입체적 유방절제생검술

Abstract

평가배경 입체적 유방절제생검술(Stereotactic Breast Excisional Biopsy)은 유방암 의심환자를 대상으로 입체적 정위기법을 이용하여 3차원적으로 위치를 정한 후 절제 생검하는 기술이다. 본 기술은 2002년 비급여로 등재된 기술로 건강보험심사평가원에서 해당 기술의 급여화 추진을 위하여 안전성 및 효과성에 대한 의료기술재평가를 한국보건의료연구원에 의뢰하였다. 이에 2021년 제5차 의료기술재평가위원회(2021.5.14.)에서는 동 기술에 대해 체계적 문헌고찰을 이용하여 소위원회를 구성하여 안전성 및 효과성에 대해 평가하도록 심의하였으며, 2022년 제4차 의료기술재평가위원회(2022.4.15.)에서 동 기술의 임상적 안전성 및 효과성 평가에 대해 최종심의하였다.

평가 목적 및 방법 본 평가는 유방암 의심환자를 대상으로 진단목적으로서 입체적 유방절제생검술이 임상적으로 안전하고 효과적인지를 평가하기 위해 체계적 문헌고찰을 수행하였다. 모든 평가방법은 평가목적을 고려하여 “입체적 유방절제생검술 소위원회(이하 ‘소위원회’라 한다)”의 심의를 거쳐 확정하였다. 소위원회는 유방외과 2인, 영상의학과 2인, 병리과 1인, 근거기반의학 1인의 전문가 총 6인으로 구성하였다. 평가의 핵심질문은 “입체적 유방절제생검술은 유방암 의심환자를 대상으로 진단적 목적으로 사용시 임상적으로 안전하고 효과적인가?”이었고, 안전성은 검사 관련 부작용 및 이상반응, 효과성은 조직학적 저평가율, 위음성률, 진단정확성, 의료결과에의 영향으로 평가하였다. 입체적 유방절제생검술은 건강보험심사평가원 고시항목 상세내용 중 주사항에 “advanced breast biopsy instrumentation (ABBI) system을 이용하여 시술한 경우에 해당한다”로 기술되어 있으나, 실제 ABBI는 2006년 1월 19일에 식품의약품안전처의 허가증을 자진반납하여 현재 사용되고 있지 않은 기술로 확인되었다. 아울러 입체적 유방절제생검술은 임상에서 주로 진공보조흡인생검법을 사용하여 임상에서 활용되고 있는 것으로 확인되었다. 이에 따라 평가는 ABBI와 입체적 정위기법을 이용한 진공보조흡인생검법(stereotactic vacuum assisted biopsy, SVAB) 두 가지를 구분하여 평가를 진행하였다. 체계적 문헌고찰은 위의 핵심질문을 토대로 국내 데이터베이스 5개(KoreaMed, 의학논문데이터베이스, 학술데이터베이스, 한국교육학술정보원, 사이언스온) 및 국외 데이터베이스 3개(Ovid MEDLINE, Ovid EMBASE, Cochrane Central Register of Controlled Trials)를 이용하여 문헌을 검색하였다. 문헌 선정기준 및 배제기준 적용을 통한 문헌선택과 자료추출, 비뚤림 위험 평가는 모두 2명의 평가자가 독립적으로 수행하였고, 의견 불일치가 있으면 제3자와 함께 논의하여 합의하였다. 비뚤림 위험 평가는 진단법평가연구의 경우 Quality assessment of diagnostic accuracy studies-2 (QUADAS-2), 비무작위 연구의 경우 Risk of bias Assessment for nonrandomized studies (RoBANS) 2.0 국문판를 이용하여 평가하였다. 소위원회의 검토의견을 고려하여 의료기술재평가위원회에서 최종심의 후 권고등급을 제시하였다.

평가 결과 최종 선택 문헌은 총 175편으로 ABBI를 사용한 경우 18편, SVAB를 사용한 경우 155편, ABBI와 SVAB 둘 다 사용한 경우는 2편으로 확인되었다. 연구유형별로 ABBI만 수행한 연구는 진단법평가연구 6편, 증례연구 12편, SVAB만 수행한 연구는 진단법평가연구 142편, 비무작위 연구 1편, 증례연구 12편이었으며, SVAB와 ABBI 모두 수행한 연구 2편은 모두 진단법평가연구로 확인되었다. 비교검사와 비교한 연구는 총 4편(ABBI 1편, SVAB 3편)으로 모두 수술적 절제생검(open surgical biopsy, OSB)과 비교하였다. 비뚤림 위험 평가결과 연구 대부분 후향적으로 연구가 이루어졌거나 특정 질환에 대한 조직학적 저평가율을 제시하고 있어 ABBI 50%, SVAB 87%에서 환자 선택 비뚤림 위험을 높게 평가하였다.

ABBI ABBI의 안전성 결과는 19편에서 확인되었다. 안전성에 대한 메타분석 결과 통합 혈종 발생률(12편) 2% (I2=32%), 통합 출혈 발생률(5편) 0.8% (I2=12%)로 이 중 임상적으로 의미 있는 통합 출혈 발생률(3편)은 0.6% (I2=0%)이었다. 통합 상처 및 감염 발생률(15편)은 0.7% (I2=54%), 장치관련 문제발생률(5편)에서 12% (I2=90%)로 확인되었다. 그 외에 통증 및 불편감 발생률(3편)은 1.83~5.88%, 미주신경성 실신 전조증상 관련 발생률(2편)은 각각 0.76%, 11.76%이었으며, 불안 발작, 기흉, 정맥혈전증 및 반흔 발생률이 각 1편에서 1.39~4.17% 보고되었다. 이에 소위원회에서는 ABBI의 검사 관련 이상반응 및 부작용은 임상적으로 수용가능한 수준으로 안전한 기술로 판단하였다. ABBI의 효과성 결과는 8편에서 확인되었다. 조직학적 저평가율은 고위험 질환군(1편)에서 1.89%로 나타났으며, 관상피내암(ductal carcinoma in situ, DCIS)(4편)은 메타분석 결과 통합 비율이 5%이었다. 진단정확성(3편)은 민감도 97~100%, 특이도 100%, 음성예측도 99% (2편)로 확인되었다. 의료결과에의 영향은 1편에서 절제연 양성(positive margin) 비율이 ABBI 63.6%, OSB 50.9%로 군간 유의한 차이를 보이지 않았다. 이에 소위원회에서는 ABBI의 조직학적 저평가율, 진단정확성이 임상적으로 수용가능한 수준으로 효과성이 있는 기술로 판단하였다.

SVAB SVAB의 안전성 결과는 65편에서 확인되었다. 해당 결과는 비교군 연구(1편, OSB와 비교)와 단일군 연구결과를 각각 구분하여 제시하였다. 비교군 연구(1편)에서 감염 발생률은 중재군 0.72% (2/276명), OSB 2.4% (13/541명), 혈종 발생률은 중재군 0% (0/276명), OSB 0.55% (3/541명)로 중재군에서 감염과 혈종 발생률 모두 더 낮게 보고되었다. 단일군 연구에서 메타분석 결과 통합 비율은 다음과 같다. 혈종 발생률(42편)은 13.1% (I2=99%)이고, 이 중 임상적으로 의미 있는 통합 혈종 발생률(8편)은 0.1% (I2=74%)이었다. 출혈 발생률(28편)은 3% (I2=94%)로 이 중 임상적으로 의미 있는 통합 출혈 발생률(17편)은 0.5% (I2=79%)이었다. 이 중 항혈전제나 항응고제 치료를 받는 여성을 대상으로 수행된 연구 2편이 확인되었다. 항혈전제를 복용하는 여성 대상 연구(1편)는 혈종 발생률이 25.5% (51/200명)이었고, 항응고제 복용 환자를 포함하여 혈종 발생률을 비교한 연구(1편)에서는 항응고 치료를 받은 환자와 그렇지 않은 환자의 혈종 발생률을 각각 45.03%, 37.50%로 유의한 차이를 보이지 않는 것으로 보고하였으며, 또한 해당 연구에서는 보고된 혈종이 모두 임상적으로 의미 있는 혈종은 아닌 것으로 보고하였다. 기타 시술관련 이상반응 또는 부작용에 대한 메타분석 결과 통합 비율은 감염, 상처 및 염증 발생률(20편) 0.1% (I2=34%), 미주신경성 실신 전조증상 관련 발생률(21편)은 1.1% (I2=69%), 통증 및 불편감 발생률(7편)은 7.2% (I2=96%)로 확인되었다. 그 외 반상출혈 발생률(3편)은 8.81~69.91%, 장치관련 이상반응 발생률(3편) 0~0.62%, 유방경화, 생검 중 불편감 또는 불안 경험, 경추 불편감, 발작, 반흔 발생률은 각 1편에서 0.03~14.6% 이었다. 이에 소위원회에서는 SVAB의 검사 관련 이상반응 및 부작용은 임상적으로 수용가능한 수준으로 안전한 기술로 판단하였다. 아울러, 일부 연구에서 항혈전제나 항응고제 치료를 받은 여성을 대상으로 SVAB 수행후 혈종 발생률을 확인하였으나, 문헌 수가 많지 않아 일반화해서 적용하기에는 무리가 있다는 의견이 있었다. SVAB의 효과성 결과는 145편에서 확인되었다. 해당 결과는 비교군 연구(OSB와 비교 3편) 및 단일군 연구로 구분하여 제시하였다. 비교군 연구결과는 다음과 같다. 진단정확성은 1편에서 SVAB, OSB 각각 위음성률(악성 종양 중 위음성 사례 비율) 4.76%, 0.96%, 음성예측도 99.61%, 99.77%, 민감도 95.24%, 99.03%로 보고하였다. 조직학적 저평가율은 비정형 관상피증식증(atypical ductal hyperplasia, ADH)에 대해 1편에서 SVAB 33.3%, OSB 0%, 1편에서 SVAB 군에서만 0%로 보고하였으며, DCIS에 대해 1편에서 SVAB 16.7%, OSB 1.3%, 1편에서 SVAB 33.3%, OSB 4.5%로 SVAB에서 조직학적 저평가율이 더 높게 나타났으며 군간 차이에 대한 통계적 유의성은 제시하지 않았다. 의료결과에의 영향은 1편에서 유방생검 결과 양성종양의 경우 추적관찰 및 재생검 비율에 있어 군간 유의한 차이를 보이지 않았으며 악성종양의 경우 추가 수술과 함께 치료받은 비율은 SVAB가 유의하게 높았다. 1편에서는 유방생검 결과 DCIS 진단받아 유방보존술을 수행한 환자를 대상으로 제거된 유방조직볼륨을 확인시 SVAB를 시행한 자는 104cm3, OSB를 시행했던 자는 183cm3으로 SVAB를 수행했던 대상자에서 유의하게 작게 나타났다. 단일군 연구결과는 다음과 같다. 고위험 질환에 대한 메타분석 결과 통합 조직학적 저평가율은 1999~2009년 연구(50편)에서 17% (I2=65%), 2010~2021년 연구(60편)에서 12% (I2=86%)로 확인되었다. DCIS의 조직학적 저평가율의 메타분석 결과 통합 비율은 13% (I2=75%)이었다. 위음성률은 SVAB 결과 양성종양으로 나온 경우 중 위음성으로 확인된 사례 비율(33편)의 경우 메타분석결과 통합 비율이 0.6% (I2=71%)이었으며, 최종 진단이 악성종양으로 확인된 경우 중 SVAB에서 위음성이었던 사례 비율(8편)은 메타분석 결과 통합 비율이 4.3% (I2=76%)로 확인되었다. SVAB의 진단정확성은 23편에서 민감도 87.5~100%, 특이도 62~100%, 음성예측도 90~100%로 확인되었다. 이에 소위원회에서는 실제 유방생검 결과 ADH나 DCIS으로 진단되면수술적 생검을 수행하고 있고 임상적으로 ADH, DCIS의 조직학적 저평가율이 15% 정도면 수용 가능한 수준으로 보고하고 있어 본 평가에서 확인된 조직학적 저평가율의 수준은 임상적으로 수용 가능하다는 의견이었다. 위음성률도 실제 임상에서 영상결과와 유방생검 결과가 불일치하는 경우에는 수술적 생검을 수행하기 때문에 문헌에서 보고된 위음성률 수준은 충분히 수용가능하여 SVAB는 효과성이 있는 기술로 판단하였다. 현재 선택문헌에서 입체적 유방절제생검술의 사용대상은 촉지성 또는 비촉지성 유방병변, 초음파에서 병변이 확인되지 않는 경우 및 병변이 확인된 경우가 모두 포함되었으며, 그 외에 구체적인 기준 없이 후향적으로 유방생검을 수행한 환자들(유방암 확진 환자 제외)까지 모두 포함되었다. 그리고 하위군으로 비촉지성 유방병변 대상이나 초음파에서 병변이 보이지 않는 경우로 제한했을 때도 효과성의 크기가 유사하게 확인되었다. 소위원회에서는 실제 임상에서는 입체적 유방절제생검술이 초음파를 이용한 경우보다 검사 소요시간이 길어 유방병변이 초음파에서 유방병변이 명확히 보이는 경우는 초음파를 이용한 유방생검을 한다는 의견이었다. 다만, 초음파에서 명확하게 드러나지 않는 유방병변이 유방촬영술에서 확인되었을 때 입체적 유방절제생검술을 수행할 수 있다는 의견이었다. 현재 건강보험심사평가원 고시항목 내 정의 및 적응증에는 ‘촉지되지 않는 실질 내의 병변’으로 제시된 부분과 관련하여, 촉지성 유방병변은 대부분 초음파에서 확인되는 경우가 많으나, 초음파에서 명확하게 드러나지 않는 경우도 있음을 고려했을 때, 유방암 의심환자 중 촉지성 및 비촉지성 유방병변 모두 포함한 대상자에서 초음파에서 명확하게 드러나지 않는 병변이 유방촬영술에서 확인되었을 때 동 기술을 수행하는 것이 가장 임상적으로 유용하다고 판단하였다.

결론 입체적 유방절제생검술 소위원회는 현재 평가 결과에 근거하여 다음과 같이 제언하였다. ABBI는 유방암 의심환자를 대상으로 진단적 목적으로 사용시 안전하고 효과적인 기술로 판단하였다. 다만, 현재 소요장비가 2006년에 식품의약품안전처의 허가증을 자진반납하여 현재 사용되고 있지 않은 기술로 확인되었다. 입체적 정위기법을 이용한 진공보조흡인생검술은 유방암 의심환자를 대상으로 진단적 목적으로 사용시 안전하고 효과적인 기술로 판단하였다. 2022년 제4차 의료기술재평가위원회(2022.4.15.)에서는 소위원회 검토 결과에 근거하여 의료기술재평가사업 관리지침 제4조제10항에 의거 “입체적 유방절제생검술”에 대해 다음과 같이 심의하였다. 의료기술재평가위원회는 ABBI에 대해서 유방암 의심환자를 대상으로 진단적 목적으로 사용시 안전하고 효과적인 기술로 판단하였으나 현재 소요장비가 2006년에 식품의약품안전처의 허가증을 자진반납하여 현재 사용되고 있지 않은 기술로 확인되어 권고등급을 결정하지 않기로 하였다. 의료기술재평가위원회는 입체적 정위기법을 이용한 진공보조흡인생검술은 초음파에서 명확하게 드러나지 않는 병변이 유방촬영술에서 확인되었을 때 진단적 목적으로 사용시 안전하고 효과적인 기술로 판단하여 ‘조건부 권고함’으로 심의하였다.

주요어 입체적 유방절제생검술, ABBI, 입체적 정위기법을 이용한 진공보조흡인생검술, 안전성, 효과성

Background Stereotactic Breast Excisional Biopsy is a technique to perform an excisional biopsy after determining the position in three demensions using a stereotaxic techniques for patients with suspected breast cancer. This technology is registered as a non-reimbursable coverage in 2002, and in order to determine health insurance coverage of the technology, the Health Insurance Review and Assessment Service (HIRA) requested the National Evidence-based Healthcare Collaborating Agency (NECA) for health technology reassessment (HTR) on the safety and effectiveness of the technology. Accordingly, at the 5th Health Technology Reassessment Committee (May 14, 2021) in 2021, it was determined that Sub-committee be formed to perform assessment on the safety and effectiveness of the technology based on systematic review. At the 4th Health Technology Reassessment Committee (April 15, 2022) in 2022, final review was performed on the clinical safety and effectiveness of this technology.

Objectives and Methods In this HTR, a systematic review was performed in order to assess whether stereotactic breast excisional biopsy is clinically safe and effective technology to be applied for diagnostic purposes for patients with suspected breast cancer. All assessment methods were finalized following the review by the “Stereotactic Breast Excisional Biopsy Sub-committee (Hereinafter Sub-committee)” in consideration of the objectives of the assessment. The Sub-committee consisted of a total of six experts in the following fields: two in Breast Surgery, two in Diagnostic Radiology, one in Diagnostic Pathology, and one in evidence-based medicine. The key question in the assessment was “Is stereotactic breast excisional biopsy clinically safe and effective when used for diagnostic purposes in patients with suspected breast cancer?” Safety was assessed based on procedure-related side effects and adverse events, and effectiveness was assessed based on underestimation rate, false negative rate, diagnostic accuracy, and impact on clinical outcomes. Stereotactic breast excisional biopsy is described as “applicable to the case when performed using the advanced breast biopsy instrumentation (ABBI) system” in the main description for details of the HIRA Notice Item, but in practice, ABBI was confirmed as a technology whose permit by the Ministry of Food and Drug Safety (MFDS) was voluntarily returned in January 19, 2006 and that is not currently in use. In addition, it was identified that stereotactic breast excisional biopsy is mainly applied in clinical practice using vacuum assisted biopsy. Accordingly, assessment was carried out by dividing ABBI and stereotactic vacuum assisted biopsy (SVAB). Based on the above key question, in the process of systematic review, literature search was performed using, five domestic databases (KoreaMed, Korean Medical database, Koreanstudies Information Service System, Research Infromation Sharing Service, ScienceON) and three international databases (Ovid MEDLINE, Ovid EMBASE, Cochrane Central Register of Controlled Trials). Selection of articles through application of inclusion and exclusion criteria for related literature and data extraction, assessment of risk of bias (RoB) were all independently performed by two reviewers, and in case of disagreement, the two reviewers held discussions with a third party to draw consensus on the matter. For RoB assessment, Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used for diagnostic test accuracy studies and the Korean version of the Risk of bias Assessment for nonrandomized studies (RoBANS) 2.0 was used for nonrandomized studies. In consideration of the results of the review by the Sub-committee, the Health Technology Reassessment Committee presented a Grade of Recommendation upon the final review.

Results A total of 175 articles were finally selected, 18 of which using ABBI, 155 of which using SVAB, and 2 of them using both ABBI and SVAB. In terms of classification by study design, for those that used ABBI only, there were six articles on diagnostic test accuracy studies, and 12 articles on case series; for those that used SVAB only, there were 142 articles on diagnostic test accuracy studies, one article on a nonrandomized study, and 12 articles on case series; the 2 articles which used both ABBI and SVAB were diagnostic test accuracy studies. There were a total of four articles (1 ABBI, 3 SVAB) that performed comparative analysis with comparator, and these were all compared with open surgical biopsy (OSB). As a result of RoB assessment, most of the studies were retrospective studies or presented underestimation rate for a specific disease; thus, the risk of patient selection bias was assessed to be high with ABBI at 50% and SVAB at 87%.

ABBI The safety outcomes of ABBI were reported in a total of 19 articles. As a result of meta-analysis on safety, the pooled rate of hematoma formation (12 articles) was 2% (I2=32%), and pooled rate of bleeding (5 articles) was 0.8% (I2=12%), out of which the pooled rate of clinically significant bleeding (3 articles) was 0.6% (I2=0%). The pooled rate of wound infection (15 articles) was 0.7% (I2=54%), and the rate of device-related adverse events (5 articles) was 12% (I2=90%). In addition, the incidence rate of pain or discomfort (3 articles) was 1.83~5.88%, the incidence rate related to signs of vasovagal syncope (2 articles) were 0.76% and 11.76%, respectively, and the incidences of anxiety attack, pneumothorax, venous thrombosis and scarring were reported to be in the range of 1.39~4.17% in one article. Therefore, the Sub-Committee considered that the procedure-related adverse events and complications of ABBI were at a clinically acceptable level and determined that ABBI was a safe technology. The effectiveness outcomes of ABBI were reported in 8 articles. The underestimate rate (%) was 1.89% in the high-risk group (1 article), and as a result of meta-analysis, the pooled underestimate rate (%) was 5% for ductal carcinoma in situ (DCIS) (4 articles). The diagnostic accuracy (3 articles) was confirmed with a sensitivity of 97~100%, a specificity of 100%, and a negative predictive value (NPV) of 99% (2 articles). As for the impact on clinical outcomes, there was no significant difference between groups with positive margin ratios of 63.6% in ABBI and 50.9% in OSB in a result reported in one article. Accordingly, the Sub-committee considered that the underestimation rate (%) and diagnostic accuracy of ABBI were at a clinically acceptable level and determined that ABBI was an effective technology.

SVAB The safety outcomes of SVAB were reported in 65 articles. The results were presented by categorizing into a comparative study (1 article, compared with OSB) and single-arm studies. In a comparative study (1 article), the rate of infection was 0.72% (2/276 patients) in the intervention group, 2.4% in the OSB group (13/541 patients), and the rate of hematoma formation was 0% (0/276 patients) in the intervention group, 0.55 % in the OSB (3/541 patients). Thus, both rate of infection and rate of hematoma formation were reported to be lower in the intervention group. As a result of meta-analysis for the single-arm studies, the pooled rates are as follows. The rate of hematoma formation (42 articles) was 13.1% (I2=99%), of which the pooled rate of clinically significant hematoma formation (8 articles) was 0.1% (I2=74%). The rate of bleeding (28 articles) was 3% (I2=94%), of which the pooled rate clinically significant of bleeding (17 articles) was 0.5% (I2=79%).

Among these studies, there were 2 articles on studies conducted on women receiving antithrombotic therapy or anticoagulant therapy. In one study for women taking antithrombotic medication (1 article), the rate of hematoma formation was 25.5% (51/200 patients), and in a study comparing the rate of hematoma formation including patients taking anticoagulant medication (1 article), the rates of hematoma formation for those who are taking anticoagulant therapy and the controls were 45.03% and 37.50%, respectively, showing no significant difference between the two groups. It was also reported in this study that all of the reported hematoma events were not clinically significant. As a result of meta-analysis for other procedure-related adverse events or complications, pooled incidence rates were as follows: infection, wound and inflammation (20 articles) at 0.1% (I2=34%), signs of vasovagal syncope (21 articles) at 1.1% (I2=69%), and pain or discomfort (7 articles) at 7.2% (I2=96%). For other adverse events or complications, incidence rate of ecchymosis (3 articles) was 8.81~69.91%, that of device-related adverse events was (3 articles) 0~0.62%, and incidence rates of breast induration, discomfort or anxiety during biopsy, cervical spine troubles, seizure, scarring were in the range of 0.03~14.6% in one article, respectively. Accordingly, the Sub-committee considered that the procedure-related adverse events or complications of SVAB were at a clinically acceptable level and determined that SVAB was an safe technology. In addition, some studies have reported on the incidence of hematoma formation after SVAB in women who have received antithrombotic therapy or anticoagulant therapy, but the Committee considered that since the number of the related articles was not many, it would be difficult to generalize and apply the finding. The effectiveness outcomes of SVAB were reported in 145 articles. The results were presented by categorizing into comparative studies (3 articles comparing with OSB) and single-arm studies. The results of comparative studies are as follows. As for the diagnostic accuracy reported in one article, false negative rate (proportion of false negative cases among malignant cases) was 4.76%, 0.96%, NPV was 99.61%, 99.77%, and sensitivity was 95.24%, 99.03%, for SVAB and OSB, respectively. In terms of underestimation rates(%), for atypical ductal hyperplasia (ADH), the underestimate rate was 33.3% with SVAB, and 0% with OSB in one article, and in another article, 0% was reported in the SVAB group only. For ductal carcinoma in situ (DCIS), the underestimate rate was 16.7% with SVAB, and 1.3% with OSB in one article, and 33.3%, with SVAB, and 4.5% with OSB in another article; thus, underestimate rate (%) was reported to be higher with SVAB, but no statistical significance was presented for the between-group difference. As for the impact on clinical outcomes, one article reported that there was no significant difference between groups in terms of follow-up and rebiopsy rates for benign lesions as a result of breast biopsy. For malignant cases, the rate of treatment with additional surgery was significantly higher in the SVAB group. In one article, the total volume of breast tissue removed for breast conservation was examined for patients who were diagnosed with DCIS as a result of breast biopsy and underwent breast-conserving surgery. The volume was 104cm3 for those that underwent SVAB and 183cm3 for those that underwent OSB, showing a significantly smaller volume in patients who underwent SVAB. The results of single-arm studies are as follows. As a result of meta-analysis for high-risk groups, the pooled underestimate rate (%) was 17% (I2=65%) for studies conducted between 1999 and 2009 (50 articles), and 12% (I2=86%) for studies conducted between 2010 and 2021 (60 articles). As a result of meta-analysis on underestimate rate (%) of DCIS, the pooled underestimate rate was 13% (I2=75%). As for false negative rates, as a result of meta-analysis (33 articles) for the percentage of cases confirmed to be false negative among the results of benign lesions diagnosed by SVAB, the pooled rate was 0.6% (I2=71%). As for the false negative rates with SVAB among cases that were confirmed as malignant cases in the final diagnosis (8 articles), meta-analysis results showed that the pooled rate was 4.3% (I2=76%). The diagnostic accuracy of SVAB was confirmed in 23 articles with sensitivity of 87.5~100%, specificity of 62~100%, and NPV in the range of 90~100%. Based on the above review, the Sub-committee considered that in practice, when ADH or DCIS is diagnosed as a result of breast biopsy, OSB is conducted, and when the underestimate rate (%) is about 15% for ADH and DCIS, it is reported as clinically acceptable level. Therefore, the Sub-committee considered that, the level of underestimater rate (%) confirmed in this study was clinically acceptable. In terms of false negative rate, since OSB is conducted when the findings of mammography and breast biopsy results are not consistent in clinical practice, the Sub-committee considered that the level of false negative rate reported in selected literature was in the sufficiently acceptable level and determined that SVAB was an effective technology. In the selected literature for the present assessment, the patients for use of stereotactic breast excisional biopsy included palpable or non-palpable breast lesions, and cases where lesions were not visible as well as visible on ultrasound. All patients who underwent biopsy (excluding patients with confirmed breast cancer) were included retrospectively without specific criteria. Also, the level of effectiveness was confirmed to be similar for subgroup analysis only including patients with non-palpable breast lesions or whose lesions were not visible on ultrasound. The Sub-committee considered that, in clinical practice, stereotactic breast excisional biopsy takes longer for examination than the ultrasound and for cases where the breast lesions are clearly visible on ultrasound, ultrasound-guided breast biopsy should be used. However, the Sub-committee considered that stereotactic breast excisional biopsy could be performed when breast lesions that were not clearly visible on ultrasound were confirmed by mammography. In the current definition and indications in the HIRA notification item, regarding the description of “non-palpable lesions within parenchyma,” considering that although most of the palpable breast lesions can be identified on ultrasound, there are some cases that the lesions are not clearly visible on ultrasound, among patients with suspected breast cancer, for all of those with palpable and non-palpable breast lesions, when lesions not clearly visible on ultrasound were identified by mammography, it would be clinically useful to apply stereotactic breast excisional biopsy.

Conclusion The Stereotactic Breast Excisional Biopsy Sub-committee suggested the following based on the results of the present assessment. The Sub-committee determined that ABBI was a safe and effective technology when used for diagnostic purposes in patients with suspected breast cancer. However, at present, the MFDS permit for the required instrument was voluntarily returned in 2006, and it was identified as a technology that was not currently in use in clinical practice. Stereotactic vacuum assisted biopsy was determined as a safe and effective technology when used for diagnostic purposes in patients with suspected breast cancer. Based on the results of the review by the Sub-committee, at the 4th Health Technology Reassessment Committee (April 15, 2022) in 2022, the following is the result of the review for “Stereotactic Breast Excisional Biopsy” in accordance with Article 4, Paragraph 10 of the Management Guidelines for Health Technology Reassessment Project. The Health Technology Reassessment Committee determined that ABBI was a safe and effective technology when used for diagnostic purposes in patients with suspected breast cancer, but at present, the MFDS permit for the required instrument was voluntarily returned in 2006, and it was identified as a technology that was not currently in use in clinical practice. Thus, it was concluded that the Grade of Recommendation for ABBI would not be determined on this assessment. The Health Technology Reassessment Committee determined that the Grade of Recommendation for stereotactic vacuum assisted biopsy was 'conditional recommendation' since it was considered a safe and effective technology when used for diagnostic purposes for cases where lesions that were not clearly visible on ultrasound were identified by mammography.

Keywords: Stereotactic breast excisional biopsy, Advanced breast biopsy instrumentation, Stereotactic vacuum assisted biopsy, Safety, Effectiveness