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Simple Summary: This research investigates the effects of South Korea's national insurance coverage (NIC) expansion and the inclusion of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. By analyzing data from the Samsung Medical Center, the study reveals a notable increase in testing rates following NIC expansion and the addition of genetic counselors. Particularly noteworthy is the rise in testing rates among triple-negative breast cancer (TNBC) patients under 60. Additionally, the involvement of genetic counselors led to a significant increase in follow-up patients undergoing testing. The NIC expansion also broadened insurance coverage for TNBC patients, thereby enhancing testing accessibility. These findings underscore the positive impact of NIC expansion and genetic counselor involvement on improving patient management. Addressing financial barriers to testing and integrating genetic counseling into healthcare practices present promising strategies for advancing early detection and tailored treatment approaches, thereby contributing to global efforts in cancer care and management. Purpose: This study aims to evaluate the impact of South Korea's national insurance coverage (NIC) expansion and the addition of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. Materials and Methods: A retrospective review was conducted at the Samsung Medical Center (SMC), dividing patients into three groups: pre-NIC expansion, post-NIC expansion, and post-extra genetic counselor involvement. The number of BRCA1/2 tests performed and the detection rates among newly diagnosed and follow-up patients, particularly focusing on triple-negative breast cancer (TNBC) cases, were analyzed. Results: Post-NIC expansion, there was a significant increase in BRCA1/2 testing rates, with a gradual rise in detection rates while maintaining statistical significance. TNBC patients under 60 experienced substantial increases in testing rates. The number of follow-up patients recalled for testing also rose significantly after the extra genetic counselor involvement. Additionally, NIC expansion increased insurance coverage for TNBC patients, enhancing accessibility to testing. Conclusion: The study highlights the positive impact of NIC expansion and genetic counselor involvement on BRCA1/2 mutation testing rates and subsequent patient management. Addressing financial barriers to testing and incorporating genetic counseling significantly improve patient outcomes. This model provides a potential strategy for enhancing early detection and personalized treatment for breast cancer patients with BRCA1/2 mutations, contributing to global cancer management efforts. [ABSTRACT FROM AUTHOR]

Purpose BRCA1/2 mutations are well-known risk factors for breast and ovarian cancers in women. Risk-reducing salpingo-oophorectomy (RRSO) is the standard treatment for preventing ovarian cancer with BRCA mutations. Postmenopausal syndrome (symptoms after RRSO can be alleviated by hormone replacement therapy (HRT); however, the use of HRT in carriers of BRCA mutations has been controversial because of the concern that HRT increases the risk of breast cancer. This study aimed to evaluate the effects of HRT in BRCA mutation carriers who underwent RRSO. Materials and Methods A total of 151 carriers, who underwent RRSO between 2013 and 2020 after the diagnosis of BRCA1 or BRCA2 mutations were selected and followed up for a median of 3.03 years. Patients were divided into two groups: those who received HRT after RRSO (n=33) and those who did not (n=118). We compared the incidence of breast cancer over time between these two groups. Results There was no significant difference in the incidence of breast cancer between women who received HRT and those who did not (p=0.229). Multivariate logistic regression analysis, adjusted for age and parity revealed no significant difference in the risk of breast cancer between these two groups (hazard ratio, 0.312; 95% confidence interval, 0.039 to 2.480; p=0.278). Conclusion In this study, we found no relationship between post-RRSO HRT and breast cancer in the population with BRCA mutations. Therefore, healthcare providers may consider the alleviation of symptoms of postmenopausal syndrome through HRT in patients who underwent RRSO. [ABSTRACT FROM AUTHOR]

Background: BRCA testing is necessary for establishing a management strategy for ovarian cancer. Several BRCA testing strategies, including germline and somatic testing, are implemented in clinical practice in Korea. We aimed to comparatively evaluate their costeffectiveness from patients' perspective. Methods: We developed a decision model comprising five BRCA testing strategies implemented in Korea: (1) germline testing first, followed by somatic tumor testing for patients without a germline variant; (2) somatic testing first, followed by germline testing for patients with a variant detected by somatic testing; (3) both germline and somatic testing; (4) germline testing alone; and (5) somatic testing alone, with no testing as the comparator. One-way sensitivity analysis was conducted to test the uncertainty of key parameters. Results: Assuming a willingness-to-pay of $20,000 per progression-free life-year gain (PFLYG), all five strategies were considered cost-effective. Strategy 4 was the most cost-effective option, with an incremental cost-effectiveness ratio (ICER) of $2,547.7 per PF-LYG, followed by strategy 1, with an ICER of $3,978.4 per PF-LYG. Even when the parameter values were varied within the possible range, the ICERs of all strategies did not exceed the willingness-to-pay threshold. Conclusions: Considering the importance of knowing a patient's BRCA gene status, germline testing first, followed by somatic testing, may be a reasonable option. [ABSTRACT FROM AUTHOR]

Purpose Double heterozygosity (DH) for BRCA1 and BRCA2 variant is very rare with only a few cases reported, and most those in Caucasians. In this article, we present seven unrelated cases of DH for BRCA1/2 identified from a single institution in Korea, and describe the characteristics and phenotype of DH individuals compared to those with a single BRCA variant. Materials and Methods This study included 27,678 patients diagnosed with breast cancer and surgically treated at Samsung Medical Center (SMC) between January 2008 and June 2020. In total, 4,215 high-risk breast cancer patients were tested for the BRCA1/2 genes, and electronic medical records from 456 cases with pathogenic/likely pathogenic variants were reviewed. Results A younger mean age at diagnosis was associated with DH than a single variant of BRCA1/2. More triple-negative breast cancer and higher nuclear and histologic grade cancer occurred with DH than BRCA2 variant. All seven cases of DH were unrelated, and their mutation combinations were different. There were no Ashkenazi founder variants detected. Conclusion We suggest that patients with DH for BRCA1/2 variants develop breast cancer at a younger age, but the histopathologic features are similar to those of BRCA1. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent studies re-classified the c.5339T->C; p.Leu1780Pro (L1780P) BRCA1 missense mutation as "likely pathogenic" in ACMG classification, which shows a high prevalence in the Korean population. This study aims to reveal the molecular mechanisms and therapeutic relevance of BRCA1 L1780P mutation in DNA damaging response of triple-negative breast cancer (TNBC). BRCA1 L1780P BRCT domain mutation has been recognized as a pathogenic mutation in patients with breast cancer. However, the molecular significance of this mutation has not yet been studied in triple-negative breast cancer (TNBC) cells in vitro. We established MDA-MB 231, HCC1937, and HCC1395 TNBC cell lines expressing BRCA1 L1780P mutant. BRCA1 L1780P mutant TNBC cells showed increased migration and invasion capacity, as well as increased sensitivity to olaparib and carboplatin compared to BRCA1 wild-type cells. BRCA1 L1780P mutant TNBC cells showed decreased RAD51 expression and reduced nuclear RAD51 foci formation following carboplatin and olaparib treatment. The molecular interaction between p-ATM and BRCA1 was abrogated following introduction of BRCA1 L1780P mutant plasmid in TNBC cells, suggesting that the BRCA1 L1780P mutation disrupts the p-ATM-BRCA1 protein–protein interaction. We established an olaparib-resistant BRCA1 L1780P mutant TNBC cell line by chronic drug treatment. Olaparib-resistant cell lines showed upregulation of RAD51 expression upon olaparib treatment, and reduction in RAD51 expression in olaparib-resistant cells restored olaparib sensitivity. Collectively, these results suggest that the BRCA1 L1780P mutation impairs RAD51 recruitment by disrupting p-ATM-BRCA1 interaction, which is a crucial molecular factor in homologous recombination and olaparib sensitivity. Further therapeutic targeting of RAD51 in BRCA1 L1780P mutant breast cancer is warranted. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to examine the level of self-concept and psychosocial well-being among women with BRCA1 or BRCA2 gene mutations and to identify factors affecting their psychosocial well-being. Methods: A cross-sectional design was used. Data were collected from an online community comprising Korean patients with breast cancer and their families. A total of 98 women with BRCA1 or BRCA2 gene mutations completed the online questionnaire comprising the BRCA self-concept scale, the psychosocial well-being index-short form, demographic characteristics, and disease-related characteristics. Descriptive statistics, frequencies, independent t-tests, one-way ANOVA, Pearson's correlation, and multiple regression were used for data analysis. Results: The total self-concept level at 82.13±15.45 (range: 17-119), and the psychosocial well-being level at 28.81±9.51 (range: 0-54) indicated a high-risk group of psychosocial well-being among the surveyed women with BRCA gene mutations compared with Korean general office workers. Self-concept (β=.57, p<.001) and monthly family income (≥4,500 USD)(β=-.24, p=.048) significantly affected the psychosocial well-being of women with BRCA1 or BRCA2 gene mutations. Conclusion: The level of self-concept and psychosocial well-being of women with BRCA1 or BRCA2 gene mutations should be assessed carefully, and tailored consultation and educational programs should be developed to overcome a negative self-concept. Supportive systems for financially vulnerable women with BRCA1 or BRCA2 gene mutations should be considered. [ABSTRACT FROM AUTHOR]

At the 73rd Annual Congress of the Japan Society of Obstetrics and Gynecology, young doctors from Japan and South Korea made presentations on the present condition of risk‐reducing surgery for hereditary breast and ovarian cancer (RRSO) in their respective country. RRSO was insured in Japan in April 2020, whereas in South Korea, it was insured 7 years earlier in 2013. In Japan, certification criteria have been set for facilities that perform RRSO, and the number of facilities is increasing, but regional disparities still exist in its distribution. The number of gBRCA1/2 testing facilities is larger, and the cost is more affordable in South Korea than in Japan. Additionally, South Korea provides genetic counseling to a wider range of relatives compared to Japan. In the future, as the indications for the gBRCA1/2 test have expanded as a companion diagnostic for the use of PARP inhibitors, it is expected that the number of candidates for the gBRCA1/2 mutation test and RRSO will increase in Japan. It is important to increase the number of BRCA tests while maintaining the quality of genetic counseling in order to provide adequate information on BRCA mutations and RRSO for patients to support their decision. For the development of hereditary breast and ovarian cancer (HBOC) medical care, it is necessary to publish a nationwide database in Japan and continue to analyze and discuss the data based on the results. [ABSTRACT FROM AUTHOR]

Purpose: The BRCA1/2 gene is the most well-known and studied gene associated with hereditary breast cancer. BRCA1/2 genetic testing is widely performed in high-risk patients of hereditary breast cancer in Korea. This study aimed to investigate the clinicopathological characteristics of BRCA1/2 mutation-positive breast cancer patients. Methods: The clinical data of 188 Korean breast cancer patients who underwent genetic testing of BRCA1/2 mutation between March 2015 and February 2020 at Pusan National University Yangsan Hospital were retrospectively reviewed. The characteristics of breast cancer according to the expression of BRCA1 and BRCA2 mutations were analyzed using the Health Insurance Review and Assessment Service guideline criteria and other clinicopathological factors. Results: The factor associated with BRCA1/2 gene expression was cancer stage, and mutation expression was significantly decreased in stage I compared to stage 0 (p = 0.033; odds ratio [OR], 0.169; 95% confidence interval [CI], 0.033–0.867), and there was a tendency to increase in stage II (p = 0.780; OR, 1.150; 95% CI, 0.432–3.064). BRCA1 was significantly associated with triple-negative breast cancer (TNBC) (p = 0.004; OR, 5.887; 95% CI, 1.778–19.498). Gene expression of BRCA2 was significantly reduced under 40 years of age (p = 0.040; OR, 0.198; 95% CI, 0.042–0.930). There was no difference in disease-free survival (p = 0.900) and overall survival (p = 0.733) between the BRCA1/2 mutation-positive and -negative groups. Conclusion: In this study, the clinicopathological characteristics of breast cancer patients with BRCA1/2 gene mutations were identified. BRCA1 gene expression was highly correlated with TNBC. BRCA1/2 mutation did not have a poor prognosis regarding recurrence and death. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment of BRCA wild-type patients with platinum-sensitive recurrent ovarian cancer remains unknown. Recently, there is an increase in the evidence to support the role of the combination of a poly(adenosine diphosphate-ribose) polymerase inhibitor, anti-angiogenic agents, and immunotherapy as maintenance therapy in BRCA wild-type patients with platinum-sensitive recurrence. We hypothesized that adding pembrolizumab and bevacizumab to olaparib maintenance can increase progression-free survival (PFS) in BRCA wild-type patients with platinum-sensitive recurrent ovarian cancer. Methods: BRCA wild-type patients who received two previous courses of platinum-containing therapy, achieved complete or partial response to last treatment, and the treatment-free interval is >6 months after the penultimate platinum-based chemotherapy offered olaparib maintenance with pembrolizumab and bevacizumab. Forty-four patients will be included from 4 sites across Singapore and Korea. The primary endpoint of the study is 6-month PFS rate. [ABSTRACT FROM AUTHOR]

Background: Poly (ADP-ribose) polymerase inhibitors combined with immunotherapy have shown antitumour activity in preclinical studies. We aimed to assess the safety and activity of olaparib in combination with the PD-L1-inhibitor, durvalumab, in patients with germline BRCA1-mutated or BRCA2-mutated metastatic breast cancer.Methods: The MEDIOLA trial is a multicentre, open-label, phase 1/2, basket trial of durvalumab and olaparib in solid tumours. Patients were enrolled into four initial cohorts: germline BRCA-mutated, metastatic breast cancer; germline BRCA-mutated, metastatic ovarian cancer; metastatic gastric cancer; and relapsed small-cell lung cancer. Here, we report on the cohort of patients with breast cancer. Patients who were aged 18 years or older (or aged 19 years or older in South Korea) with germline BRCA1-mutated or BRCA2-mutated or both and histologically confirmed, progressive, HER2-negative, metastatic breast cancer were enrolled from 14 health centres in the UK, the USA, Israel, France, Switzerland, and South Korea. Patients should not have received more than two previous lines of chemotherapy for metastatic breast cancer. Patients received 300 mg olaparib in tablet form orally twice daily for 4 weeks and thereafter a combination of olaparib 300 mg twice daily and durvalumab 1·5 g via intravenous infusion every 4 weeks until disease progression. Primary endpoints were safety and tolerability, and 12-week disease control rate. Safety was analysed in patients who received at least one dose of study treatment, and activity analyses were done in the full-analysis set (patients who received at least one dose of study treatment and were not excluded from the study). Recruitment has completed and the study is ongoing. This trial is registered with ClinicalTrials.gov, NCT02734004.Findings: Between June 14, 2016, and May 2, 2017, 34 patients were enrolled and received both study drugs and were included in the safety analysis. 11 (32%) patients experienced grade 3 or worse adverse events, of which the most common were anaemia (four [12%]), neutropenia (three [9%]), and pancreatitis (two [6%]). Three (9%) patients discontinued due to adverse events and four (12%) patients experienced a total of six serious adverse events. There were no treatment-related deaths. 24 (80%; 90% CI 64·3-90·9) of 30 patients eligible for activity analysis had disease control at 12 weeks.Interpretation: Combination of olaparib and durvalumab showed promising antitumour activity and safety similar to that previously observed in olaparib and durvalumab monotherapy studies. Further research in a randomised setting is needed to determine predictors of therapeutic benefit and whether addition of durvalumab improves long-term clinical outcomes compared with olaparib monotherapy.Funding: AstraZeneca. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data. Materials and Methods: The data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer-related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study. Results: The median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations. Conclusion: L1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P. [ABSTRACT FROM AUTHOR]

Purpose: The awareness of hereditary breast and ovarian cancer (HBOC) and BRCA testing is increasing 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 f-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 associated with age, education, occupation, genetic counseling, and BRCA mutations. There were no statistically significant factors related to anxiety and there were no statistically significant correlations 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. [ABSTRACT FROM AUTHOR]

Breast cancer is the second most common cancer in Korean women. Germline mutations in the BRCA1 and BRCA2 genes cause hereditary breast cancer and are detected in 15-20% of hereditary breast cancer. We investigated the BRCA1 and BRCA2 mutations in 114 familial breast cancer patients using next-generation sequencing. We confirmed 20 different mutations of BRCA1 and BRCA2 in 25 subjects (21.9%). Two such mutations in eight patients were novel (not reported in any variant database or previous study). Six mutations have been reported as disease-causing mutations in public databases. Seven mutations were found only in a single nucleotide polymorphism database and one mutation has been reported in Korea. The BRCA1/2 mutation frequency was similar to that of other studies on familial breast cancer patients in the Korean population. Further studies should examine more cases and mutations of whole exons. [ABSTRACT FROM AUTHOR]

Simple Summary: In pancreatic ductal adenocarcinoma, FOLFIRINOX and nab-paclitaxel are recommended as first-line chemotherapy regimens. However, there are limited data to predict the efficacy of the FOLFIRINOX regimen in patient outcomes. Platinum-based chemotherapy is tolerable and responsible in patients with DNA damage repair gene mutations. However, data are still limited, and no Asian data are available yet. Here, we sought to investigate the proportion of germline BRCA 1/2 mutations in patients with germline blood tests. Finally, we investigated the treatment response of FOLFIRINOX in patients with BRCA 1/2 mutations. We found that the presence of germline BRCA 1/2 mutations was associated with an improved overall response rate in pancreatic ductal adenocarcinoma patients treated with FOLFIRINOX. The high response rate in this analysis supports the preferential use of FOLFIRINOX therapy for patients harboring a BRCA germline mutation, and supports the need for early germline testing in order to select the best therapy. We evaluated the proportion of BRCA 1/2 germline mutations in Korean patients with sporadic pancreatic ductal adenocarcinoma (PDAC) and its effect on the chemotherapeutic response of FOLFIRINOX. This retrospective study included patients who were treated at two tertiary hospitals between 2012 and 2020, were pathologically confirmed to have PDAC, and had undergone targeted next-generation sequencing-based germline genetic testing. Sixty-six patients were included in the study (24 men; median age 57.5 years). In the germline test, BRCA 1/2 pathogenic mutations were found in nine patients (9/66, 13%, BRCA 1, n = 3; BRCA 2, n = 5; and BRCA 1/2, n = 1). There was no significant difference in the baseline characteristics according to BRCA mutation positivity. Among patients who underwent FOLFIRINOX chemotherapy, patients with a BRCA 1/2 mutation showed a higher overall response rate than those without a BRCA 1/2 mutation (71.4% vs. 13.9%, p = 0.004). Patients with a germline BRCA 1/2 mutation showed longer progression-free survival than those without a BRCA 1/2 mutation, without a significant time difference (18 months vs. 10 months, p = 0.297). Patients with a BRCA 1/2 mutation in the germline blood test had a higher response rate to FOLFIRINOX chemotherapy in PDAC. The high proportion of BRCA 1/2 germline mutations and response rate supports the need for germline testing in order to predict better treatment response. [ABSTRACT FROM AUTHOR]

Simple Summary: Although it has been suggested that cancer risk and genetic variation vary by population, there is still a lack of research on non-European populations. In this study, we applied Korean patients as a model to find out the way to conduct BRCA1/2-related clinical studies in non-European populations who do not have as much clinical data as Europeans. The BRCA1/2 variants were classified following the 2015 ACMG standards/guidelines and using a multifactorial probability-based approach. To estimate the additional sample numbers needed to resolve BRCA1/2 unclassified status, we applied a simulation analysis considering population-specific clinical characteristics. In addition, we estimated the risks of breast or ovarian cancer for BRCA1/2 carriers by mutation regions. Data from this study reveal that BRCA1/2 variants in the non-European population are highly specific; therefore, population-specific study is essential for clinical application of treatment or prevention for breast or ovarian cancer. In this study, we performed a comprehensive analysis of BRCA1/2 variants and associated cancer risk in Korean patients considering two aspects: variants of uncertain significance (VUS) and pathogenic or likely pathogenic variants (PLPVs) in BRCA1 and BRCA2. This study included 5433 Korean participants who were tested for BRCA1/2 genes. The BRCA1/2 variants were classified following the standards/guidelines for interpretation of genetic variants and using a multifactorial probability-based approach. In Korea, 15.8% of participants had BRCA1 or BRCA2 PLPVs. To estimate the additional sample numbers needed to resolve unclassified status, we applied a simulation analysis. The simulation study for VUS showed that the smaller the number of samples, the more the posterior probability was affected by the prior probability; in addition, more samples for BRCA2 VUS than those of BRCA1 VUS were required to resolve the unclassified status, and the presence of clinical information associated with their VUS was an important factor. The cumulative lifetime breast cancer risk was 59.1% (95% CI: 44.1–73.6%) for BRCA1 and 58.3% (95% CI: 43.2–73.0%) for BRCA2 carriers. The cumulative lifetime ovarian cancer risk was estimated to be 36.9% (95% CI: 23.4–53.9%) for BRCA1 and 14.9% (95% CI: 7.4–28.5%) for BRCA2 carriers. [ABSTRACT FROM AUTHOR]

Genetic diagnosis for human epidermal growth factor receptor 2-negative metastatic breast cancer patients with the germline BRCA (gBRCA) mutation has been emphasized since the development of polyadenosine diphosphate-ribose polymerase inhibitors. Myriad Genetics, Inc.'s (Salt Lake City, UT, USA) companion diagnostics service is almost exclusively used for genetic testing. The aim of this study was to compare the results of germline BRCA mutation tests returned by a local laboratory and those performed by Myriad. Between April 2014 and February 2018, 31 patients with gBRCA 1/2 mutation test results from both Samsung Medical Center (Seoul, Korea) and Myriad were enrolled. "Discordant: Opposite classification" was observed for only one among 27 (3.7%). This discrepancy was due to the detection of a deleterious large genomic rearrangement of BRCA 1 by Myriad. Samsung Medical Center performed multiple ligation-dependent probe amplifications (MLPA) to detect large genomic rearrangements only in high-risk patients. This one case was not suspected as high risk and MLPA was not performed. The concordant rate was 74.1% for all 27 patients. "Discordant: Laboratory's uncertain classification" was found in 22.2% of the sample (six patients). All discrepancies were generated during interpretation of BRCA 2 gene sequencing. Further studies and standardization of genetic testing for BRCA 1/2 genes are required. [ABSTRACT FROM AUTHOR]

Vitis coignetiaePulliat (Meoru in Korea) has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. Evidence suggests that NF-κB activation is mainly involved in cancer cell proliferation, invasion, angiogenesis, and metastasis. TNF-α also enhances the inflammatory process in tumor development. Recently, flavonoids from plants have been reported to have inhibitory effects on NF-κB activities. We investigated the effects of anthocyanins extracted from the fruits of Vitis coignetiae Pulliat (AIM, anthocyanins isolated from Meoru (AIM)) on TNF-α-induced NF-κB activities in MCF-7 human breast cancer cells and the molecules involved in AIM-induced anti-cancer effects, especially on cancer metastasis. We performed cell viability assay, gelatin zymography, invasion assay, and western blot analysis to unravel the anti-NF-κB activity of AIMs on MCF-7 cells. AIM suppressed the TNF-α effects on the NF-κB-regulated proteins involved in cancer cell proliferation (COX-2, C-myc), invasion, and angiogenesis (MMP-2, MMP9, ICAM-1, and VEGF). AIM also increased the expression of E-cadherin, which is one of the hallmarks of the epithelial-mesenchymal transition (EMT) process. In conclusion, this study demonstrates that the anthocyanins isolated from the fruits of Vitis coignetiae Pulliat acts as an inhibitor of TNF-α induced NF-κB activation, and subsequent downstream molecules involved in cancer proliferation, invasion, adhesion, angiogenesis, and thus have anti-metastatic activities in MCF-7 breast cancer cells. [ABSTRACT FROM AUTHOR]

There are few reports of breast cancer patients who carry germline mutations in both germline breast cancer susceptibility genes 1 (gBRCA1) and 2 (gBRCA2). In this study, we analyzed the clinical, pathological, and genomic characteristics of Korean breast cancer patients with both gBRCA1 and gBRCA2 mutations. Medical records of patients who received gBRCA1 and gBRCA2 testing at Samsung Medical Center between January 2007 to October 2018 were retrospectively reviewed. Genomic DNA was isolated from peripheral blood leukocytes. Among a total of 2720 patients, four patients with both gBRCA1 and gBRCA2 mutations were identified (4/2720; 0.14%). Seven patients who had a gBRCA1 mutation and gBRCA2 variants of uncertain significance (VUS) were also identified. In those patients with both gBRCA1 and gBRCA2 mutations, the mean age at diagnosis for breast cancer was 36 years (range, 31–43 years). All four tumors were infiltrating ductal carcinomas and three of the tumors were estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative (triple-negative). All four patients who carried germline mutations in both BRCA1 and BRCA2 had a family history of breast/ovarian cancer. Pathologic stage was II in three patients and I in one patient. Breast cancer patients with both gBRCA1 and gBRCA2 mutations were rare, young at diagnosis, and all but one tumor was triple-negative based on our single-center experience. [ABSTRACT FROM AUTHOR]