Objective : This study investigated the clinical background and clinicopathological results of hereditary breast and ovarian cancer (HBOC) women underwent risk-reducing salpingo-oophorectomy (RRSO) at our institution.

Methods : 37 HBOC women who underwent RRSO from January 2018 to December 2023 at the University of Tsukuba Hospital were included. Clinical information was collected retrospectively.

Results : Of 37 patients, 19 (51.4%) had BRCA1, 18 (48.6%) had BRCA2 pathogenic variants. The median age at RRSO is 50 (31-69). 36 patients (97.3%) had medical history of breast cancer. 34 patients (91.9%). After the RRSO, we reviewed 1 patient with serous tubal intraepithelial carcinoma (STIC). In the follow-up period, any patients developed the peritoneal cancer.

Conclusion : The age at RRSO for women with HBOC at our institution was higher than the recommended age. Factors related to the higher age at RRSO included delayed HBOC diagnosis and time to decision before RRSO. Both may be associated with financial burdens.

　Criteria for insurance coverage for BRCA1/2 genetic testing for the purpose of diagnosing hereditary breast and ovarian cancer (HBOC) include breast cancer onset under the age of 45, triple negative (TN) breast cancer onset under the age of 60, two or more histories of primary breast cancer, family history of breast or ovarian cancer in a third-degree relative, male breast cancer, or past history of ovarian or peritoneal cancer. We retrospectively investigated the relationship between the above criteria for insurance coverage in 62 breast cancer cases for which BRCA1/2 genetic testing was performed at our hospital. Many cases had breast cancer onset under the age of 45 or family history of breast or ovarian cancer in a third-degree relative. The majority of cases met one or two criteria. The detection rate of pathogenic variants in groups met each criterion was all over 10%, and therefore the criteria for inclusion in Japanese insurance coverage were considered appropriate. The detection rate of pathogenic variants tended to increase as the number of applicable criteria increased. In conclusion, we should actively recommend BRCA1/2 genetic testing to patients met multiple criteria.

　We herein report a case of hereditary breast and ovarian cancer syndrome (HBOC) wherein treatment during the perioperative and recurrent phases of breast cancer was conducted with respect for the patient’s reproductive rights. A 35-year-old woman with a desire for childbearing underwent embryo cryopreservation followed by breast-conserving surgery and sentinel lymph node biopsy for treatment of right primary breast cancer. Postoperatively, she was diagnosed with HBOC (BRCA1 pathogenic variant-positive). Her breast cancer, categorized as estrogen receptor (ER)-weakly positive and human epidermal growth factor receptor 2 (HER2)-negative (pT2N0M0/stage IIA), was treated with chemotherapy and radiation therapy, aiming for pregnancy and childbirth. After delivery, she planned to undergo risk-reducing salpingo-oophorectomy and endocrine therapy. However, at 18 months postoperatively (15 weeks of pregnancy), the patient developed recurrences in the chest wall, liver, and bones (ER-negative, HER2-negative). Respecting the patient’s wish to continue the pregnancy, treatment for breast cancer was commenced and she successfully delivered a child at 33 weeks of pregnancy. Treatment continued after childbirth, but the patient died 12 months following the recurrence. The presence of the child provided emotional support for the patient and her family during treatment. This case report with literature review discusses perioperative and recurrent breast cancer management in reproductive-aged patients with HBOC.

　We reported a case of Li-Fraumeni syndrome (LFS) diagnosed in her 50s. Her father developed stomach cancer in his early 30s and died within a few years. The patient had a total mastectomy and axillary lymph node dissection for right breast cancer at age 34, a total hysterectomy for cervical cancer at age 36 and right upper lobectomy for right lung cancer (Stage 3B) at age 37. A partial mastectomy and sentinel lymph node dissection for left breast cancer and underwent a resection of a soft tissue sarcoma (malignant fibrous histiocytosis) in her left side chest at age 39. At 42-year-old, a pleural recurrence of lung cancer occurred. Some anticancer drugs were administered, and she had a complete response. Later, at age 44, Gamma Knife treatment was performed for a brain tumor. At age 45, endoscopic treatment for sigmoid colon cancer and axillary lymph node dissection for left axillary lymph node metastasis were performed. In the following year, a left mastectomy was performed due to recurrence of left breast cancer. At the age of 48, she underwent radiation therapy for right supraclavicular lymph node metastasis. After the treating physician had changed, a hereditary tumor, such as LFS, Cowden syndrome and hereditary breast ovarian cancer, was suspected, and underwent a genetic testing. Eventually, a pathogenic variant in TP53 was revealed and Li-Fraumeni syndrome (LFS) was diagnosed. Patients with hereditary tumors, such as LFS, are faced with multiple medical, psychological and social problems. The awareness-raising activities for general practitioners and the establishment of a patient advocacy system are needed.

　A 46-year-old male (height, 178cm; weight, 90kg) presented with multiple esophageal glycogen acanthoses on the upper gastrointestinal endoscopy. Although family history did not present any indicators, we suspected Cowden syndrome/phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (CS/PHTS) owing to macrocephaly (head circumference, 70.5cm) and multiple skin lesions (diagnosed as trichilemmoma with pathological examination). He had a medical history of a right vertebral arteriovenous fistula that had been observed after treatment at another hospital. Ultrasonography of the thyroid revealed adenomatous nodules in both lobes. Cytological examination of the thyroid nodules revealed a benign tumor. The CS/PHTS diagnosis was based on two major (macrocephaly and multiple trichilemmomas) and three minor (esophageal glycogen acanthosis, thyroid goiter, and right vertebral arteriovenous fistula) criteria. Next-generation sequencing (NGS) analysis revealed a low frequency of pathogenic variants, suggesting a diagnosis of somatic mosaicism.

　The patient is a 91-year-old woman, 50 years of menopause. She underwent bilateral adnexectomy for suspected left ovarian cancer, both for diagnosis and tumor reduction purposes. Postoperative histopathology revealed stage IIA fallopian tube carcinoma. The patient’s family history included a mother who died of breast cancer, an older sister and a nephew who had prostate cancer, a younger sister who died after treatment for heterochronic bilateral breast cancer, and a younger brother who died of prostate cancer. Additionally, it was discovered that the sister who underwent breast cancer treatment had a pathogenic variant in BRCA2, although this information was not disclosed to the patient. Genetic testing revealed the same BRCA2 pathogenic variant as her sister. Subsequently, surveillance was initiated due to the diagnosis of Hereditary Breast and Ovarian Cancer Syndrome (HBOC), leading to the diagnosis of early-stage breast cancer one month later. This case made us recognize the issue of information sharing among the family of elderly patients with hereditary tumors. Seamless support involving family members was considered even more important.

　Objective : This report describes the aims and outcomes of Lynch syndrome (LS) screening at our hospital.

Methods : In our hospital, we are conducting two LS screening initiatives: 1) to identify cases meeting the first screening criterion, based on medical and family histories, in collaboration with the main medical department; and 2) for treatment-related purposes, to confirm all microsatellite instability (MSI) tests performed by each medical department with the genetics department. Here, a retrospective study was conducted on the outcomes of LS screening of 739 cases for which MSI tests were performed between April 2019 and December 2022.

Results : Of the 739 cases, 57 cases (7.7%) were MSI-high cases. Although no cases were diagnosed with LS before April 2019, screening resulted in the novel diagnosis of six cases with LS between April 2019 and December 2022, allowing appropriate follow-up with surveillance and genetic counseling for blood relatives.

Conclusion : As the uses for MSI tests have expanded, the number of MSI tests is increasing, leading to the diagnosis of LS. It is critical to continue to develop efforts for LS screening.

　Li-Fraumeni syndrome （LFS） is a hereditary disorder caused by a pathogenic variant of the TP53 gene, which carries a high risk of developing a variety of malignant tumors beginning in childhood and continuing throughout life. We are promoting genetic counseling and BRCA1/2 genetic testing for patients with suspected hereditary breast and ovarian cancer and are also making efforts to establish a system for TP53 genetic testing. From 2020 to 2022, we proposed TP53 genetic testing to 27 breast cancer patients under 31 years of age in our department, and a total of 8 patients underwent the test, of which 1 patient showed TP53 mosaicism. Meanwhile, there were a total of 4 patients with sarcoma as the first cancer who were diagnosed with LFS and subsequently developed breast cancer. In our institution, we have established the “LFS board” with other departments, mainly in the Department of Genetic Medicine and Services, and have been holding regular conferences on the treatment strategy for each LFS patient. In this report, we will describe the results of our survey on the treatment status related to TP53 genetic testing in our institution and outline the role of the LFS board in our institution.