Makoto Hirata

Communication Between Japanese Patients With Hereditary Breast and Ovarian Cancer and Healthcare Providers on Sexual Health After Risk‐Reducing Bilateral Salpingo‐Oophorectomy

ABSTRACTBackgroundRisk‐reducing bilateral salpingo‐oophorectomy (RRBSO) is recommended for BRCA1/2 carriers to reduce ovarian cancer risk. Although RRBSO affects sex life, discussing this with healthcare professionals (HCPs) can be challenging. Moreover, research on this topic in Asia is limited.AimsThis study aims to clarify HCPs' communication on RRBSO's impact on sex life and to consider the preferred communication methods of Japanese BRCA1/2 carriers and their partners.MethodsA web survey was conducted with BRCA1/2 carriers and their partners using snowball sampling. Participants who agreed to the additional interview underwent interviews. Thematic analysis was performed on free‐text responses and interview data. A pamphlet reflecting experiences with RRBSO was published after the survey, and feedback was obtained online.ResultsOf the 50 surveyed participants, 10 underwent interviews. Three themes emerged: (1) hesitancy to ask questions about sex life, (2) the need to inform and support couples on their sex life after RRBSO, and (3) the unhelpfulness of receiving explanations from those who have not undergone RRBSO. Only 34.0% of participants received information on post‐RRBSO sex life. Many expressed the need for themselves and their partners to receive information before RRBSO. The feedback survey revealed that digital pamphlets and paper were the preferred tools.ConclusionsProviding couples with information about post‐RRBSO sex life is essential. Additionally, cultural taboos hinder discussions on sex life leading to a preference for indirect sources of information. In Japan, some patients may face challenges in directly communicating with HCPs, highlighting the value of pamphlets and digital resources.

Multi‐gene panel analysis in BRCA1/2 ‐negative patients suspected of hereditary breast and ovarian cancer syndrome: Real‐world data from a single institution

Abstract Aim Although BRCA1/2 is most frequently associated with hereditary breast and ovarian cancer (HBOC), many other related genes have been implicated. Therefore, we investigated the prevalence of non‐ BRCA1/2 genes associated with hereditary cancer predisposition in BRCA1 /2‐negative patients from the Department of Genetic Medicine and Services with breast and ovarian cancer using a multi‐gene panel (MGP) analysis. Methods We conducted a retrospective MGP analysis (National Cancer Center Onco‐Panel for Familial Cancer; NOP_FC) in BRCA1/2 ‐negative patients with breast, ovarian, and overlapping breast/ovarian cancers who visited our genetic counseling between April 2004 and October 2022. Results NOP_FC was performed in 128 of the 390 BRCA test‐negative cases (117 breast cancer, 9 ovarian cancer, and 2 overlapping breast/ovarian cancer cases). Among the BRCA1/2 ‐negative patients, nine (7.7%) with breast cancer and one (11%) with ovarian cancer had pathogenic variants (PVs) in non‐ BRCA1/2 genes associated with breast and ovarian cancers, respectively. Five patients had PVs in RAD51D , two in PALB2 , one in BARD1 , one in ATM , and one in RAD51C . Conclusions Additional MGP testing of germline genes associated with hereditary cancer predisposition syndrome in BRCA1/2 ‐negative breast and ovarian cancer patients revealed PVs in non‐ BRCA1/2 breast cancer‐ and ovarian cancer‐related genes in 7.7% of breast cancer and 11% of ovarian cancer. Therefore, additional testing may provide useful information for subsequent risk‐reducing surgery and surveillance in BRCA1/2 ‐negative patients.

Pathogenic Germline Variants in BRCA1/2 and p53 Identified by Real-world Comprehensive Cancer Genome Profiling Tests in Asian Patients

Abstract Cancer genome profiling (CGP) occasionally identifies pathogenic germline variants (PGV) in cancer susceptibility genes (CSG) as secondary findings. Here, we analyzed the prevalence and clinical characteristics of PGVs based on nationwide real-world data from CGP tests in Japan. We analyzed the genomic information and clinical characteristics of 23,928 patients with solid cancers who underwent either tumor-only (n = 20,189) or paired tumor-normal (n = 3,739) sequencing CGP tests between June 2019 and December 2021 using the comprehensive national database. We assigned clinical significance for all variants and highlighted the prevalence and characteristics of PGVs. Our primary analysis of the tumor-normal sequencing cohort revealed that 152 patients (4.1%) harbored PGVs in 15 CSGs. Among 783 germline variants, 113 were annotated as PGVs, 70 as benign variants, and 600 as variants of uncertain significance. The number of PGVs identified was highest in BRCA1/2, with 56, followed by TP53, with 18. PGVs were the most prevalent in ovarian and peritoneal cancers, including among cancer types common in Asia. In the tumor-only sequencing cohort, of the 5,184 pathogenic somatic variants across 26 CSGs, 784 (15.1%) were extracted according to the European Society for Medical Oncology recommendations for germline-focused tumor analysis. The prevalence of PGVs was similar to that previously reported in Europe and the United States. This is the largest analysis based on real-world tumor-normal sequencing tests in Asia. The more widespread use of the tumor-normal sequencing CGP test could be reasonable for evaluating PGVs. Significance: We analyzed real-world data from over 23,000 patients in Japan, revealing 4.1% harbored PGVs, particularly in BRCA1/2 and TP53, in CSGs. It highlights the prevalence of PGVs in Asian populations and supports the broader adoption of tumor-normal sequencing CGP tests for PGV evaluation.