DICER1 syndrome is a genetic condition predisposed to various rare cancers, including pleuropulmonary blastoma, cystic nephroma, ovarian Sertoli–Leydig cell tumor, embryonal rhabdomyosarcoma of the cervix, and rare brain tumors. Genetic testing and surveillance for DICER1 syndrome are recommended in early childhood. Surveillance guidelines are published by study groups in the US and Europe. Cases suspected of or diagnosed as DICER1 syndrome are increasing with growing interest in cancer genomic medicine in Japan and the expanding number of tumors newly recognized as DICER1-related. Here, we provide an overview of genetic testing and surveillance for DICER1 syndrome.

　The purpose of this study was to clarify the emotions of patients with hereditary breast and ovarian cancer syndrome (HBOC) after risk reducing salpingo-oophorectomy (RRSO). Data were collected through semi-structured interviews with 12 HBOC patients aged 20 or older, who had undergone RRSO. The emotions of HBOC patients after RRSO were summarized into 6 categories: 【being freed from the fear of cancer and feeling at ease】, 【As it was just timing, I was able to decide to undergo the surgery】, 【desiring to make use of one’s experience for peers】, 【desiring to face cancer of relatives after completing one’s own surgery】, 【continuing to worry about one’s condition even after surgery】, and 【feeling guilty about having one’s ovaries surgically removed】. Being freed from cancer by RRSO was an irreplaceable experience for these patients, as their health was of benefit not only to themselves, but also to their relatives, and this characterized the heredity affecting families with HBOC. On the other hand, patients continued to worry about their conditions all the time, suggesting the necessity of psychological support for such patients, promoting their daily lives after RRSO.

　The most of ovarian cancer in the hereditary breast cancer ovarian cancer syndrome (HBOC) are high grade serous carcinoma (HGSC), on the other hand low grade serous carcinoma (LGSC) and serous borderline tumor (SBT) are rare. We experienced a case of SBT with BRCA2 germline pathogenic variants. The case is a 66-year-old woman, she was diagnosed with ovarian SBT in her 40s. However, this ovarian tumor shows strong cellular atypia and stromal reaction in pathologic findings, so she was treated in the same way as ovarian cancer. After more than 15 years, she wanted to have a genetic test of BRCA1/2, and consulted genetic department in our hospital. As a result, it was determined that she had germline pathogenic variants in BRCA2. Although there are only few studies that were investigated relation between BRCA1/2 pathogenic variants and borderline tumor of ovary, some cases with SBT had germline pathogenic variants in BRCA1/2. Therefor we should recommend a genetic counseling and genetic test of BRCA1/2 for the cases with borderline tumor of ovary.

　Our hospital has been designated as a cancer genomic medical center, and we have been conducting a comprehensive genomic profiling test (CGP) since 2019. In our prefecture, there are two other cooperative hospitals that provide CGPs as well. The primary purpose of a CGP is to detect variants and predict responses and the scale of resistance to certain drugs. However, CGPs also detects germline variants in cancer predisposition genes that are known as “secondary findings”.

　Between November 2019 and May 2021, 245 patients underwent CGPs at the three hospitals, and nine of them were found to have a germline variant in a cancer predisposition gene. Out of these, six variants were detected in association with cancer. In addition, seven patients were found to have a family history of cancer in first-, second-, or third-degree relatives. Seven patients fulfilled hereditary cancer testing criteria in NCCN guidelines 2022. It is important to inform all patients about the possibility of secondary findings during consultations prior to conducting a CGP. It is also important for the primary physician to refer the patient to the genetics department when necessary before the patient undergoes CGP.

　With improvements in methods of diagnosing hereditary breast cancer and ovarian cancer syndrome and insurance coverage of olaparib companion diagnostics, opportunities for BRCA gene testing have increased, but there are still few reports of breast surveillance in carriers of pathogenic variants. We examined herein 39 carriers of BRCA-related pathogenic variants who were followed up from 2010 to 2020. Five of the carriers had no breast cancer or ovarian cancer, 25 had breast cancer, and 11 had ovarian cancer. Of 14 patients in whom breast and ovarian cancer did not develop, who had not undergone contralateral risk reduction, and had curable unilateral breast cancer surgery, 13 underwent breast surveillance. Twelve patients with metastatic or recurrent breast cancer underwent computed tomography. Breast surveillance was performed in two of four patients with curable ovarian cancer and five of seven patients with metastatic or recurrent ovarian cancer. The variation in physical condition among patients at the time of BRCA pathogenic variant detection make it necessary to consider factors, such as insurance coverage, systemic diseases, and complications related to imaging tests. before carrying out surveillance.

　In June 2019, the use of maintenance therapy with Olaparib was indicated for patients with newly diagnosed advanced ovarian cancer stageⅢ/Ⅳ and a BRCA1/2 mutation. At the same time, BRCA genetic testing was approved as companion diagnostics to whether we can use Olaparib as a treatment for ovarian cancer. By August 2021, we examined 13 BRCA genetic tests. Two patients were positive with BRCA1 pathogenic variant, and one was variant of uncertain significance（VUS）. Two of pathogenic variant take Olaparib and have complete remission for 1 year. These two patients are recommended receiving genetic counseling, they do not receive because of undergoing adjuvant chemotherapy and anxiety about a test result. We must establish genetic counseling system for hereditary breast and ovarian cancer（HBOC）patients in our hospital.