The purpose of this study is to investigate awareness of BRCA1/2 genetic testing in breast cancer patients after health insurance coverage and to evaluate patient psychological conditions before genetic testing and just after disclosure of BRCA1/2 genetic testing results. A questionnaire survey was conducted at the Breast Center of Juntendo University Hospital, targeting breast cancer patients who were covered by health insurance for BRCA1/2 genetic testing. Responses were obtained from 31 patients with breast cancer (29 test takers and 2 non-test takers), suggesting that insurance coverage promotes genetic testing in these patients. The main motivation for genetic testing was “concern for siblings/children”; and over 90 percent of respondents planned to inform their relatives about the results of genetic testing. In addition, even among mutation-negative patients, there was an obvious increase in “State of Mood,” which was a negative emotional change caused by background characteristics such as family history of breast cancer, having daughters and preoperative states. These results suggested that psychological support should be provided to some extent for breast cancer patients, even those testing negative for BRCA1/2.

　In genetic counseling (GC) of hereditary cancer, it is recommended that the proband shares their genetic test result with their blood relatives (BR). In western countries, several studies reported ways to support the proband to share their genetic information with their BR in GC.

　Hereditary breast and ovarian cancer (HBOC) is one of the most common hereditary cancers. Since 2020, germline BRCA1/2 genetic testing has been covered by the national health insurance in Japan. It is expected that the number of HBOC diagnoses and need for diagnosis of BR will increase.

　To investigate the challenges with introducing GC for BR at each facility, we performed questionnaire surveys for the top 100 medical facilities for breast cancer treatment in Japan.

　We received 44 responses from 100 facilities (44%) in the first questionnaire. The second questionnaire was sent to 31 facilities in which more than five probands were diagnosed as HBOC, and we obtained responses from 29 facilities (94%).

　Although 26 facilities (90%) routinely explained the risk of HBOC to BRs, 17 facilities (59%) did not routinely distribute explanatory information specific to each family. Problems including “lack of insurance coverage for surveillance of unaffected BR" and "estrangement from BR” were extracted. There were differences in the attempts for introduction GC for BR between the facilities. To improve the consultation rate of BR, more direct involvement and support of medical genetics professionals are necessary.

　Gastrointestinal stromal tumor (GIST) is a rare cancer that can be caused by a germline pathogenic variant in the SDHB gene, which is also causative of hereditary paraganglioma-pheochromocytoma syndrome (HPPS). We report a case of a man in his 30s who was diagnosed with gastric GIST. Immunostaining of the surgical specimen revealed SDHB protein loss, while genetic analysis identified a pathogenic SDHB variant. He started paraganglioma-pheochromocytoma surveillance in addition to standard care for GIST, and we provided follow-up genetic counseling for the psychological burden of having a hereditary disease. In cases of early-onset GIST with SDH-deficient findings, it is useful to consider genetic testing for the possibility of HPPS. Furthermore, evidence is needed regarding the usefulness of surveillance and ongoing psychosocial support for such cases.

　Cowden syndrome/PTEN hamartoma tumor syndrome (CS/PHTS) is a rare disease that causes early-onset malignancies due to germline pathogenic variants in the PTEN. A 24-year-old woman with right bloody nipple discharge was diagnosed with right breast cancer. She was also diagnosed with multiple fibroadenoma, left ovarian maturation teratoma and endometrial hyperplasia. BRCA1/2 genetics testing was negative. The pathogenic variant of PTEN (p.Gly132Asp) was identified by multi gene panel testing (MGPT) after surgery for right breast cancer. Her facial rash and state of psychological development were suggested to be related to CS/PHTS. The endometrial biopsies under short intervals were performed for endometrial hyperplasia. An endometrial biopsy performed 11 months after breast cancer surgery showed atypical proliferation, total hysterectomy and bilateral oophorectomy were performed, and she is alive and recurrence-free. MGPT is helpful for patients with potential and de novo CS/PHTS.

　Li-Fraumeni syndrome (LFS) is an autosomal dominant inherited disorder caused by germline pathological variant in the tumor suppressor gene TP53, and is associated with numerous malignancies from childhood. Here, we report a case of the mother of three children, the first of whom had five malignant tumors, the second of whom had osteosarcoma at 14-year-old, and the third of whom had never developed the disease. The mother died at the age of 40 of choriocarcinoma of the liver 9 months after delivery of her third child. LFS was initially suspected when the first child was 14-year-old, and a germline pathological variant of TP53 was detected by genetic testing. The father was unaffected at the time, but genetic testing revealed that he was a carrier of the same pathological variant, and he later died of prostate cancer at the age of 54. In the course of genetic counseling and genetic testing for the marriage of his second child, we learned of a report that choriocarcinoma occurs in partners of LFS carriers upon pregnancy, and we attempted genetic testing by extracting DNA from a liver tissue sample of the mother who died 20 years ago. Although the amount of the DNA was very small, we detected the same pathological variant of TP53 by the TaqMan Probe method. We speculated that the pathological variant was transferred from the LFS carrier (father) to the partner (mother) by some mechanism when she became pregnant and developed choriocarcinoma of the liver, which is rare and caused her death.

　Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal dominant hereditary disease characterized by massive and potentially malignant polyposis of the gastric body and fundus, which has been described in 2012. Herein, we report a case of GAPPS that was successfully diagnosed based on genetic testing.

　A 44-year-old Japanese woman had a family history of her mother of gastric polyposis which disappeared without any treatment at her 30s and developing multiple fundic gland polyps after treatment of gastric cancer at the age of 73 years. Thus, esophagogastroduodenoscopy was performed which revealed polyposis limited to the greater curvature of the stomach. Additionally, whitish protuberances that differed from the other polyps were resected and histopathologically diagnosed as gastric adenocarcinoma. GAPPS was suspected and confirmed by the presence of a point mutation at the APC gene’s promoter 1B site on genetic testing. Since GAPPS is a relatively new disease-concept with limited reports on it, its clinical management, including prophylactic total gastrectomy and surveillance, remains unknown owing to insufficient evidence. Therefore, careful follow-up and continued genetic counseling are crucial.

　The of BRCA1/2 gene test has widely used as a companion diagnostic for the PARP inhibitors to diagnose hereditary breast and ovarian cancer (HBOC). Resultingly, more cases will be diagnosed with BRCA1/2 mutations. Annual breast-enhanced magnetic resonance imaging (MRI) is recommended for BRCA1/2 mutation carriers, preferably in collaboration with a facility capable of MRI-guided vacuum-assisted biopsy (MRI-VAB). In Japan, there are only a few institutions that perform MRI-VAB as a medical treatment covered by insurance. MRI-VAB was started in June 2022 at our institution. From June 2022 to May 2023, six patients underwent MRI-VAB. The pathological findings were as follows: invasive ductal carcinoma in one case, ductal carcinoma in situ in two cases, and benign lesions in three cases. Of six, a woman with a BRCA2 gene mutation who was diagnosed with DCIS was included. We hope that the medical system will be developed so that high-risk women who require MRI-VAB can receive appropriate examinations.