CASE REPORT Journal of Breast Cancer J Breast Cancer 2010 September; 13(3): 305-10 DOI: 10.4048/jbc.2010.13.3.305 유방보존술후국소재발환자에서이차유방보존술및반대측감시림프절생검술 : 2 예보고 김완욱ㆍ전영산 1 ㆍ강수환 1 ㆍ이정언ㆍ이세경ㆍ허성모ㆍ김성훈ㆍ남석진ㆍ양정현ㆍ이수정 1 성균관대학교의과대학삼성서울병원외과학교실, 1 영남대학교의과대학외과학교실 Secondary Partial Mastectomy with Contralateral Sentinel Lymph Node Biopsy for Ipsilateral Breast Cancer Recurrence after Conservative Surgery: Report of 2 Cases Wan Wook Kim, Young San Jeon 1, Su Hwan Kang 1, Jeong Eon Lee, Se Kyung Lee, Sung Mo Hur, Sung Hoon Kim, Seok Jin Nam, Jung-Hyun Yang, Soo Jung Lee 1 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; 1 Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea Mastectomy has been known to be the best strategy for treating in patients with ipsilateral breast cancer recurrence (IBCR) after conservative surgery. For the cases with a small recurrent cancer which is found in the majority of cases on the regular check-up, the patients desire for breast conserving surgery is increasing. Some recent studies have reported patients with IBCR might receive a second partial mastectomy, when a good local control can be predicted. It is not obvious that sentinel lymph node biopsy (SLNB) in the treated breast is feasible because the previous axillary dissection and/or irradiation may affected the pattern of lymphatic flow. Because of its high accuracy, SLNB may be safely performed for the patients with IBCR in the treated breast. Interestingly, there are reports that SLNB in this condition has revealed that the sentinel lymph node(s) can be found in the opposite side. We reported two cases in which contralateral SLNB were performed during the secondary partial mastectomy for the IBCR after breast conserving surgery. Key Words: Contralateral sentinel lymph node biopsy, Ipsilateral breast cancer recurrence, Secondary partial mastectomy 중심단어 : 반대측감시림프절생검술, 동측재발유방암, 이차유방부분절제술 서 최근유방보존술의비율이점차증가함에따라유방보존술후 책임저자 : 이수정 705-717 대구광역시남구대명5동 317-1, 영남대학교의과대학외과 Tel: 053-620-3587, Fax: 053-624-1213 E-mail: crystallee@medical.yu.ac.kr 접수일 : 2010년1월 12일게재승인일 : 2010년6월 25일본증례는삼성서울병원과영남대학교병원의증례를보고한것으로김완욱과전영산이공동으로제1저자로참여하였음. 본증례는 2009년제2 회유방외과술기연구회학술대회에서구연발표되었음. 론 의국소재발도증가하고있어유방보존술후국소재발암에대한치료가중요시되고있다. 유방암으로유방보존술을시행한후국소재발한환자에게있어서치료의방침은일반적으로는남은유방의전절제술이라고알려져있지만 (1,2) 이에대한근거는뜻밖에확실한것은아니다. 이에따라유방보존술에대한환자들의욕구가점차증가하고유방내에서재발한병소가수술후규칙적인진찰및검사로인하여대부분에서일찍발견되어크기가작기때문에, 재발의위험성이낮고국소적치료로좋은결과가예상되는경우에서이차유방부분절제술을시도하는연구들도발표되었다.(3-5) 305

306 Wan Wook Kim, et al. 한편, 불과 10 여년만에감시림프절생검술은수술전액와림프절의전이여부가확실하지않은조기유방암의표준술식과같이널리받아들여져왔으나, 기존에수술또는방사선치료를시행받은유방에서의감시림프절생검술은림프절의경로가바뀌었을것이라는생각때문에상대적으로금기로생각되었지만여기에는아직논쟁이있다. 2005년미국임상암학회 (American Society of Clinical Oncology, ASCO) 에서발표한감시림프절생검술의지침은이전에액와부수술과거력이있는경우에는감시림프절생검술을시행하는것을권장하지않고있으나, 감시림프절생검술의높은정확도로적응증이확대되고있는것이사실이고, 최근에여러연구에의하면이전에수술혹은방사선치료를받은유방에서도감시림프절생검술은시행될수있고그결과도양호하다고보고된바있다.(6-9) 그리고국외논문에서이전에유방혹은액와부수술또는유방에방사선치료후동측에감시림프절없이반대측액와림프절에감시림프절이있었다고보고하였고일부에서는반대측감시림프절에서전이된암세포가발견되었다고보고되었지만,(9,10) 국내의문헌을조사하였을때국내에서는이런경우가아직보고된바없으므로본저자들은유방암으로유방보존술후국소재발한환자에서이차유방부분절제술및반대측액와부에서시행한감시림프절생검술 2예를경험하였기에고찰과함께보고하는바이다. 증례증례 1 63 세여자환자는 6년 8개월전에우측하외측유방에촉지되는종괴를주소로삼성서울병원에내원하여시행한핵생검술 (core needle biopsy) 에서침윤성유방암으로진단이되었고수술은 우측유방부분절제술및동측감시림프절생검술을받았다. 수술중시행한동결절편검사에서침윤성유방암, 절제면은음성이었으며감시림프절 2개모두에서암세포는없었으나최종조직검사에서 1.7 cm 크기의침윤성유방암, 2개의감시림프절중한개에서암세포의전이소견이있어서추가로액와림프절곽청술을받았고 17 개림프절에서더이상의전이소견은없었다. 병기는 IIA (T1N1M0), 면역조직화학염색에서에스트로겐수용체음성, 프로게스테론수용체음성, HER2 +1의소견으로항암화학요법 (doxorubicin+cyclophosphamide 4회시행후 paclitaxel 4회시행 ) 과방사선치료 (6,000 cgy) 를받았고이후외래를통해정기적으로진찰과검사를받았다. 첫수술로부터 6년 6개월이경과한후시행한초음파검사에서우측하내측에서새로운 0.5 cm 크기의불규칙한경계의저에코성결절이발견이되었고핵생검술에서재발한침윤성암으로진단되었고, 동측에커진림프절은없었다 (Figure 1). 추가로시행한자기공명영상에서재발암이외에추가적인병변은없었고양전자방출단층촬영에서도비정상적인섭취증가소견은없었다. 환자가유방보존을원하였으므로재발암의크기가작고재발까지의기간이 6년이상인점을고려하여우측 2차유방부분절제술과감시림프절생검술을계획하였다. 감시림프절생검술을위해통상적인방법대로수술시작 2시간전에핵의학과에서 148 MBq 의 Tc-99m filtered phytate 0.3 ml를우측유륜부주위로피내주사하였다. 수술전시행한유방림프관조영스캔상동측액와부에섭취증가소견없이반대측 level I 액와부에국소섭취증가소견이보였으며 (Figure 2), 수술전우측하내측재발부위에염색 (tattooing) 을시행하고감마선검출기 (Gamma Finder; World of Medicine, Berlin, Germany) 의탐식자를이용하여탐측한결과동측 ( 우측 ) 액와부에감마량이검출되지않았고반대측 ( 좌측 ) 액와부에국소적으로감마량이높게측정이되어이를감시림프절로생각하였다. 따라서수술은우측 2차유방부분절제술및좌측감시림프절생검술을시행하였다. 3개의감시림프절을 ANT RT LAT Figure 1. Preoperative ultrasonogram revealed about 0.5 cm size ill defined irregular hypoechoic nodular lesion at right lower inner area. Figure 2. In preoperative lymphoscintigraphy, sentinel lymph node (arrow) was detected in the contralateral axillary level I area.

Secondary Partial Mastectomy with Contralateral Sentinel Lymph Node Biopsy 307 찾을수있었고조직검사결과유방에서는 0.6 cm 침윤성유방암이발견되었으며절제면에암세포는보이지않았고, 감시림프절 3개모두에서암세포의전이소견은없었다. 에스트로겐수용체양성으로현재보조치료로아로마타제억제제를투여중이며재발의증거는없이수술후 3개월째경과추적중이다. 증례 2 유방암으로수술을받은적이있는 63 세여자가유방정기검진을위해영남대학교병원을내원하였다. 환자의과거력에서내원 9년전 (1999년) 외부병원에서우측유방암으로진단받고우측유방종괴절제술및액와부 level I 구역임파선절제술을시행받았으며 T2N1M0, 2기유방암으로진단받고항암화학약물치료및방사선치료를완료하였다. 내원당시시행한신체검사에서우측유방상외측에약 10 cm 가량의과거수술반흔과함께수술반흔에인접하여약 1 cm 크기의단단하고경계가불규칙한종괴가촉지되었으나동측의액와부검사소견은정상이었다. 국소재발의심하에유방초음파와세침흡인세포검사를시행하였으며초음파검사상우측유방의과거수술반흔과일치한곳에약 1 cm 크기의악성소견을보이는종괴가관찰되었고 (Figure 3), 세포검사상악성세포가발견되어수술을시행하였다. 환자가유방보존술을강력히원하여다시유방보존술을계획하였으며감시림프절생검술을위해수술시작 1시간전에 1.0 mci의 99mTc-phytate 를생리식염수 0.2 ml에희석하여유륜부주위로피내주사하였다. 피내주사후검사한유방림프관조영스캔의소견은동측액 와부로림프흐름은관찰되지않았으나동측내유림프절을거쳐반대측액와부로의림프흐름이관찰되었으며반대측액와부에하나의감시림프절을관찰할수있었다 (Figure 4). 수술전감마선검출기탐식자를이용하여동위원소주입부, 우측액와부, 우측내유임파선부위, 좌측액와부와유방변연부에서감마선량을측정하였으며좌측액와부에서만감마선량이높게검출되었다. 우측내유림프절부위의감마선량은좌측액와부감마선량의약 8% 정도의감마선량이검출되었으며, 10% 미만일때는감시림프절로생각하지않는다는원칙에준하여감시림프절이라고판단하지않았다. 따라서, 수술은우측유방보존술을시행하였고액와부수술은좌측액와부의감시림프절만생검하여동결절편검사를시행하여음성을확인하고수술을마쳤다. 수술직후시행한양전자방출단층촬영상이전의림프관조영스캔에서보이던우측내유림프절부위를포함하여양측내유림프절부위의 standardized uptake value (SUV) 증가소견은보이지않았으며원격전이소견또한없었다 (Figure 5A). 그러나수술후 6개월째시행한양전자방출단층촬영에서이전의정상소견으로보였던좌측내유림프절부위와이와인접한흉막부위에강한 SUV 증가소견과함께다발성좌측흉막및좌측흉벽의연부조직전이가관찰되었다 (Figure 5B, C). 조직학적진단을위해개흉폐생검을시행하였으며전이성유방암으로진단되어현재호르몬억제요법시행중이다. 항암화학요법은환자의거부로시행되지못하였다. 두증례에대해표로정리하였다 (Table 1). RT LT Figure 3. Preoperative ultrasonogram revealed about 1.0 cm size irregular microlobulating hypoechoic mass at upper outer quadrant of right breast. This lesion was adjacent to previous surgical site. Figure 4. Dynamic image of the involved breast and axillary region was obtained for 10 min after injection of radiotracer. Focal hot uptake with lymphatic flow was noted in the ipsilateral internal mammary area (arrowhead) and contralateral axillary level I area (arrow).

308 Wan Wook Kim, et al. A B C Figure 5. There was no hypermetabolic lesion in the internal mammary area and the other sites on immediate postoperative PET-CT (A). But, 6 months later after operation, PET-CT revealed multiple hypermetabolic lesions in the left internal mammary area (B) and left hemithorax (C). Table 1. Summary of each case regarding characteristics, operation, pathology and treatment Case 1 Case 2 Age/Gender 63/Female 63/Female Initial operation Right partial mastectomy with axillary lymph Right partial mastectomy with axillary lymph node dissection node dissection Pathology (tumor size, LN number) IDC, 1.7 cm, (1/19) IDC, 2.3 cm, (2/12) ER/PR/HER2 (-/-/1+) (-/-/1+) 1st adjuvant treatment Chemotherapy Chemotherapy Radiation therapy Radiation therapy Time to recurrence 6 years 8 months 9 years 1 month Second operation Right second partial mastectomy Right second partial mastectomy with contralateral SLNB with contralateral SLNB Lymphoscintigraphy Contralateral SLN Contralateral SLN Pathology (tumor size, LN number) IDC 0.6 cm, (0/3) IDC 1.1 cm, (0/1) ER/PR/HER2 (+/-/-) (+/+/1+) 2nd adjuvant treatment Aromatase inhibitor Tamoxifen Radiation therapy LN=lymph node; IDC=invasive ductal carcinoma; ER=estrogen receptor; PR=progesterone receptor; HER2=higher human epidermal growth factor receptor 2; SLNB=sentinel lymph node biopsy. 고찰유방보존술후방사선치료를한경우의생존율이근치적유방전절제술을시행한경우와동등하다는결과가보고된이후로유방전절제술이요구되는경우를제외하고는유방보존술이첫번째치료방법으로고려되고있고, 그비율또한증가하고있다.(11,12) 생존율은그렇다고해도, 국소재발은유방보존술을시행한경우에서유방전절제술을시행한경우보다더흔하다고보고되었기때문에, 유방보존술이후유방의국소재발암에대한치료는더욱중요하게생각되고있다. Veronesi 등 (12) 에의하면유방암에있어서동측유방에서의재발은 20 년경과관찰에서유방보존술후에 8.8%, 변형근치적유방전절제술후에 2.3% 에서재발이있었 다고하였다. 재발한 30 예중 10 예는수술부위에서재발한경우였고 20 예는동측유방의다른부분에재발한이차유방암이었다. 지금까지알려진바로는유방보존술후국소재발이있는경우에는국소재발이없는경우보다원격전이의비율이높고, 따라서국소재발은원격전이여부를예측할수있는중요한지표이다.(13, 14) 그리고, 유방보존술후동측에재발한유방암에서치료원칙은일반적으로남은유방전절제술이라고알려져왔지만,(1,2) 원격전이가없는국소재발의경우에도남은유방전절제술이정당화될수있는지를뒷받침하고정당화하는근거에대해서는논란이있어왔다. 유방암의조기발견비율이늘어나면서수술후미용을포함한환자의삶의질에대해관심이높아지고있으며, 환자들의유방

Secondary Partial Mastectomy with Contralateral Sentinel Lymph Node Biopsy 309 보존에대한욕구가커지고있다. 이와함께, 수술후규칙적인진찰과검사에따라국소재발이라고할지라도대부분작은크기일때발견됨에따라유방보존술후에이차유방부분절제술을시도하는연구들이발표되었다. Gentilini 등 (3) 의주장에따르면유방보존술후동측에재발한유방암에서이차보존술을고려해야하는경우는좋은국소적치료의결과가예상될때, 즉, 재발한유방암의크기가 2 cm 이하이고재발까지의기간이 48 개월이상일때이차유방부분절제술을고려할만하다고하였고, 이차부분절제술을시행하고 5년동안관찰한결과 12.8% 의국소재발률을보였다. 또다른연구에의하면국소재발한유방암에서이차유방부분절제술을시행하였을때국소재발률은 35% 정도로첫번째유방부분절제술을시행하였을때보다국소재발률은높았지만, 이차유방부분절제술과전절제술사이에환자들의생존율에서는차이가없다고보고하고있는데,(4,5) 이는이차유방부분절제술다음에는이미방사선치료를해버려서대부분의경우에서추가적인방사선치료를시행할수없었기때문일것이라고주장하고있다. 한편, Komoike 등 (15) 은처음수술시 30 세미만으로나이가젊은경우, 유방암의가족력이있는경우, 그리고유방부분절제술후보조전신치료를하지않았던경우에서이차유방부분절제술후국소재발률이더높다고보고하였다. 이런연구결과들을고려해볼때, 국소재발및전신전이와생존간의관계에대해논쟁이있는상황에서더많은수의환자와오랜기간의경과관찰이필요하겠지만, 추가적인재발의위험성이낮고, 다발성이아닌일부의환자의경우에서환자가유방보존술을강력히원하며그에대한미용효과가좋을것으로예상될때에는무조건적으로남은유방전절제술을시행하는것보다는이차유방부분절제술을고려해볼수도있을것이다. 감시림프절생검술은임상적으로전이소견이없는환자에게서침습적인액와림프절곽청술로인한합병증을줄이고정확한액와림프절의병기를평가하는표준술식으로자리잡아가고있다. 2005년 ASCO에서발표한감시림프절생검술지침에의하면이전에액와부수술을받은과거력이있는경우에는권장되지않는다고하였고, 이는이전에수술을받거나방사선치료를받은유방에서는림프절흐름이바뀔수있기때문에일반적으로감시림프절생검술이상대적금기로생각되었지만이를뒷받침하거나부인하는연구는거의없었다. 이후이에대한여러가지연구들이발표되었는데, 이전에액와림프절곽청술을포함한유방수술을받은경우에서도감시림프절의위치를예측할수있다고하였다. Koizumi 등 (10) 은림프절흐름의변경은암세포의전이가있을경우, 이전에유방혹은액와부수술을받은경우, 이전에방사선혹은항암화학요법을받은경우등에서있을수있다고하였고이전에방사선치료시반대측림프절로, 액와부수술시내유림프절 로가는경향이있다고하였다. Taback 등 (6) 은유방암으로유방보존술, 액와림프절곽청술혹은방사선치료후에국소재발한유방암에서시행한감시림프절생검술에대한연구에서수술전유방림프관조영스캔에서는 73%, 실제로감시림프절생검술을시행하면서는 79% 에서적어도한개이상의감시림프절을찾을수있다고보고하면서국소재발한유방암에서감시림프절생검술은성공적으로시행될수있었다고하였다. 절제생검술후에시행한감시림프절생검술에서감시림프절은약 99% 에서찾을수있었고,(7) 이전에감시림프절생검술또는액와림프절곽청술후에시행한재감시림프절생검술은이전에제거한림프절개수가 10 개미만일때 87% 에서찾을수있었고이전에제거한림프절의개수가적을수록성공률이높다고하며,(8) 이전에액와부수술또는방사선치료와상관없이재발한유방에서감시림프절생검술이가능하다고보고한연구도있다.(9) 본증례들에서도감시림프절을찾을수는있었으나, 후향적으로고찰해볼때증례 2에서의감시림프절생검술은동측내유림프절에대한생검이수술당시시행되지않았다는점에서술기상에논란의여지가있다고생각된다. 즉, 통상의유방암수술시적용하는 10% 규칙 은가장높은감마량을보이는감시림프절의감마량을기준으로 10% 이상의감마량이검출되는림프절을감시림프절이라고생각하자는것인데, 이는동측액와부에서다수의감시림프절이발견될때적용되는이론이다. 즉, 증례 2의경우, 재발한종양에서동측의내유림프절을거쳐반대편액와부로림프의흐름이재편성되었을가능성이있으므로, 유방내의종양에서림프액이배액되는첫번째림프절이감시림프절이라는정의를상기한다면, 동측의내유림프절이감시림프절일가능성이매우높으므로이에대한생검을시행하는것이정당화되었을가능성이높다 (Figure 4). 비록한증례에불과하지만, 이렇게동측내유림프절을거쳐반대편액와부림프절로림프의흐름이의심될때, 내유림프절이감시림프절임에도불구하고반대쪽액와부의림프절보다감마량이낮게측정될수도있다는것을간과해서는안되겠다. 본저자들도보다많은수의연구와지속적인경과관찰이필요하겠으나이전에치료받은유방에서의감시림프절생검술도가능하다고생각하며, 2005년 ASCO 지침을무분별하게그대로따르는것은개선의소지가있는것으로보인다. 유방보존술후국소재발한유방암의치료에대해서는여전히논쟁의여지가있겠으나, 위에서살펴본바와같이유방보존술과액와림프절절제술, 혹은이에더하여방사선치료를받은환자의경우에도감시림프절생검술이시도될소지가있다고생각된다. 국소재발한유방암에서림프관조영스캔을시행하지않거나, 전통적인유방수술만시행했을경우이전의치료로인한림프절경로변경에따른다른부위로의림프절전이를놓칠수있으므로

310 Wan Wook Kim, et al. 감시림프절생검술을꼭시행하도록하고, 생물학적염표로만사용하여감시림프절생검술을시행할경우액와부이외에감시림프절을놓칠수있으므로, 이런경우에는반드시방사선동위원소를이용한유방림프관조영스캔으로감시림프절의위치를확인하고, 감마선검출기탐식자로내유림프절및반대측액와부림프절을포함하여탐색하고감시림프절생검술을시행해야할것으로생각된다. 참고문헌 1. Kennedy MJ, Abeloff MD. Management of locally recurrent breast cancer. Cancer 1993;71:2395-409. 2. Bethke KP. Breast conservation: predictors and treatment of local recurrence. Semin Surg Oncol 1996;12:332-8. 3. Gentilini O, Botteri E, Rotmensz N, Santillo B, Peradze N, Saihum RC, et al. When can a second conservative approach be considered for ipsilateral breast tumour recurrence? Ann Oncol 2007;18:468-72. 4. Kurtz JM, Jacquemier J, Amalric R, Brandone H, Ayme Y, Hans D, et al. Is breast conservation after local recurrence feasible? Eur J Cancer 1991;27:240-4. 5. Salvadori B, Marubini E, Miceli R, Conti AR, Cusumano F, Andreola S, et al. Reoperation for locally recurrent breast cancer in patients previously treated with conservative surgery. Br J Surg 1999;86:84-7. 6. Taback B, Nguyen P, Hansen N, Edwards GK, Conway K, Giuliano AE. Sentinel lymph node biopsy for local recurrence of breast cancer after breast-conserving therapy. Ann Surg Oncol 2006;13:1099-104. 7. Luini A, Galimberti V, Gatti G, Arnone P, Vento AR, Trifirò G, et al. The sentinel node biopsy after previous breast surgery: preliminary results on 543 patients treated at the European Institute of Oncology. Breast Cancer Res Treat 2005;89:159-63. 8. Port ER, Fey J, Gemignani ML, Heerdt AS, Montgomery LL, Petrek JA, et al. Reoperative sentinel lymph node biopsy: a new option for patients with primary or locally recurrent breast carcinoma. J Am Coll Surg 2002;195:167-72. 9. Sood A, Youssef IM, Heiba SI, El-Zeftawy H, Axelrod D, Seigel B, et al. Alternative lymphatic pathway after previous axillary node dissection in recurrent/primary breast cancer. Clin Nucl Med 2004; 29:698-702. 10. Koizumi M, Koyama M, Tada K, Nishimura S, Miyagi Y, Makita M, et al. The feasibility of sentinel node biopsy in the previously treated breast. Eur J Surg Oncol 2008;34:365-8. 11. Veronesi U, Banfi A, Del Vecchio M, Saccozzi R, Clemente C, Greco M, et al. Comparison of Halsted mastectomy with quadrantectomy, axillary dissection, and radiotherapy in early breast cancer: long-term results. Eur J Cancer Clin Oncol 1986;22:1085-9. 12. Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, et al. Twenty-year follow-up of a randomized study comparing breastconserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:1227-32. 13. Fisher B, Anderson S, Fisher ER, Redmond C, Wickerham DL, Wolmark N, et al. Significance of ipsilateral breast tumour recurrence after lumpectomy. Lancet 1991;338:327-31. 14. Haffty BG, Reiss M, Beinfield M, Fischer D, Ward B, McKhann C. Ipsilateral breast tumor recurrence as a predictor of distant disease: implications for systemic therapy at the time of local relapse. J Clin Oncol 1996;14:52-7. 15. Komoike Y, Motomura K, Inaji H, Kasugai T, Koyama H. Repeat lumpectomy for patients with ipsilateral breast tumor recurrence after breast-conserving surgery. Preliminary results. Oncology 2003;64:1-6.