최신임상강좌 : 부인과 영역에서 유전성 종양의 임상적 접근

이채형 ( Chae Hyeong Lee ),노주원 ( Ju Won Roh ) 대한산부인과학회 2009 Obstetrics & Gynecology Science Vol.52 No.1

유전성 종양 증후군은 가족에서 특정 유형의 암 발생이 일반인에 비하여 증가하는 유전적 배경을 지닌 경우로 정의할 수 있다. 최근 유전학의 발달로 인하여 이러한 유전성 종양의 원인이 되는 유전자들이 많이 밝혀지고, 이에 따라 이러한 종양의 예방, 선별검사 및 치료 등 모든 임상의 분야에 적용되기 시작하였다. 유전성 종양의 특징으로는 젊은 연령에서 발병하고, 투과도가 높으며, 양측으로 존재하는 기관인 경우 양측성으로 발생하는 경우가 많고, 양측 부모 중 일측으로 주로 전달되며, 여러 다른 종류의 종양이 함께 발생하는 점을 들 수 있다. 유전성 종양 증후군 중 부인과 분야와 관련이 있는 것으로 알려져 있는 대표적인 질환으로는 유전성 유방암/난소암 증후군 (HBOC), 유전성 비용종증 대장암 (HNPCC), Li-Fraumeni 증후군, Cowden 증후군 등을 들 수 있다. BRCA1, 2, TP53, PTEN, MMR, CHEK2 등의 몇 가지 특정한 유전자의 돌연변이가 이러한 부인암과 관련된 유전성 종양의 원인으로 현재 알려져 있다. 부인과 의사로서 이러한 고위험군에 해당하는 환자의 선별, 가족력 청취, 임상적 평가, 유전자검사법을 통한 확인 등을 숙지하고, 고위험군에 해당하는 환자에게 적용할 수 있는 적절한 선별검사, 암발생 위험을 낮추기 위한 처치 등을 이해하는 것은 매우 중요한 일이다. 부인과 분야의 유전성 종양의 발생 및 사망률도 이러한 적절한 임상적 접근을 통하여 감소할 수 있을 것으로 기대된다. 단, 현재의 권고안은 빠르게 발전하고 있는 분자유전학적 지식의 초기 단계 결과를 바탕으로 이루어진 것이므로, 이를 임상적으로 개개의 환자 및 가족에게 적용할 때에는 신중한 판단에 따라 탄력적으로 적용하기 위한 노력이 필요하다. Hereditary cancer syndrome is a genetic condition that causes and increases the risk for specific type of cancers. Recent advances in genetics have identified a number of genes associated with inherited susceptibility to cancer, and this rapid development of knowledge about cancer genetics have implications for all aspects of cancer management, including prevention, screening, and treatment. Hereditary patterns of cancer are often characterized by early age at onset, high penetrance, bilaterality in paired organs, vertical transmission through either parent, and an association with other types of tumors. Most representative hereditary cancer syndromes in gynecologic field are hereditary breast/ovarian cancer syndrome (HBOC), hereditary non-polyposis colorectal cancer (HNPCC), Li-Fraumeni syndrome, and Cowden syndrome. Several familial mutations of specific genes, such as BRCA1, 2, TP53, PTEN, MMR, CHEK2, are linked to hereditary cancer syndrome, which are responsible for hereditary gynecologic cancers. It would be very important for gynecologic doctors to know the inclusion criteria for the genetic assessment, taking family history, clinical evaluation, genetic testing, screening guideline and risk reduction strategies for women with hereditary high risk factor. The morbidity and mortality of gynecologic malignancies related to these syndromes could be reduced by the adequate clinical approach, although recent guidelines were developed with an acute awareness of the preliminary nature of much of our knowledge regarding the clinical application of the rapidly emerging field of molecular genetics, and with an appreciation for the need for flexibility when applying these guidelines to individual families.

차세대 염기서열 분석법을 이용한 유전성 유방암에서의 유전자 정밀 진단의 임상적 유용성

강지언 한국콘텐츠학회 2024 한국콘텐츠학회논문지 Vol.24 No.2

The incidence of breast cancer continues to increase, and about 10% of patients are diagnosed as hereditary cancer. Recently, breast cancer-related genetic panels using Next Generation Sequencing (NGS) have emerged as a standard test method that can replace existing pathological tests, leading to innovative changes in breast cancer research. Currently, more than 30 genes, including BRCA, are simultaneously examined using NGS analysis technology to find specific genes involved in the development and progression of breast cancer and to improve the effectiveness of chemotherapy and establish patient-specific treatment strategies. In addition, unnecessary chemotherapy can be omitted if the risk of breast cancer recurrence is evaluated through NGS and determined as a low-risk group in genetic prognostic analysis. It is expected to become a life changer that enhances the effectiveness of chemotherapy and provides optimal customized treatment for individual patients by implementing gene-targeted treatment beyond the existing treatment paradigm through NGS-based customized precision medical care. 유방암은 여성에서 발생률이 지속적으로 증가하는 암 중의 하나로 환자 중 약 10%는 유전성 암으로 진단되고 있다. 최근 차세대 염기서열 분석(Next Generation Sequencing, NGS)을 활용한 유방암 관련 유전자 패널들이 기존 병리검사를 대체할 수 있는 표준 검사법으로 대두되면서 유방암 치료 및 예방에 혁신적인 변화를 일으키고 있다. 현재 NGS 분석을 통하여 BRCA를 비롯한 30여종의 유전자 분석이 이루어지고 있으며 이를 통해 유방암의 발생과 진행에 관여하는 특정 유전자를 찾아 유전자로 표적치료를 시행함으로써 항암치료 효과를 높이고 유방암을 예방하는데 도움을 주고 있다. 또한 NGS 분석을 통해 유방암 재발 위험도를 평가하여 유전자 예후 예측 분석에서 저위험군으로 평가될 경우 불필요한 항암치료를 생략할 수도 있다. 이렇게 NGS 기반 맞춤 정밀의료를 통해 기존 치료 패러다임을 넘어 새로운 유전자 표적치료를 시행함으로써, 항암치료 효과를 높이고 환자별 최적의 맞춤 치료를 제공하는 라이프 체인저가 될 것으로 기대된다.

한국인 유전성 유방암 연구 이후 국내 유전성 유방암 진료 패턴의 변화

김성원,강은영,안세현,노우철,노동영,정용식,김이수,최두호,서영진,김구상,이정언,이민혁,남석진,문병인,손병호,양정현,염차경,김성용,박수경,김성원 한국유방암학회 2010 Journal of breast cancer Vol.13 No.4

Purpose: The objective of this study was to evaluate the change in the practice patterns for managing hereditary breast and ovarian cancer (HBOC) among Korean physicians after the Korean Hereditary Breast Cancer (KOHBRA) study. Methods: The first survey was performed from July to August 2007, at the initiation of the KOHBRA study, and the followup survey was conducted from July to December 2009. Members of the Korean Breast Cancer Society were invited to participate in the study by e-mail. The 2009 survey was conducted with a self-administered questionnaire concerning HBOC management and was identical to the previous questionnaire. Results: According to the 2009 survey, most physicians (60.0%) tended to draw a pedigree (48.0% in 2007 survey). The rate of genetic test recommendations for patients at risk for HBOC was higher in the 2009 survey (84.0%) than that in the 2007 survey (64.0%). Physicians tended to select a BRCA genetic testing candidate more appropriately than in the previous survey (42.4% answered right in 2007 survey; 74.4% in 2009 survey). Fifteen of 25 participants (60.0%) provided genetic counseling before their patients underwent a genetic test, which was higher than that (40.0%) in the 2007survey. According to the 2009 survey, half of the genetic counseling was being conducted by KOHBRA study research nurses; whereas most of the genetic counseling was conducted by physicians in 2007. Conclusion: The KOHBRA study has played an important role in the appropriate selection of candidates for genetic testing. However, more effort should be placed on improving the pre-test genetic counseling rate.

‘한국인 유전성유방암의 진료현황’에 대한 설문조사결과

김구상,김성원,이민혁,안세현,박수경 한국유방암학회 2008 Journal of breast cancer Vol.11 No.2

Purpose: The aim of this study is to examine surgeons’ practice patterns for management of hereditary breast cancer in Korea. Methods: The structured questionnaire was circulated to the members of Korean Breast Cancer Society through e-mail between July 6 and August 14 in 2007 and 43 surgeons from 42 hospitals responded in the survey. Results: An 81.4% of respondents (n=35) has been asking the information related to family histories of cancer and a 58.1% of respondents (n=25) has been recommending genetic testing to their patients. The indications for genetic testing of 25 surgeons who have been recommending genetic testing were as follows: breast cancer patients with family histories of breast or ovarian cancer (96%); bilateral breast cancer (80%); early-onset (64%) or male breast cancer (52%); and double primary with breast and ovarian cancer (36%). A 52% of respondents (13/25) have been doing genetic counseling before genetic testing and the genetic counseling was given by the surgeons (81.3%, 13/16) or genetic counselors (18.7%, 3/16). Although 154 BRCA1/2 mutation carriers of 95 families were identified so far, only 12 family members were managed for prophylaxis: tamoxifen chemoprevention (n=2); contralateral prophylactic mastectomy (n=2); prophylactic oophorectomy (n=8). There was no report of bilateral prophylactic mastectomy. Conclusion: Although BRCA1/2 mutation carriers for high risk patients with hereditary breast cancer have been identifying in Korea, the practices and managements for cancer prevention seems not to perform actively. The Korean Hereditary Breast Cancer (KOHBRA) Study will serve in establishing the Korean guidelines of evidence-based clinical practice for Hereditary Breast Cancer.

BRCA 유전자 돌연변이가 있는 유방암 환자에서 시행한 단일포트 복강경 예방적 양측 난관난소절제술 1예

이정언,김태중,최민영,이세경,허성모,김상민,구민영,배수연,조동희,최준호,김정한,김지수,김병기,배덕수,남석진,양정현 한국유방암학회 2010 Journal of breast cancer Vol.13 No.4

For women with a BRCA 1/2 mutation, prophylactic bilateral salpingo-oophorectomy (BSO) is known to reduce the risk of developing both ovarian and breast cancer. The increasing interest in hereditary breast cancer has recently resulted in frequent genetic testing for high-risk patients. Since breast surgeons frequently encounter BRCA-positive breast cancer patients or carriers in the outpatient clinic, it is a prerequisite that the decision of the patients and doctors should be based on a thorough understanding of the objective risk, the medical assessment and the various treatment options, including surgery and anti-cancer therapy. The risk for the ovarian cancer also makes up an important part of genetic counseling; therefore, the breast surgeons should be well aware of this. This report presents the first experience with performing single-port access laparoscopic prophylactic BSO for a BRCA-positive breast cancer patient, and this procedure was technically feasible and the patient had minimal scar. However, a future investigation is needed to properly assess the cosmetic outcome in this approach.

한국인 유전성 유방암 연구 계획서

김성원 한국유방암학회 2007 Journal of breast cancer Vol.10 No.4

Purpose: Most epidemiological and clinical studies on BRCA1/2 mutations and the risk of breast cancer have been based on Western cohorts. There have been few such studies for Korean populations. The primary aim of this paper is to report the protocol of a KOHBRA study. Methods: The multi-centers registered in the KBCS are participating in the KOHBRA study. The objectives of the KOHBRA study till 2010 is to examine the prevalence of BRCA1/2 mutation and the prevalence of ovarian cancer among the high risk group of hereditary breast cancer patients and their families. This study is a prospective cohort study that recruited 2,250 subjects 1) who were breast cancer patients with a family history of breast or ovarian cancers, 2) who were patients with a high risk of BRCA1/2 mutations (i.e. early onset, bilateral, male, multiple primary cancers), and 3) who had family members that were BRCA1/2 mutation carriers. The recruiting period will cover the 25th of May 2007 to the 24th of May 2010. Written informed consent is obtained at the time of enrollment. The family history and epidemiological data are obtained by a baseline questionnaire, the anthropometric data is measured and the clinical information is collected by chart-reviews by doctors. BRCA1/2 mutation testing and ovarian cancer screening are done. Blood samples are stored. Follow-up data are collected at 1, 3 and 5 years after enrollment. Results: Until now, 36 centers have joined the KOHBRA study and they are in the process of IRB approval. We expect to find the Korean founder mutation and to establish the Korean BRCA risk prediction model. Furthermore, the BRCA carrier cohort established from the KOHBRA study will be the groundwork to participate in an international study. Conclusion: The KOHBRA study will provide unique, important data to prove the etiology and natural history of Korean hereditary breast cancer. This study will be continued as genomic and proteomic epidemiological studies and future intervention studies for the prevention of hereditary breast cancer among Koreans.

한국인 유전성 유방암

김성원 대한의사협회 2009 대한의사협회지 Vol.52 No.10

Approximately 7% of all breast cancer cases are associated with hereditary predisposition and BRCA1 and BRCA2 gene, which accounts for half of the hereditary breast cancer (HBC). Although majority of breast cancer occur sporadically, identification of HBC is important in that active adoption of preventive strategies such as surveillance, chemoprevention, and riskreducing surgery will result in the gain of life-expectancy. According to the recent studies, the prevalence and penetrance of BRCA mutation in Korean breast cancer patients are comparable to that of western countries. Genetic testing should be done in the setting of genetic counseling, which provides the patients with comprehensive information about the test procedure, the interpretation of the test result, and possible options when the test results were positive for mutation. The management of HBC is not different from that of sporadic cancer and many clinical trials investigating the chemoprevention and targeted therapy of HBC are underway. The Korean Hereditary Breast Cancer (KOHBRA) study is a nationwide multicenter study to reveal the prevalence of BRCA mutation in Korean breast cancer patients. After the completion of the KOHBRA study, we expect important basic data which will be the backbone of clinical practice guideline for Korean HBC patients.

BRCA2 돌연변이 보인자의 양측성 예방적 유방절제술에서 우연히 발견된 유관 상피내암 1예

이정언,최민영,김성원,이세경,허성모,김상민,구민영,배수연,최준호,김정한,김지수,남석진,양정현 한국유방암학회 2010 Journal of breast cancer Vol.13 No.3

In women at high-risk for breast cancer with a BRCA mutation, bilateral prophylactic mastectomy (BPM) may achieve a risk reduction. A 35-year-old woman had a strong family history of breast and ovarian cancer. She had a regular checkup and found masses in both breasts that confirmed intraductal papillomas and atypical ductal hyperplasia after vacuum assisted mass excision. When she was referred to our clinic, the genetic testing for BRCA mutation was recommended to her sister that managed for ovarian cancer. It was resulted in the positive for the BRCA2 mutation, so she had checked the genetic testing which resulted in the same as the mutation. After sufficient counseling, she decided to undergo BPM and immediate reconstruction. She is satisfied with the result of surgery. This is the first report of BPM of asymptomatic BRCA2 mutation carrier in Korea and BPM should be considered as a risk-reducing option for BRCA mutation carriers.

장액성 난소암 환자의 유전성 난소암에 대한 지식 및 불안정도

이상희,이향규,임명철,김수 한국여성건강간호학회 2019 여성건강간호학회지 Vol.25 No.4

Purpose: The awareness of hereditary breast and ovarian cancer (HBOC) and BRCA testing is in�creasing in Korea. Compared to the sizable research on HBOC knowledge among breast cancer women, studies in the ovarian cancer population are limited. This paper aimed to investigate the level of knowledge of hereditary ovarian cancer and anxiety in women diagnosed with serous ovarian cancer in Korea and determine differences in the knowledge and anxiety according to whether genetic testing was undertaken and whether BRCA1 or BRCA2 mutations were present. Methods: Using a descriptive research design, a cross-sectional survey was conducted on 100 women diagnosed with serous ovarian cancer at N hospital in Gyeonggi-do, Korea, from July to November 2018. The collected data were analyzed by descriptive statistics, independent t-tests, one-way analysis of variance, and Pearson's correlation coefficient using the SPSS 21.0 program. Results: The hereditary ovarian cancer-related knowledge score was mid-level (mean score 8.90±3.29 out of a total of 17), as was the state anxiety level was mid-level (mean score 47.96±3.26 out of possible score range of 20–80). Genetic knowledge of hereditary ovarian cancer was asso�ciated with age, education, occupation, genetic counseling, and BRCA mutations. There were no statistically significant factors related to anxiety and there were no statistically significant correla�tions between knowledge level and anxiety. Conclusion: More comprehensive education on gene-related cancer is needed for ovarian cancer patients, especially for items with low knowledge scores. A genetic counseling protocol should be developed to allow more patients to alleviate their anxiety through genetic counseling.

한국인 유전성 유방암

손병호,안세현,이민혁,박수경,김성원 한국유방암학회 2008 Journal of breast cancer Vol.11 No.1

Hereditary breast carcinomas associated with BRCA1/2 mutations have unique clinicopathological and epidemiological characteristics. The objective of this study is to outline the prevalence, founder effect and clinicopathological characteristics of BRCA1/2 mutations for hereditary breast cancers from an analysis of reports recently published regarding Korean subjects. The prevalence of BRCA1 and/or BRCA2 mutations is 2.5–3.1% for sporadic breast cancers, 19.4–42.9% for familiar breast cancer patients with two or more affected first- and second- degree relatives with breast or ovarian cancers and 9.6–18.3% for early breast cancers. Common mutations for the Korean subjects were 2552delC, 3476insA, 4184del4, 5589del8, and 5615del111insA for BRCA1; and 7708C>T for BRCA2. These mutations were not found in Ashkenazi Jewish or Icelandic subjects. The proportion of estrogen or progesterone receptor (ER/PR) or ER/PR/HER2 triple negative status, basal-like phenotype as detected by immunohistochemical staining, and undifferentiated histological grade in Korean BRCA mutation subjects were higher than in subjects lacking BRCA1/2 mutations. Our review found that previous studies describing BRCA mutations among Korean subjects were limited. Since the clinicopathological, phenotypic and epidemiological characteristics of the BRCA1/2 mutations among Korean subjects are different from those among subjects from the Americas and Europe, more studies of hereditary or familial breast cancer including BRCA mutations must be conducted. A large-scale prospective study called KOHBRA (Korean Hereditary Breast Cancer Study) was started from May 2007, and future information provided by the KOHBRA study will make a substantial contribution to solving the basic questions in etiology, individual susceptibility and clinicopathological characteristics for hereditary breast cancer among Korean subjects.