ㅣ제 3 차유방암진료권고안 2008 ㅣ 01 제 3 차유방암진료권고안발표의배경과경과보고 한국유방암학회는 2002 년 11 월, 제 1 차유방암진료권고안을발표했다. 이권고안은한국유방암학회가국 내유방암의치료를선도하고있음을대외적으로알리는기회가되었으나근거중심의원칙에충실하지못했

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1 Contents 제 3 차유방암진료권고안 2008 한국유방암학회유방암진료권고안위원회 위원장 한세환 ( 인제의대외과 ) 간사 박우찬 ( 가톨릭의대외과 ), 김성용 ( 순천향의대외과 ) 배경 ㅣ02ㅣ 권두언 ㅣ03ㅣ 근거수준및권고등급의정의 ㅣ04ㅣ 유방암진료권고사항요약 ㅣ05ㅣ 제 1 장비침습유방암 ( 관상피내암과소엽상피내암 ) 진료권고안ㅣ12ㅣ 제 2 장조기유방암진료권고안 ㅣ19ㅣ 제 3 장국소진행유방암진료권고안 ㅣ40ㅣ 제 4 장재발및전이유방암진료권고안 ㅣ64ㅣ 유방암진료흐름도 ㅣ82ㅣ 유방암영상검사요약표ㅣ88ㅣ [ 비침습유방암진료권고안위원회 ] 위원장김이수 ( 한림의대외과 ) 간사신혁재 ( 관동의대외과 ) 위원공경엽 ( 울산의대병리과 ) 곽범석 ( 동국의대외과 ) 방사익 ( 성균관의대성형외과 ) 윤현조 ( 전북의대외과 ) 이은혜 ( 순천향의대영상의학과 ) 최두호 ( 성균관의대방사선종양학과 ) 최준영 ( 성균관의대핵의학과 ) [ 조기유방암진료권고안위원회 ] 위원장조영업 ( 인하의대외과 ) 간사김승기 ( 포천중문의대외과 ) 위원강희준 ( 한림의대외과 ) 금기창 ( 연세의대방사선종양학과 ) 김세중 ( 인하의대외과 ) 신희정 ( 울산의대영상의학과 ) 우상욱 ( 고려의대외과 ) 유대현 ( 연세의대성형외과 ) 조은윤 ( 성균관의대병리과 ) 최준영 ( 성균관의대핵의학과 ) [ 진행유방암진료권고안위원회 ] 위원장강성수 ( 관동의대외과 ) 간사이일균 ( 미즈메디병원외과 ) 위원박경미 ( 인제의대병리과 ) 박원 ( 성균관의대방사선종양학과 ) 손대구 ( 계명의대성형외과 ) 안진경 ( 을지의대영상의학과 ) 이해경 ( 관동의대외과 ) 최운정 ( 원광의대외과 ) 최준영 ( 성균관의대핵의학과 ) 한부경 ( 성균관의대영상의학과 ) 허호 ( 건강보험일산병원외과 ) [ 재발전이유방암진료권고안위원회 ] Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 위원장김권천 ( 조선의대외과 ) 간사곽금희 ( 인제의대외과 ) 위원고경란 ( 국립암센터영상의학과 ) 곽희숙 ( 부산의대외과 ) 김민석 ( 원자력의학원병리과 ) 김제룡 ( 충남의대외과 ) 신경환 ( 국립암센터방사선종양학과 ) 양경무 ( 전북의대성형외과 ) 조규란 ( 고려의대영상의학과 ) 최준영 ( 성균관의대핵의학과 )

2 ㅣ제 3 차유방암진료권고안 2008 ㅣ 01 제 3 차유방암진료권고안발표의배경과경과보고 한국유방암학회는 2002 년 11 월, 제 1 차유방암진료권고안을발표했다. 이권고안은한국유방암학회가국 내유방암의치료를선도하고있음을대외적으로알리는기회가되었으나근거중심의원칙에충실하지못했고 실제유방암치료에대한세부적인내용을포함하지못했다. 이후한국유방암학회는 2005년 6월유방암진료권고안위원회의조직을개편하고인력을보완하여 2006년제 2차유방암진료권고안을완성하였다. 제 2차유방암진료권고안은제 1차유방암진료권고안과는달리방대한문헌검색을시행하고근거수준을객관적으로평가하는도구를개발하였다. 제 2차유방암진료권고안은근거수준에따라권고등급을표기하여실제진료에도움이되도록하였고구체적인치료법과추적검사항목을추가하였다. 한국유방암학회의지속적인노력은 2007년대한의학회와공동으로모든유관학회가참여하는유방암진료권고안을발표하는결과를낳았다. 2008년제 3차유방암진료권고안은보건복지가족부의연구비지원을받아 7개유관학회가공동으로발표하는형태를취하였다. 형식적으로는다학제참여에의한공동작업이지만한국유방암학회가주도하는결과가되었다. 한국유방암학회의지속적인유방암진료권고안위원회의활동이없었다면짧은시간에방대한분량의진료권고안을완성할수없었다는것을참여학회들이모두인정하지않을수없는사실이었다. 한국유방암학회가유관학회들에게포용과배려의마음으로양보심을보인것은앞으로도한국유방암학회가유방암진료의중심이되는데많은도움이될것이다. 대승적인차원에서양보와격려와협조를아끼지않은회장님, 이사장님을비롯한모든한국유방암학회회원님들께감사의말씀을전하는바이다. 바쁜일정중에서도여러학회와의연락과조율에힘써준박우찬, 김성용교수에게감사의뜻을전하며마지 막까지교정작업에힘써준곽금희교수를비롯한진료권고안위원들의헌신적인노력에경의를표하는바이다. 2

3 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 02 권두언 2008년가을, 한국유방암학회에서는제3차유방암진료권고안을발간하게되었습니다. 2002년 1차권고안과 2006년 2차권고안에이은이번권고안은이전의권고안과여러가지로다른의미를가지고있습니다. 잘아시는바와같이한국유방암학회에서는유방암진료권고안위원회를두고두차례의권고안을발간한바있습니다. 그러나이번 3차권고안에서는한국유방암학회차원을떠나우리나라를대표할수있는진료권고안을만들고자대한의학회소속유방암관련학회가모두참여하여공동으로함께사용할진료권고안을마련했다는점에서이전과는매우다른의미가있다고하겠습니다. 물론지금까지학회가주체가되어왔던전통과명맥을유지하는점에서는부족하게보일수는있겠습니다만, 다학제진료가세계적인흐름인이시대에한국유방암진료의발전을위해대승적으로다른학회의전문가들과함께유방암진료권고안을마련한사실은한국유방암학회가우리나라유방암관련전문가들을모두포용하고함께발전해나갈수있는큰초석을마련했다는점에서높이평가하고싶습니다. 이제유방암의진료는해마다변화하고있습니다. 새롭게진행되는연구와실험으로도출되는새로운결과가거의매일쏟아져나오고있는상황속에서유방암의진료는큰변화와발전을이루고있습니다. 이에한국유방암학회에서는이러한내용을회원여러분들께알려드리고, 또정립된내용에대해서는해마다진료권고안의개정작업을통하여진료에도움이될수있도록지속적으로노력할예정입니다. 이번에발표되는진료권고안은이러한취지에따라서가능한모든내용의근거 (evidence) 를찾아서그수준을밝혔고, 우리나라진료상황을고려하여해당진료를권고 (recommendation) 하였습니다. 따라서근거중심의이번권고안은매년이루어질개정작업의훌륭한기초가될것이라고믿어의심치않습니다. 유방암진료권고안은실제로유방암의진료에직접이용되어야진정한그의미를가질수가있습니다. 이번권고안에서는본문의내용뿐만아니라유방암진료의권고사항에대한요약을일목요연하게표로정리하여참고하는사람들의편의를고려한점은좋은시도로생각되며, 회원여러분께서직접이용하면서부족한부문에대해서아낌없이지적해주시어보다나은진료권고안이될수있는기회가되기를바랍니다. 무덥고길었던 2008년여름에진료권고안작업을위해헌신적인노고를아끼지않으신진료권고안위원회한세환위원장님과참여하신여러회원님들께깊은감사를드리며, 새롭게시도된이번권고안이유방암학회회원들에게좋은참고자료로널리이롭게이용되기를기원합니다 년 10 월한국유방암학회 회장이수정 이사장이민혁 3

4 ㅣ제 3 차유방암진료권고안 2008 ㅣ 03 근거수준및권고등급의정의 근거수준 (Level of Evidence : LE) 의정의 Level 1 Level 2 Level 3 Level 4 모든무작위대조시험 (randomized controlled trial: RCT) 을체계적으로검토 (systemic review: SR) 하여얻은근거적절하게고안된하나이상의무작위대조시험에서얻은근거잘고안된대조시험 (controlled trial: CT) 에서얻은근거이거나, 다기관에서시행한코호트또는환자대조연구에서얻은근거, 혹은개입 (intervention) 없이연속적연구에서얻은근거권위있는전문가의임상경험에기초한의견이나, 전문가로구성된위원회에서발표된연구결과나보고자료에서얻은근거 권고등급 (Grade of Recommendation : GR) 의정의 Grade A Grade B Grade C 최소 1 개이상의무작위대조시험이요구되며, 내용의지속성 (consistency) 이있는경우 잘고안된대조시험 (CT) 의근거는있으나, 무작위대조시험 (RCT) 의근거가없는경우 권위있는전문가의임상경험이나전문가로구성된위원회에서발표된의견에따른경우 4

5 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 04 유방암진료권고사항요약 제 1 장비침습유방암 : 관상피내암과소엽상피내암 관상피내암의진단영상검사근거수준참고문헌 유방촬영술을기본으로하며미세석회화로나타나는경우는유방확대촬영술과조직검사가필요하다. 미세석회화병소의조직검사에서는반드시표본촬영술을시행하여미세석회화병소가포함되었는지확인해야한다. 미세석회화가없고종괴나비대칭음영으로나타나는병변은초음파검사를추가하여발견할수있다. 유방자기공명영상 (magnetic resonance imaging: MRI) 검사는다발성병소를발견하거나병소의범위를보다정확하게평가할수있으므로유방보존술을시행하기전에추가로이용할수있다. 4 2, 3, 6 4 2, 3 3 4, 5 관상피내암의병리조직검사근거수준참고문헌 병리조직검사시침윤유방암의재발억제효과를위해항여성호르몬제를사용하기전호르몬수용체 ER/PR 면역화학염색 (Immunohistochemistry Staining: IHC Staining) 을시행한다. 2 33, 34 관상피내암의치료근거수준참고문헌 유방전절제술의시행시고위험환자군이나침윤병변을배제할수없는환자에서는감시림프절생검을시행할수있다. 3 28, 29 젊은여성환자에서는국소재발률이높기때문에추가로 boost radiation 을시행할수있다 저위험군환자에서는선택적으로유방보존술후방사선요법을생략할수있다. 4 43, 44 관상피내암의추적검사근거수준참고문헌 유방전절제술을받은환자에서는매년양측유방진찰과반대측유방촬영술을시행한다. 유방보존술을받은환자에서는첫 5 년동안 6 개월이나 1 년간격으로양측유방진찰과동측유방촬영술을시행하고필요에따라유방확대촬영술을시행한다. 반대측유방촬영술은 1 년간격으로시행한다. 그이후에는매년유방진찰과유방촬영술을시행한다. 4 3, 35, 36 필요에따라유방확대촬영술과유방초음파검사를시행할수있다. 4 3 소엽상피내암의치료근거수준참고문헌 소엽상피내암의치료에추천되는방법은정기적인추적관찰이다. 1 37, 38 폐경후여성에서는이차침윤암발생의예방을위해 tamoxifen 혹은 raloxifene 을 5 년간투여할수있다

6 ㅣ제 3 차유방암진료권고안 2008 ㅣ 제 2 장조기유방암 조기유방암의진단영상검사근거수준참고문헌 유방촬영술과유방초음파검사를조직검사이전에시행하며, 이때종양의크기는적어도 2 차원 (dimension) 으로길이를측정해야한다. 조기유방암의조직학적진단은통상적으로영상유도하침생검 (core needle biopsy) 이바람직하다. 4 2 필요하면유방확대촬영술을시행할수있다. 4 2 고밀도유방에서종양이미만성이고유방촬영술과유방초음파검사소견이불확실한경우에는유방자기공명영상 (magnetic resonance imaging; MRI) 검사를추가로시행할수있다. 전신검사를위해흉부단순촬영을시행하며필요한경우병기결정목적으로뼈스캔 (bone scan), 복부초음파검사또는전산화단층촬영 (computed tomography; CT) 또는양전자방출단층촬영 ( 18 F-fluorodeoxyglucose positron emission tomography; 18 F-FDG PET) 을시행할수있다 조기유방암의병리조직검사근거수준참고문헌 병리조직검사시침윤유방암의재발억제효과를위해항여성호르몬제를사용하기전원발종양의호르몬수용체 ER/PR 면역화학염색을시행한다. 원발종양조직에서 HER-2 발현은예후예측, anthracycline 기반의수술후보조항암화학요법선택, 내분비치료에대한상대적저항성예측, 재발이나전이된환자에서 taxane 또는 trastuzumab 치료의효과예측등에사용할수있다. 2 10, 조기유방암의수술적치료근거수준참고문헌 병기 I, II 의조기유방암에서유방전절제술 ( 유방전절제술 + 액와림프절절제술 ) 과유방보존술 ( 부분유방절제술 + 액와림프절절제술 + 방사선치료 ) 은환자의장기생존율에서동등한효과가있다. 유방전절제술을받은환자는즉시또는지연유방재건술시행의대상이될수있다. 유방전절제술후방사선요법이필요치않은경우즉시유방재건술이가장좋은미용적결과를보이지만수술후방사선요법이필요한경우에는지연유방재건술이선호된다. 70 세이상의유방암환자에서림프절음성, ER 양성이고절제연음성의유방보존술을시행했을경우방사선요법을시행하지않고 tamoxifen 또는아로마타제억제제 aromatase inhibitor; AI 단독요법도가능하다. Anthracycline 기반의수술후보조항암화학요법이적응이되는경우방사선요법과항암화학요법을동시에시행하지않는것이바람직하다. 감시림프절생검의대상은임상적으로액와림프절전이가없거나전이가의심되는림프절에대한생검또는세포진검사결과음성이고, 원발종양의최대직경이 5cm 미만인경우가적합하며, 경험이많은감시림프절생검팀이있어야하는것이선행조건이다 , , 조기유방암의유방전절제술후방사선요법근거수준참고문헌 유방전절제술을받은경우종양의직경이 5cm 이상이거나절제연이양성또는 1mm 미만으로근접해있는경우에흉벽에대한방사선요법을시행한다 조기유방암의유방보존술후방사선요법근거수준참고문헌 유방보존술을시행받은경우모든환자에서전체유방에방사선조사가필요하다 액와림프절이 1~3 개전이양성인유방암에서쇄골상부림프절에방사선조사를고려할수있으며같은쪽내유방림프절에대한방사선요법에대해서는아직논란이있다. 2, 3 55, 62, 63 6

7 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 조기유방암의수술후내분비요법근거수준참고문헌 원발종양의호르몬수용체 ER/PR 발현유무를검사해야하고, 양성인경우환자의나이, 액와림프절전이여부, 수술후항암화학요법여부, HER-2 유무등에관계없이보조내분비요법을시행한다. 호르몬수용체양성인폐경전여성에서는 tamoxifen 의사용을우선적으로고려하고사용기간은 5 년을원칙으로한다. Tamoxifen 의사용중 GnRH agonist 의투여나 ovarian ablation 치료를병합하여사용할수있다. 호르몬수용체양성인폐경후여성에서는 AI 의사용을고려할수있다. 투여방법은 AI 를처음부터 tamoxifen 대신 5 년간투여하거나 ( 선행요법, upfront therapy as initial adjuvant), 2~3 년간 tamoxifen 을투여한후 AI 를투여하거나 ( 순차요법, switch therapy as sequential with tamoxifen), tamoxifen 을 5 년간사용한뒤 AI 를투여하는방법 ( 연장요법, extended therapy) 등이있다. 골다공증의위험도를감소시키기위하여 AI 사용전골밀도검사가권장되며필요한경우적절한신체운동과 calcium 제제및 vitamin D 의투여가고려될수있다. 호르몬치료의기간은 5 년에서 10 년동안이권장된다 , , 94 조기유방암의수술후항암화학요법근거수준참고문헌 항암화학요법을시행할때는적어도 2 개이상의약제를 3~6 개월동안투여해야하며, 가능한한도에서최대용량을투여하는것이바람직하다. 림프절양성이거나 HER-2 가과발현된암에서는 anthracycline 계열의약제사용이더효과적이다. HER-2 IHC 염색에서 3+ 이거나 FISH 검사양성인조기유방암환자에서림프절양성이거나림프절음성이며종양의크기가 1cm 보다큰경우에는항암화학요법과함께 1 년동안 trastuzumab 투여를고려할수있다 , 14, 16, 101, , 107, 108 Trastuzumab 사용시심장독성의증가가보고되고있어적절한평가가병행되어야한다 , 110 Paclitaxel 의투약빈도를높이는용량강도요법의우수한초기결과가보고되고있으며무병생존율과생존율에있어우수한결과를보이고있다. Docetaxel 과 cyclophosphamide(tc) 항암요법은 AC 항암요법과비교한무작위연구에서 5 년무병생존율은우월하였다. 경구용 5-FU 항암화학요법은일본을중심으로조기유방암과전이유방암, 재발유방암에서광범위하게사용되고있으며, 단독요법으로시행하거나 cyclophosphamide, doxorubicin, cisplatin, etoposide, paclitaxel 등과병용해서시행할수있다 , 조기유방암의추적검사근거수준참고문헌 유방보존술과방사선요법을받은환자에서는방사선요법이끝난후 6 개월에유방촬영술을시행하고, 이후 6 개월에서 1 년간격의추적검사를 2~5 년간시행하며, 반대쪽유방은매년정기검사를시행한다. 3 2 필요하면유방확대촬영술과유방초음파검사를시행할수있다. 3 2 원격전이를검사하기위해알칼리인산분해효소 (alkaline phosphatase) 를포함한간기능검사, 흉부단순촬영, 흉부전산화단층촬영, 뼈스캔, 복부초음파, 복부전산화단층촬영또는자기공명영상, 18 F-FDG PET, 종양표지자검사등은무증상의 1 기또는 2 기조기유방암환자에게추적관찰의정기적검사로시행하지않으나증상이있거나필요한경우시행할수있다

8 ㅣ제 3 차유방암진료권고안 2008 ㅣ 제 3 장국소진행유방암 국소진행유방암의진단영상검사근거수준참고문헌 유방촬영술과유방초음파검사를조직검사이전에시행하며이때종양의크기는적어도 2 차원 (dimension) 으로길이를재야한다. 조직진단은통상적으로영상유도하침생검 (core needle biopsy) 이권고된다. 고밀도유방에서종양이미만성인경우에유방촬영술과유방초음파검사소견이불확실하다면유방자기공명영상 (magnetic resonance imaging; MRI) 검사를추가로실시할수있으며필요시유방확대촬영술을시행할수있다. 증상이있거나국소진행유방암인환자의임상병기평가를위해뼈스캔, 복부초음파, 복부전산화단층촬영, 18 F-FDG PET 등을선택적으로시행할수있다. 4 3, , 6-8 국소진행유방암의병리조직검사근거수준참고문헌 병리조직검사시침윤유방암의재발억제효과를위해항여성호르몬제를사용하기전호르몬수용체 ER/PR 면역화학염색을시행한다. 원발종양의조직에서 HER-2 발현은예후예측, anthracycline 기반의수술후보조항암화학요법선택, 내분비치료에대한상대적저항성예측, 재발이나전이된환자에서 taxane 또는 trastuzumab 치료의효과예측등에사용할수있다. 2 2 비침습유방암참조 조기유방암참조 국소진행유방암의수술전항암화학요법근거수준참고문헌 수술전항암화학요법에의한병리학적완전관해는생존율을향상시키는예후인자로사용될수있다. 수술후보조항암화학요법에서와같이 taxane 을포함한요법이생존율의우위를보이므로수술전항암화학요법에서도 taxane 을추가한다양한요법이권장된다. 수술전항암화학요법 2~3 회를마친후에는반드시임상적, 방사선학적반응평가를실시해야한다. 반응평가에따라계획된항암화학요법을지속할것인지새로운요법으로바꾸거나국소치료를먼저시행할지결정하여야한다 , 29, 32, , 37, 38, 44 국소진행유방암의수술전내분비요법근거수준참고문헌 수술전항암요법으로서 AI 는호르몬수용체양성인폐경후여성의치료로선택할수있으며, 수술전내분비요법의적절한기간은 4-6 개월로권장되고, 항암화학요법과 AI 제제를동시에투여하는것은바람직하지않다. 2 37, 38 국소진행유방암의수술적치료근거수준참고문헌 일반적으로수술가능한국소진행유방암환자에대한수술적치료는조기유방암환자의수술적치료와동일하다. 수술전항암화학요법에반응을보인경우유방전절제술과유방보존술을모두고려할수있으며, 액와림프절절제는 level I/II 까지시행하는것을기본으로한다. 최초의임상병기가높은경우는수술전항암화학요법후유방전절제술을시행받은환자에서도국소재발의가능성이높으므로수술후방사선치료가필요하다. 수술후유방재건술은지연유방재건술이적절하지만수술후방사선요법이필요없다면즉시유방재건술을고려한다. 즉시유방재건술은유방암의재발이나생존율에영향을끼치지않는것으로보고되고있다. 2 조기유방암참조 1 49, 53,

9 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 국소진행유방암의수술후방사선요법근거수준참고문헌 유방전절제술후액와림프절전이가 4 개이상인환자에서는항암화학요법후흉벽과동측쇄골상부림프절에대한방사선요법이시행되어야한다. 액와림프절전이가 1-3 개인유방암에대해서도항암화학요법후에흉벽과동측쇄골상부림프절에대한방사선요법을적극고려해야한다. 액와림프절전이가없더라도종양크기가 5cm 이상이거나절제연이양성인경우흉벽에대한방사선요법이시행되어야한다. 수술후보조요법으로서방사선요법과항암화학요법의적절한시행시기와순서에대해서는아직까지확실치않으나, 부작용측면을고려하여동시에시행하지않는것이바람직하다. 국소진행유방암환자에서수술을용이하게하고유방보존가능성을높이기위해수술전선행항암화학요법이시행되는데, 이경우수술후방사선요법은항암화학요법의반응정도에관계없이진단시임상병기에따라시행되어야한다 , , 99 국소진행유방암의수술후보조항암화학요법근거수준참고문헌 국소진행유방암에서약제선택은강력한효과를가진 superior efficacy 약제를선택하는것이권장된다. ER 음성또는호르몬수용체저발현유방암과 HER-2 과발현유방암은우선적으로 anthracycline 기반요법 +taxane( 순차적요법또는병합요법 ) 을선택하는것이권장된다. 2 29, 32, 33, HER-2 과발현유방암에서림프절양성이거나, 림프절음성이면서고위험군인경우항암화학요법과함께 1 년동안 trastuzumab 을투여할수있다 , 104 국소진행유방암의수술후보조내분비요법근거수준참고문헌 폐경전환자에서호르몬수용체양성인경우내분비요법은 tamoxifen 5 년투여가권장되며, 또한최소 2 년간의 GnRH agonist 투여를고려할수도있다. 하지만, 최근의여러연구에서폐경전호르몬수용체양성인유방암치료에서 tamoxifen+gnrh agonist 병합요법이 tamoxifen 단독또는 GnRH agonist 단독투여군에비해무병생존율이향상되었다고보고하고있다 폐경후환자에서호르몬수용체양성인경우 3 세대 AI 사용은보조요법의일차요법 (upfront) 으로사용하거나, 총 5 년의기간중 tamoxifen 2-3 년투여한후순차적으로투여하는요법 (switch) 혹은 tamoxifen 5 년투여후연장하여사용하는요법 (extended) 중한가지방법으로시행할수있다 , 113 국소진행유방암의추적검사근거수준참고문헌 유방보존술과방사선요법을받은환자에서는방사선요법이끝난후약 6 개월에유방촬영술을시행하고, 이후 6 개월에서 1 년간격의추적검사를 2~5 년간시행하며, 유방암이없는반대쪽유방은매년정기검사를시행한다 필요시유방확대촬영술과유방초음파검사를시행할수있다 원격전이를감시하기위해 ALP, 간기능검사, 종양표지자 (CA15-3, CEA, CA27.29) 검사를통상적으로시행하지는않지만선택적으로시행할수있다. 또한뼈스캔, 흉부단순촬영, 흉부전산화단층촬영, 복부초음파검사, 복부전산화단층촬영, 복부자기공명영상또는 18 F-FDG PET은추적관찰의정기적검사로시행하지는않으나증상이있거나재발이의심되는경우시행할수있다

10 ㅣ제 3 차유방암진료권고안 2008 ㅣ 염증성유방암근거수준참고문헌 염증성유방암은비염증성유방암에비하여 HER-2 양성율과, 호르몬수용체의음성의빈도가더높고예후가불량하기때문에, 치료는반드시복합요법 ( 수술전항암화학요법, 수술, 방사선치료, 또는내분비요법등 ) 을시행하도록권유한다. 수술전항암화학요법을먼저시행하는것을표준으로하며, anthracycline 을포함하는병합요법을사용하되, taxane 계열의약제를병합하여투여하는것이전체생존율향상에도움이된다. 수술전항암화학요법후수술은유방전절제술이권장되는데유방보존술을시행할경우에는미용적인효과가불량할뿐아니라국소재발도빈번하여권장되지않는다 제 4 장재발및전이유방암 국소구역재발치료근거수준참고문헌 국소구역재발만있더라도 20%~30% 환자에서원격전이가동반되어발생하며결국전신전이를하는경우가많기때문에수술, 방사선요법등국소치료와함께항암화학요법, 내분비요법, 표적요법등전신치료를적극적으로고려해야한다 전신전이진단근거수준참고문헌 전이유방암환자의진단을위해병력청취와신체검사, 말초혈액검사, 혈소판검사, 간기능검사, 흉부엑스선검사, 뼈스캔, 증상이있는뼈나뼈스캔에서이상소견이있는뼈의엑스선검사를시행하며필요한경우복부및흉부 CT, 18 F-FDG PET, 자기공명영상도고려할수있다 전신전이내분비요법근거수준참고문헌 전신전이발생시암의치료보다는생존기간의연장, 삶의질향상이더중요하다. ER 양성이면서전신전이가광범위하지않고, 내부장기에전이가없는환자에서는우선적으로내분비요법을시도할것을권장한다. 내분비요법으로사용되는약제는 tamoxifen, AI 가대표적이고 3 번의서로다른약제를시도한후에도병이진행하거나반응이없는경우에는항암화학요법이나표적치료를고려하는것이바람직하다 전신전이항암화학요법근거수준참고문헌 항암화학요법은단일약제사용보다는두가지이상의약제를사용하는것이객관적인반응율을높이고병의진행기간 (time to progression) 을늘일수있지만병합요법은단일약제를순차적으로사용하는것보다독성이많다. 전이유방암에서지속적항암화학요법이단기항암화학요법보다병의진행이없는생존율 (progression-free survival) 을증가시킨다는증거는있지만충분하지않고, 전체생존율의차이는미약하기때문에항암화학요법의기간은전반적인삶의질에미치는영향들을고려하여결정되어야한다 , 44 10

11 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 전신전이표적치료근거수준참고문헌 전이유방암에서조직의 HER-2 검사가 FISH 양성이거나 IHC 3+ 라면 HER-2 표적치료가권장되고항암제와 trastuzumab, lapatinib 병용요법으로치료효과를얻을수있다 뼈전이치료근거수준참고문헌 뼈전이가있는경우 bisphosphonate 사용으로뼈에관련된합병증이나뼈전이로인한통증을줄일수있다 완화요법근거수준참고문헌 적극적인완화요법을고려할수있는경우는신체수행도가감소된경우 (ECOG 3 혹은 Kornofsky 신체수행도 50), 고칼슘혈증, 중추신경계전이, 상대정맥증후군, 척수압박, 영양실조 (Cachexia), 악성흉액질, 간부전, 신부전, 중증질환동반등이다. 1 83, 84 암통증치료근거수준참고문헌 암환자에서응급통증의원인은골절, 뇌전이, 경막외전이나연수막전이, 척수압박, 감염등이며, 이러한통증의원인이확인되면신속하게진통제와수술, 방사선요법, 스테로이드투여등의방법으로치료를해야한다. 통증은강도에따라 NSAID 또는 acetaminophen, 속효성경구혹은정맥항구토제, 보조진통제를필요에따라사용한다

12 ㅣ제ㅣ유방암 3차유방암진료진료권고안 ㅣㅣ 05 제 1 장비침습유방암 : 관상피내암과소엽상피내암 1.1. 관상피내암의정의 1.2. 관상피내암의진단검사 관상피내암은유관에서기원하여기저막을침범하지않은, AJCC cancer Staging Manual(6th edition, 2002) 의기준에따르면 0기 (TisN0M0) 암을말한다 1. 관상피내암의영상진단에는유방촬영술이기본적이고유용한검사이다. 미세석회화로나타나는경우는유방확대촬영술이필수적이다. 그러나 10% 정도는유방촬영술에서미세석회화가없이종괴나비대칭음영으로나타나기때문에, 이경우에는초음파검사를추가함으로써유방촬영술에서발견되기어려운병소를발견할수있다 2,3. 진행성유방암과달리상피내암에서는유방자기공명영상 magnetic resonance imaging; MRI검사의역할이아직완전히확립되지는않았으나, 다발성병소를발견하거나병소의범위를보다정확하게평가할수있으므로유방보존술을시행하기전에추가로시행할수있다 4,5 (LE 3, GR B). 수술전조직검사를시행하는것은필수적이다. 종괴음영없이미세석회화만있는경우는수술전에유방촬영술유도하에병소부위를철사 (wire) 로표시하여국소절제및수술적조직검사를시행하거나, 유방촬영술유도하에침생검을시행한다. 미세석회화를포함하는병소가초음파검사에서보이는경우는초음파유도하에침생검을시행할수있다. 미세석회화병소를조직검사한경우는반드시표본촬영술을시행하여미세석회화가포함되었는지확인한다 3,6. 관상피내암의진단검사근거수준참고문헌 유방촬영술을기본으로하며미세석회화로나타나는경우는유방확대촬영술과조직검사가필요하다. 미세석회화병소의조직검사에서는반드시표본촬영술을시행하여미세석회화병소가포함되었는지확인해야한다. 미세석회화가없이종괴나비대칭음영으로나타나는병변은초음파검사를추가하여발견할수있다. 유방자기공명영상 (magnetic resonance imaging; MRI) 검사는다발성병소를발견하거나병소의범위를보다정확하게평가할수있으므로유방보존술을시행하기전에추가로이용할수있다. 4 2, 3, 6 4 2, 3 3 4, 관상피내암의치료 수술적치료 미세석회화병소로국소절제술을시행받았거나영상유도하침생검을시행한환자는수술전에유방촬영술유도하에석회병소부위를바늘이나철사로표시하여야하며, 수술후표본촬영술을시행하여미세석회화병소가완전히절제되었는지확인해야한다 3,6. 관상피내암의수술적치료에는유방보존술후방사선치료를시행하는경우와유방전절제술을시행하는경우가있다 (LE 1, GR A). 유방촬영술이나유방초음파검사에서우연히발견된작은관상피내암의경우광범위국소절제술후조직검사에서종양과절제연사 12

13 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 이에일정거리가확보되면유방보존술로충분히국소제어를할수있다 6~10. 종양과절제연간의거리는 1cm이상이면충분하다고인정되며, 최소한 1mm이상은확보해야한다. 수술할때는동결절편검사에서종양과절제연의거리가 1mm이하이면다시절제를해야한다. 그러나다음몇가지경우에는유방전절제술을우선적으로고려한다 (LE 1, GR A). 1 상대적으로종양의크기가큰경우 12~17 2 다발성종양인경우 11,18 3 광범위미세석회화가동반된경우 18 4 국소절제술을 3번이상시행했음에도불구하고절제연양성인경우 11 5 방사선요법이금기인경우 : 임신, 교원혈관질환, 흉부에방사선요법을시행한경험이있는경우 19~21 유방전절제술이국소제어에는가장확실한방법이지만, 장기생존율을비교했을때유방전절제술을시행한경우와유방보존술에방사선요법을병합한경우, 유방보존술 ( 국소절제술 ) 만시행한경우모두에서큰차이가없는것으로보고되고있다 22~24,43,44 (LE 2, GR B). 유방전절제술을시행한경우유방재건술은어느때라도적절히시행할수있다 25 (LE 3, GR B). 순수한관상피내암의경우여러연구에서 1~2% 정도로매우낮은액와림프절전이율을보이므로액와림프절절제술및감시림프절생검은일반적으로권장되지않는다 26,27 (LE 1, GR A). 그러나, 고위험군의관상피내암으로유방전절제술을시행하는경우와침윤암을배제할수없는경우에감시림프절생검을시행할수있다 28,29 (LE 3, GR B) 방사선요법 유방보존술후에는국소재발률을낮추기위해 5~6주동안 45~50Gy의방사선요법을추가하게된다 (LE 1, GR A). 최근자료에따르면 45세이하의환자에서국소재발률이높기때문에추가방사선 (boost radiation) 을시행할수있다 42 (LE 3, GR B). 유방보존술 ( 국소절제술 ) 후에방사선요법을생략한경우국소재발률은방사선치료를시행한군에비하여유의하게높으나, 환자의나이가 50세이상, 종양의크기가 1cm이하, 종양절제연음성, 병리소견에면포성괴사음성, 낮은핵등급등의조건을모두만족하는저위험군인경우에는전체적인생존률에차이는없으며 5년국소재발률도 7% 로국소절제술만을시행할수도있다 43,44 (LE 4, GR C) 항암화학요법 관상피내암의수술적치료후항암화학요법은실시하지않는다 내분비요법 관상피내암의수술적치료후항여성호르몬제인 tamoxifen의사용이의미있게침윤암의재발을억제하는효과가있는것으로보고되었고, 이러한목적으로호르몬수용체 ( 에스트로겐수용체estrogen receptor; ER, 프로게스테론수용체progesterone receptor; PR) 양성인환자에게는수술후 5년간 tamoxifen의투여를고려할수있다. Tamoxifen을투여받는환자에서는자궁내막암의발생위험이있으므로 1년간격으로부인과검진을받아야한다 31,32. 호르몬수용체양성인폐경후여성에서 tamoxifen 투여시간독성이나심혈관계부작용을보인환자에서는제한적으로 toremifene의투여를고려할수있다. 호르몬수용체양성인폐경후여성에서예방목적의아로마타제억제제 aromatase inhibitors; AI의사용은대규모임상시행중으로현재는권장되지않는다. 13

14 ㅣ제 3 차유방암진료권고안 2008 ㅣ 관상피내암의치료근거수준참고문헌 유방전절제술의시행시고위험환자군이나침윤병변을배제할수없는환자에서는감시림프절생검을시행할수있다. 젊은여성환자에서는국소재발률이높기때문에추가로 boost radiation 을시행할수있다. 저위험군환자에서는선택적으로유방보존술후방사선요법을생략할수있다. 3 28, , 관상피내암의추적관찰 관상피내암의추적검사는, 유방전절제술을시행한경우에는매년유방의이학적진찰과반대쪽유방촬영술을시행한다. 유방보존술을받은경우에는처음 5년간 6개월이나 1년간격으로유방의이학적진찰과동측의유방촬영술을시행하고필요에따라유방확대촬영술을시행한다. 반대쪽유방촬영술은 1년간격으로시행한다. 그이후에는 1년간격으로유방의이학적진찰과유방촬영술을시행한다 3,35,36. 필요에따라유방초음파검사를시행할수있다. 관상피내암의추적검사근거수준참고문헌 유방전절제술환자에서는매년유방의진찰과반대측유방촬영술을시행한다. 유방보존술환자에서는첫 5 년동안 6 개월이나 1 년간격으로유방의진찰과동측의유방촬영술을시행하고필요에따라유방확대촬영술을시행한다. 반대측유방촬영술은 1 년간격으로시행한다. 그이후에는매년유방진찰과유방촬영술을시행한다. 4 3, 35, 36 필요에따라유방확대촬영술과유방초음파검사를시행할수있다

15 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 1.5. 소엽상피내암의정의 소엽상피암의진단검사 소엽상피내암은소엽에서기원하여기저막을침범하지않은, AJCC cancer Staging Manual(6th edition, 2002) 의기준에따르면 0기 (TisN0M0) 암을말한다 1. 소엽상피내암은다른병소의조직검사를시행하는도중우연히진단되는경우가많다 39. 소엽상피내암은다발성병소를갖는특징이있기때문에많은환자에서다발성과양측성으로발견된다 소엽상피암의치료 1) 치료원칙소엽상피내암은비교적이차암발생의위험도가낮은편이며, 15년이상관찰하여 21% 에서침윤암의발생이나타났다 37,38. 이런이유로소엽상피내암의치료에추천되는방법은정기적인추적관찰이다. 2) 이차암발생의위험감소를위한예방적치료가족력이있는고위험군여성에서는 BRCA 1 혹은 BRCA 2 유전자의변이검사를시행할수있으며변이가확인되면예방을위해양측유방전절제술을고려할수있다. 이때동시유방재건술을추가하기도한다 39. 항여성호르몬제인 tamoxifen을 5년동안투여한결과이차침윤암의발생이 56% 감소했다. 그러므로소엽상피내암이발생해서관찰하고있는여성에서는호르몬수용체양성인경우 tamoxifen의사용을고려할수있다 40. 최근발표된 Study of Tamoxifen and Raloxifene (STAR) trial의결과소엽상피내암의폐경후여성에서이차침윤암의발생을억제하기위해 raloxifene 5년투여한군과 tamoxifen 5년투여한군을비교한결과위험도감소효과가유사하다고발표되었다. 따라서소엽상피내암이발생하여관찰하고있는여성에서는호르몬수용체양성인경우페경전여성에서는 tamoxifen 5년투여를고려할수있으며, 폐경후여성에서는 tamoxifen 혹은 raloxifene 5년투여를이차침윤암예방을위해고려할수있다 45 (LE 1, GR A) 추적관찰 소엽상피내암은이차적유방암의위험도가지속적으로증가하기때문에 6개월또는 1년간격으로진찰을시행하고매년유방촬영술을시행한다 36. 소엽상피내암의치료근거수준참고문헌 소엽상피내암의치료에추천되는방법은정기적인추적관찰이다. 1 37, 38 폐경후여성에서는이차적침윤암발생의예방을위해 tamoxifen 혹은 raloxifene 을 5 년간투여할수있다

16 ㅣ제 3 차유방암진료권고안 2008 ㅣ 참고문헌 1. Greene F, Page D, et al. eds. AJCC Cancer staging manual. 6th edition. New york: Springer-Verlag, Moon WK, Myung JS, Lee YJ, Park IA, Noh DY, Im JG. US of ductal carcinoma in situ. RadioGraphics 2002;22: ACR practice guideline for the management of ductal carcinoma in-situ of the breast. ACR. 2006;21: Berg WA, Guierrez L, NessAvier MS, Carter WB, Bhargavan M, Lewis RS, et al. Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology 2004;233: 김도연, 고은숙, 양상규. 관상피내암의역동적조영증강자기공명영상과유방촬영술에크기예측비교. 대한유방암검진학회지 2005;2: Rubin E. Specimen radiography. In: Rubin E, Simpson JF. Breast specimen radiography: Needle localization and radiographic pathologic correlation. Philadelphia: Lippincott-Raven, 1998:p Lagios MD. Duct carcinoma in situ: pathology and treatment. Surg Clin North Am 1990;70: Hwang ES, Esserman LJ. Management of ductal carcinoma in situ. Surg Clin North Am 1999;79: Fisher B, Costantino J, Redmond C, Fisher E, Margolese R, Dimitrov N, et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993;328: Morrow M, Storm EA, Bassett LW, Dershaw DD, Fowble B, Harris JR, et al. Standard for the management of ductal in situ of the breast(dcis). CA Cancer J Clin 2002;52: Silverstein MJ, Parker R, Grotting JC, Cote RJ, Russell CA. Ductal carcinoma in situ(dcis) of the breast: diagnostic and therapeutic controveries. J Am Coll Surg 2001;192: Sakorafas GH, Farley DR. Breast Conservation therapy for breast cancer; atlas of the therapeutic intervention. Monograph(ebook), Digital Contents S.A,. Athens, 2003, Sakorafas GH. Breast cancer surgery-historical evolution, current status and future perspectives. Acta Oncol 2001;166: Sakorafas GH, Tsiotou AG. Selection criteria for the breast conservation in breast cancer. Eur J Surg 2000;166: Soran A, Vogel VG. Optimal management of primary breast cancer. Breast J 1999;5: Winchester DP, Cox JD. Standards for diagnosis and management of invasive breast carcinoma. American college of Surgeons. College of American Pathologists. Society of Surgical Oncology. CA Cancer J Clin 1998;48: Leach SD, Feig BW, Berger DH. Invasive breast cancer. In: Leach SD, Feig BW, Berger DH, eds. The M.D. Anderson surgical oncology handbook. Boston: Little, Brown and Company, 1995;p Corral CJ, Mustoe TA. Controversy in breast reconstruction. Surg Clin North Am 1996;76: Veraridis MP, Bland KI. Surgical and medical management of in situ and early stage breast carcinoma. In: Singletary SE, eds. Breast cancer. New York: Spinger-Verlag, 1999;p Robertson JM, Clarke DH, Pevnzer MM, Matter RC. Breast conservation therapy. Severe breast fibrosis after radiation therapy in patient with collagen vascular disease. Cancer 1991;68: Ross JG, Hussey DH, Mayr NA, Davis CS. Acute and late reaction to radiation therapy in patients with collagen vascular disease. Cancer 1993;71: Kurtz JM, Jacquemier J, Torhorst J, Spitalier JM, Amalric R, Hünig R, et al. Conservation therapy for breast cancers others than infiltrating ductal carcinoma. Cancer 1989;63:

17 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 23. Bornstein BA, Recht A, Connolly JL, Schnitt SJ, Cady B, Koufman C, et al. Results of treating ductal carcinoma in situ of the breast with conservative surgery and radiation therapy. Cancer 1991;67: Silverstein MJ, Cohlan BF, Gierson ED, Furmanski M, Gamagami P, Colburn WJ, et al. Duct carcinoma in situ: 227 cases without microinvasion. Eur J Cancer 1992;28: Fowble B, Hanlon AL, Fein DA, Hoffman JP, Sigurdson ER, Patchefsky A, et al. Results of conservative surgery and radiation for mammographically detected ductal carcinoma in situ(dcis). Int J Radiat Oncol Biol Phys 1997 Jul 15;38: Slavin SA, Schnitt SJ, Duda RB, Houlihan MJ, Koufman CN, Morris DJ, et al. Skin-sparing mastectomy and immediate reconstruction: oncologic risks and aesthetic results in patients with early-stage breast cancer. Plast Reconstr Surg 1998;102: Intra M, Rotmensz N, Veronsi P, Colleoni M, Iodice S, Paganelli G, et al. Sentinel node biopsy is not a standard procedure in ductal carcinoma in situ of the breast: the experience of the European institute of oncology on 854 patients in 10 years. Ann Surg 2008; 247: Julian TB, Land SR, Fourchotte V, Haile SR, Fisher ER, Mamounas EP, et al. Is sentinel node biopsy necessary in conservatively treated DCIS? Ann Surg Oncol 2007;14: Moore KH, Sweeney KJ, Wilson ME, Goldberg JI, Buchanan CL, Tan LK, et al. Outcomes for women with ductal carcinoma-in-situ and a positive sentinel node: a multi-institutional audit. Ann Surg Oncol 2007;14: Fisher B, Dignam J, Wolmark N, Mamounas E, Costantino J, Poller W, et al, Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17. J clin Oncol 1998;16: Julien JP, Bijker N, Fentiman IS, Peterse JL, Delledonne V, Rouanet P, et al. Radiotherapy in breast-conserving treatment for ductal carcinoma in situ: first results of the EORTC randomized phase III trial EORTC Radiotherapy Group. Lancet 2000;355; Early Breast Cancer Trialists Collaborative group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer. Lancet 2000;355: Fisher B, Land S, Mamounas E, Dignam J, Fisher ER, Wolmark N. Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience. Semin Oncol 2001;28: Fisher B, Dignam J, Wolmark N, Wickerham DL, Fisher ER, Mamounas E, et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet 1999;353: Mendelson EB. Evaluation of the postoperative breast. Radiol Clin North Am 1992;30: NCCN Practice Guidelines in Oncology v Kopan DB, Breast imaging. 2nd ed. Philadelphia; Lippincott Williams & Wilkins, 1998; Rosen PP, Kosloff C, Lieberman PH, Adair F, Braun DW Jr. Lobular carcinoma in situ of the breast. Detailed analysis of 99 patients with average follow-up of 24 years. Am J Surg Pathol 1978;2: Page DL, Kidd TE Jr, Dupont WD, Simpson JF, Rogers LW. Lobular neoplasia of the breast : higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol 1991;22: Hartmann LC, Schaid DJ, Woods JE, Crotty TP, Myers JL, Arnold PG, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Eng J Med 1999; 340: Fisher B, Costatino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention 17

18 ㅣ제 3 차유방암진료권고안 2008 ㅣ of breast cacner: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998;90: Boughey JC, Gonzalea RJ, Bonner E, Kuerer HM. Current Treatment and clinical trial Developments for Ductal Carcinoma In Situ. Oncologist 2007;12; Omlin A, Amichetti M, Azria D, Cole BF, Fourneret P, Poortmans P, et al. Boost radiotherapy in young women with ductal carcinoma in situ: a multicentre, retrospective study of the Rare Cancer Network. Lancet Oncol 2006;7: Hughes L, Wang M, Page D, et al. Five year results of intergroup study E5194: Local excision alone (without radiation treatment) for selected patients with ductal carcinoma in situ (DCIS). Breast Cancer Res Treat 2006; 100 (suppl 1):S Wong JS, Kaelin CM, Troyan SL,Gadd MA, Gelman R, Lester SC, et al. Prospective study of wide excision alone for ductal carcinoma in situ of the breast. J Clin Oncol 2006;24: Vogel GV, Joseph PC, D. Lawrence Wickerham, Cronin WM, Cecchini RS, Atkins JN, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006; 295:

19 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 06 제 2 장조기유방암 2.1. 조기유방암의정의 조기유방암은 AJCC Cancer Staging Manual(6th edition, 2002) 1 의기준에따르 면 I기 (T1N0M0), IIA기 (T0N1M0, T1N1M0, T2N0M0), IIB기 (T2N1M0, T3N0M0) 에해당하는침윤유방암이다 조기유방암의진단 영상검사 조기유방암의진단을위해병력청취, 신체검사, 말초혈액검사, 간기능검사, 흉부단순촬영및유방촬영술과유방초음파검사를시행한다. 유방촬영술이나유방초음파검사는조직검사전에시행하며, 병변의크기와다발성암의유무등을검사한다. 필요하면유방확대촬영술을시행할수있고유방촬영술이나유방초음파검사에서종양의크기는적어도 2차원 (dimension) 으로길이를측정해야한다 (LE 4, GR C). 조직진단은통상적으로영상유도하침생검 (core needle biopsy) 이권고된다. 시설이갖추어진기관에서는고밀도유방에서종양이미만성인경우유방촬영술과유방초음파검사소견이불확실하거나유방보존술을고려하는환자에서동측혹은반대측유방의다발성병변을확인하고유방암의침윤범위정도를파악하기위해유방자기공명영상 (magnetic resonance imaging; MRI) 검사를추가로시행할수있다 (LE 3, GR B). 필요한경우조기유방암환자에서병기결정목적으로뼈스캔 (bone scan), 복부초음파검사또는전산화단층촬영 (computed tomography; CT) 또는양전자방출단층촬영 ( 18 F-fluorodeoxyglucose positron emission tomography; 18 F-FDG PET) 을시행할수있다 2~7 (LE 2, GR B). 조기유방암의진단영상검사근거수준참고문헌 유방촬영술과유방초음파검사를조직검사이전에시행하며, 이때종양의크기는적어도 2 차원 (dimension) 으로길이를측정해야한다. 조직진단은통상적으로영상유도하침생검 core needle biopsy 이바람직하다. 4 2 필요하면유방확대촬영술을시행할수있다. 4 2 고밀도유방에서종양이미만성이고유방촬영술과유방초음파검사소견이불확실한경우에는유방자기공명영상 (magnetic resonance imaging; MRI) 검사를추가로시행할수있다. 전신검사를위해흉부단순촬영을시행하며필요한경우병기결정목적으로뼈스캔 (bone scan), 복부초음파검사또는전산화단층촬영 (computed tomography; CT) 또는 18 F-FDG PET 를시행할수있다

20 ㅣ제 3 차유방암진료권고안 2008 ㅣ 종양표지자 병리조직검사 수술후추적검사를위해혈청암종태아성항원carcinoembryonic antigen; CEA, CA15-3, CA27.29, HER-2 등의종양표지자를검사할수있다 8,9 (LE 3, GR B). 원발종양을생검한경우에는검체의에스트로겐수용체estrogen receptor; ER와프로게스테론수용체progesterone receptor; PR, HER-2 등을검사한다 10,11. 원발종양의조직에서 HER-2 발현은예후예측 12, anthracycline을기반으로한수술후보조항암화학요법의 CMF[cyclophosphamide-methotrexate-5-FU] 요법에대한우월성 13~16, 내분비치료에대한상대적저항성, 재발이나전이된환자에서 paclitaxel 또는 trastuzumab치료의효과예측 17~19 등에사용할수있다 (LE 2, GR B). 형광제자리부합법 fluorescence insitu hybridization; FISH으로 HER-2 유전자증폭유무를확인하는것은면역조직화학염색 immunohistochemical staining; IHC staining보다비용은많이들지만더정확한것으로보고되고있다 20,21 (LE 2, GR B). 조기유방암의병리조직검사근거수준참고문헌 병리조직검사시침윤유방암의재발억제효과를위해항여성호르몬제를사용하기전원발종양의호르몬수용체 ER/PR 면역화학염색을시행한다. 원발종양조직에서 HER-2 발현은예후예측, anthracycline 기반의수술후보조항암화학요법선택, 내분비치료에대한상대적저항성예측, 재발이나전이된환자에서 taxane 또는 trastuzumab 치료의효과예측등에사용할수있다. 2 10, 조기유방암의치료 국소치료 1) 수술 병기 I과 II의조기유방암에대한국소치료로써수술방법에는유방전절제술 ( 유방전절제술 + 액와림프절절제술 ), 유방보존술 ( 부분유방절제술 + 액와림프절절제술 ) 등이있으며, 액와림프절절제술대신감시림프절생검을시행할수있다. 유방전절제술과유방보존술은환자의장기생존율에서동등한효과가있다 22~25 (LE 2, GR B). 유방전절제술을받은환자는즉시또는지연유방재건술시행의대상이될수있다. 유방전절제술후방사선요법이필요치않은경우즉시유방재건술이가장좋은미용적결과를보이지만, 수술후방사선요법이필요한경우에는지연유방재건술이선호된다 26,27 (LE 3, GR B). 피부보존유방절제술skin-sparing mastectomy 28~31 과유두보존유방절제술 nipple sparing mastectomy 32,33 은즉시유방재건술을시행하는환자에서선택적으로시행할수있다 (LE 3, GR C). 유방보존술이절대적인금기가되는환자는 1) 유방이나흉벽에중등도또는고용량의방사선요법을받은경험이있는환자, 2) 임신중에방사선요법을받아야하는환자, 3) 유방촬영술에서악성으로의심되거나악성이명백한미만성미세석회화병소가있는환자, 4)2개이상의유방사분역에발생한다발성암등유방의병소가확산되어있어단일절개창으로는충분한절제연을형성할수없는환자, 5) 병리학적으로절제연이양성인환자등 20

21 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 이다. 병리학적으로절제연양성인경우음성절제연을얻기위해재절제 (re-excision) 를시행한다. 만약재절제후에도절제연이양성이면적절한국소치료를위해서유방전절제술을시행해야한다. 병리학적국소절제연침범이있으면서재절제를시행하지않은경우에는고용량방사선요법을고려해야한다. 유방보존술의상대적인금기는 1) 절개창을 2개이상만들어야하는다발성암, 2) 피부를침범한활동성결합조직질환 ( 공피증또는루푸스등 ), 3)5cm 보다큰종양 (LE 3, GR B), 4) 병리학적초점의절제연침범 focally positive pathologic margins 등이다. 폐경전의젊은여성이 BRCA 1 또는 2 유전자변이를보이면동측또는반대측유방에재발의위험이크므로유방전절제술이권유되며, 예방적양측유방전절제술을위험성방지목적으로시행할수있다 34~38 (LE 4, GR C). 70세이상의유방암환자에서림프절음성, ER 양성이고절제연음성의유방보존술을시행했을경우에는방사선요법을시행하지않고 tamoxifen 또는 AI 단독요법도가능하다 39,40 (LE 2, GR A). Anthracycline 기반의수술후보조항암화학요법이적응이되는경우, 방사선요법과항암화학요법을동시에시행하지않는것이바람직하다 41 (LE 2, GR A). 국소재발의위험이전신재발의위험보다유의하게크다고판단되는경우방사선요법후에항암화학요법을시행할수있다. 방사선요법은 CMF 항암화학요법과동시에시행할수있지만, methotrexate 투여는방사선요법중에중단하거나, 동시에시행한다면 2회이내로투여횟수를제한해야한다 (LE 3, GR C). 액와림프절절제술은국소구역재발의예방과병기결정이목적이기때문에적절한병기결정을위해서는충분한수 (10개이상 ) 의림프절을얻어야하며 42 (LE 4, GR C), level I( 소흉근의외측림프절군 ) 과 level II( 소흉근직하방림프절군 ) 의림프절절제를권장한다. 수술시야에서 level I 또는 level II 림프절의전이가강력히의심되거나동결절편검사에서전이가확인되었을때는 level III( 소흉근내측림프절군 ) 의림프절을절제할수있다 43 (LE 3, GR C). 감시림프절생검의대상은임상적으로액와림프절전이가없거나전이가의심되는림프절에대한생검또는세포진검사결과음성이고, 원발종양의최대직경이 5cm 미만인경우가적합하며 44~50 (LE 3, GR B), 경험이많은감시림프절생검팀이있어야하는것이선행조건이다 51 (LE 3, GR B). 림프계지도화 (lymphatic mapping) 에서감시림프절이내유방림프절에서발견되는경우에는선택적으로내유방림프절절제를시행할수있다 (LE 4, GR C). 감시림프절의전이여부는일차적으로 H&E염색 (hematoxylin-eosin staining) 의결과에따라판정하며결과가불분명할경우에는 cytokeratin IHC염색으로판정할수있다 (LE 4, GR C). 병기결정방법으로감시림프절생검을선택적으로고려할수는있으나액와림프절절제술을대체할수있는방법은아니다. 따라서수술시야에서감시림프절탐색에실패했거나동결절편검사에서전이가확인된경우또는동결절편검사에서는음성으로판정되었으나수술후영구병리조직소견에서전이가확인된경우에는액와림프절절제술을시행해야한다. 고령환자, 예후가좋은병리학적아형 ( 유두상암종, 관상암종등 ), 심각한동반질환이있는환자, 림프절전이여부가수술후보조요법의선택에영향을주지못하는경우에는액와림프절절제술을선택적으로시행할수있다. 21

22 ㅣ제 3 차유방암진료권고안 2008 ㅣ 조기유방암의수술적치료근거수준참고문헌 병기 I, II 의조기유방암에서유방전절제술 ( 유방전절제술 + 액와림프절절제술 ) 과유방보존술 ( 부분유방절제술 + 액와림프절절제술 + 방사선치료 ) 은환자의장기생존율에서동등한효과가있다 유방전절제술을받은환자는즉시또는지연유방재건술시행의대상이될수있다. 유방전절제술후방사선요법이필요치않은경우즉시유방재건술이가장좋은미용적결과를보이지만수술후방사선요법이필요한경우에는지연유방재건술이선호된다. 70 세이상의유방암환자에서림프절음성, ER 양성이고절제연음성의유방보존술을시행했을경우방사선요법을시행하지않고 tamoxifen 또는아로마타제억제제 aromatase inhibitor; AI 단독요법도가능하다. 3 26, , 40 Anthracycline 기반의수술후보조항암화학요법이적응이되는경우방사선요법과항암화학요법을동시에시행하지않는것이바람직하다. 감시림프절생검의대상은임상적으로액와림프절전이가없거나전이가의심되는림프절에대한생검또는세포진검사결과음성이고, 원발종양의최대직경이 5cm 미만인경우가적합하며, 경험이많은감시림프절생검팀이있어야하는것이선행조건이다 ) 방사선요법 유방전절제술후방사선요법유방전절제술을받은경우종양의직경이 5cm 이상이거나절제연이양성또는 1mm 미만으로근접해있는경우에흉벽에대한방사선요법을시행한다 52~54 (LE 3, GR B). 1~3 개의액와림프절전이가있는유방암에대해서는항암화학요법후에흉벽과쇄골상부림프절에대한방사선요법을고려할수있으며 (LE 2, GR B), 동측의내유방림프절에대한방사선요법도선택적으로시행할수있다 53,55 (LE 3, GR B). 조기유방암의유방전절제술후방사선요법근거수준참고문헌 유방전절제술을받은경우종양의직경이 5cm 이상이거나절제연이양성또는 1mm 미만으로근접해있는경우에흉벽에대한방사선요법을시행한다 유방보존술후방사선요법유방보존술을시행받은경우모든환자에서전유방방사선조사가필요하다 56~61 (LE 1, GR A). 선량은분획선량을 1.8~2 Gy씩, 일주일에 5회, 총 45~50 Gy를조사한다. 이후수술전종양의위치로범위를줄여분획선량을 1.8~2 Gy씩, 일주일에 5회, 총 10~15 Gy 를추가조사한다. 1~3개의액와림프절전이가있는유방암에대해서는쇄골상부림프절조사를고려할수있으며 (LE 2, GR B), 같은쪽내유방림프절에대한방사선요법에대해서는아직논란이있다 55,62,63 (LE 3, GR B). 22

23 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 조기유방암의유방보존술후방사선요법근거수준참고문헌 유방보존술을시행받은경우모든환자에서전체유방에방사선조사가필요하다. 액와림프절이 1~3 개전이가있는유방암에서쇄골상부림프절에방사선조사를고려할수있으며같은쪽내유방림프절에대한방사선요법에대해서는아직논란이있다 , 3 55, 62, 전신치료 1) 수술전전신요법 종양의크기를제외한유방보존술의적응증에해당하는병기 IIA와 IIB에서수술전항암화학요법이나내분비요법을고려할수있다. 수술전항암화학요법을계획하고있는환자에게는원발종양에대한생검이나세포진검사가필요하며, 임상적으로액와림프절전이가의심되는경우, 림프절에대한생검이나세포흡인생검을고려할수있다. 수술전항암화학요법후에완전관해가일어나육안으로원발종양을발견할수없는경우에대비하여항암화학요법시작전에유방촬영술을시행하거나초음파유도하에경피적으로금속클립을삽입하는등, 원래종양이있던영역만큼절제하는데도움을줄수있는다른방법을사용할것을권장한다. 조기유방암의수술후보조요법에권장되는약제를수술전항암화학요법에서도사용할수있다. 흔히권장되는약제로는 FEC(fluorouracil-epirubicin-cyclophosphamide), AT(doxorubicin+taxane), AC(doxorubicin-cyclophosphamide), AC+taxane 등이있다. 호르몬수용체양성이며폐경후환자에서는수술전내분비요법으로 3세대아로마타제억제제aromatase inhibitor; AI를사용할수있고 64,65 (LE 2, GR A) 이는 tamoxifen 보다더효과적이며사용기간은 4~6개월을권장한다 66 (LE 4, GR C). 만약종양이수술전항암화학요법에반응하여유방보존술을위한필요조건을충족시키는경우유방보존술을시행할수있다. 수술전항암화학요법에반응을보이지않거나계속진행하는경우유방전절제술과액와림프절절제술을시행해야하며, 즉시유방재건술을고려할수있다. 2) 수술후보조적전신요법 70세미만의모든연령군에서수술후보조적전신요법, 즉항암화학요법이나내분비요법을고려해야한다 67,68 (LE 1, GR A). 보조적전신요법의사용을결정할때에는국소치료만을했을때재발의위험, 보조치료로얻을수있는효과정도, 치료의독성, 동반질환등을고려해야한다 69,70 (LE 1, GR A). 치료방침을결정하는과정에서의사와환자의협의가있어야한다. 3) 수술후내분비요법 원발종양의호르몬수용체 ER, PR 유무를검사해야하고, 양성인경우환자의나이, 액와림프절전이여부, 수술후항암화학요법여부, HER-2 유무등에관계없이보조내분비요법을시행한다 67 (LE 1, GR A). 림프절음성이면서원발종양의크기가 0.5cm 이하인경우나림프절음성이면서양호한예후인자를가진원발종양의크기가 0.6~1cm인경우는예외가될수있다. 23

24 ㅣ제 3 차유방암진료권고안 2008 ㅣ 내분비요법에서일차적으로사용하는약제는 tamoxifen으로하루에 20mg을경구투여한다 67. Toremifene은 tamoxifen과유사한효능과독성을가지고있기때문에 tamoxifen을대체할수있으며, 하루에 40mg을 1회경구투여한다 71,72 (LE 3, GR B). 폐경전여성의유방암에대한내분비요법호르몬수용체양성인폐경전여성에서는 tamoxifen 투여를우선적으로고려하고사용기간은 5년을원칙으로한다. Tamoxifen 사용중에 GnRH agonist의투여나 ovarian ablation 치료를병합사용할수있다 73,74,82,83 (LE 2, GR A). GnRH agonist의단독투여는권장되지않으나임신이계획되어있는경우는고려해볼수있다. GnRH agonist는림프절전이가있거나 HER-2 양성인경우 5년간사용이권장된다 75 (LE 4, GR C). Tamoxifen 사용중폐경이되었을경우 tamoxifen을 5년간투여한후 AI를 5년간추가로사용하거나 tamoxifen을 2~3년사용한후나머지 5년까지 AI를투여한다 76~79 (LE 2, GR A). Tamoxifen 투여가금기인경우 ovarian function suppression과 AI를병합사용하는것은현재로서는임상연구목적외에는권장되지않는다. 난소가기능을하고있는폐경전여성에게서 GnRH agonist, 난소절제, 난소에대한방사선치료등을포함한난소억제요법과 tamoxifen의병합요법은 CMF 항암화학요법과동등한치료성적을보인다 80,81 (LE 2, GR A). 폐경후여성의유방암에대한내분비요법호르몬수용체양성인폐경후여성에서는 AI를고려할수있다. AI를처음부터 tamoxifen 대신 5년간투여하거나 ( 선행요법, upfront therapy as initial adjuvant) 84~86 (LE 2, GR A), 2~3년간 tamoxifen을투여한후 AI를투여하거나 ( 순차요법, switch therapy as sequential with tamoxifen) 87,88 (LE 2, GR A), tamoxifen을 5년간사용한뒤 AI를투여하는방법 ( 연장요법, extended therapy) 89,90 (LE 2, GR A) 등이있다. AI는난소가기능하는여성에서는효과가없다. AI 사용이금기인여성이거나 AI의사용에적합하지않은경우 tamoxifen을 5년간투여한다 91,92 (LE 1, GR A). 골다공증의위험도를감소시키기위하여 AI 사용전골밀도bone mineral density; BMD를측정하는것이권장되며필요한경우적절한신체적운동과 calcium 제제및 vitamin D의투여가고려될수있다. 호르몬치료의기간은 5년에서 10년동안으로한다 93,94 (LE 1, GR A). 크기가 0.5cm 이하이고림프절침범이없는경우예후가매우좋으므로일반적으로보조적전신요법이권장되지않으나, tamoxifen은 ER 양성인환자에서반대쪽유방의이차암발생위험을감소시키기위해서고려할수있다 95 (LE 3, GR B). 4) 수술후항암화학요법 림프절음성이면서원발종양의크기가 0.6~1cm인침윤유방암은재발의저위험군과고위험군으로나누어고려해야한다. 고위험군을구성하는나쁜예후인자는혈관림프관침습, 높은핵등급, 높은조직학적등급, HER-2 과발현, 호르몬수용체음성, 35세미만등이며고위험군은보조적전신요법이필요하다 (LE 2, GR B). 24

25 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 조기유방암의수술후내분비요법근거수준참고문헌 원발종양의호르몬수용체 ER, PR 유무를검사해야하고, 양성인경우환자의나이, 액와림프절전이여부, 수술후항암화학요법여부, HER-2 유무등에관계없이보조내분비요법을시행한다. 호르몬수용체양성인폐경전여성에서는 tamoxifen 의사용을우선적으로고려하고사용기간은 5 년을원칙으로한다. tamoxifen 의사용중 GnRH agonist 의투여나 ovarian ablation 치료를병합사용할수있다. 호르몬수용체양성인폐경후여성에서는 AI 를고려할수있다. AI 를처음부터 tamoxifen 대신 5 년간투여하거나 ( 선행요법, upfront therapy as initial adjuvant), 2~3 년간 tamoxifen 을투여한후 AI 를투여하거나 ( 순차요법, switch therapy as sequential with tamoxifen), tamoxifen 을 5 년간사용한뒤 AI 를투여하는방법 ( 연장요법, extended therapy) 등이있다. 골다공증의위험도를감소시키기위하여 AI 사용전골밀도검사가권장되며필요한경우적절한신체적운동과 calcium 제제및 vitamin D 의투여가고려될수있다. 호르몬치료의기간은 5 년에서 10 년동안이권장된다 , , 94 예후가양호한조직형의유방암에대한항암화학요법관상암종 (tubular carcinoma), 교질암종 (colloid carcinoma) 등양호한조직학적아형의침윤암에서종양의크기가 1cm 미만인경우에는보조요법이필요없으며, 1cm 이상 3cm 미만인경우에는항암화학요법, 호르몬수용체양성이면내분비요법을고려할수있고, 3cm 이상인경우에는항암화학요법, 호르몬수용체양성이면내분비요법을시행한다. 높은조직학적등급의침윤암이수질암종 (medullary carcinoma) 으로잘못분류될가능성이있으므로수질암종에대해서는침윤암과같은치료방침을따른다. 항암화학요법의대상림프절침범이있거나종양의크기가 1cm를넘는환자는보조적전신요법의대상이다. 림프절음성, 호르몬수용체음성이면서원발종양의크기가 1cm 이상인경우항암화학요법을시행한다. 림프절음성, 호르몬수용체양성이면서 1cm 이상인경우에는내분비요법과항암화학요법을시행한다. 림프절양성암은항암화학요법의대상이며, 호르몬수용체양성인경우에는항암화학요법완료후내분비요법을시행한다. 고령유방암환자의항암화학요법 70세이상인환자의경우에는수술후항암화학요법에대한임상시험자료가드물기때문에일반적인진료지침을내리기어렵다. 70세이상인환자의전신적보조요법은동반질환과전신상태등을고려하여개별적으로결정해야한다. 수술후항암화학요법의이점은 50세미만의여성에서가장현저하며, 그이상에서는연령증가에따라감소한다. 항암화학요법의약제항암화학요법은적어도 2개이상의약제를사용하여 3~6개월동안투여해야하며, 가능한한최대용량을투여하는것이중요하다 96 (LE 2, GR A). 액와림프절음성유방암에는 CMF (cyclophosphamide+ methotrexate+5-fu), FAC/CAF(5-25

26 ㅣ제 3 차유방암진료권고안 2008 ㅣ FU+doxorubicin+cyclophosphamide) 97,98, AC(doxorubicin+ cyclophosphamide) 등의항암화학요법이권장된다. 액와림프절양성유방암에서는 FAC/CAF, CEF(cyclophosph amide+epirubicin+5-fu), AC, EC(epirubicin+cyclophosphamide) 99, TAC(docetaxel+ doxorubicin+cyclophosphamide), AC 후 paclitaxel, doxorubicin 후 CMF 100,101, CMF 단독요법 102, TC(docetaxel+cyclophosphamide) 103 등의항암화학요법이권장된다 (LE 2, GR A). 림프절양성이거나 67 HER-2가과발현한암에서는 13,14,16,101,104~107 anthracycline 계열의약제를포함하는항암화학요법이더권장된다 (LE 2, GR A). 표적치료의적용최근 HER-2 유전자증폭이있는환자에서 trastuzumab을보조요법으로 1년간투여한군에서무병생존율또는전체생존율이유의하게향상되는것을보고한 NSABP B , NCCTCG N , HERA 101, BCIRG ,137 등의결과들이있다. 이를근거로하여, IHC염색에서 HER-2가 3+ 으로확인되거나 FISH검사에서증폭이있으며, 림프절양성이거나또는림프절음성이면서종양의크기가 1cm보다큰경우항암화학요법과함께 1년동안 trastuzumab을투여할수있다 101,107,108 (LE 2, GR A). FinHer 연구에의하면 trastuzumab의 9주사용으로도 3년간의추적관찰결과재발의감소를보였다 109 (LE 2, GR A). Trastuzumab 사용시심장독성의증가가보고되고있어적절한평가가병행되어야한다 109,110 (LE 1, GR A). 각종항암화학요법 Doxorubicin과 cyclophosphamide를 4주기투여하면 CMF 항암화학요법을 6주기시행한것과동등한효과를얻을수있다 108~113 (LE 2, GR A). Doxorubicin 또는 cyclophosphamide의용량을표준용량보다증가시켜서얻을수있는이점은없다 114,115. 자가골수이식, 줄기세포이식등의지지요법을이용해용량강도dose-dense를높인항암화학요법은일반적으로권장되지않는다. 림프절전이양성인유방암에서는 anthracycline에 paclitaxel을추가할수있다 116,117 (LE 2, GR B). Paclitaxel의투약빈도를높이는용량강도요법의우수한초기결과가보고되고있으며무병생존율과전체생존율에있어우수한결과를보이고있다 118 (LE 2, GR B). 림프절전이가있는유방암에서 docetaxel을사용하는 TAC와 FAC 항암화학요법을비교한무작위임상시험의초기결과에서는 TAC가 FAC보다우월한것으로나타났으나 119 (LE 2, GR B), 더긴추적관찰기간과이를지지하는다른연구결과가필요하다. Docetaxel과 cyclophosphamide (TC) 항암화학요법은 AC 항암화학요법과비교한무작위연구에서 5년무병생존율은우월하였다 103 (LE 2, GR A). 경구용 5-FU 항암화학요법은일본을중심으로조기유방암과전이유방암, 재발유방암에서광범위하게사용되고있 으며 115,120~122 단독요법으로시행하거나 cyclophosphamide, doxorubicin, cisplatin, etoposide, paclitaxel 등과병용해서시행할수있다 123~125 (LE 3, GR C). 조기유방암의수술후항암화학요법 항암화학요법을시행할때는적어도 2 개이상의약제를 3~6 개월동안투여해야하며, 가능한한도에서최대용량을투여하는것이바람직하다. 근거수준 참고문헌 2 96 림프절양성인암이나 HER-2 가과발현한암에서는 anthracycline 계열의약제사용이더효과적이다. 2 13, 14, 16, 101,

27 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ HER-2 IHC 염색에서 3+ 이거나 FISH 검사양성이며, 림프절양성이거나림프절음성이며종양의크기가 1cm 보다큰경우에는항암화학요법과함께 1 년동안 trastuzumab 을투여할수있다. trastuzumab 사용시심장독성의증가가보고되고있어적절한평가가병행되어야한다. Paclitaxel 의투약의빈도를높이는용량강도요법의우수한초기결과가보고되고있으며무병생존율과생존율에있어우수한결과를보이고있다. Docetaxel 과 cyclophosphamide(tc) 항암요법은 AC 항암요법과비교한무작위연구에서 5 년무병생존율은우월하였다. 경구용 5-FU 항암화학요법은일본을중심으로조기유방암과전이유방암, 재발유방암에서광범위하게사용되고있으며, 단독요법으로시행하거나 cyclophosphamide, doxorubicin, cisplatin, etoposide, paclitaxel 등과병용해서시행할수있다 , 107, , , 조기유방암의추적관찰 문진과진찰은첫 3년동안 3~6개월간격으로하며다음 2년동안은 6~12개월간격으로하고이후에는 1년간격으로시행한다. 유방자가검진은매달 1회시행하게한다. 유방보존술과방사선요법을받은환자에서는치료받은유방에대해방사선요법이끝난후약 6개월에유방촬영술을시행하고, 이후 6개월에서 1년간격의추적검사를 2~5년간시행하며, 유방암이없는반대쪽유방은매년유방촬영술을시행한다. 유방전절제술을시행한환자의경우에는반대쪽유방의유방촬영술을 1년간격으로시행하며 (LE 1, GR A), 유방초음파검사로유방절제부위와반대쪽유방을검사하는것이도움이될수있다 (LE 3, GR B). 이때필요한경우 ( 악성석회화로보인유방암을제거한경우잔여석회화유무를평가하기위해 ) 확대촬영술을시행할수있다 2. 원격전이를검사하기위한알칼리인산분해효소 (alkaline phosphatase) 를포함한간기능검사, 흉부단순촬영, 흉부전산화단층촬영, 뼈스캔, 복부초음파, 복부전산화단층촬영또는자기공명영상, 18 F-FDG PET, 종양표지자검사등은무증상의 1기또는 2기조기유방암환자에게추적관찰의정기적검사로시행하지않으나증상이있거나필요한경우시행할수있다 126~134 (LE 1, GR A). 흡연환자에서매년흉부단순촬영을할수있다 (LE 3, GR B). Tamoxifen 요법을받고있는환자에게는자궁내막암발생의위험이증가하므로자궁을절제하지않은여성은 1년마다골반진찰을, AI를사용하고있는환자에게는골감소증, 골다공증과골절의위험이증가하므로투여전초기골밀도검사와추적골밀도검사를시행한다. 골다공증으로진단된환자에게는 bisphosphonate 제제의사용을권고한다 (LE 3, GR B). 27

28 ㅣ제 3 차유방암진료권고안 2008 ㅣ 조기유방암의추적검사 유방보존술과방사선요법을받은환자에서는방사선요법이끝난후 6 개월에유방촬영술을시행하고, 이후 6 개월에서 1 년간격의추적검사를 2~5 년간시행하며, 반대쪽유방은매년정기검사를시행한다. 근거수준 참고문헌 3 2 필요하면유방확대촬영술과유방초음파검사를시행할수있다. 3 2 원격전이를검사하기위한알칼리인산분해효소 (alkaline phosphatase) 를포함한간기능검사, 흉부단순촬영, 흉부전산화단층촬영, 뼈스캔, 복부초음파, 복부전산화단층촬영또는자기공명영상, 18 F-FDG PET, 종양표지자검사등은무증상의 1 기또는 2 기조기유방암환자에게추적관찰의정기적검사로시행하지않으나증상이있거나필요한경우시행할수있다 표 2-1. 림프절전이에따른항암화학요법 림프절음성 CMF(cyclophosphamide+methotrexate+5-fluorouracil) FAC/CAF(5-fluorouracil+doxorubicin+cyclophosphamide) AC(doxorubicin+cyclophosphamide) 림프절양성 FAC/CAF(5-fluorouracil+doxorubicin+cyclophosphamide) 또는 FEC/CEF(cyclophosphamide+epirubicin+5-fluorouracil) AC(doxorubicin+cyclophosphamide) 에이어서 paclitaxel EC(epirubicin+cyclophosphamide) TAC(docetaxel+doxorubicin+cyclophosphamide) 와함께 filgrastim 보조투여 A CMF(doxorubicin 투여후 cyclophosphamide+methotrexate+5-fluorouracil) E CMF(epirubicin 투여후 cyclophosphamide+methotrexate+5-fluorouracil) CMF(cyclophosphamide+methotrexate+5-fluorouracil) AC 4(doxorubicin+cyclophosphamide)+ 이어서 paclitaxel 4, 2 주마다 filgrastim 보조요법 A T C(doxorubicin 투여후 paclitaxel 투여후 cyclophosphamide) 2 주마다 filgrastim 보조요법 FEC T(5-fluorouracil+epirubicin+cyclophosphamide 투여후 docetaxel) 표 2-2. CMF 및 anthracyline(a) 기반항암화학요법 CMF 항암화학요법 Cyclophosphamide 100mg/m 2 PO 1~14 일 Methotrexate 40mg/m 2 IV 1 일과 8 일 5-Fluorouracil 600mg/m 2 IV 1 일과 8 일 6 주기로 28 일마다반복 A(E)C 항암화학요법 Doxorubicin 60mg/m 2 IV 1 일 ( 또는 Epirubicin 100mg/m 2 IV 1 일 ) Cyclophosphamide 600mg/m 2 IV 1 일 4 주기로 21 일마다반복 28

29 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ A 투여후 CMF Doxorubicin 75mg/m 2 IV 1 일 4 주기로 21 일마다반복이어서 Cyclophosphamide 600mg/m 2 IV 1 일 Methotrexate 40mg/m 2 IV 1 일 5-Fluorouracil 600mg/m 2 IV 1 일 8 주기로 21 일마다반복 E 투여후 CMF Epirubicin 100mg/m 2 IV 1 일 4 주기로 21 일마다반복이어서 Cyclophosphamide 100mg/m 2 PO 1~14 일 Methotrexate 40mg/m 2 IV 1 일과 8 일 5-Fluorouracil 600mg/m 2 IV 1 일과 8 일 4 주기로 28 일마다반복또는 Cyclophosphamide 750mg/m 2 IV 1 일 Methotrexate 50mg/m 2 IV 1 일 5-Fluorouracil 600mg/m 2 IV 1 일 4 주기로 21 일마다반복 FAC 항암화학요법 5-Fluorouracil 500mg/m 2 IV 1 일과 8 일또는 1 일과 4 일 Doxorubicin 50mg/m 2 IV 1 일 ( 또는 72 시간동안지속적으로투여 ) Cyclophosphamide 500mg/m 2 IV 1 일 6 주기로 21 일마다반복 CAF 항암화학요법 Cyclophosphamide 100mg/m 2 PO 1~14 일 Doxorubicin 30mg/m 2 IV 1 일과 8 일 5-Fluorouracil 500mg/m 2 IV 1 일과 8 일 6 주기로 28 일마다반복 FEC 항암화학요법 Cyclophosphamide 75mg/m 2 PO 1~14 일 Epirubicin 60mg/m 2 IV 1 일과 8 일 5-Fluorouracil 500mg/m 2 IV 1 일과 8 일이와함께 cotrimoxazole 보조투여 6 주기로 28 일마다반복 표 2-3. anthracyline-taxane 기반항암화학요법 AC항암화학요법후 paclitaxel 항암화학요법 Doxorubicin 60mg/m 2 IV 1일 Cyclophosphamide 600mg/m 2 IV 1일 4주기로 21일마다반복이어서 Paclitaxel 175~225mg/m 2 3시간동안 IV 1일 4주기로 21일마다반복 용량강도 AC 항암화학요법후 paclitaxel 항암화학요법 Doxorubicin 60mg/m 2 IV 1 일 29

30 ㅣ제 3 차유방암진료권고안 2008 ㅣ Cyclophosphamide 600mg/m 2 IV 1일 4주기로 14일마다반복이어서 Paclitaxel 175mg/m 2 3시간동안 IV 1일 4주기로 14일마다반복 ( 모든주기에는 filgrastim을보조투여한다.) 용량강도 A-T-C 항암화학요법 Doxorubicin 60mg/m 2 IV 1 일 4 주기로 14 일마다반복이어서 Paclitaxel 175mg/m 2 3 시간동안 IV 1 일 4 주기로 14 일마다반복이어서 Cyclophosphamide 600mg/m 2 IV 1 일 4 주기로 14 일마다반복 ( 모든주기에는 filgrastim 을보조투여한다.) TAC 항암화학요법 Docetaxel 75mg/m 2 IV 1 일 Doxorubicin 50mg/m 2 IV 1 일 Cyclophosphamide 500mg/m 2 IV 1 일 6 주기로 21 일마다반복 ( 모든주기에는 filgrastim 을보조투여한다.) FEC 항암화학요법에이어서 docetaxel 항암화학요법 5-Fluorouracil 500mg/m 2 IV 1 일 Epirubicin 100mg/m 2 IV 1 일 Cyclophosphamide 500mg/m 2 1 일 3 주기로 21 일마다반복이어서 Docetaxel 100mg/m 2 1 일 3 주기로 21 일마다반복 표 2-4. Anthracylcline 을포함하지않는 taxane 기반항암화학요법 TC 항암화학요법 Docetaxel 75mg/m 2 IV 1 일 Cyclophosphamide 600mg/m 2 IV 1 일 4 주기로 21 일마다반복 표 2-5. Trastuzumab 포함항암화학요법 보조요법 AC T+Trastuzumab(doxorubicin+cyclophosphamide 투여후 paclitaxel+trastuzumab) Docetaxel+Trastuzumab FEC TCH(docetaxel, carboplatin, trastuzumab) Chemotherapy followed by trastuzmab sequentially AC docetaxel+trastuzumab 수술전항암화학요법 T+Trastuzumab CEF+Trastuzumab (paclitaxel+trastuzumab 투여후 cyclophosphamide+epirubicin+5-fu+trastuzumab) 30

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40 ㅣ제 3 차유방암진료권고안 2008 ㅣ 07 제 3 장국소진행유방암 3.1. 국소진행유방암의정의 국소진행유방암은 AJCC Cancer staging manual(6th edition, 2002) 1,2 의기준에따르면, 병기 IIIA기 (anytn2m0, T3N1M0), 병기 IIIB기 (T4N0M0, T4N1M0, T4N2M0), 병기 IIIC기 (anytn3m0) 에해당한다. 임상적병기에따라수술할수있는국소진행유방암operable locally advanced disease( 임상병기 T3N1M0) 과수술할수없는국소진행유방암inoperable locally advanced disease( 임상병기 T3N1M0를제외한 IIIA, IIIB, IIIC) 으로분류할수있다. 이와더불어본권고안에서는염증성유방암을추가하여기술한다 국소진행유방암의진단검사 국소진행유방암의진단을위해서신체진찰과유방촬영술, 유방초음파검사를시행한다 3,4. 유방촬영술이나유방초음파검사에서종괴의정확한크기측정을위해적어도 2차원 (dimension) 의길이를재야한다. 고밀도유방에서종양이미만성인경우유방촬영술과유방초음파검사소견이불확실하다면유방자기공명영상 (magnetic resonance imaging; MRI) 검사를추가로실시할수있으며 3~6 (LE 3, GR B) 필요한경우유방확대촬영술을시행할수있다 3. 국소진행유방암의조직진단은통상적으로영상유도하침생검core needle biopsy이권고된다 3. 경험이많은세포병리의사가있는경우세침흡인세포검사fine needle aspiration cytology; FNAC로진단할수있으나채취한검체의양이충분치않아대부분의예후인자들에대한검사 (ER/PR, HER-2, PCNA, p-53 등 ) 가불가능한경우가많고, 무엇보다도침윤암과비침윤암을감별할수없다는단점이있다. 유방암의생물학적특성 (ER/PR, HER-2 등 ) 은수술전항암요법neoadjuvant therapy 시행후특성이변화될수있으며 7, 예후와치료제선택에중요한예측정보를제공하기때문에침생검을통해검체를충분히획득하는것이더욱권고된다. 유방암이확진되면다시한번문진과신체진찰 ( 유방과구역림프절 ), 흉부단순촬영 4.8~10 (LE 2, GR B), 일반혈액검사 ( 전혈구수, 혈소판수 ), 일반화학검사 ( 알칼리인산분해효소 alkaline phosphatase; ALP, 간기능검사 ), 종양표지자 ( 암종태아성항원 carcinoembryonic antigen; CEA, CA15-3, CA ~13 ) 검사를시행한다. 유방초음파검사로종괴및종괴이외의소견이나구역림프절평가가충분히이루어지지않았다고판단되는경우유방암확진후초음파검사를다시시행할수있다. 유방초음파검사시구역림프절 ( 액와부, 쇄골하부, 쇄골상부, 내유방림프절 ) 전이유무를확인한다. 동측혹은반대측유방의다발성병변을확인하고유방암의침윤범위정도를파악하기위해유방자기공명영상검사를시행할수있다 3,14~16 (LE 3, GR B). 증상이있는환자나국소진행유방암의임상병기평가를위해뼈스캔, 복부초음파, 복부전산화단층촬영, 18 F-FDG PET을선택적으로시행할수있다 4.6~8,17,18 (LE 2, GR B). 유방암에서 18 F-FDG PET은액와림프절전이에대한음성예측도가낮아감시림프절생검을대신할수없으므로모든국소진행유방암환자에게일상적으로수술전액와림프절의병기결정을목적으로시행하는것은권고되지않는다 (LE 3, GR B). 그러나 40

41 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 18 F-FDG PET은초기부터최근의연구에이르기까지일관되게높은특이도를보이고있어 18 F-FDG PET에서액와림프절양성일경우에는불필요한감시림프절생검을피할수있고, 종격동림프절과내유방림프절전이발견을위해사용할수도있으며 (LE 3, GR B), 뼈전이진단에는뼈스캔과상호보완적으로유용하다고보고되고있다. 또한전체환자의 32~58% 에서 PET으로인하여치료계획이변경되었고, 원발종양의 18 FDG 섭취정도는예후와관계가있는것으로보고되어, 국소진행유방암의임상병기평가를위해증상이있거나필요한경우선택적으로 18 F-FDG PET을사용할수있다 19~24. 최근국소진행유방암에서수술전항암화학요법을통한임상적완전관해또는부분관해가흔하기때문에유방보존술을시행할기회가많아지고, 또한임상적또는병리학적완전관해가국소진행유방암의예후에대한정보를제공한다. 따라서수술전항암화학요법시행전과후에정확한종양의범위를측정하는것이매우중요하며종양의크기변화를측정하기위해신체진찰과유방촬영술또는유방초음파검사를시행한다 25. 특히, 유방자기공명영상검사는유방보존술을계획한여성에서정확한종양의범위를결정하는데큰도움이된다 26. 국소진행유방암의진단영상검사근거수준참고문헌 유방촬영술과유방초음파검사를조직검사이전에시행하며이때종양의크기는적어도 2 차원 (dimension) 으로길이를재야한다. 조기유방암의조직진단은통상적으로영상유도하침생검 core needle biopsy 이권고된다. 고밀도유방에서종양이미만성인경우에유방촬영술과유방초음파검사소견이불확실하다면유방자기공명영상 magnetic resonance imaging; MRI 검사를추가로실시할수있으며필요시유방확대촬영술을시행할수있다. 증상이있는환자나국소진행성유방암의임상병기평가를위해뼈스캔, 복부초음파, 복부전산화단층촬영또는자기공명영상검사, 18 F-FDG PET 등을선택적으로시행할수있다. 4 3, , 국소진행유방암의치료 수술전치료 1) 항암화학요법 수술전항암화학요법의목적은수술이불가능한환자에서종양혹은전이된림프절의반응을유도하여수술이나방사선치료등의국소치료가가능하도록하는것과수술가능한환자에서는유방보존술이가능하게하는데있다. 더불어종양의화학요법감수성을알아볼수있다는점과, 이론상으로미세전이에대한조기치료를시행할수있다는장점이있다 27. 하지만, 대부분의연구에서수술전항암화학요법의효과가수술후항암화학요법과비교하여보다우월한생존율을나타내지는못하였다. 다만, 수술전항암화학요법에의한병리학적완전관해는생존율을향상시키는예후인자로사용될수있다 28~30 (LE 1, GR A). 원칙적으로수술후항암화학요법에사용되는약제들이수술전항암화학요법에도사용될수있다. Doxorubicin을근간으로하는병합요법이주로시행되어왔으나 31, 수술후보조항암화학요법에서 taxane을포함한요법이생존율에우위를보임에따라수술전항 41

42 ㅣ제 3 차유방암진료권고안 2008 ㅣ 암화학요법에서도 taxane을추가한다양한요법이활발하게연구되었고, 보다우수한병리학적완전관해를보고하였다 (LE 2, GR A). 2400여명을대상으로한 NSABP B-27 연구에서 AC(doxorubicin, cyclophosphamide) 요법시행후에 docetaxel을추가한군이추가하지않은군에비해완전관해율이높았으며 (26% vs 13%) 29, 162명을대상으로한 Aberdeen 연구에서도 CVAP(cyclophosphamide, vincristine, doxorubicin, prednisolone) 반응군에서 docetaxel로전환하여투여한군이 CVAP요법을지속한군보다병리학적완전관해율이높았다 (34% vs 16%) 명을대상으로한 GEPARDUO 연구에서는 2주간격 (dose dense) ADOC(doxorubicin, docetaxel) 동시병합요법보다 AC(doxorubicin-cyclophosphamide) 후에 DOC(docetaxel) 순차요법이병리학적완전관해율이높았다 (14.3% vs 7%) 34. 치료횟수와관련된연구로 ED(epirubicin, docetaxel) 3회보다 6회가병리학적완전관해율이높았으나 35.36, 최근 2000여명을대상으로한 GEPARTRIO 연구에서는 2회의 TAC(docetaxel, doxorubicin, cyclophosphamide) 시행후반응군인 1390명에대해 6회의추가 TAC을시행한군과 4회의추가 TAC 군사이에병리학적완전관해율의차이가없는것으로보고하였다 37. 수술이가능한유방암환자의수술전항암화학요법의투여기간및횟수는 2006년 international expert panel들의권고안에서 anthracycline 또는 taxane을포함한병합요법을 4~6개월동안최소 6회를투여하도록권장하였다 (LE 4, GR B). HER-2 양성인국소진행유방암에서는 trastuzumab을포함한병합요법을고려할수있다 40~42. Buzdar 등은수술전 paclitaxel 3회요법후 FEC(5-FU, epirubicin, cyclophosphamide) 3회요법에 trastuzumab을병용사용하여 50~60% 에달하는병리학적완전관해율을보고하였으며, anthracycline제제의동시투여로우려되는치명적인심독성은없었다고보고하였다 Coudert 등은 HER-2 양성환자에서수술전 trastuzumab, docetaxel, carboplatin 병용요법으로 43% 의병리학적완전관해와안전성을보고하였다 42. 따라서, HER-2 양성인국소진행유방암에서 trastuzumab을포함한병합요법은심독성이우려되는환자에서사용할수있으나, 심독성증가의보고또한있어적절한평가가병행되어야한다 43. 수술전항암화학요법을 2~3회마친후에는반드시임상평가, 영상검사를통한반응평가를실시해야한다. 반응평가에따라계획된항암화학요법을지속할것인지새로운요법으로바꾸거나국소치료를먼저시행할지결정하여야한다 31~ (LE 2, GR A). 수술이나방사선요법등의국소치료를마친후호르몬수용체양성인환자에게호르몬치료를추가할수있다. Doxorubicin 혹은 taxane을근간으로하는수술전항암화학요법이완료된상태라면, 국소치료후에추가의보조항암화학요법을시행하는근거는아직마련되지않았다. 국소진행유방암의수술전항암화학요법근거수준참고문헌 수술전항암화학요법에의한병리학적완전관해는생존율을향상시키는예후인자로사용될수있다 수술후보조항암화학요법에서와같이 taxane 을포함한요법이생존율의우위를보이므로수술전항암화학요법에서도 taxane 을추가한다양한요법이권장된다. 2 27, 29, 32, 33 42

43 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 수술전항암화학요법 2~3 회를마친후에는반드시임상평가, 영상검사를통한반응평가를실시해야한다. 반응평가에따라계획된항암화학요법을지속할것인지새로운요법으로바꾸거나국소치료를먼저시행할지결정하여야한다 , 37, 38, 44 2) 내분비요법 호르몬수용체양성인폐경전여성에서의수술전내분비요법에관한연구는매우제한적인상태이며 GnRH agonist 와 letrozole 의병합요법에서 3% 병리학적완전관해와 42% 의유방보존술의결과를나타낸보고가있다 45. 폐경후여성의수술전내분비치료에대한여러연구들은 tamoxifen, anastrozole, anastrozole과 tamoxifen, 혹은 letrozole사이에서객관적반응율과유방보존율을비교하였으며, anastrozole 단독혹은 letrozole 단독요법은유방보존율과객관적반응율에서우수한성적을보여주었다. 이러한연구를토대로수술전항암요법으로서 AI는호르몬수용체양성인폐경후여성의치료법으로선택할수있으며, 수술전내분비요법의적절한기간은 4~6개월이권장되고, 항암화학요법과 AI제제를동시에투여하는것은바람직하지않다 (LE 2, GR A). 수술전내분비요법근거수준참고문헌 수술전항암요법으로서 AI 는호르몬수용체양성인폐경후여성의치료법으로선택할수있으며, 수술전내분비요법의적절한기간은 4-6 개월로권장되고, 항암화학요법과 AI 제제를동시에투여하는것은바람직하지않다. 2 37, 38 3) 방사선요법 수술전항암화학요법또는내분비요법에반응하지않거나진행되는유방암환자에서수술전또는고식적목적의방사선요법을고려한다. 또한, 국소진행유방암으로수술전항암화학요법후임상적반응을보인환자에서근치적수술대신고선량방사선요법을시행한경우와표준병합요법이시행된경우를비교하였을때장기간국소제어율과생존율이동등했다는소규모개별연구의보고에따라수술전항암화학요법후환자가수술을원하지않는경우또는수술위험성이높은경우에제한적으로고선량방사선요법을고려할수있겠다 46 (LE 4, GR B) 수술적치료 1) 수술가능한국소진행유방암 ( 임상적병기 T3N1M0) 임상병기에따라첫치료로수술을시행했을때모든병변을제거하는것이가능한수술할수있는국소진행유방암 ( 병기 T3N1M0) 과모든병변을병리학적으로완전히제거하는것이불가능하다고판단되는수술할수없는국소진행유방암 ( 병기 T3N1M0를제외한 IIIA, IIIB, IIIC) 으로분류할수있다. 일반적으로임상병기 T3N1M0 환자들인수술가능한국소진행유방암환자에대한수술적치료는조기유방암환자의수술적치료와동일하다. 유방보존술의적응증종양의크기그자체가유방보존술의금기는아니지만유방보존술에대한대부분의보 43

44 ㅣ제 3 차유방암진료권고안 2008 ㅣ 고는 5cm 이하의종양에서시행한것이고, 5cm 이상인종양에서시행한유방보존술에대한보고는찾아보기힘들다. 국소진행유방암은종양의크기가 5cm 이상으로큰경우가많아유방보존술을시행하는경우가많지않다. 하지만덴마크임상시험 Danish trial에서는대상환자군에 I, II, III기를모두포함시켰고유방전절제술군과유방보존술군간에생존율이나국소재발에차이는없다고보고했다. 따라서유방의크기가유방보존술을시행하기에충분할정도로크다면종양의크기는큰문제가되지않을것이다. 반대로유방의크기가작다면종양의크기가작더라도유방보존술을시행하기가어려울것이다. 다른유방보존술의금기사항들은조기유방암에서와동일하다 47. 수술전항암화학요법후유방보존술국소진행유방암에서수술전항암화학요법후유방보존술을시행할수있다 48~55 (LE 1, GR A). 그러나수술전항암화학요법후종양이주변에서부터중심쪽으로작아지지않고주변에흩어진형태로작아질경우에대한우려가있었다. 이런우려에대해 Singletary 등은국소진행유방암환자들을대상으로수술전항암화학요법후유방전절제술을시행하였고, 세밀한병리학적검사를통해 23% 의환자에서하나의종양으로작아져 (4cm이하) 유방보존술이가능한상태로전환되었음을확인하였다 49. 또한조기유방암과국소진행유방암환자를대상으로수술전항암화학요법후시행한유방보존술이국소재발률을증가시키지않음을보여주는보고들도있다 절제연유방보존술을시행할때절제연에종양세포가존재하는것 ( 양성절제연 positive margin) 은국소재발의중요한위험인자이다. 절제연에종양세포가남아있는경우절제연에종양세포가남아있지않은경우 ( 음성절제연 negative margin) 에비해국소재발률이높고 56 (LE 3, GR B), 유방암특이생존breast cancer specific survival에대한독립적예후인자이다 57 (LE 3, GR B). 절제연에가깝게종양세포가있는경우 ( 근접절제연 close margin, 절제연에서 1~3mm 이내 ) 에대해서는상반된보고들이있다. 종양세포가절제연에가까운경우절제연에종양세포가존재하지않는경우와같은국소재발을보였다는보고가있는반면 58~61, 절제연에종양세포가남아있는경우와같은국소재발을보였다는보고도있고 62.63, 그중간정도의국소재발을보였다는보고도있다 64~67. 따라서수술할때절제연에종양세포가남지않도록절제하는것이중요하며, 절제연에종양세포가남아있는경우에는가능하면다시절제하는것이안전하다 (LE 1, GR A). 사분역절제술 vs 종괴절제술밀란 II 연구 Milan II trial에따르면유방보존술에서사분역절제술quadrantectomy은종괴절제술lumpectomy에비해국소재발이적지만원격전이나생존율에는차이가없다 68. 또유방보존술후미용효과측면에서는종괴절제술이우월하기때문에사분역절제술이우수하다고단정할수는없다. 액와림프절절제국소진행유방암중병기 IIIA는액와부림프절의병기결정을위해액와림프절 level II 까지제거하는것이권장된다. 광범위한액와림프절절제는림프절전이가양성일지라도 44

45 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 국소재발은감소시키나예후에영향이없으며합병증만더증가시킨다. 즉 level II까지제거하는방법은전이가있는경우에는효과적인국소치료방법이지만, 림프절전이가없는경우에는다른보조요법으로도동일한효과를얻을수있다 69 (LE 3, GR B). 수술전항암화학요법후감시림프절생검수술전항암화학요법후감시림프절생검률은 82~100% 로보고자에따라다양하며, 위음성률역시 0~39% 로다양하게보고되고있다 70. 수술전항암화학요법을시행한경우항암화학요법으로인한조직학적변화때문에림프배액lymphatic drainage에영향을주게되어감시림프절생검률과위음성률에변화를초래한다는보고도있으나이에대해서는아직논란의여지가많은상태이다. 수술가능한유방암환자를대상으로한무작위다기관시험인 NSABP B-27 연구의결과에따르면수술전항암화학요법을시행한군의감시림프절생검률은 84.4%, 위음성률은 12.5% 로항암화학요법을시행하지않은군의감시림프절생검률 86.6%, 위음성률 10.7% 와비교해큰차이가없다 71. 따라서수술가능한국소진행유방암의경우에있어수술전항암화학요법후임상적으로액와부림프절이음성으로전환되었을것이라고판단될때에는감시림프절생검의시행을고려할수있다 72~75 (LE 1, GR A). 유방재건술국소진행유방암에서수술후유방재건술의효과에대해서는수술후재발발견, 정신과적문제, 경제적비용과성형결과평가등을고려하기때문에보고자에따라차이가있다. 일반적으로수술후합병증이발생하면항암화학요법이나방사선요법시작이늦어지기때문에수술후보조요법이종료된후에시행하는지연유방재건술delayed breast reconstruction이적절하지만, 수술후방사선요법이필요없다면즉시유방재건술 immediate breast reconstruction을고려하고이는미용효과측면이나환자의편리함을고려할때더우수하다고할수있다 또한즉시유방재건술은유방암의재발이나생존율에영향을끼치지않는것으로보고되고있다 78 (LE 3, GR B). 재건술방법보형물삽입술은횡복직근-근피부피판 (transverse rectus abdominis myocutaneous flap; TRAM flap) 이나광배근-근피부피판 (latissimus dorsi myocutaneous flap; LD flap) 과비교대상이되는방법이라기보다는환자의상태나원발암의치료계획등에따라선택할수있는한가지방법이다 79. 국소재발은남아있는피부나피하조직, 흉벽 ( 근육 ) 에서주로발생하므로국소재발을조기발견하는것은대흉근아래에보형물을삽입한경우가 TRAM이나 LD피판보다쉽지만종양학적측면에서는차이가없으며, 미용효과측면도환자의상황에따라달라질수있으므로큰차이가있다고보기는어렵다 80. 보형물삽입을이용한유방재건수술은보형물을덮을만한충분한양의건강한조직이있어야가능하며, 양측혹은예방적유방전절제술 (bilateral or prophylactic mastectomy) 후의재건, 공여부의조직이충분하지않은경우, 유방의크기가비교적작은경우, 공여부에흉터가생기는것을원하지않는경우, 장시간수술을견디기힘든경우에적합하다. 그러나환자가실리콘에알레르기가있거나보형물에대한혐오나공포가있는경우에는피해야한다 수술후방사선치료가예정되어있는환자에서자가조직을이용한재건수술이불가능한경우조직확장 / 보형물을이용한재건술을고려해볼수있 45

46 ㅣ제 3 차유방암진료권고안 2008 ㅣ 다. 보형물로인한합병증과구형구축등의합병증은방사선치료를하지않았을때보다높다 82. 최근에는피부보존유방절제수술 (skin sparing mastectomy) 또한비교적많이시행되고있다. 2) 수술불가능한국소진행유방암 ( 임상적병기 IIIA[T3N1M0제외 ], IIIB, IIIC) 수술불가능한국소진행유방암환자들은우선수술전항암화학요법을시행받은후임상적으로반응을보였을때수술을고려하게되며수술전항암화학요법에반응을보이지않는경우는수술전방사선치료를고려할수있다 83~85 (LE 2, GR B). 수술전항암화학요법에반응을보인경우수술방법은유방전절제술과유방보존술을모두고려할수있다 (LE 1, GR A). 이경우액와림프절절제는 level I/II까지시행하는것을권장한다. 그러나수술전항암화학요법후유방보존술에대한연구들이염증성국소진행유방암은포함하고있지않으므로염증성국소진행유방암에서는수술전항암화학요법에반응을보인경우에도유방전절제술을시행하는것이적절하다. 최초의임상병기가높은경우는수술전항암화학요법후유방전절제술을시행받은환자에서도국소재발의가능성이높으므로수술후방사선치료가필요하며 87 (LE 4, GR B) 자가조직 autologous tissue을이용한유방재건술을고려할때는지연유방재건술을고려해야한다. 수술불가능한국소진행유방암환자에서수술전항암화학요법후액와부림프절병기결정방법으로감시림프절생검을시행하는것은현재권고되지않는다. 국소진행유방암의수술적치료근거수준참고문헌 일반적으로임상병기 T3N1M0 환자들인수술가능한국소진행유방암환자에대한수술적치료는조기유방암환자의수술적치료와동일하다. 2 조기유방암참조 수술전항암화학요법에반응을보인경우수술방법은유방전절제술과유방보존술을모두고려할수있으며, 액와림프절절제는 level I/II 까지시행하는것을기본으로한다. 최초의임상병기가높은경우는수술전항암화학요법후유방전절제술을시행받은환자에서도국소재발의가능성이높으므로수술후방사선치료가필요하다. 지연유방재건술이적절하지만수술후방사선요법이필요없다면즉시유방재건술을고려한다. 즉시유방재건술은유방암의재발이나생존율에영향을끼치지않는것으로보고되고있다. 1 49, 53, 수술후보조요법 1) 방사선요법 국소진행유방암환자에서먼저유방전절제술이시행된경우방사선치료시행유무및방사선요법범위는종양의크기, 림프절전이상태및절제연상태에따른다 (LE 2, GR A). 또한, 국소진행유방암이라도유방보존술이시행된경우는남은유방에대한전유방방사선치료 (whole breast irradiation) 와추가조사 (boost radiation) 가시행되어야하며, 방사선요법범위는유방전절제술과마찬가지로림프절전이상태에따른다 (LE 2, GR A). 국소진행유방암을대상으로한무작위임상연구와메타분석은유방전절제술후액와림프절에전이가있는경우에흉벽과동측국소림프절에방사선요법을시행하여국소재발률을낮추고무병생존율과전체생존율을향상시킨다고보고하였다 88~96 (LE 1, GR A). 유방전절제술후액와림프절 4개이상양성인환자에서는항암화학요법후흉벽과동측쇄 46

47 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 골상부림프절에대한방사선요법이시행되어야하고 (LE 1, GR A), 액와림프절 1~3개양성인유방암에대해서도항암화학요법후에흉벽과동측쇄골상부림프절에대한방사선요법을적극고려해야한다 (LE 2, GR B). 그리고, 액와림프절전이가없더라도종양크기가 5cm 이상이거나절제연이양성인경우흉벽에대한방사선요법이시행되어야하며 (LE 3, GR B), 이경우동측쇄골상부림프절에대한방사선요법이함께시행될수있다 (LE 4, GR C). 액와림프절양성이거나종양크기가 5cm 이상인경우에방사선요법범위에동측내유방림프절을포함시키는것에대해서는논란이있다. 임상적또는병리학적으로내유방림프절양성으로판단되면방사선요법시내유방림프절이반드시포함되어야하지만, 내유방림프절양성이라판단할수없을때방사선요법범위에내유방림프절을포함시켜야하는지에관한임상적증거들은아직까지불충분하다. 그러나유방전절제술후방사선요법의필요성을보고한무작위임상시험들이치료범위에내유방림프절을포함한연구들이었기에방사선요법을시행한다면내유방림프절포함을고려할수있다 (LE 4, GR C). 수술후보조요법으로서방사선요법과항암화학요법의적절한시행시기와순서에대해서는아직까지확실치있으나, 부작용측면을고려하여동시에시행하지않는것이바람직하다 (LE 2, GR B). 국소진행유방암환자에서수술을용이하게하고유방보존가능성을높이기위해수술전항암화학요법을시행하는데, 이경우수술후방사선요법은항암화학요법의반응정도에관계없이진단시임상적병기상태에따라시행되어야한다 (LE 4, GR C). 유방보존술이시행된경우는남은유방에대한전유방방사선치료whole breast irradiation와추가조사boost radiation 및동측쇄골상부림프절에대한방사선요법이시행되어야하고, 유방전절제술이시행된경우에는흉벽과동측쇄골상부림프절에대한방사선요법을시행한다. 내유방림프절을방사선범위에포함시킬지는아직까지논란이있으나, 내유방림프절양성이라고판단된경우에는반드시포함해야한다. 국소진행유방암의수술후방사선요법근거수준참고문헌 유방전절제술후액와림프절전이가 4 개이상인환자에서는항암화학요법후흉벽과동측쇄골상부림프절에대한방사선요법이시행되어야한다. 액와림프절전이가 1-3 개인유방암에대해서도항암화학요법후에흉벽과동측쇄골상부림프절에대한방사선요법을적극고려해야한다 액와림프절전이가없더라도종양크기가 5cm 이상이거나절제연이양성인경우흉벽에대한방사선요법이시행되어야한다 수술후보조요법으로서방사선요법및항암화학요법의적절한시행시기와순서에대해서는아직까지확실치있으나, 부작용측면을고려하여동시에시행하지않는것이바람직하다. 2 96, 97 국소진행유방암환자에서수술을용이하게하고유방보존가능성을높이기위해수술전항암화학요법이시행되는데, 이경우수술후방사선요법은항암화학요법의반응정도에관계없이진단시임상병기상태에따라시행되어야한다. 4 98, 99 47

48 ㅣ제 3 차유방암진료권고안 2008 ㅣ 2) 항암화학요법 수술전항암화학요법을시행한경우계획된투여주기가수술후에남아있으면이를완료하도록한다. 유방암환자의수술후항암화학요법약제는표준효과standard efficacy의약제 (AC 4, CMF 6) 와, 강력한효과superior efficacy의약제 [anthracycline 기반요법 ( 표 1), anthracycline 기반요법 +taxane 계열 ( 표 2)] 로분류되며, 국소진행유방암에서약제선택은강력한효과의약제를선택하는것이권장된다. ER 음성또는호르몬수용체저발현유방암과 HER-2 과발현유방암은우선적으로 anthracycline 기반요법 +taxane( 순차적요법또는병합요법 ) 을선택하는것이권장된다 100~102. 최근의연구에따르면 HER-2 과발현유방암에서림프절양성이거나, 림프절음성이면서고위험군인경우항암화학요법과함께 1년동안 trastuzumab을투여할수있다 수술후보조항암화학요법근거수준참고문헌 국소진행유방암에서약제선택은강력한효과 superior efficacy 의약제를선택하는것이권장된다. ER 음성또는호르몬수용체저발현유방암과 HER-2 과발현유방암은우선적으로 anthracycline 기반요법 +taxane( 순차적요법또는병합요법 ) 을선택하는것이권장된다. 2 29, 32, 33, HER-2 과발현유방암에서림프절양성이거나, 림프절음성이면서고위험군인경우항암화학요법과함께 1 년동안 trastuzumab 을투여할수있다 , 104 표 3-1. 강력한 anthracycline(a) 기반요법 1) FA(E)C 6 5-Fluorouracil 500mg/m 2 IV 1 일과 8 일 Doxorubicin 50mg/m 2 IV 1 일 ( 또는 72 시간까지지속적으로투여 ) (Epirubicin 100mg/m 2 IV 1 일 ) Cyclophosphamide 500mg/m 2 IV 1 일 6 주기로 21 일마다반복 2) CAF( 경구 ) 6 Cyclophosphamide 100mg/m 2 PO 1~14 일 Doxorubicin 30mg/m 2 IV 1 일과 8 일 5-Fluorouracil 500mg/m 2 IV 1 일과 8 일 6 주기로 28 일마다반복 CEF( 경구, Canadian) 6 Cyclophosphamide 75mg/m 2 PO 1~14 일 Epirubicin 60 mg/m 2 IV 1 일과 8 일 5-Fluorouracil 500mg/m 2 IV 1 일과 8 일 6 주기로 28 일마다반복 3) A(E) 4 이어서 CMF 8 Doxorubicin 75mg/m 2 IV 1 일 (Epirubicin 100mg/m 2 IV 1 일 ) 48

49 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 4 주기로 21 일마다반복이어서 Cyclophosphamide 600mg/m 2 IV 1 일 Methotrexate 40mg/m 2 IV 1 일 5-Fluorouracil 600mg/m 2 IV 1 일 8 주기로 21 일마다반복 표 3-2. Anthracycline-taxane 기반요법 1) TAC Docetaxel 75mg/m 2 IV 1 일 Doxorubicin 50mg/m 2 IV 1 일 Cyclophosphamide 500mg/m 2 IV 1 일 6 주기로 21 일마다반복 2) AC 4, P 4 Doxorubicin 60mg/m 2 IV 1 일 Cyclophosphamide 600mg/m 2 IV 1 일 4 주기로 21 일마다반복이어서 Paclitaxel 175~225mg/m 2 3 시간동안 IV 1 일 4 주기로 21 일마다반복 3) A 4, P 4, C 4 Doxorubicin 60mg/m 2 IV 1 일 4 주기로 21 일마다반복이어서 Paclitaxel 175mg/m 2 3 시간동안 IV 1 일 4 주기로 21 일마다반복이어서 Cyclophosphamide 600mg/m 2 IV 1 일 4 주기로 21 일마다반복 ( 모든주기에는 filgrastim 을보조투여한다.) 4) 용량강도 AC 4, P 4 Doxorubicin 60mg/m 2 IV 1 일 Cyclophosphamide 600mg/m 2 IV 1 일 4 주기로 14 일마다반복이어서 Paclitaxel 175mg/m 2 3 시간동안 IV 1 일 4 주기로 14 일마다반복 GCSF 3~10 일, 1~8 주기 5) 용량강도 A 4, P 4, C 4 Doxorubicin 60mg/m 2 IV 1 일 4 주기로 14 일마다반복이어서 Paclitaxel 175mg/m 2 3 시간동안 IV 1 일 49

50 ㅣ제 3 차유방암진료권고안 2008 ㅣ 4 주기로 14 일마다반복이어서 Cyclophosphamide 600mg/m 2 IV 1 일 4 주기로 14 일마다반복 GCSF 3~10 일, 1~12 주기 6) FEC->T FU 500mg/m 2 1 일 Epirubicin 100mg/m 2 1 일 Cyclophosphamide 500mg/m 2 1 일 3 주기로 21 일마다반복이어서 Docetaxel 100mg/m 2 1 일 3 주기로 21 일마다반복 7) TC103 Docetaxel 75mg/m 2 1 일 Cyclophosphamide 600mg/m 2 1 일 4 주기로 21 일마다반복 표 3-3. Trastuzumab 포함요법 ( 조기유방암치료참조 ) 수술전항암화학요법 trastuzumab 4mg/kg IV ( 이후 1 주마다 2mg/kg IV 23 주간 ) paclitaxel 225mg/m 2 24h IV infusion 매 3 주마다 4 회이어서 FEC(5-FU 500mg/m 2 1 일 4 일, Epirubicin 75mg/m 2 1 일, Cyclophosphamide 500mg/m 2 1 일 ) 3 주마다 4 회 3) 내분비요법 지난 30여년간 tamoxifen은 ER 또는 PR 양성유방암과호르몬수용체상태를확인할수없는유방암에서환자의나이, 림프절전이유무, 폐경상태, 항암화학요법시행여부와무관하게재발위험률을 50%, 사망위험률을 31% 감소시켰다 107. 최근폐경후유방암환자의치료에서, 호르몬수용체양성인유방암의경우 3세대 AI(anastrozole, letrozole, exemestane) 사용에대한수많은임상시험결과는 tamoxifen 표준요법에비해재발위험도를더욱낮추었지만, 생존율향상에대한결과는추적관찰중이다. 또한심혈관계와골밀도에대한장기부작용에대한평가가남아있다 108~113 (LE 2, GR B). 수술적난소절제와 GnRH agonist를이용한난소절제는폐경전유방암환자의치료에효과적이라는것이밝혀져있다 114~116 (LE 3, GR B). 유방암치료를위한내분비요법은호르몬수용체양성유방암환자를대상으로시행해야하며, 호르몬수용체음성유방암환자에서내분비요법을시행하는것은바람직하지않다. HER-2 과발현유방암에서 tamoxifen에저항성이있는경우 AI가유용하다는임상결과들이있으나, 현재 HER-2 상태는내분비요법시행을결정하기위한종양표지자로인정되지않는다. Tamoxifen은폐경전과폐경후환자에서모두효과적이며, AI는폐경후유방암환자에서만사용해야한다. 난소의기능이있는환자의치료효과에대한 AI의임상자료는제한되어있다. 따라서폐경전유방암환자에게 AI를임상적으로사용이권장되지않는다. Tamoxifen 투여와항암화학요법을모두필요로하는환자에서의 tamoxifen 50

51 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 투여는항암화학요법을마친후시작하는것이바람직하다. 현재까지의임상자료를근거로폐경전환자에서내분비요법은 tamoxifen 5년투여가표준요법이며, 또한최소 2년간의 goserelin 투여를고려할수도있다. 하지만, 최근의여러연구에서폐경전호르몬수용체양성인유방암치료에서 tamoxifen+gnrh agonist 병합요법이 tamoxifen 단독또는 GnRH agonist 단독투여군에비해무병생존율이향상되었다고보고하고있다 117~120 (LE 2, GR A). 치료중폐경이된환자에게는폐경후내분비요법과동일하게치료할수있으나, 정기적으로 estradiol, FSH의혈중치를확인하여 AI 의지속적인투여여부를결정한다. 폐경후환자의내분비요법으로는 AI를우선사용할것을권유하며 (LE 2, GR A), tamoxifen 역시폐경후환자의내분비요법에사용할수있다. AI가금기이거나, AI로인한극심한근, 골격계통증등의부작용으로환자가복용할수없거나환자가원할때는 tamoxifen을사용한다. 그렇지만 tamoxifen과 AI 사용의선택은각약제들의이점과부작용에대해환자와상의한후결정하는것이바람직하다. 3세대 AI 사용은폐경후유방암환자에게보조요법의일차요법 (upfront) 으로사용하거나, 총 5년의기간중 tamoxifen 2~3년투여한후순차적으로투여하는요법 (switch) 혹은 tamoxifen 5년투여후연장하여사용하는요법 (extended) 중한가지방법으로시행한다 (LE 2, GR A). Toremifene은조기유방암에서 tamoxifen과유사한효능과독성을가진것으로보고되어, 이연구들을근거로폐경후림프절양성인유방암환자에서호르몬수용체양성인경우 tamoxifen을대체하여사용할수있다 국소진행유방암의수술후보조내분비요법근거수준참고문헌 폐경전환자에서내분비요법은 tamoxifen 5 년투여가표준요법이며, 또한최소 2 년간의 GnRH agonist 투여를고려할수도있다. 하지만, 최근의여러연구에서폐경전호르몬수용체양성인유방암치료에서 tamoxifen+gnrh agonist 병합요법이 tamoxifen 단독또는 GnRH agonist 단독투여군에비해무병생존율이향상되었다고보고하고있다 세대 AI 사용은폐경후유방암환자에게보조요법의일차요법 (upfront) 으로사용하거나, 총 5 년의기간중 tamoxifen 2-3 년투여한후순차적으로투여하는요법 (switch) 혹은 tamoxifen 5 년투여후연장하여사용하는요법 (extended) 중한가지방법으로시행한다 , 국소진행유방암의병리학적평가 절제된유방암조직에대한병리학적검사를통해결정된인자들은유방암의치료에서병기결정, 재발위험도의추정, 치료에대한반응도를예측하는데정보를제공한다. 최종병리보고는 TNM 병기체계 (2002) 에따라보고해야한다 1,2. 또한미국병리학회의유방암에대한병리조직검사결과보고지침서 ( 는병리조직학적검사의표준화에도움이될수있다. 이방법에따르면절제된림프절상태또는감시림프절생검시평가, 종양의크기, 조직학적분화도와핵분화도, 종양의조직학적형태, 절제연의상태, 혈관과림프관암세포침윤을보고해야한다. 또한면역조직화학염색법 immunohistochemical staining; IHC staining을이용한 ER/PR과 HER-2 상태에대한검사는필수적이다. IHC 염색에서 ER/PR 양성세포와 HER-2 과발현의비율역시검사해야하며, HER-2가 2+ 일때는형광제자리부합법fluorescence in-situ hybridization; FISH 또는색소제자리부합법chromogenic in situ hybridization; CISH 을고려해야한다. 이외에증식지수proliferation index, 유사분열지수mitotic index, upa/pa-1, p53, Ki-67에대한검사는유방암의예후와예측인자로서도움을준다 123~125 (LE 4, GR C). 51

52 ㅣ제 3 차유방암진료권고안 2008 ㅣ 국소진행유방암의병리학적평가근거수준참고문헌 면역조직화학염색법을이용하여 HER-2 과발현의비율을검사해야하며, HER-2 가 2+ 일때는형광제자리부합법 fluorescence insitu hybridization; FISH 또는색소제자리부합법 chromogenic in situ hybridization; CISH 을고려해야한다 국소진행유방암의추적관찰 증상이없는잠복원격전이에대한전향적, 무작위임상시험들의결과는전체생존율이나삶의질을향상시켰다는것을증명하지못했지만 , 국소재발이나반대편유방에발생한새로운암의조기발견은환자의생존율을증가시킬수있다. 몇몇기관에서권장하는재발감시권고안은거의모두유사하며, 이들의권고안은다음과같다 128~130. 문진과진찰은첫 3년동안 3~6개월간격으로하며다음 2년동안은 6~12개월간격으로하고이후에는 1년간격으로시행한다. 유방자가검진은매달 1회시행하게한다. 유방보존술과방사선치료를받은경우에치료받은유방에대해방사선요법이끝난시점에서 6개월후유방촬영술을시행한다음 6개월에서 1년간격으로 2~5년간유방촬영술을시행하며, 유방암이없는반대쪽유방은매년정기검사를시행한다 131. 유방절제술을시행한환자의경우에는반대쪽유방촬영술을 1년간격으로시행하며 3.4 유방초음파검사로유방절제부위와반대쪽유방을검사하는것이도움이될수있다 132~135 (LE 3, GR B). 원격전이를감시하기위해 ALP, 간기능검사, 종양표지자 (CA15-3, CEA, CA ~13 ) 검사를통상적으로시행하지는않지만선택적으로시행할수있다. 또한뼈스캔, 흉부단순촬영, 흉부전산화단층촬영, 복부초음파검사, 복부전산화단층촬영, 복부자기공명영상또는 18 F-FDG PET은추적관찰의정기적검사로시행하지않으나증상이있거나재발이의심되는경우시행할수있다 133~139 (LA 1, GR A). Tamoxifen을사용하고있는환자에게는 1년마다골반진찰, AI를사용하고있는환자에게는투여전기준골밀도검사와추적골밀도검사를시행하고골다공증으로진단된환자에게는 bisphosphonate제제의사용을권고한다. 국소진행유방암의추적검사근거수준참고문헌 유방보존술과방사선요법을받은환자에서는방사선요법이끝난후약 6 개월에유방촬영술을시행하고, 이후 6 개월에서 1 년간격의추적검사를 2 ~ 5 년간시행하며, 유방암이없는반대쪽유방은매년정기검사를시행한다 필요시유방확대촬영술과유방초음파검사를시행할수있다 원격전이를감시하기위해 ALP, 간기능검사, 종양표지자 (CA15-3, CEA, CA27.29) 검사를통상적으로시행하지는않지만선택적으로시행할수있다. 또한뼈스캔, 흉부단순촬영, 흉부전산화단층촬영, 복부초음파검사, 복부전산화단층촬영, 복부자기공명영상또는 18 F-FDG PET 은추적관찰의정기적검사로시행하지않으나증상이있거나재발이의심되는경우시행할수있다 염증성유방암 염증성유방암의진단은임상적인소견에의하며, 한쪽유방피부의 1/3 이상의구역에서발적과피부부종 (peau d orange) 을동반한경우를말한다. 6판 AJCC의분류에의하면액와림프절전이유무또는원격전이유무등에따라 stage IIIb, IIIc, 또는 IV에속할수있으며, 병리검사에서해당부위의진피림프관에서암세포가보이지않을수도있다 1,140. 임상적또는병리학적으로염증성유방암으로진단되었고원격전이가발견되지않은 52

53 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 환자에대해서는병기결정을위한검사가필요하며, 여기에는병력청취및신체진찰, 일반혈액검사, 일반화학검사, 종양표지자검사등이반드시필요하다. 원격전이여부를알아보기위하여뼈스캔, 흉부전산화단층촬영, 복부전산화단층촬영, 18 F-FDG PET을시행할수있다 (LE 2, GR B). 국소질환의범위를결정하기위하여양측유방촬영술을시행하며, 초음파검사를추가할수있다. 유방자기공명영상검사는선택적으로추가할수있다. 병리학적평가및수술전항암요법을위한호르몬수용체와 HER-2의상태를반드시확인한다. 염증성유방암은비염증성유방암에비하여 HER-2 양성율과, 호르몬수용체의음성율이더높고예후가불량하기때문에 141~144, 치료는반드시복합요법 ( 수술전항암화학요법, 수술, 방사선요법, 또는내분비요법등 ) 을시행하도록권유한다 145~147 (LE 3, GR A). 최근수술을먼저시행한경우가그렇지않은경우에비하여열등하지않거나우월하다는보고도있으나 148, 수술전항암화학요법을먼저시행하는것을표준으로하며, anthracycline을포함하는병합요법을사용하되, taxane계열의약제를병합하여투여한경우향상된전체생존율이보고되었다 (LE 2, GR A). 또한이환자들을수술전항암화학요법후수술할경우에는유방절제술을권유하며, 유방보존술을시행할경우에는미용적인효과가불량할뿐아니라국소재발도빈번하여권장되지않는다 151 (LE 4, GR A). HER-2 양성인환자에대해서수술전또는수술후에 trastuzumab을투여할수있다. 수술및보조항암화학요법이완료된후에는흉벽및동측림프절구역에방사선치료를추가하기를권유한다. 염증성유방암근거수준참고문헌 염증성유방암은비염증성유방암에비하여 HER-2 양성율과, 호르몬수용체의음성의빈도가더높고예후가불량하기때문에, 치료는반드시복합요법 ( 수술전항암화학요법, 수술, 방사선치료, 또는내분비요법등 ) 을시행하도록권유한다. 수술전항암화학요법을먼저시행하는것을표준으로하며, anthracycline 을포함하는병합요법을사용하되, taxane 계열의약제를병합하여투여하는것이전체생존율향상에도움이된다. 수술전항암화학요법후수술할경우에는유방전절제술을권하며, 유방보존술을시행할경우에는미용적인효과가불량할뿐아니라국소재발도빈번하여권장되지않는다 ,

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64 ㅣ제 3 차유방암진료권고안 2008 ㅣ 08 제 4 장재발및전이유방암 4.1. 재발및전이유방암의정의 재발암이란유방암에대한근치적치료후원발병소인유방과그주위조직에서다시발생한유방암을말하며, 전이유방암이란원발유방암의치료와관계없이원격장기에서발견된유방암을말한다. 치료할때는유방암의원발병소를치료함과동시에원격전이에대한국소치료와전신치료를고려해야하며, 환자의삶의질을향상시키기위한완화요법을시행하게된다. 치료목표는가능하다면근치적치료, 암진행의최대한억제, 암관련증상의완화, 생활활동능력증진, 생존기간연장, 삶의질향상이다. 치료방법은국소구역재발과전신전이에따라구분하며국소구역재발의치료는수술, 방사선치료와국소항암화학요법등을병합사용한다. 국소치료와동시에필요하면전신치료인항암화학요법, 내분비요법, 표적치료, bisphosphonate, 완화요법등을시행한다 국소구역재발 (Locoregional recurrence) 국소구역재발의진단검사 국소재발이란최초의치료후동측유방, 흉근, 피부에암이다시발생하는경우를말하며구역재발이란동측액와림프절, 쇄골상부와쇄골하부림프절, 내유림프절등에암이발생하는것을말한다. 수술과방사선요법후에수술반흔과방사선으로인한염증소견이국소재발과비슷한형태로나타날수있기때문에유방촬영술을시행하고, 필요에따라유방확대촬영술및유방초음파를추가할수있다. 만약재발이의심되면조직검사를시행하고호르몬수용체와 HER-2 상태도확인하는것이치료에도움이된다. 국소구역재발한환자에서흉부컴퓨터단층촬영은매우유용한진단법이될수있다 1. 국소구역재발이있는경우재발범위를알아보고동반된원격전이유무등으로병기를결정하기위해뼈스캔, 18 F-FDG PET 를시행할수있다 2~12 (LE 2, GR B). 국소구역재발의진단근거수준참고문헌 국소구역재발이의심되면 ER, PR, HER-2 검사를포함한조직검사를시행하고전신재발을확인하기위하여혈액검사와흉부엑스선검사, 뼈스캔, 흉부및복부 CT, 18 F-FDG PET 등을시행할수있다 국소구역재발에대한수술및방사선치료 최초치료로유방전절제술을받았던환자는절제할수있다면재발부위를수술로절제하고방사선치료를시행한다. 수술적절제는절제경계가암세포없이깨끗한, 완전절제를목적으로시행할수있다. 국소재발한종양의육안병소완전절제후방사선치료는국소제어율 (local control) 을의미있게증가시킨다 13~15 (LE 1, GR A). 단, 흉부방사선치 64

65 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 료의과거력이있는환자는이전에조사된방사선량을고려하여방사선치료를추가로시행할수있다. 방사선조사범위는방사선치료과거력이없는경우전체흉벽을반드시포함하며, 액와림프절, 내유림프절, 쇄골상림프절등주변림프절을포함할수있다 16 (LE 2, GR A). 최초치료로유방보존술이시행되었던환자는유방전절제술을시행해야하나 17,18 (LE 1, GR A), 국소재발병변이매우작아유방보존술이가능한경우엔선택된환자에서유방보존술을시행할수도있다 19,20 (LE 4, GR C). 유방보존술후국소재발은방사선치료를시행하지않는것이일반적이나추가적으로시행하는경우이전에조사된방사선량을고려하여시행할수있다. 국소재발이너무광범위하여완전절제를할수없는경우, 방사선치료를수술을대신하는목적으로시행할수있으며이경우에도높은수준의국소제어율을얻을수있다 21 (LE 3, GR B) 국소구역재발에대한전신치료 국소구역재발만있는환자라도 20`~30% 에서원격전이가먼저발생하거나동반하여발생하고많은수에서전신전이를하기때문에수술, 방사선요법등국소치료와함께항암화학요법, 내분비요법, 표적요법등전신치료를적극적으로고려해야한다 22,23 (LE 3, GR B). 특히처음부터전이성재발로나타난경우와는달리적절한국소제어로완치를기대할수있는경우도있기때문에항암화학요법을적극적으로고려해야한다 24 (LE 3, GR B). 국소구역재발치료근거수준참고문헌 국소구역재발만있더라도 20%-30% 환자에서원격전이가동반되어발생하며결국전신전이를하는경우가많기때문에수술, 방사선요법등국소치료와함께항암화학요법, 내분비요법, 표적요법등전신치료를적극적으로시행해야한다 전신전이 (Systemic metastasis) 전신전이의진단 전이유방암환자의진단을위해시행해야하는검사로는병력청취와신체검사, 말초혈액검사, 혈소판검사, 간기능검사, 흉부엑스선검사, 뼈스캔, 증상이있는뼈나뼈스 18 캔에서이상소견이있는뼈의엑스선검사이다. 필요한경우복부및흉부 CT, F-FDG PET 2~12 (LE 3, GR B), 자기공명영상도고려할수있다. 가능하면첫재발부위의조직검사를시행하고이전에시행하지않았다면호르몬수용체검사 (ER, PR) 와 HER-2검사를시행하는것이치료에도움이될수있다. 전신전이진단근거수준참고문헌 전이유방암환자의진단을위해병력청취와신체검사, 말초혈액검사, 혈소판검사, 간기능검사, 흉부엑스선검사, 뼈스캔, 증상이있는뼈나뼈스캔에서이상소견이있는뼈의엑스선검사를시행하며필요한경우복부및흉부 CT, 18 F-FDG PET, 자기공명영상도고려할수있다

66 ㅣ제 3 차유방암진료권고안 2008 ㅣ 전신전이의치료 유방암진단당시전신전이가있을때유방전절제술을통해원발병소의종양을제거함으로서항암화학요법이나내분비요법등전신치료의효과를높일수있고생존율의향상을기대할수있다 25,26 (LE 4, GR C). 전이유방암의치료목적은생존기간을연장시키고삶의질을향상시키는것이다. 따라서독성이적은치료법이권장되나젊은여성의유방암비율이높은한국의현실을감안하면적극적인항암화학요법도고려해볼만하다. 그러나전이병변이광범위하지않고호르몬수용체양성인합리적인경우엔독성이적은내분비치료가항암화학요법보다우선적으로선택될수있다 27 (LE 3, GR B). 전이유방암환자는처음부터뼈전이가있는가와호르몬수용체및 HER-2 상태에따라치료지침을나눌수있다 전신전이의내분비요법 재발및전이유방암환자에서내분비요법을먼저고려할수있는경우는 ER이나 PR 양성, 뼈또는연부조직단독전이, 국소화된무증상내부장기전이등이다. 이전에내분비요법을시행받은폐경전재발환자에게는난소기능억제제인황체형성호르몬분비호르몬유사체 GnRH agonist를단독또는항에스트로겐제와병용투여하거나 28 (LE 1, GR A), 수술이나방사선조사를통한난소절제술을시행할수있으며, 프로게스테론제, 안드로겐제와고용량에스트로겐제를사용할수있다 29,30 (LE 1, GR A). 항에스트로겐 fulvestrant는이전에항에스트로겐치료를받은폐경후호르몬수용체양성전이성유방암환자에게사용할수있다. Fulvestrant는 tamoxifen의에스트로겐유사작용이적고매달둔부근육주사가가능해내약성이좋다. Fulvestrant는적어도이전에내분비요법으로병이진행되었던환자에서 anastrozole 만큼효과적이다 31~35 (LE 1, GR A). 이전에내분비요법을시행받은폐경후재발환자에게는 AI(Anastrozole, letrozole, and exemestane), 순수항에스트로겐 (fulvestrant), 프로게스테론제 (Megesterol acetate), 안드로겐제 (Fluoxymesterone), 고용량에스트로겐제 (Ethinyl estradiol) 등을사용할수있다 36`~38 (LE 1, GR A). 이전에내분비요법을시행받지않은폐경전재발및전이유방암환자에게는항에스트로겐제를단독투여하거나 GnRH agonist와병용투여하거나수술및방사선난소절제술, 프로게스테론제 (Megesterol acetate), 고용량에스트로겐제 (Ethinyl estradiol) 등을시행할수있다. 폐경후재발및전이유방암환자에게는선택적 AI를투여하거나항에스트로겐제를사용할수있다. 내분비요법에반응하는유방암환자는재발하거나전이가발생하면추가적인내분비요법으로효과를볼수있으며, 특히병소의감소나안정화되는양상을보이면지속적으로투여해야한다. 전신전이내분비요법근거수준참고문헌 전신전이발생시암의치료보다는생존기간의연장, 삶의질향상이더중요하다. ER 양성이면서전신전이가광범위하지않고, 내부장기에전이가없는환자에서는우선적으로내분비요법을시도할것을권장한다. 내분비요법으로사용되는약제는 tamoxifen, AI 가대표적이고 3 번의서로다른약제를시도한후에도병이진행하거나반응이없는경우에는항암화학요법이나표적치료를고려하는것이바람직하다

67 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 전신전이의항암화학요법 재발및전이유방암환자에서항암화학요법의치료목표는근치, 생존연장, 암진행억제, 삶의질향상, 증상완화이며, 반응율, 병의진행기간 time to progression, 생존율, 독성, 삶의질등에따라효과를판정한다. 항암화학요법은호르몬수용체음성이면서전이가뼈나연부조직에만국한되지않는경우, 증상이있는내부장기전이가있는경우, 호르몬수용체양성이나이전호르몬치료에반응이없었던경우등에서시행해야한다. 한가지약제를사용하는것보다두가지이상의약제를사용하는것이객관적인반응율을높이고병의진행기간을늘일수있다. 그러나병합요법은단일제를순차적으로사용하는것보다독성이많이나타나고생존율에큰차이가없다 39~42 (LE 2, GR A). 일반적으로재발및전이유방암에서표준임상치료지침은병의진행이있을때까지 1차항암화학요법을계속하는것이다. 병이진행하기전항암화학요법의부작용들이심하게나타나면약의용량을줄이거나사용을중단해야한다. 재발및전이유방암에서지속적항암화학요법이단기항암화학요법보다병의진행이없는생존 progression-free survival을증가시킨다는증거는있지만충분하지않고, 전체생존율의차이는미약하기때문에항암화학요법의기간은전반적인삶의질에미치는영향들을고려하여결정되어야한다 43,44 (LE 2, GR A). 현재많이사용되는 1 차단독요법항암제 Doxorubicin, Epirubicin, Pegylated liposomal doxorubicin, Paclitaxel, Albumin-bound paclitaxel Docetaxel, Capecitabine, Vinorelbine, Gemcitabine 많이사용되는 1 차병합요법항암제 FAC/CAF(Cyclophosphamide+doxorubicin+5-Fluorouracil), FEC(5-Fluorouracil+epirubicin+cyclophosphamide), AC(Doxorubicin+ cyclophosphamide), EC(Epirubicin+cyclophosphamide), AT(Doxorubicin+docetaxel/paclitaxel), ET(Epirubicin+docetaxel/paclitaxel), CMF(Cyclophosphamide+methotrexate+5-Fluorouracil), Capecitabine+docetaxel/paclitaxel, Gemcitabine+docetaxel/paclitaxel, Vinorelbine+docetaxel/paclitaxel, Vinorelbine+epirubicin, Vinorelbine+5-FU, Gemcitabine+ vinorelbine 다른효과적인약제로는 cisplatin, carboplatin, 경구 etoposide, vinblastine, fluorouracil 지속투여가있다. 경구 5-Fluorouracil은조기유방암과재발및전이유방암에서광범위하게사용되고있으며, 단독또는다른항암제들과병용투여할수있다 67

68 ㅣ제 3 차유방암진료권고안 2008 ㅣ 47~59 (LE 2, GR A). 이전항암화학요법으로 CMF 보조요법후재발하거나전이된유방암환자에게는 FAC/FEC, AC/EC, docetaxel 단독또는병합용법, paclitaxel 단독또는병합용법, capecitabine 단독또는병용요법을시행할수있다. 이전에 anthracycline 보조용법을받은후재발되거나전이된유방암환자에게는단독요법으로 paclitaxel, docetaxel, gemcitabine, vinorelbine, capecitabine 등을사용할수있고, 병용요법으로 paclitaxel+capecitabine, paclitaxel+ vinorelbine, paclitaxel+ carboplatin(cisplatin), paclitaxel+ ifosfamide, docetaxel+ capecitabine, docetaxel+ vinorelbine, gemcitabine+ vinorelbine, gemcitabine+ paclitaxel, gemcitabine+ docetaxel, CMF 등을사용할수있다. 병용요법의원칙은각항암제의교차내성이없어야하고, 각항암제의전체용량을투여해야하며, 각항암제를병용투여했을때치료효과가상승한다는증거가있어야하고, 각항암제의독성이증가하지말아야한다. 전이유방암에서 1차항암화학요법으로 paclitaxel을단독투여와 bevacizumab과의병용투여를비교했을때 bevacizumab과의병용투여가 paclitaxel 단독투여에비해병의진행이없는생존율은우수하지만전체생존율에서의미있는차이는없었다 60 (LE 2, GR A). 연속적인 3번의항암화학요법에반응이없는경우나 Eastern Cooperative Oncology Group(ECOG) 수행도가 3 이상인경우완화또는고식적요법만을시행할수있다 (LE 2, GR A). 전신전이항암화학요법근거수준참고문헌 항암화학요법은단일약제사용보다는두가지이상의약제를사용이객관적인반응율을높이고병의진행기간 (time to progression) 을늘일수있지만병합요법은단일약제를순차적으로사용하는것보다독성이많다. 전이유방암에서지속적항암화학요법이단기항암화학요법보다병의진행이없는생존율 (progression-free survival) 을증가시킨다는증거는있지만충분하지않고, 전체생존율의차이는미약하기때문에항암화학요법의기간은전반적인삶의질에미치는영향들을고려하여결정되어야한다 , 재발및전신전이의표적치료 재발및전이유방암환자에서조직의 HER-2 검사가 FISH 양성이거나 IHC 3+ 라면 HER-2 표적치료가권장되고 FISH에서음성이고 IHC 0, 1+ 이면 HER-2 표적치료의반응율은매우낮고 trastuzumab이나 lapatinib의사용은권장되지않는다 61~66 (LE 2, GR A). 재발및전이유방암환자에서 HER-2 IHC 3+ 이거나 FISH 양성인경우 paclitaxel과 trastuzumab의병용요법 57~59 (LE 2, GR A) 과 docetaxel, vinorelbine, platinum 계열과 trastuzumab의병용요법이효과적이다. 그러나 doxorubicin/ cyclophosphamide와 trastuzumab을병용한환자중 27% 정도에서심기능이상이관찰되어상당한치료위험률이있다 69~72 (LE 2, GR A). Capecitabine과 lapatinib 병용요법은 HER-2 양성인재발및전이유방암환자에서또다른효과적인치료법이될수있다 62 (LE 2, GR A). 제3상연구에서이전에 anthracycline, taxane, 그리고 trastuzumab 을투여받았던재발및전이유방암환자에서진행하는경우 capecitabine 단독요법과 lapatinib과 capecitabine 병합요법을비교했을때병진행기간은 capecitabine 단독투 68

69 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 여군에비해 capecitabine, lapatinib 병합투여군이길어효과를기대할수있다 73 (LE 2, GR A). 전신전이표적치료근거수준참고문헌 전이유방암에서조직의 HER-2 검사가 FISH 양성이거나 IHC 3+ 라면 HER-2 표적치료가권장되고항암제와 trastuzumab, lapatinib 병용요법으로치료효과를얻을수있다 뼈전이에서 Bisphosphonate 치료 뼈전이, 특히파골성뼈전이가있지만여명이 3개월이상으로예상되고 creatinine 수치가 3.0 mg/dl 이하인경우인유방암환자에게 bisphosphonate를칼슘제제. 비타민 D와병용투여한다 74,75 (LE 1, GR A). 뼈전이가있는유방암환자에서 bisphosphonate 투여는뼈관련합병증및뼈전이로인한통증과병적골절을감소시켜 76, 이로인한수술및방사선치료를줄일수있다. 또한항암화학요법이나내분비요법을시행할때진통제투여를감소시키는효과가있다 77 (L1, G A). Bisphosphonate의유방암환자치료적응증은단순방사선검사에서파골병소를보이는경우, 또는 CT나 MRI로뼈파괴가명확히입증된경우에뼈전이합병증을감소시키기위해사용된다. 일단 bisphosphonate를사용하게되면환자의전체수행상태가악화되기전까지는 bisphosphonate를계속사용하는것이권장된다. 새로운뼈관련합병증의나타난후에도 bisphosphonate의사용은효과적일수있고 bisphosphonate를중단해야할뚜렷한근거는없다 74 (LE 2, GR A). 장기간의 IV bisphosphonate 사용에서턱의뼈괴사가보고되고있어항암치료중이거나스테로이드를사용하고있거나구강질환이있는경우는 bisphosphonate 사용전후로구강관리를권장한다 78,79 (LE 3, GR B). Bisphosphonate는다른전신요법 ( 내분비요법, 항암화학요법, 생물학적요법 ) 과같이사용할수있다. 신독성이있어매투약시혈청 creatinine level 측정이필수적이며신기능이감소하였을때는약용량을감량하든지투약을중단해야한다 82 (LE 1, GR A). 현재사용되고있는 bisphosphonate 제제별투여방법으로하루에 clodronate 1,600`~3,200mg 경구투여, 3`~4주간격으로 pamidronate 90mg 2시간정맥투여, 3`~4주간격으로 ibandronate 6mg 15~30분정맥투여, 하루에 ibandronate 50mg 경구투여, 3`~4주간격으로 zoledronic acid 4mg 15분정맥투여가사용되고있다 80~82 (LE 1, GR A). 뼈전이치료근거수준참고문헌 뼈전이가있는경우 bisphosphonate 사용으로뼈에관련된합병증이나뼈전이로인한통증을줄일수있다 완화요법또는고식적요법 재발및전이유방암환자의치료에서우선적으로고려해야할것은삶의질이다. 오심, 피로, 동통과같은증상을완화시키고암으로인한합병증발생을예방하거나지연시켜사회활동을유지하고심리적안정을찾을수있게도와주는치료를완화요법이라하고전신항암치료자체가완화요법에포함될수있다. 완화요법의목적은환자의증상완화, 정신적, 종교적지지와더불어삶의질을향상시키는것이며전이유방암환자전체가대상이된다. 전이유방암환자에서전신항암치료와완화요법은동시에이루어져야하며암 69

70 ㅣ제 3 차유방암진료권고안 2008 ㅣ 이진행될수록전신항암치료의역할은감소되고완화요법의역할은증대된다. 적극적인완화요법을고려할수있는경우는신체수행도가감소된경우 (ECOG 3 혹은 Kornofsky 신체수행도 50), 고칼슘혈증, 중추신경계전이, 상대정맥증후군, 척수압박, 영양실조 (Cachexia), 악성흉액질, 간부전, 신부전, 중증질환동반등이다 83,84 (LE 3, GR B). 완화요법을위한사전평가는항암치료의이득과위험도, 신체증상, 사회정신적고통, 개인적인목표와기대, 교육과정보의수준, 치료에영향을미치는문화적요소등이다 85~87 (LE 3, GR B). 또한환자의증상을세밀하게파악하여, 환자와가족이우선순위를치료와삶의질향상중어느쪽에두고있는지충분한대화로확인하고사회적, 재정적상태도고려해야한다. 완화요법과병행하는항암치료의목적은근치가아닌생명의연장과증상의완화이며, 항암화학요법, 방사선요법, 내분비요법, 면역요법등이있다. 완화요법에는통증, 식욕부진, 쇠약감, 오심, 구토, 불면증, 호흡곤란, 우울, 불안같은증상치료와더불어정신적, 사회적, 영적지지, 사후를대비한사전관리계획, 호스피스의뢰, 진정제투여가포함된다 88~ 외부방사선또는방사성동위원소를이용한완화요법 방사선요법의적응증에는뇌전이척수압박, 뼈전이, 동통을유발하는연부조직전이, 소화기폐쇄, 요로폐쇄, 담도폐쇄, 기도폐쇄, 조절되지않는암성출혈등이있다. 전이부위에따른완화목적또는치료목적의방사선치료는다음과같다. 척수압박 (Spinal cord compression) 척수압박이발생하면스테로이드를전신투여한후수술적치료를시행한경우, 방사선치료를추가하고 92 (LE 3, GR B). 수술적치료를하지않은경우, 방사선치료를즉시시행한다 93 (LE 3, GR B). 이때방사선치료는증상완화측면에서수술과동일한효과를가지며, 특히방사선치료전에보행가능하고, 방광또는배변기능을유지하고있던경우에가장양호한신경학적결과를얻을수있다 94,95 (LE 3, GR B). 뼈전이 (Bony metastases) 고식적방사선치료는뼈전이로인한통증등의증상완화에매우효과적이다 96. 방사선치료는 8Gy 1회, 4Gy 5회, 3Gy 10회등이흔히시행되고, 이들사이의통증완화차이는없다 97 (LE 2, GR A). 긴뼈등의뼈전이가우려되는경우, 정형외과적내고정 (internal fixation) 등을한후방사선치료를시행할수있다. 이때방사선치료의목적은통증완화및종양의국소적제어등이다. 항암화학요법혹은내분비요법에반응하지않는광범위한뼈전이가있는환자에서반신방사선치료 (hemibody radiation therapy) 를고려할수있다 98 (LE 3, GR B). 또한스트론튬 (Sr-89) 등을이용한전신방사성동위원소치료도뼈전이에의한통증완화에유용하다 99,100 (LE 3, GR B). 뇌전이 (Cerebral metastases) 단일혹은제한된숫자의뇌전이가있는경우외과적절제수술및전뇌방사선치료또는방사선수술 (radiosurgery) 을시행한다 101~104 (LE 2, GR A). 이때방사선수술은 1회혹은분할뇌정위적방사선수술 (fractionated stereotactic radiosurgery) 을시행할수있으며, 외과적절제수술을대체하여시행할수있다 105. 다수의뇌전이가있으면뇌전이로인한증상완화를목적으로전뇌방사선치료를시행한다 106,107 (LE 2, GR A). 전뇌방사선치료는 3Gy씩 10회가가장보편적이나, 8Gy 1회, 2Gy 20 회등도사용되고, 이들사이의증상완화혹은병소진행기간 time to disease progression 등의차이는없다 107~109 (LE 2, GR A). 그러나고용량의방사선치료는부작용 70

71 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 이심해특별한경우외에는잘사용되지않는다. 완화요법시행후결과에따라치료방향을수정하게되는데죽음을지연시키지않으면서증상이개선되고환자의삶의질이좋아졌다면바람직한결과로판단하여치료를지속한다. 반대로환자상태가악화되면치료를재평가하여치료를중단하거나강화된완화요법, 호스피스의뢰를고려한다. 완화요법근거수준참고문헌 적극적인완화요법을고려할수있는경우는신체수행도가감소된경우 (ECOG 3 혹은 Kornofsky 신체수행도 50), 고칼슘혈증, 중추신경계전이, 상대정맥증후군, 척수압박, 영양실조 (Cachexia), 악성흉액질, 간부전, 신부전, 중증질환동반등이다 1 83, 암통증의치료 재발및전이유방암환자에서발생하는암통증을치료하기위해서는통증의강도, 위치, 원인을파악해야하고통증의양상이체간통, 내장통, 신경병통중어느것에해당하는지확인해야한다 110. 암환자의응급상태를나타내는통증의원인은골절, 뇌전이, 경막외전이나연수막전이, 척수압박, 감염등이며, 이러한통증의원인을확인하면신속하게진통제와수술, 방사선요법 111, 스테로이드투여같은원인치료를시행해야한다 (LE 2, GR B). 종양학적응급상태와무관한통증은강도에따라치료방향을결정하는데 112 동통등급이 1`~3인환자는비스테로이드소염제 nonsteroidal antiinflammatory drug; NSAID 또는 acetaminophen, 속효성마약진통제, 항구토제, 보조진통제를필요에따라병용한다. 동통등급 4~6인환자는속효성경구마약진통제, 항구토제, 진통보조제를투여하며강도가심한동통등급인 7~10인환자는속효성경구또는경정맥마약진통제, 항구토제와진통보조제를투여한다 113~116 (LE 1, GR A). 종양학적응급상태와무관한통증치료이후에는반드시통증에대한재평가를하여용량을조절하고, 응급상태로인한통증이아닌것을확인해야한다. 통증이사라지지않으면 4시간마다속효성마약진통제의경구투여나경정맥연속투여를고려해야하고이에반응하지않으면지속적인마약진통제로대체한다 116 (LE 2, GR A). 진통제는 ibuprofen, nonacetylated salicylate, 선택적 COX-2 억제제, acetaminophen 같은 NSAID와마약진통제를사용하며, 진통보조제로항우울제, 항경련제, bisphosphonate를병용투여할수있다 117~118 (LE 3, GR B). 마약진통제의부작용으로변비, 오심, 구토, 진정작용이있으며이에대한적절한예방과치료가필요하다. 마약진통제사용후나타나는변비는수분섭취, 식이섬유섭취, 운동, 하제나대변완화제투여로예방할수있으며, 부작용이발생하면마약진통제의감량, 보조진통제투여, 하제투여로치료한다. 변비가지속적으로발생하면 MgO, bisacodyl, lactulose, sorbitol, metoclopromide, 관장, neuroaxial 진통제또는신경차단치료를고려한다 119 (LE 3, GR B). 마약진통제부작용인오심, 구토는예방이중요하며발생하면 prochloroperazine, thioethylperazine, haloperidol, metoclopromide 투여로치료하고이에반응하지않고오심이나구토가지속될때는세로토닌길항제, 마약진통제교체나감량, 보조진통제, neuroaxial 진통제나신경차단치료를고려한다. 마약진통제로인한진정작용은마약진통제를감량하거나소량씩자주투여하여예방한다 120 (LE 2, GR A). 잘조절되지않는만성통증이발생하면국소마약진통제투여나신경파괴를고려할수있는데국소마약진통제는 71

72 ㅣ제 3 차유방암진료권고안 2008 ㅣ 경막외, 척수강내, 국소신경총에투여할수있고, 신경차단술, 신경용해술같은신경파괴술을시행할수있으며, 필요에따라경피적척추성형술를시행할수도있다 121~123 (LE 4 GR C). 암통증치료근거수준참고문헌 암환자에서응급통증의원인은골절, 뇌전이, 경막외전이나연수막전이, 척수압박, 감염등이며, 이러한통증의원인이확인되면신속하게진통제와수술, 방사선요법, 스테로이드투여등의방법으로치료를해야한다. 통증은강도에따라 NSAID 또는 acetaminophen, 속효성경구혹은정맥항구토제, 보조진통제를필요에따라사용한다 표 4-1. 재발및전이유방암치료에사용되는대표적항암제 단독요법 1) Doxorubicin 60-75mg/m 2 IV 2) Doxorubicin 20mg/m 2 IV 3) Epirubicin 60-90mg/m 2 IV 4) Pegylated liposomal encapsulated Doxorubicin 50mg/m 2 IV 5) Paclitaxel 175mg/m 2 IV 3 시간동안 6) Paclitaxel 80mg/m 2 IV 1 시간동안 7) Docetaxel mg/m 2 IV 1 시간동안 8) Docetaxel 40mg/m 2 IV 1 시간동안 9) Vinorelbine 25mg/m 2 IV 10) Capecitabine mg/m 2 경구매일 2 회 2 주동안 11) Gemcitabine mg/m 2 IV 1,8,15 일째투여 12) Albumin-bound paclitaxel 250 mg/m 2 IV 30 분동안 3 주마다반복 1 주마다반복 3 주마다반복 4 주마다반복 2 주마다반복 1 주마다반복 3 주마다반복매주, 6 주뒤 2 주휴식다시반복 1 주마다반복 3 주마다반복 4 주마다반복 3 주마다반복 표 4-2. 재발및전이유방암치료에사용되는대표적인항암제 - 병합요법 1) CAF Cyclophosphamide 100mg/m 2 경구 1-14 일 Doxorubicin 30mg/m 2 IV 1, 8 일 5-Fluorouracil 500mg/ m 2 IV 1, 8 일 2) FAC 5-Fluorouracil 500mg/ m 2 IV 1, 8 일 Doxorubicin 50mg/m 2 IV 1 일 Cyclophosphamide 500mg/m 2 IV 1 일 3) AC Doxorubicin 60mg/m 2 IV 1 일 Cyclophosphamide 600mg/m 2 IV 1 일 4) CMF Cyclophosphamide 100mg/m 2 경구 1-14 일 Methotrexate 40mg/m 2 IV 1, 8 일 5-Fluorouracil 600mg/m 2 IV 1, 8 일 4주마다반복 3주마다반복 3주마다반복 4주마다반복 72

73 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 5) DX Docetaxel 75mg/m 2 IV 1일 Capecitabine 950mg/m 2 경구 1-14일, 하루 2번 6) GT Paclitaxel 175mg/m 2 IV 3시간동안 1일 Gemcitabine 1250mg/m 2 IV 1, 8일 7) FEC 5-Fluorouracil 500mg/m 2 IV 1, 8일 Epirubicin 50mg/m 2 IV 1, 8일 Cyclophosphamide 400mg/m 2 IV 1, 8일 3 주마다반복 3 주마다반복 4 주마다반복 표 4-3. 재발및전이유방암치료에사용하는대표적항암제 -HER 표적치료포함 1) Trastuzumab 단독요법 Trastuzumab 4mg/m 2 IV 90분동안, 1일이어서 Trastuzumab 2mg/m 2 IV 30분동안, 8일또는 Trastuzumab 8mg/m 2 IV 90분동안, 1일이어서 Trastuzumab 6mg/m 2 IV 90분동안, 8일 2) Trastuzumab과단독항암화학요법 Trastuzumab component plus Paclitaxel 175mg/m 2 IV 3시간동안 Paclitaxel 80~90mg/m 2 IV 1시간동안 Docetaxel 80~100mg/m 2 IV 30분동안 Docetaxel 35mg/m 2 IV 30분동안 3) Trastuzumab과병합항암화학요법 1 PCH Trastuzumab component plus Carboplatin AUC 분당 6mg/m 2 IV, 1일 Paclitaxel 175mg/m 2 IV 3시간동안, 1일 2 weekly TCH Trastuzumab component plus Carboplatin AUC 분당 2mg/m 2 IV, Paclitaxel 80mg/m 2 IV 1시간동안, 매주반복 매주반복 3 주마다반복매주반복 3 주마다반복매주반복 3 주마다반복 매주반복 4) Bevacizumab 과항암화학요법 Paclitaxel 90mg/m 2 IV 1시간동안 1,8,15일 Bevacizumab 10mg/kg IV 1, 15일 4 주마다반복 5) Lapatinib 과항암화학요법 Capecitabine 1000mg/m 2 경구하루 2 번 1-14 일 Lapatinib 1250mg 경구매일한번 3 주동안 3 주마다반복 73

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82 ㅣ제 3 차유방암진료권고안 2008 ㅣ 비침습유방암의진료흐름도 관상피내암의진료흐름도 진단진단검사치료 Ductal Carcinoma In Situ(DCIS) Stage 0 Tis, N0, M0 병력청취와이학적검진 유방촬영술, 양측 병리슬라이드재검사 ER 상태에대한평가 겨드랑이릴프절수술을포함하지않는유방보존술 유방방사선요법혹은유방전절제술 ± 겨드랑이감시림프절생김 ± 유방재건술혹은제한적으로저위험군에서방사선요법없이유방보존술만시행 수술후치료 추적관찰 유방보존술을시행받은 ER 수용체양성인환자에서동측유방의이차침윤암발생을예방하기위하여타목시펜 5 년투여를시행한다. 반대편유방의이차암발생위험도를낮추기위한타목시펜의 5 년간투여를고려할수있다. 유방전절제술 : 매년유방의이학적진찰과반대쪽유방촬영술을시행유방보존술 : 처음 5 년간 6 개월이나 1 년간격으로유방의이학적진찰과동측의유방촬영술을시행 + 확대촬영술을시행한다. 반대쪽유방촬영술은 1 년간격으로시행, 이후에는 1 년간격으로유방의이학적진찰과유방촬영술을시행. 추가 : 필요에따라유방초음파검사를시행할수있다. 소엽상피내암의진료흐름도 진단진단검사치료 Lobular Carcinoma In Situ(LCIS) Stage 0 Tis, N0, M0 유방촬영술, 양측 조직검사 경과관찰 수술후치료 추적관찰 폐경전 : 타목시펜 5년간투여펴경후 : 타목시펜혹은 Raloxifene 5년간투여혹은고위험군환자의경우 ( 유전성유방암, 가족성유방암, 젊은여성의경우 ) 예방적유방전절제술, 양축 + 유방재건술고려 6 개월에서 1 년마다이학적검사 및매년유방촬영술. 82

83 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 조기유방암의진료흐름도 임상병기 진단검사 병기 I T1N0M0 병기 IIA T0N1M0 T1N1M0 T2N0M0 병기 IIB T2N1M0 T3N0M0 필수사항 병력청취, 진찰 말초혈액검사 ( 전혈구수치, 혈소판수치 ) 일반화학검사 ( 간기능검사포함 ) 흉부단순촬영 유방촬영술, 유방초음파검사 병리조직검사 ER/PR 및 HER-2 검사선택사항 유방확대촬영술 유방 MRI 뼈스캔 복부초음파검사또는 CT 18 F-FDG PET 종양표지자검사 종양의크기를제외한유방보존술의적응증에해당하는병기 (IIA, IIB) 에서수술전항암화학요법이나수술전내분비요법 ( 호르몬수용체양성인폐경여성 ) 고려반응 (+) 반응 (-) 국소영역치료전신적보조요법추적검사 유방전절제술 : 유방전절제술 + 액와림프절절제술 (level I/II) 또는감시림프절생검술 ± 유방재건술 : ( 방사선요법이필요한경우지연유방재건술선호 ) ± 방사선요법 : 종양의크기 5cm 절제연양성또는 1mm 미만근접 1~3 개의림프절양성인경우시행 유방보존술 : 유방부분절제술 + 액와림프절절제술 (level I/II) 또는감시림프절생검술 + 방사선요법 항암화학요법 : 림프절음성, 0.6~1.0cm 의고위험군림프절양성종양의크기 1.0 cm 표적치료 (trastuzumab) : HER-2 가 IHC 염색에서 3+ 양성또는 FISH 검사에서증폭이있으며, 림프절양성이거나, 림프절음성이면서종양의크기가 1cm 보다큰경우 1 년동안투여가능내분비요법 : 항암화학요법후시행 호르몬수용체양성인폐경전여성에서는 tamoxifen 을 5 년투여 호르몬수용체양성인폐경후여성에서는 AI 를고려 - 처음부터 5 년간투여 ( 선행요법, upfront therapy as initial adjuvant) - 2~3 년간 tamoxifen 을투여후 AI 를투여 ( 순차요법, switch therapy as sequential with tamoxifen) - Tamoxifen 을 5 년간투여후 AI 를투여 ( 연장요법, extended therapy) 문진, 진찰 (3년동안 3~6개월, 이후 2년동안 6~12개월, 이후 1년마다시행 ) 유방촬영술 (6개월 ~1년간격 ) 부인과검진 (1년간격 ): 자궁있는 tamoxifen 투여환자골밀도검사 (1년간격 ) AI 투여환자그외필요시유방초음파유방확대촬영술간기능검사 (ALP 포함 ) 흉부단순촬영 /CT 복부초음파 /CT 뼈스캔 18 F-FDG PET 종양표지자검사등 83

84 ㅣ제 3 차유방암진료권고안 2008 ㅣ 국소진행유방암 ( I ) 임상병기 병기 IIIA T0N2M0 T1N2M0 T2N2M0 T3N1M0 T3N2M0 병기 IIIB T4AnyNM0 병기 IIIC AnyTN3M0 진단검사 필수사항 문진, 진찰 일반혈액검사 ( 전혈구수치, 혈소판수치 ) 일반화학검사 ( 간기능검사포함 ) 흉부단순촬영 유방촬영술, 유방초음파검사 병리검사 수술전항함화학요법결정을위한 ER/PR 및 HER-2 검사선택사항 확대유방촬영술 유방 MRI 뼈스캔 복부 - 초음파, CT, MRI 18 F-FDG PET 검사 수술전항암화학요법 내분비요법 ( 호르몬수용체양성인폐경후여성인경우 ) 국소치료 국소진행유방암 ( II ) 국소치료 보조치료 추적검사 수술전항암화학요법 Anthracyclin ± Taxane, Trastuzumab 포함요법 반응 (+) 반응 (-) 유방전절제술 + 액와림프절절제술 (level I/II)+ 흉벽과쇄골상부림프절에대한방사선조사 ( 내유방림프절이침범된경우는포함 )± 유방재건술 부분유방절제술 + 액와림프절절제술 (level I/II)+ 유방과쇄골상부림프절에대한방사선조사 ( 내유방림프절이침법된경우는포함 ) 추가의다른항암화학요법 ± 수술전방사선요법 반응 (+) 반응 (-) 수술전항암화학요법과정이남아있는경우추가종결 + 호르몬수용체양성인경우내분비요법 ( 항암화학치료후시행 ) 상기치료 환자개별치료 문진, 진찰 (3 년동안 3-6 개월, 이후 1 년마다시행유방촬영술 Tamoxifen 요법 (1 년간격골반진찰 - 자궁있는환자 ) AI 제재요법 ( 매년골밀도측정 ) 그외필요시유방확대촬영술유방초음파간기능검사 (ALP 포함 ) 흉부단순촬영 /CT 복부초음파 /CT 뼈스캔, 18 F-FDG PET 종양표지자검사등 84

85 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 염증성유방암 임상양상 임상적, 병리학적진단 T4d,anyN,M0 진단검사 필수사항 문진, 진찰 일반혈액검사 ( 전혈구수치, 혈소판수치 ) 일반화학검사 ( 간기능검사포함 ) 병리진단재확인 유방촬영술 유방초음파검사 ER/PR 및 HER-2 검사선택사항 유방 MRI 뼈스캔 전산화단층촬영 ( 흉부, 복부 ) 18 F-FDG PET 검사 반응 (+) 수술전항암화학요법 anthracycline ±taxane Trastuzumab 포함요법 (anthracycline 과순차적 ) 반응 (-) 유방전절제술 + 액와림프절절제술 (level I/II)+ 흉벽과쇄골상부림프절에대한방사선조사 ( 내유방림프절이침범된경우는포함, 임상적으로의심되지않는경우도가능 ± 유방재건술 추가의다른항암화학요법 ± 수술전방사선요법 반응 (+) 반응 (-) 수술전항암화학요법과정이남아있는경우추가종결 + 호르몬수용체양성인경우내분비요법 ( 항암화학치료후시행 ) HER2 양성인경우 trastuzumab 1 년간투여 상기치료 환자개별치료 재발전이유방암의진료흐름도 국소구역재발유방암의국소치료 유방전절제술 수술적절제 ( 가능하면 ) + 방사선요법 ( 가능하면 ) 국소치료 전신치료고려 유방절제술 유방보존술 + 방사선치료 유방보존술 + 부분방사선치료 85

86 ㅣ제 3 차유방암진료권고안 2008 ㅣ 재발및전이유방암의전신요법 전신치료 ER혹은 PR 양성 HER-2 음성 ER혹은 PR 양성 HER-2 양성뼈전이가있는경우 Bisphosphonate 추가 1 년이내내분비요법경험있음 1 년이내내분비요법경험없음 폐경전폐경후내부장기전이폐경전폐경후내부장기전이 난소젤제술및난소기능억제제 + 항에스트로젠제 항암화학요법 난소절제술및난소기능억제제 + 항에스트로겐제 아로마타제억제제혹은항에스토겐제 항암화학요법 3 차례다른호르몬제연속치료에반응이없거나병이진행하는경우, 부작용이심하게나타나는경우, 항암화학요법과 HER- 2 양성인경우 HER-2 표적치료고려 ER and PR음성, ER 혹은 RP 양성이나내분비요법에무반응 HER-2 음성 1 년이내내분비요법경험있음 예 아니오 내분비요법혹은항암화학요법 항암화학요법 세차례상이한항암화학요법연속치료에반응없음또는전신수행능력 ECOG 3 증상완화또는임상시험 ER/PR 음성 HER-2 양성 1 년이내내분비요법경험없음 예 아니오 내분비요법혹은 HER2 표적치료 + 항암화학요법 HER2 표적치료 + 항암화학요법 Anthracycline, taxane. Trastuzumab 우선치료후 capcitabine+lapatinib 86

87 ㅣ Korea Breast Cancer Society Practice Recommendations of Breast Cancer 2008 ㅣ 재발및전이유방암의완화요법 환자선별 사전평가 환자선별 조절되지않는증상암과관련된중증의증상심한정신적, 신체적중증질환추정여명이 12개월이하 - 불량한신체수행도 (ECOG 3 or kornofsky PS 50) - 고칼슘혈증 - 뇌및척수전이 - 상대정맥증후군 - 척수압박 - cachexia - 악성흥액증 - bilirubin 2.5 creatinine 3 환자와가족의요구도 항암치료의이득과위험도평가증상정신사회적고통개인적기대와목표교육과정보의수준치료에영향을주는문화적요소완화요법 조기에완화요접전문가와협진 여러전문가와협력 지역사회의지원동원 적절한시기에호스피스위탁 환자요소 치료법에한계가있는경우 조절되지않거나치료에반응이없는통증 정신과적인질환의과거력 치료에반응이없는증상 암관련통증및증상치료에과잉면역반응이나타난경우 인공삽관등중환자실입원이필요한경우 높은고통점수 (>5) 인지기능의저하 중증의동반질환 의사소통의장애 죽음에대한반복적인요구 사회환경적요소 / 예정된사별문제 가족이나간병인의문제 부적절한사회적지원 심한의존적인관계 제정적한계 의료기관의접근성부족 가족간의불화 부양가족의문제 정신적혹은존재감의위기 해결되지못한반복된사별 만족 불만족 사후간호 항암치료에대한반응에환자가만족 암통증이나증상의적절한조절 환자나가족의고통완화 삶의질을최대한개선 지속적인재분석환자 / 치료자 / 간병인의사소통 다른완화요법을고려 정신과자문이전에가지고있던정신질환, 약물남용, 적응기능장애를진단하고치료하기위함 가족에대한간호가족의암위험도평가와처지 87

88 ㅣ제 3 차유방암진료권고안 2008 ㅣ 유방암영상검사요약표 비침습유방암 : 관상피내암 / 소엽상피내암 조기유방암 국소진행유방암 재발및전이성유방암 진단검사 ( 필수 ) 유방촬영술확대유방촬영술 ( 미세석회화 ) 영상유도하조직검사표본촬영술 ( 미세석회화 ) 유방촬영술유방초음파검사영상유도하침생검흉부단순촬영 유방촬영술유방초음파검사영상유도하침생검흉부단순촬영 유방촬영술 ( 국소재발의심시 ) 흉부단순촬영뼈스캔 진단검사 ( 선택 ) 유방초음파검사유방자기공명영상검사 확대유방촬영술유방자기공명영상검사뼈스캔복부초음파검사또는전산화단층촬영양전자방출단층촬영 확대유방촬영술유방자기공명영상검사뼈스캔복부초음파검사또는전산화단층촬영양전자방출단층촬영 확대유방촬영술유방초음파검사 ( 국소재발의심시 ) 흉부또는복부전산화단층촬영양전자방출단층촬영이상부위뼈의단순촬영 추적검사 ( 필수 ) 반대쪽유방은 1 년간격으로유방촬영술유방보존술을받은유방은방사선요법이끝난후 6 개월에유방촬영술, 이후 6 개월 -1 년간격으로 5 년간, 그후에는 1 년간격으로유방촬영술 반대쪽유방은 1 년간격으로유방촬영술유방보존술과방사선치료를받은유방은방사선요법이끝난후 6 개월에유방촬영술, 이후 6 개월 - 1 년간격으로 2-5 년간유방촬영술 반대쪽유방은 1 년간격으로유방촬영술유방보존술과방사선치료를받은유방은방사선요법이끝난후 6 개월에유방촬영술, 이후 6 개월 -1 년간격으로 2-5 년간유방촬영술 추적검사 ( 선택 ) 확대유방촬영술 ( 유방보존술 ) 유방초음파검사 확대유방촬영술 ( 유방보존술 ) 유방초음파검사흉부단순촬영흉부전산화단층촬영뼈스캔복부초음파검사또는전산화단층촬영 ( 또는자기공명영상검사 ) 양전자방출단층촬영 확대유방촬영술 ( 유방보존술 ) 유방초음파검사흉부단순촬영흉부전산화단층촬영뼈스캔복부초음파검사또는전산화단층촬영 ( 또는자기공명영상검사 ) 양전자방출단층촬영 88

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