Lee A and Moon BI 행성유방암을수술이가능하게할경우, 수술종양의크기를감소시켜유방보존술의가능성을증가시킬경우, 환자의사정으로당장수술이불가능할경우등에서신보강화학요법을시행할수있다. 이러한점이외에도항암제에대한종양의감수성정도를평가할수있으며, 항암제에대한종양의반응정도를평

Size: px

Start display at page:

Download "Lee A and Moon BI 행성유방암을수술이가능하게할경우, 수술종양의크기를감소시켜유방보존술의가능성을증가시킬경우, 환자의사정으로당장수술이불가능할경우등에서신보강화학요법을시행할수있다. 이러한점이외에도항암제에대한종양의감수성정도를평가할수있으며, 항암제에대한종양의반응정도를평"

혜린 삼
5 years ago
Views:

1 Review Article Ewha Med J 204;37(2):-82 pissn eissn 유방암특집 유방암의항암치료 이안복, 문병인 이화여자대학교의학전문대학원외과학교실 Chemotherapy in Breast Cancer Anbok Lee, Byung-In Moon Department of Surgery, Ewha Womans University School of Medicine, Seoul, Korea Breast cancer is the second most common cancer in Korean women and its incidence has increased. Among the various treatment methods for breast cancer, chemotherapy plays an important role. The use chemotherapy to treat breast cancer began at the mid 20th century and first combination chemotherapy was conducted in mid 970s. This chemotherapy reduced breast cancer mortality up to 25~30%, anthracycline and taxane based chemotherapeutic regimens are widely used. Chemotherapy could be classified to neoadjuavnt, adjuvant and palliative setting according to its aim and role. In this review, various drug therapeutic options and their backgrounds are considered based on neoadjuvant, adjuvant and metastatic systemic therapies. (Ewha Med J 204;37(2):- 82) Received July 3, 204 Accepted August 25, 204 Corresponding author Byung-In Moon Department of Surgery, Ewha Womans University School of Medicine, 07 Anyangcheon-ro, Yangcheon-gu, Seoul 58-70, Korea Tel: , FAX: mbit@ewha.ac.kr Key Words Breast neoplasms; Chemotherapy 서론유방암은매우다양한생물학적특성을가지고있으며, 이에따른치료도발전해왔다. 유방암의치료법에는여러가지가있으며, 이중대표적인것이항암치료일것이다. 9 세기후반 Halsted 는유방암치료를위하여서근치적유방암절제술을시행하였으나수술을시행받은환자의 0 년생존율은약 2% 정도에만머물렀으며, 이러한결과는확대근치적수술과같은더욱광범위한수술을시행한경우에도차이가없었다. 이에대해 Fisher 등은유방암은진단당시의이미미세전이가존재하며, 수술만시행받은유방암환자의낮은생존율은이러한미세전이에기인한다고제안하였다 []. 유방암의미세전이는림프절전이가있는경우에는약 35~90% 의경우에존재하며, 림프절전이가없는경우에는 0~30% 정도에서존재한다고보고되고있다 [2]. 이러한배경을바탕으로수술후보조적항암요법이등장하였으며, 실제적으로이는수술후유방암의사망률을 25~30% 정 도감소시키는결과를가지고왔다. 유방암의첫보조항암치료는 Watson 과 Turner 등 [3] 에의해 958 년시행되었으며, 현재많이쓰이고있는복합항암요법의경우 976 년 Bonadonna 등 [4] 에의한 CMF (cyclophophamide, methotrexate, 5-fluorouracil) 요법이최초로시행되었다. 현재의항암요법은 anthracycline 과 taxane 계통의약물을근간으로한복합항암요법이주를이루고있다. 항암요법은시행목적에따라수술후에잠재적미세전이성장을억제하여암의재발을막기위한보조요법, 수술전암의크기를최소화하고미세전이를없애기위한신보강화학요법과전이성환자들에게서질병의완화및삶의질향상을위해시행하는완화화학요법등이있다. 본론. 신보강화학요법신보강화학요법의목적은다음과같다. 수술이불가능한국소진 THE EWHA MEDICAL JOURNAL

Lee A and Moon BI 행성유방암을수술이가능하게할경우, 수술종양의크기를감소시켜유방보존술의가능성을증가시킬경우, 환자의사정으로당장수술이불가능할경우등에서신보강화학요법을시행할수있다. 이러한점이외에도항암제에대한종양의감수성정도를평가할수있으며, 항암제에대한종양의반응정도를평가하여환자의예후를판단하는것이가능하며, 또한미세전이를조기에치료할수있다는장점이있다.

또한항암치료전조직검사를통하여서유방암세포의생물학적특성을검사하지않았을경우, 항암요법을통하여이러한생물학적특성이변할수있으므로정확한종양세포의특성을판별하기가힘든경우가발생하기도한다. 신보강화학요법은 anthracycline 을기본으로하는치료가주가되고있으며, 최근에는여기에 taxane 을추가하는요법이많이시행되고있다.

2 Lee A and Moon BI 행성유방암을수술이가능하게할경우, 수술종양의크기를감소시켜유방보존술의가능성을증가시킬경우, 환자의사정으로당장수술이불가능할경우등에서신보강화학요법을시행할수있다. 이러한점이외에도항암제에대한종양의감수성정도를평가할수있으며, 항암제에대한종양의반응정도를평가하여환자의예후를판단하는것이가능하며, 또한미세전이를조기에치료할수있다는장점이있다. 하지만보조화학요법과비교하여서예후의차이는없는것으로알려져있다 [5-7]. 그러나, 수술전항암요법을시행함으로인하여서환자의정확한병기를판단하기가어려우며, 종양의완전관해가일어날경우수술시원발종양의위치판단이어려운경우가발생하기도한다. 또한항암치료전조직검사를통하여서유방암세포의생물학적특성을검사하지않았을경우, 항암요법을통하여이러한생물학적특성이변할수있으므로정확한종양세포의특성을판별하기가힘든경우가발생하기도한다. 신보강화학요법은 anthracycline 을기본으로하는치료가주가되고있으며, 최근에는여기에 taxane 을추가하는요법이많이시행되고있다. 실제적으로미국 National Surgical Adjuvant Breast and Bowel Project Protocols (NSABP) B-27 에따르면신보강화학요법을시행한환자들을항암요법에따라비교해보았을때 AC (doxorubicin + cyclophophamide) 요법을받은군보다 AC 항암치료후 taxane (docetaxel) 을추가하여서치료한군에서병리학적완전관해율이높은것으로보고되었다 [8]. Taxane 시기에대해서는 German Preoperative Adriamycin Docetaxel (GEPARDO) 그룹에서연구를시행하였다. 이연구는 93 명의유방암환자들을대상으로 AC 시행후순차적으로 taxane (docetaxel) 항암치료를시행한군과 AT 항암치료를결과를비교분석하였으며, 각각의완전관해율이 4.3% 와 7.0% 로 AC 후 taxane (docetaxel) 순차요법을시행한환자군에서완전관해율이의미있게높은것으로보고되었다 (P<0.00) [9]. 따라서 taxane 추가요법의경우순차적항암요법이병행요법보다결과가우수한것을알수있다. Anthracycline 및 taxane 을기본으로한항암요법의회수에관해서는몇몇연구가있으며이에대해서는 3차보다는 6차항암요법을시행하는것이병리학적관해율이높은것으로보고하였다 (Fig. ) [0,]. Steger 등 [0] 은 292 명의환자들을대상으로 epirubicin+taxane (docetaxel) 을 3회투여하였을경우와 6회투여하였을경우의병리학적완전관해율을비교하였으며, 이결과완전관해율이 7.7% 와 8.6% 로 6회의신보강화학요법을시행하였을경우완전관해율이더높은것으로나타났다 (P=0.0045). Reitsamer 등 [] 도임상병기 2기와 3기의환자들을대상으로하여 3주기와 6주기의 epidoxorubicin+taxane (docetaxel) 의반응률을평가하였으며 6주기의항암요법에서더욱높은관해율을보고하였다. 최근유방암의분자생물학적연구가많이진행됨에따라서 HER-2 양성유방암에서 anthracycine 과 taxane 요법에 trastuzumab 을추가하여항암요법을시행한임상연구결과가보고되었으며, 이결과완전관해율이 3.7% 로서기존의보고치인 5.7% 보다훨씬좋은결과를보여주었다 [2]. 이러한결과를바탕으로 HER-2 양성유방암에서기존의 anthracycine 및 taxane 요법에 trastuzumab 을추가하는것이추천되고있다 [3]. 이외에도현재유방암의신보강화학요법으로 gemcitabine 의효과에대하여연구가시행되고있으나, 병리학적관해율에는크게영향을미치지않는것으로보고되었다 [4]. 또한 lapatinib 이나 bevacizumab 같은표적치료제를함께사용한연구가발표되고있으나, 이에대한연구결과는좀더지켜봐야할것으로생각한다 [5,6]. 2. 보조항암요법보조항암치료여부를결정하는데있어서가장대표적인권고안은미국의 NCCN (National Comprehensive Cancer Network) 권고안 [7], 유럽의 St. Gallen 권고안 [8] 과한국유방암학회권고 Fig.. Magnetic resonance imagings of 40-years-old woman, who was diagnosed with breast cancer and received 6 cycles of neoadjuvant AT (doxorubicin+docetaxel) chemotherapy. Pathologic complete response was identified after 6 cycles of neoadjuvant chemotherapy. (A) Before the neoadjuvant chemotherapy, tumor mass occupied over the half of right breast and axillary node is enlarged due to metastasis. (B) After 6 cycles of neoadjuvant chemotherapy, tumor mass and metastatic axillary nodes are completely resolved. 76 THE EWHA MEDICAL JOURNAL

3 Chemotherapy in Breast Cancer 안 [3] 등을들수있다. NCCN 권고안과한국유방암학회권고안의경우에는 2 mm 이상크기의암세포가겨드랑이림프절에전이가있는경우에는반드시항암요법을시행하는것을권고하고있으며, 겨드랑이림프절의전이가없거나전이가있더라도 2 mm 미만의미세전이일경우에는종양의크기와특성에따라서항암여부를결정하도록권고하고있다. 종양의크기에관해서는 cm 보다큰경우에는항암요법을권고하고있으며, cm 이하의경우에는종양의특성및겨드랑이림프절의미세전이여부에따라서생략이가능할수도있다고권고하고있다. 하지만 St. Gallen 권고안의경우항암치료를생략할수있는종양의크기를 2 cm 기준으로권고하고있다. 최근우리나라도고령화사회로진입하면서고령의유방암환 자가증가하고있는실정이며, 이들에게서의보조항암요법의시행여부를결정하여야하는경우가많다. 유방암에서의항암요법은대개 70 세이상의고령의환자들에게서시행하지않고있으나, 경우에따라서는항암제의종류에따른독성, 환자의신체상태에따라서시행할수도있다. 하지만이러한경우에는항암제의독성및환자의신체적상황과항암치료로얻을수있는환자의이득을고려하여신중한판단을하여야할것이다. 유방암의보조항암요법에서주로쓰이는항암제는 CMF 요법, anthracycline 기반요법, taxane 기반요법이있다 (Table ). ) CMF 요법 970 년대중반 Bonadonna 등 [4] 은겨드랑이림프절전이가있 Table. Regimens for adjuvant chemotherapy [7] Regimen Drugs Dose (mg/m 2 ) Route Day Interval and cycle CMF () CMF () AC EC FAC CAF FEC FEC00 AC taxane TAC TC, per os;, Intravenous. Methotrexate Methotrexate Paclitaxel/docetaxel Docetaxel Docetaxel / 50 4,8,8,8,8,8,8 or,4 4,8,8,8,8 4,8,8 4 days, 6 cycles days, 6 cycles 2 days, 4 cycles 2 days, 8 cycles 2 days, 6 cycles days, 6 cycles days, 6 cycles days, 6 cycles 2 days, 8 cycles 4 cycles 4 cycles 5 8 cycles 2 days, 6 cycles 2 days, 4cycles THE EWHA MEDICAL JOURNAL 77

4 Lee A and Moon BI 는 386 명의원발성유방암환자들을대상으로하여서, 이중 207 명의환자들에게수술후 CMF 보조항암치료요법을실시하였다. 27 개월의추적관찰결과 CMF 의유효성을입증하였으며, 이들환자를 20 년추적관찰한결과대조군과비교하여 35% 의재발위험율감소와 24% 의사망률감소효과를보여주었다 [9]. CMF 요법과 anthracycline 기반요법의효능성에대한연구로서는 NSABP B-5 및 B-23 가있다. NSABP B-5 연구의경우 개이상의겨드랑이림프절전이가있는 2,94 명의유방암환자들을대상으로 4주기 AC 요법과 6주기의 CMF 항암요법을시행하였으며, 이결과 3년무병생존율및전체생존율의차이는없는것으로나타났다 [20]. NSABP B-23 의경우 2,008 명의겨드랑이림프절전이가없는환자들에게서 CMF 6주기요법과 AC 4주기요법을비교하였으며, 이결과역시두군간의유효한차이는보이지않았다 [2]. CMF 는 6주기요법을시행하고있으며투여방법에는경구및정맥주사방법이있으며, 경구투여방법이더욱더효과적이다 [2]. 최근겨드랑이림프절전이가있는환자군에서 AC, taxane 순차요법의효용성이밝혀짐에따라 [22], CMF 요법은겨드랑이림프절전이가없는조기유방암환자들을대상으로하여서시행하고있다. Topoisomerase IIα 는유전자복제에있어서핵심적인역할을하는효소이며, 이는많은항암치료제의표적이되고있다. 이효소의유전자는 7번염색체에위치하고있으며, 이는 HER-2/ neu 종양유전자와매우가까이위치하고있다. 이러한연관성때문에 HER-2 양성유방암의경우많게는약 40% 정도에서까지 topoisomerase IIα 유전자가같이과발현된다. 의경우 topoisomerase IIα 을억제하여서항암제로서의기능을하게되며, 따라서 HER-2/neu 가과발현되는유방암의경우 topoisomerase IIα 유전자과발현이같이동반될경우다른항암제보다높은 doxorubicin 의효과를기대할수있다 []. 하지만모든환자에게서이러한유전자검사를시행할수없기때문에 HER-2 양성유방암의경우 CMF 보다는 anthracycline 을포함한항암요법을시행하는것을권고하고있다 [3]. Anthracycline 계열의항암제의주요부작용으로서는심장독성을들수가있다. 이는항암제의누적용량에비례하게되며, doxorubicin 의경우누적용량이 450/m 2, epirubicin 의경우 0/ m 2 를초과하는경우심부전의위험성은증가하게된다. 심장독성을예방하기위해 dexrazoxane 을 anthracycline 과병용투여할수있다 [2]. 2) Anthracycline 기반항암요법 Anthracycline 계열의약제로는 doxorubicin, epiru bicin 등이있으며, 이를기반으로한항암요법은 AC (doxorubicin+cyclophophamide), EC (epirubicin+cyclophophamide), FAC (5-fluorouracil [FU]+ doxorubicin+cyclophophamide), FEC (5-FU+epirubicin+cyclo phophamide), CAF (cyclophophamide+doxorubicin+5-fu) 등이있다. Martin 등 [23] 은 985 명의근치적유방암수술을받은환자들을대상으로 CMF 와 FAC 의효과에대해비교연구를시행하였으며, 이결과겨드랑이림프절전이가있는군에서만 FAC 가 CMF 요법에비해 5년무병생존율의경우 2%, 7.5년무병생존율의경우 5% 의생존향상률을보여주었다. 또한전체생존율에있어서도 FAC 요법이유의하게높은생존율을보여주었다 (P=0.0378). 을기반으로한요법과 CMF 요법을비교한연구들을살펴보면, 겨드랑이림프절양성인환자들을대상으로 EC 8 주기와 CMF 6주기를비교하였을때무병생존율이나전체생존율의차이는보여주지못하였다 [24]. 하지만 FEC 6주기요법과 CMF 6주기의요법을비교분석하였을때에는겨드랑이림프절전이여부에상관없이 FEC 가좀더좋은결과를보여주었다 [25-27]. 이상의결과들을종합하여볼때림프절전이여부와상관없이 4주기 AC 요법이 6주기 CMF 요법과비슷한효과를나타내는것을알수있었으며, 6주기의 FAC 나 FEC 요법이 6주기의 CMF 요법보다는좀더우수한효과를보이는점을알수있다. 3) Taxane 기반항암요법 Taxane 계통의약물로는 paclitaxel 과 docetaxel 이있으며. 이들은세포분열시 microtubule 에작용하여서항암효과를나타낸다. 이러한 taxane 약물을포함하는항암요법은 AC 4주기후 taxane 4주기요법 ( 총 8주기 ), 6주기 TAC (docetaxel + doxorubicin + cyclophophamide), 4주기 TC (docetaxel + cyclophophamide) 요법등이있다. 보조항암요법으로서의 taxane 의효과는 Cancer and Leukemia Group B (CALGB) 9344 연구를통하여서보고되었다. 이연구에서는 3,2 명의림프절전이가있는환자를대상으로 4주기 AC 후순차적으로 4주기추가 paclitaxel 항암요법을시행한군과시행하지않은군을비교분석을시행하였다. 이결과추가 paclitaxel 항암요법시행군에서무병생존율과전체생존율이의미있게향상되었다 [22]. TAC 요법의경우 Breast Cancer International Group (BCIRG) 00 연구에서 FAC 요법과비교분석을시행하였다. 이연구에서는,49 명의겨드랑이림프절양성인환자를대상으로 6주기의 TAC 요법과 6주기의 FAC 요법을비교분석하였으며, 이결과 TAC 요법을받은그룹에서 % 의재발위험률감소 (P=0.00) 와 30% 의사망률감소 (P=0.008) 를보여주었다 [29]. US Oncology Trial 9735 경우,06 명의환자들을대상으로하여서 4주기의 TC 와 4주기의 AC 요법을 5년및 7년추적관찰을시행후비교분석하였다. 이연구의 5년추적관찰의결과무병생 78 THE EWHA MEDICAL JOURNAL

5 Chemotherapy in Breast Cancer 존율의경우 TC 군에서좋은결과를보였으나, 전체생존율의경우두군간의유의한차이는보이지않았다 [30]. 하지만 7년추적관찰결과무병생존율의경우 TC 군이 8%, AC 군이 % 로 TC 군에서유의하게높았으며 (P=0.032), 전체생존율도 TC 87%, AC 가 82% 로 TC군에서유의하게높았다 (P=0.032) [3]. 따라서이러한결과를살펴볼때심장독성의위험성이높은환자에게서 AC 요법대신 TC 요법을사용할수도있을것으로생각된다. 이러한연구결과들을종합하여현재겨드랑이림프절전이가있는유방암환자의보조치료에서 taxane 을포함한보조요법을시행하고있다. Paclitaxel 의주요부작용으로서는말초신경병증이있으며이는약 % 의환자에서나타나는것으로보고되고있다. 이는약제의용량과관련이있으며, 주로사지말단의감각이상의형태로나타나게된다. 하지만경우에따라서는운동장애나자율신경병증이나타나는경우도있다. 약 5~5% 의환자들에게서는관절통과근육통이동반될수있다. Docetaxel 의경우에도 paclitaxel 과유사한부작용들이나타날수있으며, 특이적인부작용으로는체액저류의빈도가 paclitaxel 보다높다는점이다. 이는주로 docetaxel 의누적사용량과관련이있으며, 총누적용량이 400 mg/m 2 이상일때발생률은급격히증가하게된다. 이로인해말초부종, 늑막삼출, 체중증가와같은현상이생길수있다 [32]. 3. 전이성유방암의항암요법전이성유방암의치료의목적은환자의삶의질을향상시키고, 질병의완치보다는완화를목적으로하고있다. 전이성유방암의치료에는항호르몬치료, 표적치료, 항암요법등과같은여러방법이있다. NCCN 권고안에서는호르몬수용체, HER-2 의발현여부와는상관없이뼈나연부조직전이를제외한내부장기로의 전이가있으며이로인한증상이있을경우항암요법을우선으로선택하는것을제시하고있으며, 또한특별한분자생물학적표적이없는삼중음성유방암의경우에도항암요법을우선치료방법으로권유하고있다. 아울러호르몬수용체가발현하더라도항호르몬치료에반응하지않는경우도항암요법의대상이된다. 항암치료약제의선택에있어서고려하여야할점은먼저종양에대한적절한관해율이나종양의안정화를이룰수있는지여부이다. 종양의적절한관해율은적어도 20~30% 이상이되어야하며, 종양이안정화되어더이상성장을안하는경우에는부분관해를보인환자와비슷한생존기간을보인다. 전이성유방암의약제선택에있어서항암제감수성검사가도움이될수있을것이다. 다음으로고려하여야할것이부작용을최소화할수있으며, 아울러가능하면간편하게시행할수있는항암제를선택하는것이고려의대상이될것이다 []. 전이성유방암항암요법에서는단독요법보다는병합요법이병의진행기간을늦출수있다고보고되고있으나, 단독요법과병합요법두군간의전체생존율의차이는크게차이가없는것으로나타났다 [33-36]. 선호되는단독항암제들로서는 doxorubicin, paclitaxel, capecitabine, gemcitabine, vinorelbine, eribulin 등이있으며, 주로사용하는병합요법들로서는 CAF/FAC, FEC, AC, EC, CMF, docetaxel/capecitabine, GT (gemcitabine/paclitaxel) 등을들수있다 (Tables 2, 3). HER2 양성전이성유방암일경우에는기존의항암제에 trastuzumab 을포함한요법을사용할수있으며, 이러한약물들에는 paclitaxel, docetaxel, vinorelbine, gapecitabine 등이있다. 병용요법에서항암제선택시고려사항은각약물간의교차내성이없어야하며, 병용투여시치료효과가상승한다는증거가있어야하며, 항암제의독성이증가하지않아야한다 [7]. Table 2. Single agent chemotherapy regimens for metastatic breast cancer [7] Single regimen Drug Dose (mg/m 2 ) Route Day Interval (day) Prefer drug Others, Intravenous;, per os. Paclitaxel Capecitabine Gemcitabine Vinorelbine Eribulin Docetaxel Cisplatin ,000-, , , 2/day 4, 8, 5, (after 6 cycles, 2 wk rest) 3 3 THE EWHA MEDICAL JOURNAL 79

6 Lee A and Moon BI Table 3. Combination chemotherapy regimens for metastatic breast cancer [7] Combination regimen Drug Dose (mg/m 2 ) Route Day Interval (day) CAF FAC FEC AC EC CMF Docetaxel/capecitabine GT, per os;, Intravenous. Methotrexate Docetaxel Capecitabine Paclitaxel Gemcitabine ,250, 2/day 4, 8, 8, 8 or, 4, 8, 8, 8 4, 8, 8 4, 8 (after paclitaxel on st day) 최근에는 mtor 억제제인 everolimus 와스테로이드성아로마타제억제제의병용요법이비스테이드성아로마타제억제제에저항성을나타내는유방암에서사용되어효과를보이고있다 [37]. 또한신생혈관억제제인 bevacizumab 을포함한여러항암요법이연구되었으며, 이결과병의진행기간을늦추기는하였으나전체생존율에는차이가없는것을보여주었다 [38,39]. 전이성유방암환자에게있어서항암요법의적정기간은정해진바는없으나, 항암요법에대한반응평가를시행후암이악화되지않으면항암요법을계속지속하는것을권유하고있다. 하지만이는환자의삶의질및항암제의독성등을고려해서진행하여야할것이며, 이러한조건이만족하지못할경우항암요법의중단을고려할수있다. 결론유방암의치료에있어항암요법은매우중요한부분을차지하고있으며, 이는유방암의재발률과사망률을낮추는데혁혁한공을세우고있다. 아울러서과거에는수술이불가능하였던유방암을수술을가능하게하거나, 유방보존술이가능하게하는등의부가적인활약까지하고있다. 하지만이러한이면에는항암요 법의부작용으로인한삶의질저하와같은어두운면이존재하는 실정이며이로인해항암치료를포기하는경우가다수발생하기도 하며, 이는특히전이성유방암환자와같이지속적인항암치료를 요하는경우에는더욱더그러하다. 현재의유방암의약물치료에 대한연구의가장큰흐름중의하나는종양유전자들에대한표 적치료다. 이러한방향은항암치료에서오는부작용을최소화할 수있는방향으로진행될수있을것이라기대하며, 아울러항암 제치료에있어항암효과뿐만아니라환자의삶의질문제에더 욱초점을맞추었으면한다. 참고문헌. The Korean Breast Cancer Society. The breast. 2nd ed. Seoul: Ilchokak; Korean Hereditary Breast Cancer Study Group; The Korean Breast Cancer Society. Hereditary breast cancer. Seoul: Koonja; Watson GW, Turner RL. Breast cancer; a new approach to therapy. Br Med J 959;: Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med 976;294: THE EWHA MEDICAL JOURNAL

7 Chemotherapy in Breast Cancer Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 2006;24: van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial J Clin Oncol 200;9: Fisher ER, Wang J, Bryant J, Fisher B, Mamounas E, Wolmark N. Pathobiology of preoperative chemotherapy: findings from the National Surgical Adjuvant Breast and Bowel (NSABP) protocol B-8. Cancer 2002;95: Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-8 and B-27. J Clin Oncol 2008;26: von Minckwitz G, Raab G, Caputo A, Schutte M, Hilfrich J, Blohmer JU, et al. with cyclophosphamide followed by docetaxel every 2 days compared with doxorubicin and docetaxel every 4 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 2005;23: Steger GG, Galid A, Gnant M, Mlineritsch B, Lang A, Tausch C, et al. Pathologic complete response with six compared with three cycles of neoadjuvant epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable breast cancer: results of ABCSG-4. J Clin Oncol 2007;25: Reitsamer R, Peintinger F, Prokop E, Hitzl W. Pathological complete response rates comparing 3 versus 6 cycles of epidoxorubicin and docetaxel in the neoadjuvant setting of patients with stage II and III breast cancer. Anticancer Drugs 2005;6: Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol 200;: The Korean Breast Cancer Society. Breast cancer treatment guideline. 5th ed. Seoul. d_5_08.pdf ; von Minckwitz G, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, et al. Capecitabine in addition to anthracycline- and taxanebased neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol 200;: Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, et al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol 202;3: von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 202;366: The National Comprehensive Cancer Network. NCCN guideline ver. 3. Fort Washington, PA: The National Comprehensive Cancer Network; A. Goldhirsch, E. P. Winer, A. S. Coates, R. D. Gelber, M. Piccart- Gebhart, B. Thürlimann, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 203. Annals of Oncology 203;24: G. Bonadonna, P. Valagussa, A. Moliterni, M. Zambetti, C. Brambilla. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med 995;332: Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-5. J Clin Oncol 990;8: Martin M, Villar A, Sole-Calvo A, Gonzalez R, Massuti B, Lizon J, et al. in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day, 2) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day, 2) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. Ann Oncol 2003;4: Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, et al. Improved outcomes from adding sequential Paclitaxel but not from escalating dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 2003;2: Martin M, Villar A, Sole-Calvo A, Gonzalez R, Massuti B, Lizon J, et al. in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day, 2) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day, 2) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. Ann Oncol 2003;4: Piccart MJ, Di Leo A, Beauduin M, Vindevoghel A, Michel J, Focan C, et al. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol 200;9: Coombes RC, Bliss JM, Wils J, Morvan F, Espie M, Amadori D, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The International Collaborative Cancer Group. J Clin Oncol 996;4: Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H, et al. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared THE EWHA MEDICAL JOURNAL 8

8 Lee A and Moon BI with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 998;6: Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, et al. and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med 2006;355: Jarvinen TA, Tanner M, Rantanen V, Barlund M, Borg A, Grenman S, et al. Amplification and deletion of topoisomerase IIalpha associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer. Am J Pathol 2000;56: Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005;352: Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 2006;24: Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, Mc- Intyre KJ, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of us oncology research trial J Clin Oncol 2009;27: Verweij J, Clavel M, Chevalier B. Paclitaxel (Taxol) and docetaxel (Taxotere): not simply two of a kind. Ann Oncol 994;5: Albain KS, Nag SM, Calderillo-Ruiz G, Jordaan JP, Llombart AC, Pluzanska A, et al. Gemcitabine plus Paclitaxel versus Paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol 2008;26: Carrick S, Parker S, Wilcken N, Ghersi D, Marzo M, Simes J. Single agentversus combination chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev 2005;(2):CD O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 2002;20: Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, et al. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E93). J Clin Oncol 2003;2: Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, et al. Everolimus in postmenopausal hormone-receptorpositive advanced breast cancer. N Engl J Med 202;366: Miles DW, Chan A, Dirix LY, Cortes J, Pivot X, Tomczak P, et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 200;: Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, et al. RIBBON-: randomized, double-blind, placebocontrolled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol 20;29: THE EWHA MEDICAL JOURNAL

02-임상종양학회지4-2_전운천

02-임상종양학회지4-2_전운천 ORGINAL ARTICLE 유방암환자의보조적항암화학요법 Department of Surgery, Ajou University School of Medicine, M.D. 아주대학교병원외과학교실정용식 초록유방암은다학제적치료를통해가장큰효과를볼수있는대표적인악성종양이며수술후의보조적항암화학요법은환자의생존율을높일수있는효과적인방법으로서지금까지많은약제들이등장하였고그보다더많은조합들이임상시험에이용되었다.