DOI:.857/jkstro.8.6.. 초기유방암의유방보존수술후방사선치료결과 인제대학교의과대학방사선종양학교실 *, 임상시험센터, 세계로병원유방클리닉 조흥래 * ㆍ김철진 * ㆍ박성광 * ㆍ오민경 ㆍ이진용 ㆍ안기정 * 목적 : 유방보존수술후방사선치료를받은환자에서치료의성적과무병생존율및재발에영향을주는위험인자에대해알아보고자하였다. 대상및방법 : 997년 월부터 년 월까지유방보존수술시행후방사선치료를받은환자 77명을대상으로후향적으로분석하였다. 추적관찰기간의중앙값은 58. 개월 (.8 9. 개월 ) 이었다. 전체환자의평균연령은 세, 중앙연령은 세이었다. 수술후조직학적 T 병기는 Tis가 7명, T 8명 (9.%), T 8명 (6.%), T 명, 미확인이 명이었다. 액와림프절전이가없는경우가 5명 (67.5%), 개전이가 명 (8.%), 개이상이 명 (.%) 이었다. 절제연이음성인환자는 명이었고, mm 이내로근접한경우는 5명, 양성인경우는 명이었다. 방사선치료는전체유방에접사면으로조사한후원발병소부위에전자선으로추가조사하여총. Gy에서 66. Gy를시행하였다. 액와림프절의개수가 개이상인경우에는액와림프절과쇄골상림프절을포함하여. 6. Gy를조사하였다. 항암화학요법은 명에서시행되었고, 호르몬치료로는 tamoxifen 또는 fareston을사용하였으며 9명에서시행하였다. 결과 : 5년생존율은 98.% 이었으며, 5년무병생존율은 9.5% 이었다. 총 77명의환자중 명 (5.%) 의환자가재발을하였다. 명은쇄골상림프절재발, 명은쇄골상림프절과동시에다발성원격전이, 다른 명은원격전이가발견되었다. 원발병소주위의국소재발은추적관찰기간중발견되지않았다. 림프절전이유무나숫자는재발이나 (p=.95) 무병생존율 (p=.) 에영향을미치지않았다. 절제연이양성인 명중 명이 7개월만에재발을하였고, 재발기간까지걸린기간인무병생존기간이통계적으로의미있게짧은것으로나타났으며 (p<.), 재발빈도도절제연이음성이거나가까운경우에비해서통계적으로의미가있는것으로나타났다 (p=.57). 그러나절제연이근접한경우에는절제연음성인경우와비교하여통계적으로재발빈도에차이가없었다 (p=.). 재발된 명은모두 세이하로 9.% 의재발률을보인반면, 세이상에서는재발이없었으나두그룹간에통계적으로유의한차이는없었다 (p=.55). 수술후조직학적 T 병기는 T의경우 명 (%) 이재발한반면, T에서는재발이발견되지않았으며통계적으로유의한차이를보였다 (p=.8). 무병생존율도 T 환자의경우에통계적으로의미있게낮은것으로나타났다 (p=.79). 무병생존율에영향을미치는단변량분석에서수술후조직학적 T 병기, 절제연의상태, p5 수용체변이가통계적으로의미있게나왔다. 결론 : 초기유방암에서유방보존수술후방사선치료는높은국소제어율과무병생존율을보이는안전한치료이다. 절제연양성, 수술후조직학적 T 병기, p5 수용체변이등은통계적으로유의하게재발위험이높은군에속하였으며, 무병생존율에영향을미치는것으로밝혀졌다. 핵심용어 : 유방암, 유방보존수술, 방사선치료 서 론 이논문은 8 년 7 월 일접수하여 8 년 월 일채택되었음. 책임저자 : 조흥래, 인제대학교의과대학방사선종양학교실 Tel: 5-89-6695, Fax: 5-89- E-mail: oncodoc@inje.ac.kr 본연구는인제대학교학술연구조성비지원에의하여연구되었음. 유방암의발병양상은한국에서는서구와달리 대에서가장높은발병률을보이고, ) 최근빠른속도로발병률이증가하여서여성암발생률 위를차지하며, ) 사회적으로도유방암에대한진단과치료에대한관심이커지고있다. 초기유방암에대한치료는 NSABP B-6 5) 연구결과 - -
조흥래외 5 인 : 초기유방암의유방보존수술후방사선치료결과 를통해서유방보존수술후방사선치료의성적이변형근치적유방절제술과비교하여생존율에있어서차이가없음이입증된이후로초기유방암에서는유방보존수술후방사선치료가표준화된치료로받아들여졌다. 한국에서도 9년대초부터본격적으로유방보존수술후방사선치료가시행되어점차대상환자수가증가하고있다. Ahn 과 Yoo 등 6) 의보고에의하면 년도에는약.9% 가유방보존수술을받은것으로보고되었고앞으로더욱증가할것으로예상된다. 본연구는유방보존수술후본원에서방사선치료를받은환자에서치료성적과무병생존율및재발에영향을주는위험인자에대해알아보고향후치료지침으로활용하고자한다. 대상및방법 997년 월부터 년 월까지유방보존수술시행후방사선치료를받은환자 77명에대해후향적으로분석하였다. 추적관찰기간은최소.8개월부터 9.개월이었고, 평균값은 6.개월, 중앙값은 58.개월이었다. 전체환자의평균연령은 세, 중앙연령은 세, 연령분포는 세 66세이었다. 세이하는 명 (55.8%), 세이상은 명이었다 (Table ). 조직학적유형별로는침윤성관암종 (infiltrating ductal carcinoma) 이 58명으로가장많았으며, 관내상피암종 (ductal carcinoma in situ; DCIS) 이 7명, 점액암종 (mucinous carcinoma) 이 명, 수질암종 (medullary carcinoma) 이 명, 침윤성소엽상피암종 (invasive lobular carcinoma) 이 명, 관상암종 (tubular carcinoma) 이 명, 기타조직학유형이 8명이었다. 조직학적등급은 등급이 8명, 가 명, 이 명, 미확인이 명이었다. 절제연음성이 명, mm 이내근접한경우가 5명, 양성이 명, 미확인이 명이었다. 월경은폐경전이 명이었고폐경이 7명, 폐경근처가 명, 미확인이 명이었다. T 병기가 8명, T가 8명, T는 명, Tis가 7 명, 미확인이 명이었다. 액와림프절절제는 69/77명 (89.6%) 에서시행하였다. 개에서부터 8개가절제되었고중앙값은 개였다. 림프절전이가없는경우가 5명, 개전이된환자가 명, 개이상이 명이었다. 감시림프절절제는 5명에서시행되었다. 방사선치료는 6 MV X선선형가속기로전체유방에접사면 (tangential field) 으로 5. Gy를조사한후원발병소부위에절제연의상태에따라 9 6 Gy를 MeV의전자선으로추가조사하였다. 절제연이양성인경우 6 Gy Table. Patient Characteristics (n=77) Characteristics N (%) Age 66 (median ) > Menopausal status Pre Post Peri Histology IDC* DCIS Mucinous Medullary Tubular ILC Others & unknown Histologic nuclear grade Grade Grade Grade Margin status Close Positive T Stage Tis T T T LN status ER Positive PR Positive p5 Positive Chemotherapy Yes No 7 57 7 8 5 7 8 8 5 7 5 5 5 9 9 9 8 * infiltrating ductal carcinoma, ductal carcinoma in situ, infiltrating lobular carcinoma, lymph node, estrogen receptor, progesteron receptor - 5 -
를원발병소부위에조사하였다. 액와림프절의개수가 개이상이거나충분한절제를하지못한 6명의경우에는액와림프절과쇄골상림프절을포함하여. 6. Gy 를조사하였다. 항암화학요법은 명에서시행하였다. 대부분의환자들은 (5명) CMF 요법으로시행하였으며, FAC 가 명, AC와 Taxol이 명, 기타요법이 명이있었다. 호르몬치료는 9명에서 Tamoxifen 또는 Fareston으로시행하였다. 생존율및재발률위험분석, 무병생존율계산을위한통계처리는 SAS 9.. (SAS Institute Inc., Cary, NC, USA) 를사용하였다. 결과 5년생존율은 98.8% 이었으며 (Fig. ), 5년무병생존율은 9.9% 이었다 (Fig. ). 병기별 5년생존율및 5년무병생존율은 기에서모두 % 이었으며, 기에서는각각 9.7%, 8.95% 이었다. 총 77명의환자중 명 (5.%) 의환자가재발을하였는데 (Table ), 림프절재발은 명 (.6%) 에서발생하였으며, 동측쇄골상림프절에서각각 78.개월, 5.6개월만에재발 하였고, 후자는골전이가동시에발생하였다. 원격전이는쇄골상림프절재발과동시에전이가발견된 명의경우와원격전이단독으로재발된경우 명을포함하여총 명 (.9%) 이었고원격전이단독으로재발된 명의경우는 7.,.6 개월만에발견되었다. 원격전이는간 (예), 골 ( 예 ), 뇌 (예) 의전이를보였다. 원격전이가발견된환자중 명은.5 cm 크기의병소와 9개의림프절중에서 개가전이되었으며절제연이양성이었는데, 7개월만에간, 골, 뇌에서다발성으로전이가발견되었으며, 방사선치료종결시점부터 9.9개월만에사망했다. 추적조사기간중사망한환자는 명이었으며원발병소주위의국소재발은추적관찰기간중발견되지않았다. 림프절재발은액와림프절전이가없었던 5명중 명 (.9%) 이 78.개월에쇄골상림프절에서재발을하였다. 림프절전이가 개이상있었던 7명중 명 (5.9%) 이 5.6 개월에쇄골상부림프절에서재발을하였는데, 이환자의경우는 8개림프절중 개가전이가되었던경우였고림프절에대한방사선치료는시행되지않았다. 림프절전이유무나숫자에따른재발은통계적으로유의성이없었으며 (p=.89), 무병생존율에도영향을미치지않았다 (p=., Table ). Fig.. 5 year overall survival in early breast cancer patients who treated with conserving surgery and radiation therapy. Fig.. 5 year disease free survival in early breast cancer patients who treated with conserving surgery and radiation therapy. Table. The Patterns of Failure Failure pattern Site Age Time (months) Histology Tumor size (cm) LN* Resection margin Status LN* D D LN*+D SCL Bone, Liver, Brain Liver SCL, Bone 9 5 7 78. 7..6 5.6 IDC IDC IDC IDC.5 /9 /9 / /8 ( ) (+) ( ) ( ) AWD Dead AWD AWD *lymph node, distant metastasis, supraclavicular lymph node, infiltrating ductal carcinoma, alive with disease - 6 -
조흥래외 5 인 : 초기유방암의유방보존수술후방사선치료결과 Table. Univariate Analysis of Prognostic Factors Associated with Disease Free Survival Factors Age > Menopause Pre Post Peri Uknown Tumor size T T Resection margin Positive Close LN* status ER Positive unknown PR Positive p5 Positive Chemotherapy Yes No Number of patients 6 7 8 8 8 5 5 7 5 5 5 9 9 9 8 Events of recurrences DFS(%) p-value 9.7 9. 85.7 9.9 5 96. 85.7 9. 9. 9. 96.7 9.9 9. 8. 9..5.78.79 <...686.5..56 *lymph node, estrogen receptor, progesteron receptor, disease free survival 절제연의상태가유방보존수술후방사선치료시국소재발및무병생존율에미치는영향을알아보기위하여분석을시행하였다. 절제연이음성인환자는 명이었고, mm 이내로근접한경우는 5명, 양성인경우는 명이었다. 재발된환자 명중 명은절제연이음성이었고 명은양성이었으며, 절제연양성인 명중 명이재발하였다. 재발까지의기간은절제연이양성인경우는 7개월이었고, 음성인경우는각각.6, 5.6, 78.개월이었다. 절제연이양성인경우음성이나근접한경우보다무병생존기간이통계적으로의미있게짧은것으로나타났으며 (p<.), 재발빈도도절제연이음성이거나가까운경우에비해서통계 적으로다소유의한차이가있는것으로나타났다 (p=.57). 그러나절제연이근접한경우에는절제연음성인경우와비교하여재발유무에있어서통계적으로유의한차이가없었다 (p=.). 나이에따른재발영향을보기위해서 세를기준으로나누었을때재발된 명은모두 세이하로 9.% 의재발률을보인반면, 세를넘는환자들에서는재발을발견할수없었다. 이는연령별로 세이하의경우더높은재발률을보였지만, 통계적으로는유의한차이를보이지않았다 (p=.55). 무병생존율에서도두군간에통계적유의성은없었다 (p=.5). 수술후조직학적원발병소의크기는재발한환자 명중,.5 cm이 명이었고나머지 명은 cm로모두 T에해당하였다. T 환자 8명중 명 (%) 이재발한반면, T 환자는 8명중재발을보인환자는없었으며 T 병기에따른재발율을비교할경우통계적으로유의한차이를보였다 (p=.8). 무병생존율도 T 환자의경우에통계적으로의미있게낮은것으로나타났다 (p=.79). 나이, 월경상태, 수술후조직학적 T 병기, 림프절전이수, 절제연의상태, 호르몬수용체유무, p5 수용체변이, 항암치료유무등을대상으로무병생존율에영향을미치는지를알아보기위한단변량분석에서, 절제연상태 (p<.), 수술후조직학적 T 병기 (p=.79), p5 수용체변이 (p=.) 가통계적으로유의한인자임을알수있었다 (Table ). 고안및결론유방암은다른고형암과달리 5년이후에도지속적으로재발되는것으로보고되고, 최근 년동안추적관찰결과를발표한 Milan 그룹 ) 과 NSABP-6 보고 5) 에의하면 년이후에도재발이관찰되는것으로보고하였다. 따라서본연구에서 5년동안추적관찰한기간은충분한추적관찰기간이되지못하고계속관찰해야할필요가있다. 그러나 Early Breast Cancer Trialists' Collaborative Group (EBC- TCG) 의보고 7) 에의하면 5년내에약 분의 정도가재발하는것으로보고하므로, 5년추적관찰을통해유방보존수술후방사선치료의재발에대한경향을분석하고향후치료방침으로삼을수있을것으로생각된다. 국내연구자들 8 ) 에의하면국소재발률이 % 에서 6% 로보고하고있으며, 외국의다른연구자들 7,,) 은 5년국소재발률을 7% 전후로보고하였다. 한편 Bartelink에의하면원발병소에대한추가방사선조사로인하여 5년국소재발률이 - 7 -
7.% 에서.% 로감소하였으며, ) 년추적관찰조사결과국소재발률이.% 에서 6.% 로감소하였다고보고하였다. 5) 본원의 5년추적관찰기간중원발병소주위의국소재발이발견되지않은것은모든환자에서원발병소에추가방사선조사를시행한효과때문일것으로추정되지만, 대상환자및재발환자의수가적고, 관찰기간이짧은편에속하기때문에국소제어율에대한분석은더많은환자를대상으로오랜추적관찰이필요할것으로판단된다. 초기유방암의원격전이는 9년대국내저자들 7 9) 의보고에의하면약 7% 전후로보고하고있으나, 년대들어서서약 % 로감소하는추세를보였으며 6) 본연구결과의.9% 와비슷한수치이다. 외국의보고에의하면 5년원격전이는국소재발률보다조금높은 8% 전후로보고하고있다.,) 초기유방암에서국소재발률보다원격전이율이다소높은것은초기에이미미세암세포가전이가되어있을가능성이높다는것을의미하고, 치료성적을향상시키기위해서위험인자분석을통해서고위험군에대해서는보다적극적인항암화학요법이필요하다고생각한다. Fowble 등 7) 과 Halverson 등 8) 의연구에의하면초기유방암의 5년림프절재발률을 % 로보고하였는데, 본연구에서도액와림프절전이는총 77명중 명 (.5%) 에서발생하였다. 림프절절제당시전이가없었던 5명중 명이 78. 개월에쇄골상부림프절에서재발을하였고림프절전이가 개이상있었던 7명중 명이 5.6 개월에쇄골상림프절에서재발을하였는데, 이환자의경우는 8 개림프절중 개가전이가되었던경우였고림프절방사선치료는시행되지않았다. 연구에의하면림프절전이가 개인경우림프절방사선조사가재발을낮추는데도움이되지않으므로액와림프절방사선치료를추천하지않았다. 9 ) 본연구에서도림프절전이유무나숫자에따른재발은통계적으로유의성이없었다 (p=.89). 또한무병생존율도통계적으로유의한차이가없는것으로나타났다 (p=., Table ). 그러나림프절전이가 개이상인경우 Grills 등 ) 에의하면 년림프절재발률을 % 에서 % 로낮추는효과를기대할수있으므로국소림프절치료를추천하였고, Fortin 등 ) 은재발률을 5% 정도낮추는효과를기대할수있으므로이부위의방사선치료를추천하였다. 본연구에서는액와림프절이 개이상전이가된환자가 명에불과하고이들중국소재발한환자는관찰되지않아서림프절방사선치료가재발을낮추는지에대한분석은따로시행하지않았다. 많은연구자들 5 8) 이수술후절제연의상태를중요한예후인자중하나로보고하고있다. 절제연이양성인경우연구자에따라서 5년국소재발률을 % 에서높게는 % 이상으로보고하고있다. 9 ) 특히 Jobsen 등 ) 은절제연이양성일경우나이가국소재발률에미치는영향이크다고주장하였다. 또한절제연이양성일경우 세보다많은경우의 5년국소재발률은 8.%, 5년무병생존율은 8.% 로보고하였으나, 세이하인경우절제연이양성인경우는 5년국소재발률은 6.9%, 5년무병생존율은 7.% 로보고하였다. 본연구에서는절제연이양성인 명의환자중 명이 7개월만에원격전이에의한재발이발견되었고, 치료종결후 9.9개월만에사망했다. 7개월이라는빠른시간내에재발을하며짧은생존기간을보이는것으로보아서절제연이양성인경우는예후가좋지않을것으로판단이된다. 통계적으로도절제연이양성인경우재발기간까지걸린기간인무병생존기간이의미있게짧은것으로나타났다 (p<.). 또한재발가능성도절제연이음성이거나가까운경우에비해서다소높은것으로나타났다 (p=.57). 그러나절제연이양성이더라도적극적으로재수술을통해서절제연음성을얻을경우의국소재발률은절제연이음성인경우와비슷한것으로보고하므 로 ) 절제연이양성인경우에는절제연음성을얻기위한 재절제술이권고된다. 본연구에서절제연이근접한경우는 5명이었는데, 5년추적관찰기간동안재발이발견되지않았으며절제연이음성인경우와비교하여통계적으로재발가능성이높지않았다 (p=.). Recht 등 ) 도절제연이근접한경우, 항암화학요법이전에방사선치료를시행할경우국소재발을발견할수없었다고보고하고있다. 따라서절제연이근접한경우에는방사선치료시점이늦어지지않는다면비슷한결과를얻을수있을것으로사료된다. 그러나본연구는 5년동안의추적관찰이므로장기간의추적관찰이필요할것으로판단된다. 한국유방암학회의 년도발표에의하면우리나라유방암환자의연령별분포특징은미국과다른양상을보이고있다. ) 미국의경우대부분의환자들이폐경이후인반면, 5) 한국인은 6% 이상의환자가 5세이하의젊은환자라는특징이있고그중 대에가장많이발생하는양상을보이고있다. ) 본원에서치료를받은환자의나이분포는 세이하가 명 (55.8%) 으로가장많았고, 세에서 5세까지는 명, 5세이상은 명이었다. 발생연령이 대에서점차 대쪽으로옮겨가는경향을보이고있고폐경이전에주로발생한다는점에서서구와는다른양상을보인다. 세이하의젊은나이에서발생하는경우 - 8 -
조흥래외 5 인 : 초기유방암의유방보존수술후방사선치료결과 예후가좋지않은것으로보고,,5) 하고있는데, 본연구에서는 세이하의경우재발률이 9.% 인반면 세보다나이가많은경우에는재발이발견되지않았다. 그러나나이에따른 5년재발률과무병생존율이통계적으로유의한차이는없는것으로나타났다 (p=.55). 이러한결과는대상환자의수와재발한환자의수가적기때문인것으로추정된다. 젊은나이에발생하는유방암은유전자변이가관계하는것으로알려져있다. 6 8) Choi 등 9) 에의하면한국에서 세이전에발생하는유방암환자의 8.7% 에서 BRCA과 BRCA의유전자변이가발견된다고보고하였고 Ahn 등 ) 에의하면고위험군에서 BRCA과 BRCA의유전자변이빈도가 5배높은것으로보고하고있다. 또한 Wazer 등 5) 에의하면 5세이하의젊은여성에서는절제연의상태와관계없이수술후유방내에암이남아있을가능성이훨씬높다고보고하였다. 따라서젊은여성환자인경우유전자변이에대한검사및치료완료후잔존암가능성에대한추적관찰이필요할것으로판단된다. 본연구에서는수술후조직학적병소의크기가 cm 보다클경우 (T), cm 이하 (T) 보다재발률이높았고 (% vs %), 통계적으로유의한차이가있었으며 (p=.8), 무병생존율에도통계적으로유의한영향을미치는것으로나타났다 (p=.79). 다른보고에서도동일하게병소의크기가예후인자로중요하게작용한다고보고하였다. ) p5 수용체변이에대한메타분석에따르면 p5 수용체변이가있을경우비교위험도가.7로서무병생존율및전체생존율에영향을미치는독립적인인자로서발표하였다. ) 다른많은저자들 5 9) 도 p5가생존율에영향을미치는인자로보고하고있다. 본연구에서도재발된 명에서 p5 수용체변이가있는경우였고, 통계적으로무병생존율에영향을미치는것으로나타났다 (p=.). 그러나유방암의종양표지자검사에대한 7년도 ASCO (American Society of Clinical Oncology) 권고안 5) 에따르면 p5가유방암의치료를위한임상적표지자로권고하지는않는다고발표하였다. 그이유는 p5 수용체변이가있을경우예후인자로의미가있는것으로보이지만, 현재임상에서사용되고있는면역조직화학염색법으로는변이된 p5 뿐만아니라변이가일어나지않은 p5도검출될가능성이높기때문에권고되지않는다고보고하였다. 본연구에서도비록 p5 수용체변이가있는경우통계적으로는유의하게무병생존율이감소하는것으로나왔지만, p5 수용체분석이면역조직화학염색법에의해시행되었고변이를보인환자의수가적어서그결과를분석하는데신 중을기하여야할것으로생각된다. 결론적으로유방보존수술후방사선치료는낮은재발률과높은무병생존율을보이는안전한치료임이본연구를통해서확인되었다. 절제연이양성인경우, 수술후조직학적원발병소의크기가 cm 보다큰경우 (T), p5 수용체변이등이재발과무병생존율에영향을미치는것으로나타났다. 향후더많은환자를대상으로 년이상의장기적인추적관찰및분석이필요할것으로판단된다. 참고문헌. The Korean Breast Cancer Society. Nationwide Korean breast cancer data of. J Korean Breast Cancer Soc 6;9:5-6. Annual report of the central cancer registry in Korea ( ). Ministry of Health and Welfare. Republic of Korea 5. Fisher B, Anderson S, Redmond CK, et al. Reanalysis and results after years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 995;:56-6. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med ;7:- 5. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med ;7:7-6. Ahn SH, Yoo KY. The Korean Breast Cancer Society. Chronological changes of clinical characteristics in,5 new breast cancer patients amon Koreans during 996-. Breast Cancer Res Treat 6;99:9-7. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 5-year survival: an overview of the randomised trials. Lancet 5;66:87-6 8. Koh KO, Kim MS, Yoo SY, et al. The results of primary radiotherapy following breast-conserving surgery for early breast cancer. J Korean Soc Ther Radiol 995;:6-7 9. Suh CO, Chung EJ, Lee HD, Lee KS, Oh KK, Kim GE. Risk factors for recurrence after conservative treatment in early breast cancer: preliminary report. J Korean Soc Ther Radiol 997;5:-8. Kim KJ, Huh SJ, Yang JH, et al. Treatment results and prognostic factors of early breast cancer treated with a breast conserving operation and radiotherapy. Jpn J Clin Oncol 5; 5:6-. Hong SG, Lee JH, Lee SK, Yoon SO. Breast-conserving surgery with or without radiation radiation therapy for early breast cancer. J Korean Surg Soc 998;55:-9-9 -
. Touboul E, Buffat L, Belkacémi Y. Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys 999;:5-8. Kurtz JM, Amalric R, Delouche G, et al. The second ten years: Long time risks of breast conservation in early breast cancer. Int J Radiat Oncol Biol Phys 987;:7-. Bartelink H, Horiot JC, Poortmans P, et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med ; 5:78-87 5. Bartelink H, Horiot JC, Poortmans PM, et al. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: -year results of the randomized boost versus no boost EORTC 88-88 trial. J Clin Oncol 7;5:-65 6. Lee SH, Lee KC, Choi J, et al. Radiation Therapy and chemotherapy after breast conserving surgery for invasive breast cancer: an interim result. J Korean Soc Ther Radiol 7;5:6-5 7. Fowble B, Solin LJ, Schultz DJ, et al. Frequency, sites of relapse, and outcome of regional node failures following conservative surgery and radiation for early breast cancer. Int J Radiat Oncol Biol Phys 989;7:7 7 8. Halverson KJ, Taylor ME, Perez CA, et al. Regional nodal management patterns of failure following conservative surgery and radiation therapy for stage I and II breast cancer. Int J Radiat Oncol Biol Phys 99;6:-9 9. Recht A, Pierce SM, Abner A, et al. Regional nodal failure after conservative surgery and radiotherapy for early-stage breast carcinoma. J Clin Oncol 99;9:988 996. Vicini FA, Horwitz EM, Lacerna MD, et al. The role of regional nodal irradiation in the management of patients with early-stage breast cancer treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys 997;9:69 76. Fodor J, Toth J, Major T, et al. Incidence and time of occurrence of regional recurrence in Stage I II breast cancer: value of adjuvant irradiation. Int J Radiat Oncol Biol Phys 999;:8 87. Galper S, Recht A, Silver B, et al. Factors associated with regional nodal failure in patients with early stage breast cancer with - positive axillary nodes following tangential irradiation alone. Int J Radiat Oncol Biol Phys 999;5:57-66. Grills IS, Kestin LL, Goldstein N, et al. Risk factors for regional nodal failure after breast-conserving therapy: regional nodal irradiation reduces rate of axillary failure in patients with four or more positive lymph nodes. Int J Radiat Oncol Biol Phys ;56:658-67. Fortin A, Dagnault A, Larochelle M, Vu TT. Impact of locoregional radiotherapy in node-positive patients treated by breast-conservative treatment. Int J Radiat Oncol Biol Phys ;56:- 5. Borger J, Kemperman H, Hart A, et al. Risk factors in breast conserving therapy. J Clin Oncol 99;:65 66 6. Fourquet A, Campana F, Zafrani B, et al. Prognostic factors of breast recurrence in the conservative management of early breast cancer: a 5-year follow-up. Int J Radiat Oncol Biol Phys 989;7:79-75 7. Smitt MC, Nowels KW, Zdeblick MJ, et al. The importance of the lumpectomy surgical margin status in long-term results of breast conservation. Cancer 995;76: 67 8. Kini VR, Vicini FA, Frazier R, et al. Mammographic, pathologic, and treatment-related factors associated with local recurrence in patients with early-stage breast cancer treated with breast conserving therapy. Int J Radiat Oncol Biol Phys 999;:-6 9. Anscher MS, Jones P, Prosnitz LR, et al. Local failure and margin status in early-stage breast carcinoma treated with conservation surgery and radiation therapy. Ann Surg 99;8: -8. DiBiase SJ, Komarnicky LT, Heron DE, et al. Influence of radiation dose on positive surgical margins in women undergoing breast conservation therapy. Int J Radiat Oncol Biol Phys ;5:68 686. Gage I, Schnitt SJ, Nixon AJ, et al. Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy. Cancer 996;78:9 98. Jobsen JJ, van der Palen J, Ong F, et al. The value of a positive margin for invasive carcinoma in breast-conservative treatment in relation to local recurrence is limited to young women only. Int J Radiat Oncol Biol Phys ;57:7 7. Freedman G, Fowble B, Hanlon A, et al. Patients with early stage invasive cancer with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy. Int J Radiat Oncol Biol Phys 999;:5-5. Recht A, Come SE, Henderson IC, et al. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med 996;: 56-6 5. Wazer D, Schmidt-Ullrich R, Ruthazer R, et al. The influence of age and extensive intraductal component histology upon breast lumpectomy margin assessment as a predictor of residual tumor. Int J Radiat Oncol Biol Phys 999;5:885-89 6. Robson M, Gilewski T, Haas B, et al. BRCA-associated breast cancer in young women. J Clin Oncol 998;6:6-69 7. Garber J. Inherited breast cancer: increasingly familiar territory. J Clin Oncol 998;6:69-6 8. Ford D, Easton DF, Peto J. Estimates of the gene frequency of BRCA and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 995;57:57-6 9. Choi DH, Lee MH, Bale AE, Carter D, Haffty BG. Incidence of BRCA and BRCA mutations in young Korean breast cancer patients. J Clin Oncol ;:68-65. Ahn SH, Hwang UK, Kwak BS, et al. Prevalence of BRCA and BRCA mutations in Korean breast cancer patients. J Korean Med Sci ;9:69-7 - -
조흥래외 5 인 : 초기유방암의유방보존수술후방사선치료결과. Aebi S, Gelber S, Castiglione-Gertsch M, et al. Is chemotherapy alone adequate for young women with oestrogen receptor-positive breast cancer? Lancet ;55:869-87. Weiss RB, Woolf SH, Demakos E, et al. Natural history of more than years of node-positive primary breast carcinoma treated with cyclophosphamide, methotrexate, and fluorouracilbased adjuvant chemotherapy: a study by the Cancer and Leukemia Group B. J Clin Oncol ;:85-85. Chia SK, Speers CH, Bryce CJ, et al. Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast cancers without adjuvant systemic therapies. J Clin Oncol ;:6-67. Pharoah PD, Day NE, Caldas C. Somatic mutations in the p5 gene and prognosis in breast cancer: a meta-analysis. Br J Cancer 999;8:968-97 5. Bull SB, Ozcelik H, Pinnaduwage D, et al. The combination of p5 mutation and neu/erbb- amplification is associated with poor survival in nodenegative breast cancer. J Clin Oncol ;:86-96 6. Goffin JR, Chappuis PO, Begin LR, et al. Impact of germline BRCA mutations and overexpression of p5 on prognosis and response to treatment following breast carcinoma: -year follow up data. Cancer ;97:57-56 7. Linderholm B, Lindh B, Tavelin B, et al. p5 and vascularendothelial-growth -factor (VEGF) expression predicts outcome in 8 patients with primary breast carcinoma. Int J Cancer ;89:5-6 8. Overgaard J, Yilmaz M, Guldberg P, et al. TP5 mutation is an independent prognostic marker for poor outcome in both node-negative and node positive breast cancer. Acta Oncol ;9:7-9. Cuny M, Kramar A, Courjal F, et al. Relating genotype and phenotype in breast cancer: An analysis of the prognostic significance of amplification at eight different genes or loci and of p5 mutations. Cancer Res ;6:77-8 5. Harris L, Fritsche H, Mennel R, et al. American society of clinical oncology 7 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 7;5: 587-5 - -
Abstract Clinical Outcome after Breast Conserving Surgery and Radiation Therapy for Early Breast Cancer Heunglae Cho, M.D.*, Cheoljin Kim, M.D.*, Sungkwang Park, Ph.D.*, Minkyung Oh, Ph.D., Jinyong Lee, M.D., and Kijung Ahn, M.D.* Departments of Radiation Oncology* and Clinical Research Center, College of Medicine, Inje University, Breast Clinic Saegyaero Hospital, Busan, Korea Purpose: This study was performed to evaluate the disease-free survival and risk factors of recurrence in early breast cancer patients who have undergone breast conserving surgery and radiation therapy. Materials and Methods: From March 997 to December, 77 breast cancer patients who underwent breast conserving surgery and radiation therapy were reviewed retrospectively. The median follow-up time was 58. months (range.8 9. months) and the mean subject age was years. The frequency distribution of the different T stages, based on the tumor characteristics was 8 (9.%) for T, 8 (6.%) for T, for T, 7 for Tis and for an unidentified sized tumor. In addition, 5 patients (67.5%) did not have axillary lymph metastasis, whereas patients (8.%) had lymph node metastases and (.%) had more than lymph node metastases. The resection margin was negative in patients, close ( mm) in 5, and positive in. All patients received radiation therapy at the intact breast using tangential fields with a subsequent electron beam boost to the tumor bed at a total dose ranging from. Gy to 66. Gy. Patients with more than four positive axillary lymph nodes received radiation therapy (. 6. Gy) at the axillary and supraclavicular area. Chemotherapy was administered in patients and tamoxifen or fareston was administered in 9 patients. Results: The 5 year overall survival and disease-free survival rates were 98.8% and 9.9%, respectively. Of the 77 patients, a total of relapses (5.%), including isolated supraclavicular relapse, supraclavicular relapse with synchronous multiple distant relapses, and distant relapses were observed. No cases of local breast relapses were observed. Lymph node metastasis or number of metastatic lymph nodes was not found to be statistically related with a relapse (p=.89) nor disease-free survival (p=.). Patients with positive margins had a significantly shorter disease-free survival period (p<.) and higher relapse rates (p=.57). However, patients with close margins were at equal risk of relapse and disease-free survival as with negative margins (p=.). Patients younger than years of age had higher relapse rates (9.% vs. %) and lower disease-free survival periods, but the difference was not statistically significant (p=.55). The relapse rates for patients with tumors was % for tumor stage T, compared to % for tumor stage T tumors (p=.8). A univariate analysis found that disease-free survival and relapse rates, T stage, positive resection margin and mutation of p5 were significant factors for clinical outcome. Conclusion: The results of this study have shown that breast conservation surgery and radiation therapy in early breast cancer patients has proven to be a safe treatment modality with a low relapse rate and high disease-free survival rate. The patients with a positive margin, T stage, and mutation of p5 are associated with statistically higher relapse rates and lower disease-free survival. Key Words: Breast cancer, Breast conserving surgery, Radiation therapy - -