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Aim: Ovarian surveillance in women with hereditary breast and ovarian cancer who do not undergo risk‐reducing salpingo‐oophorectomy has been controversial. Therefore, this study aimed to demonstrate the clinical features of ovarian surveillance at our institution using a technique that combines serum cancer antigen 125 measurements, transvaginal ultrasonography, and uterine endometrial cytology. Methods: We retrospectively examined 65 women, who had not undergone risk‐reducing salpingo‐oophorectomy diagnosed with hereditary breast and ovarian cancer between 2000 and 2021 at our hospital. Clinical information was obtained and analyzed through a chart review. The details of the treatment course were reviewed for patients who had developed ovarian cancer. Results: Overall, 5 of the 65 women were diagnosed with ovarian cancer based on abnormal findings during periodic surveillance. All patients who developed ovarian cancer were asymptomatic, even if the cancer was at an advanced stage. Two of the 65 patients had endometrial cytology abnormalities, both of whom had ovarian cancer. All patients who developed ovarian cancer underwent primary debulking surgery, and complete gross resection was achieved. None of the patients experienced ovarian cancer recurrence. Conclusions: The ovarian surveillance strategy at our institution for women with hereditary breast and ovarian cancer who do not undergo risk‐reducing salpingo‐oophorectomy can identify asymptomatic ovarian cancer and contribute to achieving complete gross resection during primary surgery. Ovarian surveillance may contribute to a reduction in ovarian cancer mortality. [ABSTRACT FROM AUTHOR]

Cancer genomic profile (CGP) testing, which is covered by the national health insurance system in Japan, has been introduced as a routine clinical practice. However, the effects of CGP testing on prognoses remain unclear. Drug accessibility rates and prognoses after CGP testing were retrospectively investigated in 713 patients who underwent CGP testing examined by our molecular tumor board between November 2019 and October 2022,. Overall survival (OS) was examined using the log‐rank test and the Kaplan–Meier method. The median age of patients (326 males and 387 females) was 58 years (12–85 years). CGP testing revealed one or more gene mutations in 681 cases (95.5%), among which actionable gene mutations were detected in 439 (61.6%). Although treatment options were recommended for 285 cases (40.0%) by the molecular tumor board, only 45 received treatment based on their gene mutations. During the median observation period of 8.6 months, 351 (49.2%) patients died of the exacerbation of existing diseases. No significant differences were observed in OS between patients treated with and without genomically matched therapy (p = 0.285). According to clinical responses to treatment based on gene mutations, median OS was significantly longer in patients who achieved partial response and stable disease (26.5 months; 95% CI 14.4–38.6) than in those with progressive disease and not evaluated (9.8 months; 95% CI 5.8–13.8, p = 0.013). Responses to treatment based on gene mutations may improve prognoses, and it is important to increase the drug accessibility rate after CGP testing. [ABSTRACT FROM AUTHOR]

Substantial numbers of variants of unknown significance (VUSs) have been identified in BRCA1/2 through genetic testing, which poses a significant clinical challenge because the contribution of these VUSs to cancer predisposition has not yet been determined. Here, we report 10 Japanese patients from seven families with breast or ovarian cancer harboring the BRCA2 c.7847C>T (p.Ser2616Phe) variant that was interpreted as a VUS. This variant recurs only in families from Japan and has not been reported in the global general population databases. A Japanese patient with Fanconi anemia with compound heterozygous variants c.7847C>T (p.Ser2616Phe) and c.475+1G>A in BRCA2 was reported. In silico predictions and quantitative cosegregation analysis suggest a high probability of pathogenicity. The clinical features of the variant carriers were not specific to, but were consistent with, those of patients with hereditary breast and ovarian cancer. A validated functional assay, called the mixed‐all‐nominated‐in‐one‐BRCA (MANO‐B) method and the accurate BRCA companion diagnostic (ABCD) test, demonstrated the deleterious effects of the variant. Altogether, following the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines, this variant satisfied the "PS3," "PM2," "PM3," and "PP3" criteria. We thus conclude that the BRCA2 c.7847C>T (p.Ser2616Phe) variant is a "likely pathogenic" variant that is specifically observed in the Japanese population, leading to a breast and ovarian cancer predisposition. [ABSTRACT FROM AUTHOR]

Background: In Japan, microsatellite instability (MSI) testing for solid tumors was introduced in clinical practice in December 2018. Although immune checkpoint inhibitors (ICIs) are established standards of care for patients with MSI‐high tumors, the status of implementing MSI testing in clinical practice remains unclear. Methods: We retrospectively reviewed the medical records of patients with solid tumors who underwent MSI testing between January 2019 and December 2020 at our institution. Results: In total, 1,052 MSI tests were performed in 1,047 patients. Regardless of specimen volume and condition, the MSI status was successfully determined in 1,041 (99.0%) tests, encompassing 27 tumor types (microsatellite stable [MSS] or MSI‐low: n = 991 [95.2%] and MSI‐high: n = 50 [4.8%]). Patients whose specimens were fixed with 20% neutral buffered formalin (NBF) and who had specimens with prolonged storage (98.4% and 95.4%) showed lower success rates than those whose specimens were fixed with 10% NBF and who had specimens with nonprolonged storage (100.0% and 99.6%), respectively. The prolonged turnaround time (TAT) in MSI‐high cases (median TAT: 24 days) was a critical issue that directly resulted in treatment delay. Of the 50 patients with MSI‐high tumors, 24 (48.0%) received ICIs and 34 (68.0%) were referred to the Department of Clinical Genetic Oncology where 6 (12.0%) patients were diagnosed with Lynch syndrome. Conclusions: MSI testing was successfully performed for various types of tumors and specimens in clinical practice. Our study results identified certain issues associated with the clinical implementation of MSI testing, including optimal specimen selection, extended TAT in MSI‐high cases, and awareness of hereditary tumors. [ABSTRACT FROM AUTHOR]