성의경우치밀유방의비율이 60% 에달하여서젊거나마른여성에서는그검사민감도가문제가되리라는것을짐작할수있다. 기존에관찰된선별유방촬영술로인한사망률의감소는모두 40대이상의여성에서밝혀진것이어서 40대이하여성에서의생존이득에대해서는명확히밝혀진바가없다. 17) 따라서 ACR(American college of radiology) 및 ACS(American Cancer Society), USPSTF(U.S. Preventive Services Task Force) 및한국의국가암검진지침에서도추천검사간격의차이는있으나모두 40대이상의여성을대상으로선별적유방암검사를실행할것을추천하고있다. 3,18) 그러나실제로국내의많은수의사설검진센터의수진현황을보면빠르면18세이상부터를대상으로하여유방촬영술이널리행해지고있는실정이다. 3) 이러한젊은연령층을대상으로한유방암검사의경우결과에서살펴본바와같이젊고마른여성에서치밀유방의빈도가높은것을고려할때그검사의민감도및위양성율이문제가될뿐만아니라방사선위해역시문제가된다. 유방촬영술의선별검진에의해유방암이발생할가능성은희박하나노출되는나이가어릴수록이로인한유방암의발생확률과사망률이높다는점을고려할때 19) 젊은연령에서의무분별한선별적유방촬영술의사용은재고되어야할사항이라생각된다. 비록선별검사로서유방초음파의효과나역할에대해서는 아직명확히정립된바는없으나최근활발히유방초음파의선별검사로서의유용성에대한연구가이루어지고있다. 2001년 Radiology에 Kaplan 등의연구에따르면 1862명의임상진찰과유방촬영상에서음성소견이었던무증상의여성들을대상으로유방초음파를추가적으로실시한결과치밀유방여성중 51명이추가적으로생검을권유받았으며이중 6명에서유방초음파에서관찰되지않았던유방암이발견되었다. 20) 이외에도많은연구에서유방촬영술에서발견되지않았던암이유방초음파에서발견되는경우가있음을보여주고있었으며 21) 이러한경향은치밀유방에서두드러지게나타나는경향이있었다. 15,22) 이러한결과에따라 2007년 11월 SBI(Society of Breast Imaging) 에서치밀유방의가능성이높은젊은여성에서는추가적인유방촬영술이추천된다는 position statement 를발표하였으며일부에서는 35세또는 30세이하의여성을대상으로는선별검사로유방초음파를일차적으로고려하자는의견을제시하고있다 ) 2006년미국암협회에서는연령및비만도및가족력등을고려하여유방검진의방법을개인별로다양화할것을권고한바있다. 4) 이번연구에서도확인되었듯이한국여성의경우연령및비만도에따른유방밀도의분포에있어서구여성과차이가있었으며또한저체중의젊은여성의경우치밀유방의비율이상대적으로높은것이관찰되었다. 따라서젊은연령에서유방암의비율이높고치밀유방의비율이서양에비해높은우리나라의경우연령및비만도를고려한개별적인검진방법을선택하는것이필요하겠으며젊고마른여성의경우유방촬영술과함께유방초음파를병행하는것이유방촬영술의낮은검사민감도를보완할수있는선택이될것이다. 본연구는국내여성의유방촬영술의유방밀도에대한가장많은수의인구를대상으로한연구이다. 그러나단면적연구이며일개병원을대상으로하여선택편견이있을수있다. 또한폐경여부, 호르몬치료등의치밀유방에영향을미칠수있는다른변수들을보정하지못한점이한계로생각되나폐경전과후를나누어분석한기존의연구결과에따르면폐경을전후로하여비만도가유방의밀도에미치는영향의방향이다르지않았었으므로본연구의주요결과를희석시킬정도는아니라고생각된다. 14) 20, 30대의젊은여성의경우에는인구수가적어보다정확한분석이어려웠던점이아쉬웠다. 향후국내의 40대이하의여성들을대상으로한유방촬영술의민감도및특이도및비용효과에대한추가적인연구가필요할것이며이를바탕으로한유방선별검사의개별적가이드라인이제시되어야할것으로생각된다. 284

5 [Breast Density in Mammography According to Body Mass Index(BMI) in Korean Women] 참고문헌 1. 보건복지부. 한국중앙암등록사업연례보고서 ( ). 서울 대한가정의학회. 가정의학. 임상편. 2003: 유근영, 노동영, 이은숙. 유방암의조기검진. 대한의사협회지 2002; 45(8): Bradbury A, Olopade OI. The Case for Individualized Screening Recommendations for Breast Cancer. J Clin Oncol 2006;24(21): Carney PA, Kasales CJ, Tosteson ANA, Weiss JE, Goodrich ME, Poplack SP, et al. Likelihood of additional work-up among women undergoing routine screening mammography: the impact of age, breast density, and hormone therapy use. Preventive medicine 2004;39(1): Buist DSM, Porter PL, Lehman C, Taplin SH, White E. Factors Contributing to Mammography Failure in Women Aged Years. J Natl Cancer Inst 2004;96(19): Kerlikowske K, Grady D, Barclay J, Sickles EA, Ernster V. Effect of age, breast density, and family history on the sensitivity of first screening mammography. JAMA 1996;276(1): Mandelson MT, Oestreicher N, Porter PL, White D, Finder CA, Taplin SH, et al. Breast Density as a Predictor of Mammographic Detection: Comparison of Interval- and Screen-Detected Cancers. J Natl Cancer Inst 2000;92(13): Sellers TA, Vachon CM, Pankratz VS, Janney CA, Fredericksen Z, Brandt KR, et al. Association of Childhood and Adolescent Anthropometric Factors, Physical Activity, and Diet with Adult Mammographic Breast Density. Am J Epidemiol 2007;166(4): Banks E, Reeves G, Beral V, Bull D, Crossley B, Simmonds M, et al. Influence of personal characteristics of individual women on sensitivity and specificity of mammography in the Million Women Study: cohort study. BMJ (Clinical research ed 2004; 329(7464): Hunt KA, Sickles EA. Effect of Obesity on Screening Mammography: Outcomes Analysis of 88,346 Consecutive Examinations. J Clin Oncol 2000;174(5): Habel LA, Capra AM, Oestreicher N, Greendale GA, Cauley JA, Bromberger J, et al. Mammographic density in a multiethnic cohort. Menopause : 김승형, 김미혜, 오기근. 유방촬영술상연령에따른한국여성의유방 밀도분석과서양여성과의비교. 대한방사선의학회지 2000;42: 조정진, 송홍지, 고은영, 송윤미, 한부경, 윤영숙, et al. 다기관연구를통해살펴본한국여성에서유방밀도와유방암위험요인. 대한가정의학회지 2006;27: Kolb TM, Lichy J, Newhouse JH. Comparison of the Performance of Screening Mammography, Physical Examination, and Breast US and Evaluation of Factors that Influence Them: An Analysis of 27,825 Patient Evaluations. Radiology 2002: Stomper PC DSD, DiNotto PA, Arredondo MA. Analysis of parenchymal density on mammograms in 1353 women years old. Am J Roentgenol 1996;167: 유근영, 윤하정, 신애선, 신혜림. 유방암조기검진의한계. 암예방학회지 2001;6(3): Radilogy ACo. ACR Practive Guideline for the performance of a breast ultrasound examination. Breast Ultrasound. 2007: Atkins CD. Potential Hazards of Mammography. J Clin Oncol 2007;25(5): Kaplan SS. Clinical Utility of Bilateral Whole-Breast US in the Evaluation of Women with Dense Breast Tissue. In 2001: PB G, SL G. Malignant masses detected only by US. A retrospective review. Cancer 1995;76: A. BW. Supplemental screening sonography in dense breasts. Radiol clin North Am 2004;42(5): Berg WA. Rationale for a Trial of Screening Breast Ultrasound: American College of Radiology Imaging Network (ACRIN) Am J Roentgenol 2003;180(5): 오기근. 유방영상학 1판. 서울 : 고려의학 (p.71-84) 25. Gerson ES, Berg WA.Screening breast sonography. Am J Roentgenol 2003:1477-a Carolyn F.Nemec M, Jay Listinsky M, PhD, Alice Rim M. How should we screen for breast cancer? Mammography, ultrasonography, MRI. CLEVELAND CLINIC JOURNAL OF MEDICINE 2007;74: Crystal P, Strano SD, Shcharynski S, Koretz MJ. Using Sonography to Screen Women with Mammographically Dense Breasts. Am J Roentgenol 2003;181(1): Ji Hyung Kim MD, Ki Keun Oh MD, Sang Wook Yoon MD. Usefulness of Ultrasonography for Detection of Breast Cancer in Patients under 30 Years of Age. Korean Radiological Society 1995;32(4):

6 Korean J Health Promot Dis Prev Vol. 8, No. 4, 2008 [Abstract] Breast Density in Mammography According to Body Mass Index(BMI) in Korean Women Eurah Goh, Kee Weon Shin, Yun Young Seo, Jung A Ko, Min Seon Park, Belong Cho, Woo Kyung Bae Department of Family Medicine, Seoul National University Hospital Background Methods Results It is well known that low BMI and younger age are associated with high breast density in western women, but there is a lack of researchin Korean women. Mammographic dense breast has been reported both as a cause of false-negative findings on mammography and as an indicator of increased breast cancer risk. The purpose of this study was to evaluate the relationship between breast density and BMI. Furthermore, we considered proper screening method of breast cancer in Korean women. From February 2000 to March 2006, 16,482 asymptomatic women who underwent screening mammography in the health promotion center were included. Those with prior history of breast cancer or breast surgery were excluded. Breast density distribution and further breast sonography recommendation rate were evaluated. 25.9% of women (n=4,275) had dense breasts. Both Age and BMI were negatively associated with breast density respectively (P < 0.001, P < 0.001). BMI after adjusting for age was negatively associated with breast density (OR of underweight 1.381, 95% CI ; OR of overweight 0.792, 95% CI ; OR of obesity 0.540, 95% CI ; OR of severe obesity 0.298, 95% CI ). 17.8% (n=2,939) of women were recommended further breast sonography due to low sensitivity of mammography. Young age and low BMI were associated with sonography recommendation rate (P < 0.001, P < 0.001). Conclusions BMI is negatively associated with breast density after adjusting for age. Mammography combined with breast sonography may increase sensitivity of breast cancer screening in especially young and thin women in Korea. (Korean J Health Promot Dis Prev 2008 ; 8(4): ) Key words 16 mammography, mammographic density, breast density, body mass index, breast cancer screeningfatty liver, metabolic syndrome, body mass index, waist-to-hip ratio, percent body fat Address for correspondence : Woo Kyung Bae Department of Family Medicine, Seoul National University Hospital Tel : naslig@hanmail.net 286

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°ûÁø¿µ 451 Table 1. Comparison of Medial Audit Data of Additional Whole Breast US with Previously Published Data of Screening Mammography in Korea and the Ideal Goal ACR in America Audit Data This study Shin