No algorithm has been established for the diagnosis of Lynch syndrome (LS) in patients with endometrial cancer (EC). We retrospectively examined the diagnostic process and clinical characteristics of 12 patients with LS diagnosed with EC at our hospital. Three patients were diagnosed with LS based on a retrospective study for lower uterine segment cancer, four were diagnosed with LS based on clinical suspicion, four were diagnosed with LS in a prospective universal screening study for all EC, and one was diagnosed with LS after microsatellite instability testing as a companion diagnosis. The family history and medical history were unclear in some of the patients diagnosed by universal screening, and these patients might not have been successfully diagnosed without universal screening. Our study findings suggest that LS can be diagnosed with fewer failures by universal screening for all patients with EC. Our goal is to establish highly accurate primary screening criteria by accumulating cases of LS that were difficult to diagnose without universal screening.

　The rate of providing hereditary breast and ovarian cancer (HBOC) information in regular practice has increased since its insurance coverage was introduced in April 2020, therefore its implementation rate is essential. We examined 188 patients who underwent surgery for primary breast cancer at our hospital between April 2020 and December 2022 and were eligible for genetic testing (GT) under the insurance system. The information provision rate was 62.2%, and this rate decreased with increasing age. About half (49.6%) of the cases had only one eligible item for GT, and the rate among those who did not have a GT was significantly lower for those aged > 40 years. Furthermore, after receiving information, 65% of the cases proceeded to genetic counseling, and 96% of these individuals underwent GT. These findings highlight the need for improved information provision to patients with only one eligible item. Additionally, increasing the rate of information provision, especially for patients aged > 40 years, is crucial.

　In this study, 45 Japanese breast cancer (BC) patients with BRCA1 or BRCA2 pathogenic variants (PVs) were divided into two groups; 10 patients with contralateral breast cancer (CBC) and 35 patients without CBC, and the clinicopathological characteristics of the two groups were compared to evaluate risk factors for developing CBC. The median follow-up after initial surgery for initial BC was 7.4 years, and the median time from the initial surgery to the diagnosis of CBC was 8.1 years. Patients with CBC were significantly younger at the initial BC, had lower rate of receiving chemotherapy for the initial BC, and had lower rate of receiving risk reducing salpingo-oophorectomy (RRSO) than patients without CBC. Patients with CBC also tended to have higher rate of premenopausal status at the initial BC and higher rate of no endocrine therapy for estrogen receptor-positive initial BC. Age at the initial BC, systemic therapy for the initial BC, and RRSO may be associated with CBC in Japanese BC patients with BRCA PVs. It is important to develop a CBC risk assessment model to allow patients to make choices according to their CBC risk, rather than recommending contralateral risk reducing mastectomy to all BC patients with BRCA PVs.

　Genetic tests for the breast cancer 1 and 2 (BRCA1/2) genes (BRACAnalysis^®) are now covered by insurance for adolescents and young adults; AYA, but the AYA has not been investigated in detail. We compared rates of BRACAnalysis^® tests and positivity, as well as the outcomes of 748 breast cancer surgeries conducted between April 2020 and December 2022 between women aged ≤ 39 (n = 37; younger) and ≥ 40 y (n = 711; older). The test rates were 22 (59.5%) of 37 and 203 (28.6%) of 711 younger and older women, respectively (P < 0.001). The preoperative germline (g)BRCA1/2 pathological mutation-positive, a variant of uncertain significance (VUS), and negative, were in 11.1%, 22.2%, 66.7%, and 4.7%, 3.4%, and 91.9% in the younger and older groups, respectively (P = 0.01). The most prevalent procedures in the younger group were total mastectomy and breast re-construction (P = 0.003).

　RRSO is recommended for individuals with BRCA pathogenic variants within a certain age range. Conventional transvaginal natural orifice endoscopic surgery (vNOTEs) cannot detect the presence of peritoneal dissemination in the pouch of Douglas or minimal ascites prior to scope insertion. Considering the possibility of incidental peritoneal dissemination in the pouch of Douglas, applying conventional vNOTEs directly to RRSO is deemed unsafe. Furthermore, it does not allow for detailed observation within the abdominal cavity. In our study, we performed RRSO on female BRCA1 pathogenic variant carriers using a hybrid vNOTEs approach. This involved inserting a flexible scope through a 5mm port inserted from the pouch of Douglas, a 12mm port at the umbilicus, and a direct insertion of a 2.4mm diameter trocarless grasping forceps at the lower midline of the abdomen. Our proposed hybrid vNOTEs approach for RRSO offers excellent postoperative pain control, cosmetic outcomes, and enables the necessary surgical manipulations required for RRSO.

　　Application of health insurance coverage for some parts of HBOC practice accelerated our opportunity of genetic medicine in the treatment of breast cancer. We report actual decision making of risk-reducing surgery for patients with BRCA1/2 pathogenic variant. Ten patients affected with breast cancer visited our genetic counseling and considered the indication of risk-reducing surgery. Four decided to undergo both risk-reducing mastectomy (RRM) and risk reducing salpingo‒oophorectomy (RRSO), one did only RRM, and two did only RRSO. Patients preferring RRM included one with past peritoneal cancer and one during chemotherapy for bone metastases of breast cancer. In the decision-making of various breast cancer patients, especially with possible poor prognosis, we should carefully consider the indication of surgery, taking into account the balance between each disease condition and operative stress. Genetic counseling by multi-occupations and further cooperative practice of multi-department will help the determination of intent of patients.

　We report a case of germline BRCA2 mutated hormone receptor-positive breast cancer with multiple recurrent liver metastases in the early postoperative period that showed a long-term response to first-line olaparib treatment. The patient was diagnosed with left breast cancer (cT4dN1M0, Stage ⅢB, Luminal B type) at the age of 32. After neoadjuvant chemotherapy, she underwent surgery, and the pathology assessment indicated pCR. Seven months after surgery, multiple liver metastases and germline BRCA2 mutation are revealed and the patient was treated with olaparib as primary therapy. Three years and 10 months later, one 3-cm liver metastasis was found in S5 of the liver. Radiofrequency ablation was performed after biopsy of the liver tumor. Olaparib was continued and no relapse was observed 5 months after ablation. Early administration of olaparib may improve the long-term prognosis in patients with germline BRCA mutation, even in patients with a short disease-free interval and poor prognosis with liver metastases.

　The number of patients who requires genetic test for BRCA1/2 are increasing after the indication was expanded to include companion diagnosis for olaparib. The backgrounds and purposes of patients seeking analyses are diverse. There is also an increasing demand for genetic test from unaffected family members of patients with BRCA1/2 pathogenic variants. Single-site analyses for BRCA1/2 genetic test was performed on three unaffected adults and one postoperative breast cancer patient at our institution. As single-site analyses are not being covered by public health insurance system, it was noted that additional testing of BRACAnalysisⓇ would be required for a companion diagnosis in cases considering the eligibility for Olaparib. Comprehensive screening system in several cancer surveillance has not been established enough for unaffected carriers with BRCA1/2 pathogenic variants. The demand for single-site analyses of unaffected family members with BRCA1/2 pathogenic variants is expected to increase in the future. It is anticipated that expansion of support systems to support unaffected carriers, including an appropriate medical care.

　As a phenotype of Li-Fraumeni syndrome (LFS), extracutaneous malignant melanoma is rare. In this case, we estimated LFS based on the family history of a female patient who developed ovarian malignant melanoma at the age of 24 and performed genetic testing to confirm the diagnosis. This patient first visited the hospital with a chief complaint of constipation, and her mother had a history of breast cancer when she was 15 years old. CT scan revealed a 13 cm cystic tumor in the pelvis. We performed bilateral salpingo-oophorectomy, and the diagnosis was malignant melanoma derived from the epithelial component of a mature teratoma. We detected TP53 missense variant c.476C>T (p.Ala159Val) by cancer genome profiling with tumor tissue while searching for therapeutic drugs and determined this variant to be pathogenic. She, her mother, and one of his three siblings were diagnosed with LFS by subsequent single-site confirmatory testing using blood samples. This patient did not meet the existing recommended criteria for TP53 testing, and we felt that it would be difficult to diagnose patients with non-core LFS tumors, so we here present her case report to share the information.

　The patient is a 64-year-old woman. Her mother and brother had colorectal cancer and her maternal uncle had gastric cancer. She was diagnosed as appendiceal cancer (pT4aN0M1c) with localized peritoneal dissemination at surgery and was treated with adjuvant chemotherapy. 18 months after surgery, she was diagnosed with bilateral ovarian metastases and peritoneal dissemination. Tumor-only cancer genomic profiling test revealed that the patient had tumor mutational burden-high and was eligible for pembrolizumab, but also had pathogenic variants in the MSH6 and BRCA2 genes. Genetic testing confirmed that both MSH6 and BRCA2 genes were pathological variants of germline origin, and the patient was dually diagnosed with Lynch syndrome and hereditary breast-ovarian cancer.

　With the spread of cancer genomic profiling tests, the number of cases of detection of hereditary diseases as secondary findings is expected to increase, but there are still few reports of dual genetic diagnosis, in which two hereditary diseases are detected simultaneously.

　We established an outpatient clinic specializing in hereditary breast and ovarian cancer (HBOC) in April 2020 when the Japanese insurance began covering BRCA1/2 genetic testing for HBOC. In the HBOC outpatient clinic, patients undergo a detailed interview of family history and explanation of BRCA1/2 genetic testing provided by a panel of clinical experts, including a breast surgeon, a certified breast cancer nurse, and a genetic counselor, to support the patient in decision-making for BRCA1/2 genetic testing. Between May 2020 and December 2021, 166 patients visited the clinic and 20 patients (12.0%) were found to harbor pathogenic variants in BRCA1 or BRCA2. During this period, several issues, such as the establishment of an efficient system to reduce the workload of medical staff in future, have emerged. We will report the results of patients visiting the HBOC outpatient clinic and the clinical characteristics of patients with pathogenic variants in BRCA1/2 and discuss future prospect.

　At our hospital, BRCA1/2 genetic testing is performed in each department, and when a pathogenic germline variant is detected, the physician in charge refers the patient to genetic counseling (GC). To ensure the quality of Hereditary breast and ovarian cancer (HBOC) care, there is a need for a system that can comprehensively monitor and manage factors such as the number of tests conducted, attendance at GC, and the implementation status of risk-reducing surgeries across departments. Recognizing this need, the relevant departments collaborated to establish an HBOC database. This database has enabled the selection of HBOC patients who are eligible for GC and helped certified genetic counselors to effectively remind physicians to refer patients for GC. Additionally, the database has enabled the provision of up-to-date information to individuals carrying a pathogenic germline variant, and has also deepened cooperation among clinicians, clinical geneticists, and genetic counselors, which has in turn improved the quality of HBOC treatment. We believe that the creation and operation of the HBOC database will contribute to the systematization of support for those with hereditary tumors.

　The BRCA1/2 gene test has been covered by insurance since 2018 as a companion diagnosis for PARP inhibitors and the diagnosis of hereditary breast and ovarian cancer syndrome (HBOC) in Japan. In response to the insurance coverage of HBOC diagnosis and the coronavirus disease (COVID-19) pandemic in 2020, we opened an outpatient genetic counseling clinic in obstetrics and gynecology department to establish a genetic counseling system within the secondary medical care area. In collaboration with neighboring medical institutions, we conducted the BRCA1/2 gene test in 31 cases in the first two years, leading to surveillance and risk-reducing salpingo-oophorectomy (RRSO). On the other hand, we found the importance of multidisciplinary cooperation within the hospital and regional collaboration in order to establish a sustainable system. In Tochigi Prefecture, access to advanced medical institutions, which are unevenly distributed in the southern part of the prefecture, is still difficult in some areas. Therefore, it is important in each area to develop a solid system based on cooperation with related departments and the community to meet the increasing need for genetic testing.