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This study was performed to investigate the prevalence, clinical characteristics, and treatment response according to BRCA1 and BRCA2 (BRCA) mutations in Korean patients with epithelial ovarian cancer (EOC). Two‐hundred and ninety‐eight Korean women diagnosed with high‐grade serous and/or endometrioid EOC from 2010 to 2015 were tested for germline and 86 specimens for somatic BRCA mutations, regardless of the family history. Clinical characteristics including survival outcomes were compared in patients with and without BRCA mutations (NCT02963688). A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. Haplotype analysis demonstrated no founder mutations in our Korean patient cohort. Insignificant differences in age at diagnosis, primary site, and residual disease after surgery were observed between patients with and without BRCA mutations. In multivariate analysis for overall survival (OS), the presence of BRCA mutation was significantly associated with OS (P =.049) in addition to platinum sensitivity (P <.001), indicating it is an independent prognostic factor for survival regardless of platinum sensitivity to first‐line chemotherapy. In addition, a higher response rate to subsequent chemotherapy after recurrence was observed in EOC patients with BRCA mutations resulting in better OS. In the current study, the prevalence of BRCA mutations in Korean patients with EOC was higher than previously reported in other ethnic groups. We demonstrated characteristics and treatment response in Korean EOC patients with BRCA mutations. These findings may provide valuable information to be considered in future clinical trials including Asian patients. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence has demonstrated platinum-based chemotherapy followed by maintenance therapy with a poly Adenosine diphosphate (ADP)-ribose polymerase inhibitor (olaparib) show benefits in unresectable pancreatic cancer with a germline (g)BRCA1/2 mutation. Evaluation of the germline BRCA1 and BRCA2 mutation is essential for making decisions on a treatment strategy for patients with unresectable pancreatic cancer. However, the detection rates of germline BRCA1 and BRCA2 mutations and efficacy of maintenance with olaparib remain undetermined, prospectively, in Japan., Methods & Results: In this prospective analysis, the rate of germline BRCA1 and BRCA2 mutations and efficacy of chemotherapy were analyzed in 136 patients with pancreatic cancer who underwent BRACAnalysis® (85 patients) or FoundationOne® CDx (51 patients) between January 2020 and July 2022. A total of six patients (4.4%) had a germline BRCA1 and BRCA2 mutation. Five patients were treated with modified FOLFIRINOX and one with fluorouracil and oxaliplatin. All patients continued platinum-based chemotherapy for ˃4 months and were subsequently treated with olaparib as a maintenance therapy. The response rate to platinum-based chemotherapy in the germline BRCA1 and BRCA2 mutation-positive group was significantly better than that of the germline BRCA1 and BRCA2 mutation-negative group (66% vs 23%, P = 0.04). All patients harbouring a germline BRCA1 and BRCA2 mutation were able to switch to olaparib. The median progression-free survival using olaparib was 5.7 months (range 3.0-9.2)., Conclusions: The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies.An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Purpose We investigated the clinical relevance and spectrum of BRCA1/2mutations in Korean ovarian cancer (KoOC) patients. Materials and Methods Two hundred seventy-nine KoOC patients were enrolled from three university hospitals between 2012 and 2017. Their peripheral blood samples were obtained for BRCA1/2 mutation analysis by direct sequencing. Clinicopathological characteristics were retrospectively reviewed, and spectrum analyses of BRCA1/2mutation were assessed by systematic literature review. Results Frequency of BRCA1/2mutations was 16.5% in KoOC patients. BRCA1/2mutations were significantly associated with family history of breast/ovarian cancer (p < 0.001), serous histology (p=0.044), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV, p=0.018) but not with early age-of-onset (age < 50, p=0.729). Literature review of BRCA1/2mutations in KoOC patients found 111 (55 distinct) mutations with high proportion of Korean-specific mutations (24/55, 43.6%). Comparing the spectrum of BRCA1/2 mutation between KoOC and Korean breast cancer (KoBC) patients, the ratio of BRCA1-to-BRCA2mutations was different, with BRCA1 (78.4%) being predominant in KoOC and BRCA2 in KoBC (59.2%). The most common mutation also differed between the two (c.3627insA of BRCA1 in KoOC and c.7480C>T of BRCA2 in KoBC). Conclusion The clinical relevance of BRCA1/2 mutations in KoOC patients was confirmed but that of early age-of-onset was not. Possible inconsistency in the ratio of BRCA1-to-BRCA2mutations and the most common mutation between KoOC and KoBC may probably suggest presence of mutation sequence-associated penetrance tendency in hereditary Korean breast and ovarian cancer. These data may provide insights for optimal genetic counseling and prophylactic treatment for at-risk relatives of KoOC patients. [ABSTRACT FROM AUTHOR]

Porous silicon double-layer (PSiDL) was fabricated to reduce noise for biosensing measurements via reflectometric interference Fourier transform spectroscopy (RIFTS). The design of the top layer was performed to trap the bio-analyte molecules by their larger diameter pores. However, by constructing the smaller diameter pores on the bottom layer, attempts were made to prevent these molecules from entering the pores as much as possible. Thus, the top layer acted as the sensing layer, whereas the bottom layer played a reference layer role. The Field emission scanning electron microscopy (FE-SEM) revealed that the top and bottom layers had pores with the highest diameter frequency of about 19 and 7 nm, respectively. Surface modification was performed for both layers and was confirmed by Fourier transform infra-red spectroscopy (FTIR) and RIFTS. Modified PSiDL nanostructure was then used to detect the high penetrance breast cancer susceptibility gene, BRCA1, via RIFTS. Examination of both the peaks' location in fast Fourier transform (FFT) of reflection graphs and amplitude value of these peaks was performed. Both analyses showed that the top layer noise could be reduced by using the bottom layer signal. [Display omitted] • Two-step porosity was created on silicon: larger (smaller) pores on top (bottom). • Fourier transform of reflection spectrum analyzed the signal of layers separately. • In biosensing process, top layer noise was reduced by the bottom layer signal. [ABSTRACT FROM AUTHOR]

Background: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for BRCA1/2 mutation carriers because of their increased risk of ovarian carcinoma. Despite RRSO, metachronous peritoneal carcinomatosis occasionally is diagnosed.Methods: The literature was searched for BRCA1/2 mutation carriers with peritoneal carcinomatosis after risk-reducing surgery. The authors were asked for additional data. Clinical and histopathological data were descriptively analyzed. Cases were compared with a single-institution control cohort.Results: Of 36 cases, 86.1% concerned BRCA1 mutation carriers. The median age of the patients was 52 years (range, 30-71 years) at the time of risk-reducing surgery and 60 years (range, 37-75 years) at the time of diagnosis of peritoneal carcinomatosis. The median interval between the 2 events was 54.5 months (range, 11-292 months). Peritoneal carcinomatosis was mostly high-grade serous carcinoma. Histopathological details of the RRSO specimens were retrieved in 8 cases; 5 (62.5%) were found to have serous tubal intraepithelial carcinoma and 1 had epithelial atypia. Cases were older (P = .025) at the time of risk-reducing surgery and harbored more serous tubal intraepithelial carcinomas (P<.001) compared with women from the control cohort.Conclusions: Metachronous peritoneal carcinomatosis after risk-reducing surgery occurs predominantly in BRCA1 mutation carriers, usually within 5 years. Data have suggested that surgery at a younger age lowers the rates of peritoneal carcinomatosis. These data can be used in the gynecologic counseling of BRCA1/2 mutation carriers. RRSO should include complete salpingectomy. Detailed histopathological examination of specimens removed during RRSO is essential. Cancer 2018;124:952-9. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

The Korean Hereditary Breast Cancer (KOHBRA) study was established to evaluate the prevalence and spectrum of BRCA1/ 2 mutations in Korean breast cancer patients at risk for hereditary breast and ovarian cancer. A total of 2953 subjects (2403 index patients and 550 family members of affected carriers) from 36 centers participated in this study between May 2007 and December 2013. All participants received genetic counseling and BRCA genetic testing. In total, 378 mutation carriers among 2403 index patients were identified. The prevalence of BRCA mutations in specific subgroups was as follows: 22.3 % (274/1228) for breast cancer patients with a family history of breast/ovarian cancers, 8.8 % (39/441) for patients with early-onset (<35 years) breast cancer without a family history, 16.3 % (34/209) for patients with bilateral breast cancer, 4.8 % (1/21) for male patients with breast cancer, and 37.5 % (3/8) for patients with both breast and ovarian cancer. From an analysis of the mutation spectrum, 63 BRCA1 and 90 BRCA2 different mutations, including 44 novel mutations, were identified. The c.7480 (p.Arg2494Ter) mutation in BRCA2 (10.1 %) was the most commonly identified in this cohort. The KOHBRA study is the largest cohort to identify BRCA mutation carriers in Asia. The results suggest that the prevalence of BRCA mutations in familial breast cancer patients is similar to that among Western cohorts. However, some single risk factors without family histories (early-onset breast cancer, male breast cancer, or multiple organ cancers) may limit the utility of BRCA gene testing in the Korean population. [ABSTRACT FROM AUTHOR]

Purpose To address the widespread concern that false-positive results during breast MRI screening may have adverse psychological effects. Methods Impact of Event Scale measurements in 103 high-risk women enrolled in a longitudinal MRI screening study and comparison of subjects with normal results vs. those with prior recall events. Results Of 189 MRI scans performed, 64 (34%) prompted further evaluation. Subjects with previously abnormal results had significantly higher Avoidance scores at the time of their second MRI. Multivariate analysis showed this was driven by the greater number of BRCA1/2 carriers in that group but was not related to screening recall. Conclusions Practitioners’ concerns about the high false positive rate of breast MRI may not be matched by actual psychological effects in most high-risk women. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the clinical relevance and spectrum of BRCA1/2 mutations in Korean ovarian cancer (KoOC) patients., Materials and Methods: Two hundred seventy-nine KoOC patients were enrolled from three university hospitals between 2012 and 2017. Their peripheral blood samples were obtained for BRCA1/2 mutation analysis by direct sequencing. Clinicopathological characteristics were retrospectively reviewed, and spectrum analyses of BRCA1/2 mutation were assessed by systematic literature review., Results: Frequency of BRCA1/2 mutations was 16.5% in KoOC patients. BRCA1/2 mutations were significantly associated with family history of breast/ovarian cancer (p<0.001), serous histology (p=0.044), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV, p=0.018) but not with early age-of-onset (age < 50, p=0.729). Literature review of BRCA1/2 mutations in KoOC patients found 111 (55 distinct) mutations with high proportion of Korean-specific mutations (24/55, 43.6%). Comparing the spectrum of BRCA1/2 mutation between KoOC and Korean breast cancer (KoBC) patients, the ratio of BRCA1-to-BRCA2 mutations was different, with BRCA1 (78.4%) being predominant in KoOC and BRCA2 in KoBC (59.2%). The most common mutation also differed between the two (c.3627insA of BRCA1 in KoOC and c.7480C>T of BRCA2 in KoBC)., Conclusion: The clinical relevance of BRCA1/2 mutations in KoOC patients was confirmed but that of early age-of-onset was not. Possible inconsistency in the ratio of BRCA1-to-BRCA2 mutations and the most common mutation between KoOC and KoBC may probably suggest presence of mutation sequence-associated penetrance tendency in hereditary Korean breast and ovarian cancer. These data may provide insights for optimal genetic counseling and prophylactic treatment for at-risk relatives of KoOC patients.

Purpose: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1 , BRCA2 , or non- BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status., Methods: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non- BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1 , RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed., Results: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non- BRCA1/2 mutation tumors. BRCA2 -associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2 -associated tumors was significantly higher than in non- BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups., Conclusion: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors., Competing Interests: CONFLICT OF INTEREST: The authors declare that they have no competing interests.

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., Competing Interests: CONFLICT OF INTEREST: The authors declare that they have no competing interests.

Objective: The aim of our study was to determine the rate of participation in genetic testing, to determine the reasons for non-participation and to identify the factors affecting participation in BRCA genetic testing for high-risk patients., Methods: This study was performed through a retrospective review of 804 individuals who underwent genetic counseling for BRCA1/2 gene mutations at Seoul National University Bundang Hospital between July 2003 and September 2012., Results: In total, 728 (90.5%) individuals underwent BRCA1/2 mutation screening after the initial genetic counseling; 88.2% of 647 probands and 100% of 157 family members were screened. In multivariate analysis, family history of breast cancer and younger age were independent variables affecting participation in genetic testing. Of the 132 people who initially declined genetic testing, 58 (43.9%) postponed the decision, 30 (22.7%) needed time to discuss the issue with family members, 22 (16.7%) did not want to know if they had a BRCA1/2 mutation, and 22 (16.7%) declined the test because of financial problems. When analyzing refusal of testing according to the time period before and after the implementation of national health insurance coverage for BRCA1/2 genetic testing, the critical reason given for refusal was different. After insurance coverage, refusal for financial reason was decreased from 61.1 to 9.6%., Conclusions: A family history of breast cancer and a younger age were important factors associated with participation in genetic testing. National health insurance decreased the proportion of individuals who did not participate in testing owing to a financial reason. In genetic counseling, we have to understand these issues and consider several factors that may influence an individual's decision to be tested., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Mutations in BRCA genes are the main cause of hereditary breast cancer in Korea. The aim of this study was to investigate the characteristics of breast cancers involving BRCA1 (BRCA1 group) and BRCA2 (BRCA2 group) mutations., Methods: We retrospectively reviewed the medical records of patients with BRCA1 (BRCA1 group) or BRCA2 (BRCA2 group) mutation positive breast cancer from multiple centers and compared the data to that of the Korean Breast Cancer Society registry (registry group)., Results: The patients of the BRCA1 group were diagnosed at a younger age (median age, 37 years) and had tumors of higher histological (61.3% with histological grade 3) and nuclear (37.5% with nuclear grade 3) grade than those of the registry group. In addition, the frequency of ductal carcinoma in situ in the BRCA1 group was lower (3.7%) than in the registry group, and the BRCA1 group were more likely to be triple-negative breast cancer (61.3%). Patients in the BRCA2 group were also younger at diagnosis (mean age, 41 years) and were more likely to have involvement of the axillary node than the registry group (45.5% vs. 33.5%, p=0.002). The BRCA1 and BRCA2 groups did not show a correlation between tumor size and axillary node involvement., Conclusion: We report the characteristics of BRCA mutation positive breast cancer patients in the Korean population through multicenter data and nation-wide breast cancer registry study. However, BRCA-mutated breast cancers appear highly complex, and further research on their molecular basis is needed in Korea.

Most studies related to BRCA mutations have been performed in Western populations, and only a few small studies have been conducted in Korean populations. In 2007, the Korean Hereditary Breast Cancer (KOHBRA) Study was established to obtain evidence for the accurate risk assessment and management of hereditary breast and ovarian cancer (HBOC) in Korea. Between May 2007 and May 2010, the first phase of the KOHBRA Study was performed to estimate the prevalence of BRCA1/2 mutations among patients and their families at risk for HBOC. Between June 2010 and May 2013, the second phase of the KOHBRA Study was performed to identify the clinical characteristics and prognostic indicators of BRCA-related breast cancer and environmental and genetic modifiers of BRCA mutations and to develop a Korean BRCA risk calculator and nationwide genetic counseling network for HBOC. Herein, we review the results of the KOHBRA Study and describe the future perspectives of the study.

Purpose: We investigated the relationship between BRCA mutations, pathological findings, and magnetic resonance imaging (MRI) features in patients with breast cancer at risk for the mutation., Methods: Genetic testing for BRCA mutations was performed in 275 breast cancer patients with at least one risk factor for the mutation. Using the breast imaging reporting and data system MR lexicon, morphological and kinetic features were reviewed on MRI scans of 230 tumors in 209 patients. The relationship between BRCA mutations, pathologic findings, and MRI data was examined, and disease recurrence was estimated., Results: BRCA mutations were detected in 48 patients (23.0%), of which 21 (10.0%) were in BRCA1, and 25 (12.0%) in BRCA2. Additionally, two patients (1.0%) had mutations in both genes. Cancers in patients with BRCA1 mutations more frequently showed a higher nuclear grade (p=0.0041), and triple-negative (TN) phenotype (p<0.0001). On MRI scans, the cancers were seen as mass-type in 182 out of 230 lesions (79.1%), and nonmass type in 48 cases (20.9%). Among the features indentified by MRI, rim enhancement was significantly associated with molecular subtypes based on immunohistochemistry (p<0.0001), and nuclear grade (p=0.0387) in multiple logistic regression analysis. Rim enhancement on MRI, along with advanced pathologic N stage, was associated with increased disease recurrence (p=0.0023) based on multivariate analysis. However, the proportion of mass and nonmass tumors, and the distribution of morphological shape, margin, internal enhancement, and kinetic features assessed by MRI were not different according to BRCA mutation status., Conclusion: BRCA1 mutations were associated with aggressive pathological characteristics, and the TN phenotype. Rim enhancement was frequently seen on MRI scans of high-grade cancers and in the TN phenotype. And it was a significant predictor of disease recurrence. However, a direct association with BRCA mutations was not observed.