09-057

Size: px

Start display at page:

Download "09-057"

을동 위
5 years ago
Views:

1 ORIGINAL ARTICLE Journal of Breast Cancer J Breast Cancer 2010 March; 13(1): DOI: /jbc 피부보존유방전절제술에서유두 - 유륜복합체의보존유무에따른종양학적안정성 : 5 년추적관찰결과 전영산ㆍ강수환ㆍ배영경 1 ㆍ이수정 영남대학교의과대학외과학교실 1 병리학교실 The Oncologic Safety of Skin Sparing Mastectomy with or without Conservation of the Nipple-areolar Complex: 5 Years Follow up Results Young San Jeon, Su Hwan Kang, Young Kyung Bae 1, Soo Jung Lee Departments of Surgery and 1 Pathology, Yeungnam University College of Medicine, Daegu, Korea Purpose: Little is known about long term results of nippleareola preserving skin-sparing mastectomy (NASSM), and there are no such reports on this from South Korea. We studied 5 years follow up results of NASSM and skin sparing mastectomy (SSM) and compared clinical outcomes between NASSM and SSM. Methods: Two hundred two patients who underwent SSM (69 patients) or NASSM (133 patients) from September 1996 to December 2006 were included. Frozen section analysis of retroareolar resection margin was done to make the decision on preserving or not preserving nippleareolar complex (NAC). In the case of positive result on the frozen section, NAC was sacrificed. The local relapse (LR) rate and local relapse free survival (LFS) were analyzed for comparing between NASSM and SSM. Results: The mean age was 40.2 years (range, 24-65), the mean follow-up was 67.6 months. 52 NACs (25.7%) were involved by tumor cells. The invasion to the NAC by tumor cell was more common for invasive carcinoma with extensive intraductal component (p<0.001), central located tumor (p=0.025) and invasive carcinoma with multiplicity (p=0.001). There were 12 cases (9.0%) of local relapse in NASSM group and 4 (5.8%) in SSM group, but there was no significant correlation for the LR rate (p>0.05). Regional or distant recurrence after surgical treatment for local relapse occurred in only one SSM case. Five years LFS rate of the NASSM group was 92.1% and that of the SSM group was 95.2%. There was no significant difference for the LFS (p>0.05). Conclusion: Our long term follow up study showed that NASSM and SSM are much alike for their LR rate and LFS. Even if relapse occurs in the NAC, this recurrence cannot affect the progression of relapse after adequate local treatment. Thus, NASSM is alternative method for SSM with oncological safety and better cosmetic outcome. Key Words: Breast, Carcinoma, Mastectomy, Nipples, Prognosis 중심단어 : 유방, 암, 유방절제술, 유두, 예후 서 론 책임저자 : 이수정 대구광역시남구대명5동 317-1, 영남대학교의과대학외과학교실 Tel: , Fax: crystallee@medical.yu.ac.kr 접수일 : 2009년7월 10일게재승인일 : 2009년 9월 21일본논문은 2008년춘계유방암학회에서구연발표되었음. 유방암의수술적치료로는확대근치적유방전절제술부터유방보존술식까지다양하다. 그중에서도현재유방보존술식은유방암의치료에있어서기본적인술식으로인식되고있고대부분의기관에서많이시행되고있다. 그러나병소가다발성또는광범위한경우, 미만성석회화를동반한경우, 유방의부피에비해종양 65

66 Young San Jeon, et al. 이너무커유방보존술식후유방모양의심각한변형이예상되는경우, 방사선치료의금기사항이있는경우, 환자가원하지않는경우등에는유방전절제술을피할수없다.

SSM 의술식은대부분의피부및피하지방은보존하면서유두 -유륜복합체와피하지방아래의유방실질은모두제거한후즉시재건술을시행하는방법으로수술후유두 -유륜복합체의재건및색소문신을이용하여미용효과를극대화하는방법이다. 그러나재건된유두-유륜복합체의만족도는그리높지않다.

(3) 이에시대가변함에따라젊은유방암환자들을중심으로미적요구도증가되면서이를충족하기위해개발된새로운술식이유두-유륜복합체및피부보존유방전절제술 (nipple-areolar preserving skin-sparing mastectomy, NASSM) 이며여러기관에서유두-유륜복합체절단면에대한수술중동결절편검사를이용하여많이시도되고있다.

이에본연구는 SSM 또는 NASSM 후즉시유방재건술을시행한환자를대상으로유두-유륜복합체의암세포침윤빈도와위험인자를분석하고수술중유두 -유륜복합체절단면에대한동결절편검사의정확도와이에따른유용성을알아보고자하였으며 5년이상의장기적인평균추적관찰기간을통해 SSM 과 NASSM 의국소재발양상과재발률및무병생존율을비교분석하고자수행되었다.

2 66 Young San Jeon, et al. 이너무커유방보존술식후유방모양의심각한변형이예상되는경우, 방사선치료의금기사항이있는경우, 환자가원하지않는경우등에는유방전절제술을피할수없다. 과거부터유방전절제술을시행해야하는경우유방의모양을복원하여환자의만족도를높이기위한많은노력이있었으며그중하나가 1962년 Freeman(1) 에의해처음시도되었고, 1991년 Toth와 Lappert(2) 에의해정의및기본개념이정립된피부보존유방전절제술 (skin-sparing mastectomy, SSM) 후즉시재건술이다. SSM 의술식은대부분의피부및피하지방은보존하면서유두 -유륜복합체와피하지방아래의유방실질은모두제거한후즉시재건술을시행하는방법으로수술후유두 -유륜복합체의재건및색소문신을이용하여미용효과를극대화하는방법이다. 그러나재건된유두-유륜복합체의만족도는그리높지않다. 한보고에의하면재건된환자의 16% 만이자신의재건된유두에만족하였으며나머지는반복적시술, 불만족스러운유두의모양, 색상, 크기, 위치등의이유를들어자신의유두-유륜복합체에대해만족하지못한다고하였다.(3) 이에시대가변함에따라젊은유방암환자들을중심으로미적요구도증가되면서이를충족하기위해개발된새로운술식이유두-유륜복합체및피부보존유방전절제술 (nipple-areolar preserving skin-sparing mastectomy, NASSM) 이며여러기관에서유두-유륜복합체절단면에대한수술중동결절편검사를이용하여많이시도되고있다. 그러나 NASSM의우수해진미용효과와단기적인근치적수술로서의안정성은여러연구에서보고된것에반해 5년이상의장기예후에대한보고는 SSM 에비해그수가매우제한적이다. 더욱이서양의유방암평균발생연령보다더낮다고알려져있는한국에서의보고는전혀없는실정이다. 이에본연구는 SSM 또는 NASSM 후즉시유방재건술을시행한환자를대상으로유두-유륜복합체의암세포침윤빈도와위험인자를분석하고수술중유두 -유륜복합체절단면에대한동결절편검사의정확도와이에따른유용성을알아보고자하였으며 5년이상의장기적인평균추적관찰기간을통해 SSM 과 NASSM 의국소재발양상과재발률및무병생존율을비교분석하고자수행되었다. 방법대상 1996년 9월부터 2006년 12 월까지유방암으로진단받은환자중내원시임상적으로액와부임파선이만져지지않고육안적또는영상학적으로유두-유륜복합체에암의침윤및이상소견이없으며, 6th American Joint Committee on Cancer (AJCC) 분류를토대로임상적 T병기가 Tis, 1기, 2기이고 N병기는 0기, 1기인환자중본원에서 SSM 또는 NASSM 후즉시유방재건술을시행한 202 명의환자를대상으로하였다. 방법피부보존유방전절제술은본원의단일외과의에의해서, 즉시재건술은 2명의성형외과의에의해시행되었다. 피부절개는유륜주위를반구모양으로절개한후절개선의양끝단을중심으로외측과내측으로약 4 cm 가량연장하는횡절개를주로시행하였다. 유방보존술식후절단면의암침윤으로수술술기가피부보존유방전절제술로변경된경우에는유방보존술식시의방사형절개면을그대로이용하여피부보존유방전절제술을시행하였다.(4) 피부보존유방전절제술은수술후피부괴사의방지를위해피하지방과유방실질과의경계를따라시행하여불필요한피하지방의제거없이최소약 1 cm 두께의피하지방을남기고유방실질을모두제거하였으며이는피하지방을충분히남기는것과피부를더많이남긴다는것외에는변형유방전절제술시의수술과크게다르지않았다. 유두-유륜복합체및피부보존유방전절제술을시행함에있어서가장중요한수술술기상의문제는유두-유륜으로의혈행을보존하는것이다. 본저자들은유두-유륜부의혈액공급은주로유방실질의전방부피하지방내의혈행에의해공급된다 (5,6) 는이론적배경을바탕으로남겨지는피부쪽의피하지방두께와동일한두께로유륜하부의유방실질을남겨서피하지방으로부터유두 -유륜부로유입되는혈관의노출을방지하였다 (Figure Dissection line Mammary gland Subcutaneous adipose tissue 3 mm 2-3 mm <1 mm A C D Figure 1. Dissection line of mastectomy and frozen section analysis of nipple-areolar resection margin. (A) A flap of subcutaneous adipose tissue (more than 1 cm thickness) was created and nipple-areolar resection margin was inked by blue ink and then, blue inked resection margin was sliced in 2-3 mm interval with perpendicularly 5 mm thickness.(b) In (C) case, the distance from resection margin to tumor cells was 3 mm. So, nipple-areolar complex could be preserved. But, if the distance was less than 2 mm (D), nipple-areolar complex was removed (C, D, H&E stain, 10). B

3 Prognosis of Nipple-areola Preserving Skin Sparing Mastectomy 67 1A). 특히, 피하지방과유륜하부의유방실질이만나는부위대한수술은매우조심스럽게시행되었으며수술도중혈관이노출된경우에는세심한박리를통해유륜부로유입되는혈관을보존하여시행하였다. 액와부임파선절제술은침윤성암의경우감시림프절생검술을시행하였으며액와부임파선에대한동결절편검사상 4개이상의임파선전이가확인된경우지연유방재건술로재건방법을변경하였으며이경우본연구의대상환자에서는제외하였다. 관상피내암의경우에는수술전조직검사결과와종양의크기에따라감시림프절생검술을하거나시행하지않았다. 유륜하부의유방실질에대한절단면검사는절단면을청색염료로색칠한후 2-3 mm 간격으로수직으로절단면을잘라동결절편검사를시행하여암침윤여부를확인하였으며절단면에암침윤이존재할경우또는절단면과암침윤과거리가 2 mm 이내일경우유두-유륜복합체를 cm 가량주위정상유방피부조직을포함하여절제하였다 (Figure 1). 즉시재건술은영구유방삽입물, 광배근근피판, 횡복직근근피판등을사용하여재건하였다. 수술후림프절에전이된경우와 T2 이상의병변에대해서는보조항암화학요법을시행하였고호르몬수용체의발현이있는경우호르몬억제요법을시행하였으나방사선치료는시행하지않았다. 유두-유륜복합체의암세포침윤에영향을미치는위험인자분석은암의침윤성여부, 평균나이, 광범위관내상피암성분 (extensive intraductal component, EIC) 동반유무, 혈관침윤유무, 조직분화도, 에스트로겐수용체 (estrogen receptor) 발현유무, 다발성유무, 종양의크기, 임파선전이유무, 종양의위치등을의무기록과병원전산화시스템을이용하여후향적으로조사하여유두-유륜복합체의암세포침윤과위험인자사이의상관관계를분석하였다. EIC 는침윤성유방암에서관상피내암이전체종양의 25% 이상차지할때로정의하였으며조직분화도는 Scarff- Bloom-Richardson분류법에따라저분화와중분화또는고분화암으로분류하였다. C-erbB2는면역조직화학염색법을이용해종양세포의 30% 이상이염색된경우를과발현양성으로정의하였다. 종양의다발성은종양의개수가 2개이상일때로정의하였으며종양의크기는 2 cm 를기준으로그이하와초과로나누어분석하였다. 종양의위치는중심부또는미만성인경우와그렇지않은경우로나누었다. 수술후추적관찰은 6개월마다이학적검사, 초음파, 유방촬영술을주로사용하여추적관찰및국소재발여부를검사하였다. 국소재발이의심되는경우에는세침검사, 핵침생검 (core needle biopsy), 절제생검술등의조직검사를통해확진하였다. 통계분석통계처리는 SPSS for Window 12.0 (SPSS Inc., Chicago, USA) 을사용하였으며두군사이의평균비교는 independentsamples T test 방법을사용하였고유두-유륜복합체의암세포침윤에영향을미치는위험인자와수술방법에따른재발률분석은 Pearson chi-square test 방법및 Fisher s exact test 방법으로분석하였다. 수술방법에따른무병생존율분석은 Kaplan- Meier 방법에의해분석하였다. 통계학적유의성검정은 p값이 0.05 미만인경우를유의한것으로평가하였다. 대상환자의특성 결 전체대상환자 202 예중 NASSM 은 133 예 (65.8%), SSM 은 Cases 133 (65.8%) 69 (34.2%) 202 Mean FU (months) Mean age (yr) Mean tumor size (cm) Chemotherapy No 55 (39.9%) 38 (55.1%) 93 (46.0%) Yes 78 (60.1%) 31 (44.9%) 109 (54.0%) Hormone therapy No 34 (25.6%) 14 (20.3%) 48 (23.8%) Yes 99 (74.4%) 55 (79.7%) 154 (76.2%) Poorly differentiation* No 41 (50.6) 21 (58.3) 62 (53.0) Yes 40 (49.4) 15 (41.7) 55 (47.0) Unknown ER positivity Negative 38 (29.2%) 17 (25.0) 55 (27.8%) Positive 92 (70.8%) 51 (75.0) 143 (72.2%) Unknown C-erbB2 overexpression No 100 (77.5%) 45 (66.2%) 145 (73.6%) Yes 29 (22.5%) 23 (33.8%) 52 (26.4%) Unknown Vascular invasion* No 51 (52.6%) 26 (59.1%) 77 (54.6%) Yes 46 (47.4%) 18 (40.9%) 64 (45.4%) Unknown T stage (25.6%) 22 (27.7%) 56 (27.7%) I 67 (50.3%) 34 (50.0%) 101 (50.0%) II 32 (24.1%) 13 (22.3%) 45 (22.3%) N stage (78.9%) 58 (84.1%) 163 (80.7%) I 28 (21.1%) 11 (15.9%) 39 (19.3%) NASSM=nipple-areola preserving skin sparing mastectomy; SSM= skin sparing mastectomy; FU=follow up; ER=estrogen receptor. *In the patient with invasive cancer. 과 Table 1. Characteristics of patients NASSM SSM Total p-value

4 68 Young San Jeon, et al. 69예 (34.2%) 에서시행되었다. 진단당시의평균나이는 40.2세 (24-65세) 였으며 NASSM 시행환자의평균나이는 40.2세, SSM 시행환자의평균나이는 40.1세로수술방법에따른평균나이의차이는없었다 (p>0.05). 대상환자전체의평균추적관찰기간은 67.6개월 (±28.8) 이었으며 NASSM군의평균추적관찰기간은 71.4개월 (±29.1), SSM군은 60.2개월 (±26.8) 였다. 종양의평균크기는 2.0 cm ( cm) 였고, 임파선전이는전체환자의 39예 (19.3%) 에서전이가있었으며전이된임파선의평균개수는 1.51개 (1-3개) 였다. 병기분포는관상피내암이 56 예 (27.7%), 1기가 78 예 (38.6%), 2기가 68 예 (33.7%) 였다. NASSM군과 SSM군사이의평균나이, 평균종양크기, 수술후보조치료요법, 에스트로겐수용체양성률, c-erbb2의과발현동반유무, 종양의혈관침윤유무, T병기, N병기등에서의차이는없었다 (Table 1). 유두-유륜복합체의암세포침윤위험인자분석전체대상 202예중유두 -유륜복합체에암세포침윤이확인된예는 52예 (25.7%) 였다. 이중관상피내암으로수술을시행한경우침윤성암으로수술을시행한경우보다유두-유륜복합체의암세포침윤이많았다 (p=0.045). 그외에나이, 호르몬수용체발현유무는암세포침윤에영향을미치지못하였으며 (p>0.05), 종양의위치가중심부또는미만성인경우 41.9% 에서, 그렇지않은경우는 22.8% 에서유두 -유륜복합체의암세포침윤이발견되어중심부또는미만성일때암세포침윤이통계학적으로의미있게더많았다 (p=0.025). 침윤성병변 146예를대상으로시행한분석에서는 32 예 (21.9%) 에서암세포침윤이확인되었으며병소가다발성인경우 (p=0.001) 와광범위관내상피암성분을동반하는경우 (p<0.001) 에는유두 -유륜복합체의암세포침윤이유의있게많았지만혈관침윤유무, 임파선전이유무, 종양의크기, 조직학적분화도는영향을미치지못하였다 (p>0.05) (Table 2). 유두-유륜복합체절단면의동결절편검사에대한분석유두-유륜복합체절단면에대한동결절편검사는모든예에서시행되었다. 동결절편검사에서절단면의종양침윤에대해양성으로보고된예는총 202 예의대상중 50 예에서양성으로보고되었으며최종보고서에서도모두절단면에종양세포를확인할수있었다. 동결절편검사에서음성으로보고된예는 152 예였으며이중최종보고서에서양성으로보고된예는 2예였으며이경우추가적으로국소마취하에유두-유륜복합체를절제하였다. 최종보고서에서절단면이양성으로보고된 52 예중 2예가동결절편검사상위음성의결과를보고하여절단면의동결절편검사에대한위음성률은 3.9% 였다. 국소재발빈도와국소재발의특징에대한분석 총대상환자 202명중관찰기간동안발생한국소재발은총 16예였다. 이중 NASSM군에서 12예 (9.0%), SSM군에서 4예 (5.8%) 발생하였으며두군사이의수술방법에따른국소재발률은유의한차이가없었다 (p=0.585). 국소재발에대한 5년무병생존율 (5 year local relapse free survival) 은 NASSM인경우 92.1%, SSM인경우 95.2% 이었으며수술방법에따른국소재발에대한무병생존율또한유의한차이를보이지않았다 (p= 0.652) (Figure 2). 국소재발에영향을미치는인자는환자의나이가 35 세이하인경우 (p=0.038) 와다발성종양인경우 (p=0.002), 침윤성종양의 Table 2. Risk factors of the neoplastic involvement in the nippleareolar complex Variables No. of neoplastic involvement (%) No. of nonneoplastic involvement (%) p-value Total cases 52 (25.7) 150 (74.3) Mean age Invasiveness DCIS 20 (35.7) 36 (64.3) Invasive 32 (21.9) 114 (78.1) Tumor location Central or diffuse 13 (41.9) 18 (58.1) Other site 39 (22.8) 132 (77.2) Estrogen receptor Positive 36 (25.2) 107 (74.8) Negative 15 (27.3) 40 (72.7) Unknown 1 (25.0) 3 (75.0) Invasive cases 32 (21.9) 114 (78.1) Involvement of ALN No 26 (24.3) 81 (75.7) Yes 6 (15.4) 33 (84.6) Poorly differentiation No 14 (22.6) 48 (77.4) Yes 11 (20.0) 44 (80.0) Unknown 7 (24.1) 22 (75.9) Coexistence with EIC <0.001 No 5 (6.8) 68 (93.2) Yes 27 (37.0) 46 (63.0) Vascular invasion No 15 (21.7) 54 (78.3) Yes 13 (20.3) 51 (79.7) Unknown 4 (30.8) 9 (69.2) Multiplicity <0.001 No 21 (16.8) 104 (83.2) Yes 11 (52.4) 10 (47.6) Tumor size cm 6 (13.0) 40 (87.0) >2 cm 26 (26.0) 74 (74.0) DCIS=ductal carcinoma in situ; ALN=axillary lymph node; EIC=extensive intraductal component.

5 Prognosis of Nipple-areola Preserving Skin Sparing Mastectomy 69 크기가 2 cm 보다큰경우 (p=0.017) 등이통계학적인유의성이있었으며그외에혈관침윤, 종양의크기, 임파선전이유무, c- erbb-2 과발현유무, 조직학적분화도, 종양의위치등은영향을미치지못하였다 (p>0.05) (Table 3). 그러나, 국소재발에영향을미치는인자인환자의나이가 35 세이하인경우, 다발성종양인경우, 침윤성종양의크기가 2 cm 보다큰경우에대해각각분석한 NASSM군과 SSM군사이의국소재발에대한무병생존율은유의한차이를보이지않았다 (p>0.05) (Table 4). NASSM을시행한경우, 국소재발한 12예의병기에따른분포는관상피내암이 5예, 1기가 4예, 2기가 3예였다. 국소재발장소는유두-유륜복합체가 8예였으며피부재발이 4예였다. 유두- 유륜복합체에재발한 8예의재수술은 5예에서는유두-유륜복합체를포함한변연절제술을시행하였으며 3예에서는환자가모두제거하기를원해변형근치적유방절제술에준하여유두-유륜복합체를포함한피부및피하지방을모두제거하였다. 피부에재발한 4예의재수술은병변을포함한변연절제술이 3예에서시행되었으며 1예에서는변형근치적유방절제술에준하여시행되었 Local relapse free survival rate p =0.652 Method of operation NASSM SSM Months Figure 2. Local relapse free survival curves of breast cancer patients operated by NASSM vs. SSM. The curve shows that there was no significant difference in the survivals. NASSM=nipple areola preserving skin sparing mastectomy; SSM=skin sparing mastectomy. Table 4. Comparison of 5-yr LRFS between NASSM and SSM according to risk factors of local relapse 5-yr LRFS of NASSM (%) 5-yr LRFS of SSM (%) p- value Age Tumor size >2 cm Multiple tumors yr LRFS=5-yr local relapse free survival; NASSM=nipple-areola preserving skin sparing mastectomy; SSM=skin-sparing mastectomy. 다. 국소재발한 12 예의첫수술후국소재발까지의평균기간은 45.4개월이었으며, 재수술후 44.3개월의평균추적관찰기간동안추가적인국소재발및진행된재발소견을보인예는한예도없었다. SSM 을시행한경우, 국소재발한 4예의병기는모두 1기였으며재발장소는 4예모두피부재발이었다. 재수술은모든예에서병변을포함한변연절제술이시행되었으며첫수술후국소재발까지의평균기간은 35.0개월이었다. 재수술후관찰기간동안 3예에서는추가적인재발소견을보이지않았지만 1예에서는재수술후 24 개월째에폐와간으로의원격전이가발생하였으며이로인해첫수술후 66 개월째사망하였다 (Table 5). Table 3. Clinicopathologic features influencing to local relapse Features No. of cases with local relapse (%) No. of cases without local relapse (%) p-value Total cases 16 (7.9) 186 (92.1) Operation 0.585* NASSM 12 (9.0) 121 (91.0) SSM 4 (5.8) 65 (94.2) Age (14.3) 48 (85.7) >35 8 (5.5) 138 (94.5) Tumor location 0.475* Central or diffuse 1 (3.2) 30 (96.8) Other site 15 (8.8) 156 (91.2) Estrogen receptor 0.796* Positive 12 (8.4) 131 (91.6) Negative 4 (7.3) 51 (92.7) Unknown 0 (0.0) 4 (100) Invasive cases 11 (7.5) 135 (92.5) Tumor size 0.017* 2 cm 0 (0.0) 46 (100) >2 cm 11 (11) 89 (89.0) Nodal status 0.965* Positive 3 (7.7) 36 (92.3) Negative 8 (7.5) 99 (92.5) Coexistence with EIC No 5 (6.8) 68 (93.2) Yes 6 (8.2) 67 (91.8) Vascular invasion No 5 (7.2) 64 (92.8) Yes 5 (7.8) 59 (92.2) Unknown 1 (7.7) 12 (92.3) Multiplicity No 6 (4.8) 119 (95.2) Yes 5 (23.8) 16 (76.2) Poorly differentiation 0.873* No 5 (8.1) 57 (91.9) Yes 4 (7.3) 51 (92.7) Unknown 2 (6.9) 27 (93.1) NASSM=nipple-areola preserving skin sparing mastectomy; SSM= skin-sparing mastectomy; EIC=extensive intraductal component. *Fisher s exact test.

6 70 Young San Jeon, et al. Table 5. Characteristics and clinical outcomes of the patient with local relapse Case Stage Site of LR LRFI (mo) 2nd Op Adjuvant therapy after 2nd Op Progress after 2nd Op Alive or death FU (mo) Nipple areolar preserving skin sparing mastectomy 1 0 NAC 55 Wide excision None No Alive NAC 54 Wide excision None No Alive NAC 34 Wide excision None No Alive NAC 5 Wide excision None No Alive NAC 24 Wide excision None No Alive 49 6 I NAC 66 Mastectomy None No Alive I Skin 37 Wide excision CTx No Alive I Skin 100 Wide excision RTx+CTx No Alive I NAC 43 Mastectomy CTx No Alive II Skin 30 Mastectomy None No Alive II NAC 71 Mastectomy None No Alive II Skin 26 Wide excision CTx No Alive 31 Skin sparing mastectomy 1 I Skin 38 Wide excision RTx+CTx Yes Death 66 2 I Skin 15 Wide excision CTx No Alive 89 3 I Skin 64 Wide excision CTx No Alive 69 4 I Skin 23 Wide excision RTx+CTx No Alive 54 LR=local relapse; LRFI=local relapse free interval; mo=months; Op=operation; FU=follow up; NAC=nipple-areolar complex; CTx=chemotherapy; RTx=radiotherapy. 유두-유륜복합체의괴사빈도총 133예의 NASSM 수술중 3예 (2.3%) 에서괴사가발생하였다. 이중 2예 (1.5%) 는부분괴사로괴사발생약 30 일경과후 2예모두에서괴사로부터완전회복되었다. 그러나 1예 (0.8%) 는완전괴사로진행하여유두-유륜복합체를제거후 SSM 으로수술이전환되었다. 고찰고식적인변형근치적유방절제술에비해 SSM 의가장큰이점은유방실질을싸고있는피부및피하지방과유방하단주름선 (inframammary fold) 의보존후즉시유방재건술을시행함으로써보다자연스럽고미용적으로우수한유방모양을재건할수있다는것이다. 과거에는피부를추가적으로남김으로인해유방암의근치적수술로의안전성에의구심이있어유방암의고위험군에대해예방적인전절제술의목적으로주로시행되었다. 그러나, 고식적인변형근치적유방절제술에비해 SSM 의장기국소재발률이높지않음이많은연구들에의해보고되었으며,(7-9) 그후 SSM 은유방보존술식의적응증이되지않는유방암환자들을대상으로많이시행되어왔다. 그러나 SSM 의술식은유두-유륜복합체를완전절제하는술식이다. 이에따라우울증등의정신과적문제가증가되고 (10) 유두재건술이라는 2차적인수술을필요로 하며재건술을하더라도반복적인색소문신과재건된유두의불만족등으로인해 NASSM이라는술식이시행되기시작하였다. SSM에비해 NASSM을꺼리게되는주요원인은유두 -유륜복합체의암세포에의한침윤위험성때문이다. 유방전절제술을시행한표본으로조사한연구들에의하면유두-유륜복합체의암세포침윤은 5-38% 까지다양하게보고하고있으며, 종양의위치, 종양의크기, 다발성유무, 액와부임파선침범유무, 광범위관내상피암성분동반유무등이유두 -유륜복합체의종양침윤에영향을미친다고하였다.(11-15) 본연구에서의암세포침윤빈도는 25.7%, 침윤성암만을대상으로하였을경우 21.9% 로다른보고들과유사하였으며종양이다발성으로존재할경우, 종양의위치가중앙또는미만성일경우, 광범위관내상피암성분동반할경우유두-유륜복합체의암침윤빈도가높았다. 그러나, 종양의크기와액와부임파선침범이암침윤빈도에영향을주지못하였는데그이유는본연구대상환자의병기가 2기이하인경우를대상으로하였으므로종양의평균크기가 2.0 cm이고 4 cm보다큰경우가 3예밖에없었으며임상적으로임파선전이가의심되지않는환자를대상으로하였기때문으로생각된다. 그리고침윤성암에비해관상피내암으로수술한경우유두-유륜복합체의암침윤빈도가높았는데이또한관상피내암이다발성또는미만성석회화를동반하는경우유방전절제술을시행한다는일반적인적응증에따라시행하였기때문으로생각된다.

7 Prognosis of Nipple-areola Preserving Skin Sparing Mastectomy 71 수술전유두 -유륜복합체의암세포침윤을알기위해 Govindarajulu 등 (16) 은맘모톰시술로, Palmieri 등 (17) 은수술적생검술로미리검사를하여 NASSM 가능여부를검사하자고하였으며, Friedman 등 (18) 은자기공명영상촬영 (magnetic resonance imaging, MRI) 이침윤여부를정확히파악할수있다고하여 NASSM 시행전 MRI로검사할것을주장하였다. 그러나 Petit 등 (19) 은수술전이학적검사및초음파검사와수술중유륜하부유방실질의절단면에대한동결절편검사로충분히유두- 유륜복합체의암세포침윤여부를파악할수있다고하였으며, 본연구에서도 3.9% 의낮은위음성률로동결절편검사를시행할수있었고대부분의예에서피부보존유방전절제술이끝나기전에동결절편검사에대한결과를보고받을수있었다. 그러므로동결절편검사가가능하다면수술전침습적인검사는불필요할것으로생각되며일률적으로모든환자에서 MRI 를시행하기보다는앞에서언급한유두-유륜복합체의암세포침윤위험성이매우높으며수술전에미리수술방법을결정해야하는한정적인경우에만시행하는것이바람직할것이다. 그리고, 본연구의분석에의하면추적관찰기간동안 NASSM을포함한피부보존유방전절제술의국소재발률은 7.9% 로나타났으며나이가 35 세이하인경우와다발성인경우, 종양의크기가큰경우등이국소재발에영향을미쳤으므로이런경우쿠퍼씨인대를따라피하지방까지연결되어있는소량의유방실질과유두-유륜복합체의암침윤여부를파악하기위해 MRI 등의수술전검사가도움이될것으로사료된다. SSM 시행후 60 개월이상의장기추적관찰을통한국소재발률에대한결과는많이보고되어있다. AJCC 병기분류법에의해 0-2 기로판명된조기유방암환자를대상으로변형근치적유방절제술과 SSM 의국소재발률을비교분석한연구들에의하면 SSM 의국소재발률은 %, 변형근치적유방절제술의국소재발률은 % 로나타나 SSM과변형근치적유방절제술의장기국소재발률은유사함을보고하였으며,(7,8,20,21) 본연구에서도 SSM 의국소재발률은 5.8% 로나타났다. 따라서, 유방보존술식이불가능한조기유방암을대상으로 SSM 을시행하는경우 SSM 의근치적수술로서의안정성은확립되어있다. 그러나 NASSM의경우 SSM에비해장기추적관찰을통한국소재발률에대한보고는매우드물다. Caruso 등 (22) 은 0-2 기의환자를대상으로 NASSM 시행후 66 개월의평균추적관찰기간동안 2.2% 의국소재발률을보고하였고, Gerber 등 (20) 은 0-2기의환자를대상으로 101 개월의평균추적관찰기간동안 10.0% 의국소재발률을보고하였다. 특히 Gerber 등 (20) 은 SSM과 NASSM, 변형근치적유방절제술사이의장기추적관찰을통한국소재발률을비교하였으며 SSM 의국소재발률은 10.4%, 변형 근치적유방절제술의국소재발률은 11.5% 로보고하여세가지술식사이의국소재발률은차이가없음을주장하였다. 동양인을대상으로 NASSM의국소재발에대한장기예후를분석한연구는 Teruhisa 등 (23) 의연구가유일하다. 이들은 87 개월의평균추적관찰기간을통해 NASSM과변형근치적유방절제술의국소재발률및생존율을분석하여비교하였으며 NASSM의국소재발률은 8.2%, 변형근치적유방절제술의국소재발률은 7.6% 로보고하였으며두술식사이에서국소재발률의차이는없음을주장하였다. 본연구에서도 NASSM군에서 9.0% 의국소재발률을보여 Teruhisa 등의연구와유사한국소재발률을보였으나, SSM 군과의비교에서는 Gerber 등 (20) 의연구결과와는다르게 SSM 군에서 5.8% 의국소재발률을보여 NASSM군에서국소재발의빈도가높게나타났으나통계학적인유의성은관찰되지않았다 (p=0.59). 국소재발을낮추기위한수술후보조적치료로방사선치료의효과는잘알려져있다. Petit 등 (19) 은 579예의 NASSM을시행한환자를대상으로유두-유륜복합체아래에남겨진유방실질에대한수술중방사선치료를시행후즉시재건술을시행하였으며추적관찰기간동안 NAC 에발생한재발은없었다고하였다. Benediktsson과 Perbeck 등 (24) 의보고에서도 NASSM의국소재발률은방사선치료를시행한경우 8.5%, 시행하지않은경우 28.4% 라고하였으며 NASSM 후방사선치료의필요성을주장하였다. 그러나방사선치료에의한이식편또는영구유방삽입물에대한합병증은이들보고에서는자세히기술되어있지않다. 문헌고찰에의하면즉시재건술후방사선치료에의한합병증에대한결과는회의적이다. Barreau-Pouhaer 등 (25) 에의하면방사선치료를시행한경우영구유방삽입물을제거해야하는경우가시행하지않는경우에비해 27 배높다고하였으며, Victor 등 (26) 은방사선치료에의해심각한미용상의문제가생긴다고하였다. Williams 등 (27) 은횡복직근근피판을이용하여재건후방사선치료를시행한경우이식편제거, 지방괴사, 부피의감소, 섬유화등의합병증이흔하게동반된다고하였다. 따라서본연구의대상환자도수술후방사선치료가필요없는 T병기가 Tis, 1기, 2기이고 N병기는 0기, 1기인환자를대상으로하였으며수술후국소재발을줄이기위한방사선치료는시행하지않았다. 따라서, 합병증의발생증가없이방사선치료를시행할수있다면가장이상적인치료가될것이며이러한방법에대한연구가필요할것으로사료된다. 유두 -유륜복합체에재발한경우수술적치료로 Teruhisa 등 (23) 은 29 예의재발예에서유두-유륜복합체를포함한단순변연절제술을시행하였고재수술후 5년무병생존율은 93% 라고보고하면서피부에발생한국소재발보다예후가좋다고하였다. 본

8 72 Young San Jeon, et al. 연구에서도 8예의유두 -유륜복합체에발생한국소재발중 5예에서수술적치료로유두-유륜복합체를포함하여약 1 cm 의피부변연을확보후절제하였으며재수술후 46.0개월의평균추적관찰기간동안추가적인재발이나원격전이는발견되지않았다. 결론본연구결과, 미용효과를위해유두-유륜복합체를남김으로써생길수있는유방암의근치적수술로서의안정성에대한문제는없었다. 그리고비록유두-유륜복합체에재발하여단순변연절제술을시행한대상환자가 5예에불과하지만, 유두-유륜복합체에국소재발을하더라도비교적간단한수술로좋은예후를얻을수있었다. 그러므로 SSM 을시행할유방암환자중동결절편검사등을통해 NAC 의보존이가능하다면환자의삶의질향상을위해 NASSM을시행하는것도좋은방법이라생각된다. 그러나 NASSM의수술적응증은아직까지정확히정립되지않고있으며유두-유륜복합체에재발한환자의단순변연절제술에대한예후도대상환자수의부족으로정확히판단하기는힘들다. 따라서이러한문제해결을위해더많은환자수를대상으로하는다기관연구가필요할것으로생각되며한국에서 NASSM의장기예후를분석한첫번째연구인본연구가향후의다기관연구의초석이되길바라는바이다. 참고문헌 1. Freeman BS. Subcutaneous mastectomy for benign breast lesions with immediate or delayed prosthetic replacement. Plast Reconstr Surg Transplant Bull 1962;30: Toth BA, Lappert P. Modified skin incisions for mastectomy: the need for plastic surgical input in preoperative planning. Plast Reconstr Surg 1991;87: Jabor MA, Shayani P, Collins DR Jr, Karas T, Cohen BE. Nippleareola reconstruction: satisfaction and clinical determinants. Plast Reconstr Surg 2002;110: Kang SH, Lee SJ, Woo SH, Jeong JH, Seul JH. Subcutaneous mastectomy with immediate reconstruction as treatment for early breast carcinomas. J Korean Surg Soc 1999;57: Nakajima H, Imanishi N, Aiso S. Arterial anatomy of the nipple-areola complex. Plast Reconstr Surg 1995;96: van Deventer PV. The blood supply to the nipple-areola complex of the human mammary gland. Aesthetic Plast Surg 2004;28: Kroll SS, Schusterman MA, Tadjalli HE, Singletary SE, Ames FC. Risk of recurrence after treatment of early breast cancer with skinsparing mastectomy. Ann Surg Oncol 1997;4: Simmons RM, Fish SK, Gayle L, La Trenta GS, Swistel A, Christos P, et al. Local and distant recurrence rates in skin-sparing mastectomies compared with non-skin-sparing mastectomies. Ann Surg Oncol 1999;6: Medina-Franco H, Vasconez LO, Fix RJ, Heslin MJ, Beenken SW, Bland KI, et al. Factors associated with local recurrence after skinsparing mastectomy and immediate breast reconstruction for invasive breast cancer. Ann Surg 2002;235: Wellisch DK, Schain WS, Noone RB, Little JW 3rd. The psychological contribution of nipple addition in breast reconstruction. Plast Reconstr Surg 1987;80: Santini D, Taffurelli M, Gelli MC, Grassigli A, Giosa F, Marrano D, et al. Neoplastic involvement of nipple-areolar complex in invasive breast cancer. Am J Surg 1989;158: Smith J, Payne WS, Carney JA. Involvement of the nipple and areola in carcinoma of the breast. Surg Gynecol Obstet 1976;143: Vlajcic Z, Zic R, Stanec S, Lambasa S, Petrovecki M, Stanec Z. Nipple-areola complex preservation: predictive factors of neoplastic nipple-areola complex invasion. Ann Plast Surg 2005;55: Wertheim U, Ozzello L. Neoplastic involvement of nipple and skin flap in carcinoma of the breast. Am J Surg Pathol 1980;4: Luttges J, Kalbfleisch H, Prinz P. Nipple involvement and multicentricity in breast cancer. A study on whole organ sections. J Cancer Res Clin Oncol 1987;113: Govindarajulu S, Narreddy S, Shere MH, Ibrahim NB, Sahu AK, Cawthorn SJ. Preoperative mammotome biopsy of ducts beneath the nipple areola complex. Eur J Surg Oncol 2006;32: Palmieri B, Baitchev G, Grappolini S, Costa A, Benuzzi G. Delayed nipple-sparing modified subcutaneous mastectomy: rationale and technique. Breast J 2005;11: Friedman EP, Hall-Craggs MA, Mumtaz H, Schneidau A. Breast MR and the appearance of the normal and abnormal nipple. Clin Radiol 1997;52: Petit JY, Veronesi U, Rey P, Rotmensz N, Botteri E, Rietjens M, et al. Nipple-sparing mastectomy: risk of nipple-areolar recurrences in a series of 579 cases. Breast Cancer Res Treat 2009;114: Gerber B, Krause A, Dieterich M, Kundt G, Reimer T. The oncological safety of skin sparing mastectomy with conservation of the nippleareola complex and autologous reconstruction: an extended followup study. Ann Surg 2009;249:461-8.

9 Prognosis of Nipple-areola Preserving Skin Sparing Mastectomy Greenway RM, Schlossberg L, Dooley WC. Fifteen-year series of skin-sparing mastectomy for stage 0 to 2 breast cancer. Am J Surg 2005;190: Caruso F, Ferrara M, Castiglione G, Trombetta G, De Meo L, Catanuto G, et al. Nipple sparing subcutaneous mastectomy: sixty-six months follow-up. Eur J Surg Oncol 2006;32: th Annual San Antonio Breast Cancer Symposium. Can Nipple- Areola-Sparing Mastectomy Be an Alternative to Mastectomy? Over 10 Years of Follow Up At A Japanese Institution. San Antonio: American Cancer Society; Benediktsson KP, Perbeck L. Survival in breast cancer after nipplesparing subcutaneous mastectomy and immediate reconstruction with implants: a prospective trial with 13 years median follow-up in 216 patients. Eur J Surg Oncol 2008;34: Barreau-Pouhaer L, Le MG, Rietjens M, Arriagada R, Contesso G, Martins R, et al. Risk factors for failure of immediate breast reconstruction with prosthesis after total mastectomy for breast cancer. Cancer 1992;70: Victor SJ, Brown DM, Horwitz EM, Martinez AA, Kini VR, Pettinga JE, et al. Treatment outcome with radiation therapy after breast augmentation or reconstruction in patients with primary breast carcinoma. Cancer 1998;82: Williams JK, Carlson GW, Bostwick J 3rd, Bried JT, Mackay G. The effects of radiation treatment after TRAM flap breast reconstruction. Plast Reconstr Surg 1997;100:

Jkbcs016(92-97).hwp

Jkbcs016(92-97).hwp Expression of bcl-2 and Apoptosis and Its Relationship to Clinicopathological Prognostic Factors in Breast Cancer - A Study with Long Term Follow-up correlated with the survival rate.(journal of Korean