Survival Outcomes of Patients With Breast Cancer Diagnosed Using Vacuum-Assisted Biopsy:A Nationwide Study From the Korean Breast Cancer Society / 한국유방암학회지

Purpose@#Breast cancer is mainly diagnosed using core needle biopsy (CNB), although other biopsy methods, including vacuum-assisted biopsy (VAB), may also be used. We compared differences in clinical characteristics and prognoses of patients with breast cancer according to biopsy methods used for diagnosis. @*Methods@#A total of 98,457 patients who underwent various biopsy methods (CNB, fine-needle aspiration [FNA], VAB, and excisional biopsy) for diagnosing breast cancer were recruited. Using CNB as a reference, related clinicopathological factors and prognostic differences between biopsy methods were analyzed retrospectively using large-scale data from the Korean Breast Cancer Society Registration System. The associations between biopsy methods and clinicopathological factors were compared using multinomial logistic regression analysis, and the prognoses of patients undergoing the different biopsy methods, as breast cancer-specific survival (BCSS) and overall survival (OS), were compared using the Kaplan-Meier method and Cox proportional hazard model. @*Results@#Univariate and multivariate analyses showed that unlike FNA, both VAB and excisional biopsy were significantly associated with tumor size, palpability, tumor stage, and histologic grade as relatively good prognostic factors compared to CNB. In particular, VAB showed lower odds ratios for these factors than excisional biopsy. In the univariate analysis, the prognosis of patients undergoing VAB was better than that of those undergoing CNB with respect to BCSS (hazard ratio [HR], 0.188, p < 0.001) and OS (HR, 0.359; p < 0.001). However, in the multivariate analysis, there were no significant prognostic differences from CNB in both BCSS and OS; differences were only evident for FNA. @*Conclusion@#In this study, we showed that the characteristics of breast cancer differed according to various biopsy methods. Although VAB is not a standard method for breast cancer diagnosis, it showed no prognostic differences to CNB.

Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006) / 한국유방암학회지

Purpose@#In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. @*Methods@#In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. @*Results@#Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. @*Conclusion@#Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006) / 한국유방암학회지

Purpose@#In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. @*Methods@#In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. @*Results@#Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. @*Conclusion@#Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Prognostic Value of Skeletal Muscle Depletion Measured on Computed Tomography for Overall Survival in Patients with Non-Metastatic Breast Cancer / 한국유방암학회지

PURPOSE: The purpose of this study was to evaluate the prognostic value of skeletal muscle depletion measured on computed tomography (CT) in patients with non-metastatic invasive breast cancer.METHODS: This retrospective study included 577 consecutive women (mean age ± standard deviation: 48.9 ± 10.2 years with breast cancer who underwent a preoperative positron-emission tomography (PET)/CT scan and curative surgery between January 2012 and August 2014. The total abdominal muscle area (TAMA), subcutaneous fat area (SFA), and visceral fat area (VFA) were measured on CT images at the L3 vertebral level. Univariate and multivariate Cox proportional-hazard regression analyses were performed to evaluate whether there was an association between sarcopenia and overall survival (OS) outcome.RESULTS: Of the 577 women, 49 (8.5%) died after a mean of 46 months. The best TAMA threshold for predicting OS was 83.7 cm². The multivariate Cox proportional-hazard analysis revealed that sarcopenia (TAMA ≤ 83.70 cm²) was a strong prognostic biomarker (hazard ratio [HR], 1.951; 95% confidence interval [CI], 1.061–3.586), along with large tumor size, axillary lymph node metastasis, high nuclear grade, estrogen receptor status, and adjuvant radiation therapy. In the subgroup analysis of patients aged ≥ 50 years, TAMA (≤ 77.14 cm²) was a significant independent factor (HR, 2.856; 95% CI, 1.218–6.695).CONCLUSION: Skeletal muscle depletion measured on CT was associated with worse OS outcome in patients with non-metastatic breast cancer.

Intraoperative Specimen Mammography for Margin Assessment in Breast-Conserving Surgery / 한국유방암학회지

Small bowel obstruction from distant metastasis of primary breast cancer: a case report

Gastrointestinal (GI) tract metastasis of primary breast cancer is very rare. We present a patient with small bowel obstruction from distant metastasis of primary breast cancer. Each characteristic features of concern of GI tract distant metastasis from many pervious studies has been reported differently. We should remember that GI tract metastasis may coexist when patients with breast cancer have intermittent or recurrent abdominal pain with or without obstructive symptoms.

Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment / 한국유방암학회지

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from −0.39 at baseline to −0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.

Clinical Characteristics and Prognosis Associated with Multiple Primary Cancers in Breast Cancer Patients / 한국유방암학회지

PURPOSE: Breast cancer is one of the most common malignancies worldwide and the second most common cancer among Korean women. The prognosis of breast cancer is poor in patients with other primary cancers. However, there have been few clinical studies regarding this issue. Therefore, we analyzed the characteristics and prognosis of patients with breast cancer with multiple primary cancers (MPCs). METHODS: Data from the Korean Breast Cancer Society Registry were analyzed. Data from enrolled patients who underwent surgery for breast cancer were analyzed for differences in prognosis dependent on the presence of MPCs, and which MPC characteristics affected their prognosis. RESULTS: Among the 41,841 patients analyzed, 913 patients were found to have MPCs, accounting for 950 total MPCs. There was a significant difference in survival rates between the breast cancer only group and the MPC group. The 5-year survival rates were 93.6% and 86.7% and the 10-year survival rates were 87.5% and 70.4%, respectively. Among the 913 patients with MPCs, patients with two or more MPCs had significantly worse prognoses than patients with a single MPC. With respect to the time interval between breast cancer and MPC occurrence, patients with a 5-year or greater interval had significantly better prognoses than patients with less than 1 year between occurrences. Among MPCs, thyroid cancer was the most common primary cancer. However, this type was not related to the prognosis of breast cancer. Gynecologic cancer, colorectal cancer, upper gastrointestinal cancer, and lung cancer were related to breast cancer prognosis. CONCLUSION: MPCs were a poor prognostic factor for patients with breast cancer. Two or more MPCs and a shorter time interval between occurrences were worse prognostic factors. Although MPCs were a poor prognostic factor, thyroid cancer did not affect the prognosis of patients with breast cancer.

Identification of the Thioredoxin-Like 2 Autoantibody as a Specific Biomarker for Triple-Negative Breast Cancer / 한국유방암학회지

Triple-negative breast cancer (TNBC) has a higher risk of death within 5 years of being diagnosed than the other forms of breast cancer. It is the second leading cause of death due to cancer among women. Currently, however, no diagnostic blood-based biomarker exists to identify the early stages of TNBC. To address this point, we utilized a human protein microarray system to identify serum autoantibodies that showed different expression patterns between TNBC and normal serum samples, and identified five autoantibodies showing TNBC-specific expression. Among them, we selected the thioredoxin-like 2 (TXNL2) autoantibody and evaluated its diagnostic relevance by dot blot analysis with the recombinant TXNL2 protein. We demonstrated that the TXNL2 autoantibody showed 2- to 6-fold higher expression in TNBC samples than in normal samples suggesting that serum TXNL2 autoantibodies are potential biomarkers for TNBC.

The Effect of Reproductive Factors on Breast Cancer Presentation in Women Who Are BRCA Mutation Carrier / 한국유방암학회지

PURPOSE: Germline mutations in the BRCA1 and BRCA2 genes confer increased risks for breast cancers. However, the clinical presentation of breast cancer among women who are carriers of the BRCA1 or BRCA2 (BRCA1/2 carriers) mutations is heterogenous. We aimed to identify the effects of the reproductive histories of women with the BRCA1/2 mutations on the clinical presentation of breast cancer. METHODS: We retrospectively analyzed clinical data on women with proven BRCA1 and BRCA2 mutations who were recruited to the Korean Hereditary Breast Cancer study, from 2007 to 2014. RESULTS: Among the 736 women who were BRCA1/2 mutation carriers, a total of 483 women had breast cancers. Breast cancer diagnosis occurred at significantly younger ages in women who experienced menarche at ≤14 years of age, compared to those who experienced menarche at >14 years of age (37.38±7.60 and 43.30±10.11, respectively, p<0.001). Additionally, the number of full-term pregnancies was significantly associated with the age of diagnosis, especially in women with the BRCA2 mutation. The prevalence of advanced stages (stage II or III vs. stage I) of disease in parous women was higher than in nulliparous women (68.5% vs. 55.2%, p=0.043). This association was more pronounced in women with the BRCA2 mutation (hazard ratio, 2.67; p=0.014). CONCLUSION: Our results suggest that reproductive factors, such as the age of onset of menarche and the presence of parity, are associated with the clinical presentation patterns of breast cancer in BRCA1/2 mutation carriers.

A Multicenter Phase II Trial of Neoadjuvant Chemotherapy with Docetaxel and Gemcitabine in Locally Advanced Breast Cancer / 한국유방암학회지

PURPOSE: The current multicenter phase II study was conducted to evaluate the efficacy and safety of the combination of docetaxel and gemcitabine as neoadjuvant chemotherapy (NAC) for locally advanced breast cancer. METHODS: A total of 98 patients with stage II–III breast cancer were enrolled. The primary endpoint was pathological complete response (pCR) rate of invasive cancer after the completion of the fourth cycle of NAC. The secondary endpoints included response rate (RR), rate of breast-conserving surgery, toxicity, and disease-free survival (DFS). This study is registered with ClinicalTrials.gov (NCT01352494). RESULTS: pCR in the breast and the axillary lymph node was observed in seven of the 98 enrolled patients (7.1%). The overall clinical RR, including partial responses, was 65.3%. Breast-conserving surgery was performed in 75 of the 98 assessable patients (76.5%). Neutropenia was frequent and was observed in 92 of the 98 patients (93.9%), including grade 3 and 4 in 24 patients (24.5%) and 63 patients (64.3%), respectively. Dose reductions were required for 30 of the 92 patients (32.6%). After a median follow-up of 24 months, the overall DFS of the group was 86.7%. CONCLUSION: The combination of docetaxel and gemcitabine did not improve pCR. However, this regimen has shown potential as a NAC by producing a reasonable rate of breast-conserving surgery and favorable responses in patients with locally advanced breast cancer. The therapeutic efficacy of this regimen will be determined in additional trials to overcome the limitations of the current study.

Metabolic Activity of Normal Glandular Tissue on ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: Correlation with Menstrual Cycles and Parenchymal Enhancements / 한국유방암학회지

PURPOSE: The aims of our study were to correlate the degree of metabolic activity in normal glandular tissue measured on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) with qualitative background parenchymal enhancement (BPE) grades on magnetic resonance imaging (MRI), and to investigate the change in standardized uptake value (SUV) according to the patients' menstrual cycles. METHODS: From January 2013 to December 2015, 298 consecutive premenopausal patients with breast cancer who underwent both breast MRI and 18F-FDG PET/CT were identified. BPE was evaluated in the contralateral breast of cancer patients and categorized as minimal, mild, moderate, or marked based on Breast Imaging Reporting and Data System criteria. We analyzed the correlation between BPE and maximum SUV (SUVmax) and mean SUV (SUVmean) values. We also analyzed the metabolic activity of normal glandular tissue according to the patients' menstrual cycles. RESULTS: The mean SUVmax and SUVmean values differed significantly according to BPE grade (p < 0001), with the lowest values occurring in the minimal group and the highest values occurring in the marked group. Spearman's correlation coefficients revealed moderate correlations between BPE grade and SUVmax (r=0.472, p < 0.001) and BPE and SUVmean (r=0.498, p < 0.001). The mean SUVmax and SUVmean values differed significantly according to the patients' menstrual cycles, with the highest values in the 3rd week and the lowest value in the 2nd week. Of 29 patients with low metabolic parenchyma (high BPE but low SUVmean values), 17 (58.6%) were in the 4th week of their menstrual cycle. CONCLUSION: The metabolic activity of normal breast parenchyma, which is highest in the 3rd week and lowest in the 2nd week of the menstrual cycle, correlates moderately with BPE on MRI. Metabolic activity tends to be lower than blood flow and vessel permeability in the 4th week of the menstrual cycle.

Sentinel Lymph Node Biopsy Alone after Neoadjuvant Chemotherapy in Patients with Initial Cytology-Proven Axillary Node Metastasis / 한국유방암학회지

PURPOSE: Neoadjuvant chemotherapy (NAC) has been recently used to downstage breast cancer. However, in patients with initial axillary lymph node (ALN) metastasis, ALN dissection regardless of the NAC response remains the standard treatment. The purpose of this study was to identify the feasibility and accuracy of sentinel lymph node biopsy (SLNB) after NAC in patients with ALN metastasis at diagnosis. METHODS: From January 2007 to August 2013, data of patients who were diagnosed with invasive breast cancer and ALN metastasis and treated with NAC followed by definitive surgery in two centers were collected retrospectively. A total of 386 patients were enrolled and classified into five groups according to surgical procedure for the ALNs and pathologic results. RESULTS: At SLNB after NAC, sentinel lymph nodes (SLNs) that stained blue or were hot, including suspicious nodes, were identified; the SLN identification and false-negative rates was 96% and 10%, respectively. There was no difference in the overall survival among the groups. For patients who revealed a pathologic complete node response, there was a significant difference in the disease-free survival rate between the SLNB only and complete ALN dissection groups (p=0.031). However, the rate of axillary recurrence demonstrated no significant differences among the groups (p>0.050). CONCLUSION: SLNB after NAC in breast cancer patients with initial ALN metastasis may help identify downstaging to negative nodal status and thereby reduce the surgical morbidity by avoiding standard ALN dissection.

Histologic Grade and Decrease in Tumor Dimensions Affect Axillary Lymph Node Status after Neoadjuvant Chemotherapy in Breast Cancer Patients / 한국유방암학회지

PURPOSE: The purposes our study was to find out any histologic factors associated with negative conversion of axillary lymph node (ALN) after neoadjuvant chemotherapy (NAC). We also evaluated the association between the decrease in size of primary breast tumor and negative conversion of ALN. METHODS: From January 2012 to November 2014, we included 133 breast cancer patients who underwent NAC and who had ALN metastases which were confirmed on fine-needle aspiration or core needle biopsy at initial diagnosis. All 133 patients underwent initial magnetic resonance imaging (MRI) at the time of diagnosis and preoperative MRI after completion of NAC. We measured the longest dimension of primary breast cancer on MRI. RESULTS: Of 133 patients, 39 patients (29%) showed negative conversion of ALN and of these 39 patients, 25 patients (64%) showed pathologic complete remission of primary breast. On univariate analysis, mean percent decrease in longest dimension, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status and histologic grade were significantly associated with the ALN status after NAC (p<0.001, p=0.001, p< 0.001, p=0.001, p=0.002, respectively). On multivariate logistic regression analysis, percent decrease in longest dimension (odds ratio, 1.026; 95% confidence interval [CI], 1.009-1.044) and histologic grade (odds ratio, 3.964; 95% CI, 1.151-13.657) were identified as being independently associated with the ALN status after NAC. The area under the receiver operating characteristic curve was 0.835 with the best cutoff value of 80% decrease in longest dimension. Combination of high histologic grade and more than 80% decrease in longest dimension showed 64% sensitivity and 92% specificity. CONCLUSION: High histologic grade and more than 80% decrease in primary tumor dimension were associated with negative conversion of ALN after NAC.

Validation of Risk Assessment Models for Predicting the Incidence of Breast Cancer in Korean Women / 한국유방암학회지

PURPOSE: The Gail model is one of the most widely used tools to assess the risk of breast cancer. However, it is known to overestimate breast cancer risk for Asian women. Here, we validate the Gail model and the Korean model using Korean data, and subsequently update and revalidate the Korean model using recent data. METHODS: We validated the modified Gail model (model 2), Asian American Gail model, and a previous Korean model using screening patient data collected between January 1999 and July 2004. The occurrence of breast cancer was confirmed by matching the resident registration number with data from the Korean Breast Cancer Registration Program. The expected-to-observed (E/O) ratio was used to validate the reliability of the program, and receiver operating characteristics curve analysis was used to evaluate the program's discriminatory power. There has been a rapid increase in the incidence of breast cancer in Korea, and we updated and revalidated the Korean model using incidence and mortality rate data from recent years. RESULTS: Among 40,229 patients who were included in the validation, 161 patients were confirmed to have developed breast cancer within 5 years of screening. The E/O ratios and 95% confidence intervals (CI) were 2.46 (2.10-2.87) for the modified Gail model and 1.29 (1.11-1.51) for the Asian American Gail model. The E/O ratio and 95% CI for the Korean model was 0.50 (0.43-0.59). For the updated Korean model, the E/O ratio and 95% CI were 0.85 (0.73-1.00). In the discriminatory power, the area under curve and 95% CI of the modified Gail model, Asian American Gail model, Korean model and updated Korean model were 0.547 (0.500-0.594), 0.543 (0.495-0.590), 0.509 (0.463-0.556), and 0.558 (0.511-0.605), respectively. CONCLUSION: The updated Korean model shows a better performance than the other three models. It is hoped that this study can provide the basis for a clinical risk assessment program and a future prospective study of breast cancer prevention.

The Change of Practice Patterns of the Hereditary Breast Cancer Management in Korea after the Korean Hereditary Breast Cancer Study / 한국유방암학회지

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 follow-up 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 2007 survey. 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.

The Breast and Ovarian Cancer Risks in Korea Due to Inherited Mutations in BRCA1 and BRCA2: A Preliminary Report / 한국유방암학회지

PURPOSE: To estimate the cumulative risk till each age (penetrance) of breast and ovarian cancers among female family members with BRCA1 and BRCA2 mutation. METHODS: Among the 61 BRCA1 mutation carriers in the 42 families and 47 BRCA2 mutation carriers in 31 families identified at 5 academic breast clinics, the probands were excluded to estimate the cumulative risk till each age of breast cancer in the Korean BRCA1 and BRCA2 carriers. Using Kaplan-Meier analyses, cumulative cancer risk estimates were determined. RESULTS: By the age 70, the female breast cancer risk for the BRCA1 and BRCA2 mutation carriers was 72.1% (95% confidence interval [CI]=59.5% to 84.8%) and 66.3% (95% CI=41.2% to 91.5%), respectively, and the ovarian cancer risk was 24.6% (95% CI=0% to 50.3%) and 11.1% (95% CI=0% to 31.6%), respectively. The contralateral breast cancer risk at 5 years after primary breast cancer was estimated as 16.2% (95% CI=9.3% to 23.1%) for the 52 breast cancer patients with the BRCA1 mutation and 17.3% (95% CI=9.7% to 24.0%) for the 35 breast cancer patients with the BRCA2 mutation. CONCLUSION: The penetrance of BRCA mutations in Korea is largely consistent with the previous studies on Western populations. However, the small number of the cases, the high proportions of probands in the study subjects, the short term follow-up, and large confidence intervals are the limitations of the current study. The Korean Hereditary Breast Cancer Study (KOHBRA Study) may definitely answer this question.