We conducted a systematic review to examine the increased risk of breast cancer in patients with neurofibromatosis type 1 (NF1). Molecular biological studies demonstrate that loss of NF1 gene function increases breast cancer risk through multiple mechanisms, including sustained activation of the RAS pathway, metabolic reprogramming, development of endocrine resistance, and promotion of genomic instability. 　Epidemiological studies consistently report a significant increase in breast cancer risk among NF1 patients, particularly in younger women (under 50 years), with standardized incidence ratios (SIRs) ranging from approximately 4 to 11-fold higher than the general population. The most pronounced risk is observed in women under 40 years (SIR 11.1 in the Finnish study). Age-specific analysis shows a clear pattern of decreasing risk with increasing age, from relative risk (RR) 6.5 in women aged 30-39 years to RR 0.8 in those aged 70-79 years. 　Importantly, the annual absolute risk of breast cancer in NF1 women aged 30-39 years (1 in 359) is comparable to that of the general population aged 50-59 years (1 in 363), for whom regular mammography screening is recommended. Additionally, NF1-associated breast cancers exhibit unfavorable prognostic factors, including larger tumor size, higher grade, and a higher proportion of estrogen receptor-negative tumors. 　These findings support the implementation of early screening strategies, with experts recommending annual breast cancer screening beginning at age 30 for women with NF1.

　Accurate classification of variant pathogenicity and the accumulation of information are essential for building a genomic information-based medical system in Japan. The germline BRCA1 variant, NM_007294.4:c.3927_3930del p.(Asn1309Lysfs*8), presumed to be a rare pathologic variant uncommon to Japanese individuals, was identified via a comprehensive genomic profiling test in cases with High-grade serous ovarian carcinoma: (HGSOC). The case, a woman in her forties, presented with FIGO stage IV. Initially, this mutation was classified as a variant of uncertain significance (VUS) by ClinVar, however it was subsequently reclassified as pathogenic based on the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classification criteria. Further examination of BRCA1 protein expression and BRCA1 DNA methylation revealed a loss of protein expression and promoter hyper methylation in the cancer cells. BRCA1 dysfunction was hypothesized to result from a “two-hit” mechanism: one allele inactivated by germline variant (first hit) and the other by DNA methylation (second hit). The NM_007294.4:c.3927_3930del p. (Asn1309Lysfs*8) variant was inferred to be a rare BRCA1 variant unique to Japanese individuals, associated with an increased risk of ovarian cancer. To date, only one other Japanese ovarian cancer case harboring this variant has been reported.

　We report the case of a 4-year-old boy who underwent magnetic resonance imaging for the evaluation of status epilepticus, which revealed a tumor lesion in the left temporal and parietal lobes. A craniotomy biopsy confirmed the diagnosis of a diffuse pediatric-type high-grade glioma. The patient’s father had a family history of Li-Fraumeni syndrome (LFS), and had developed osteosarcoma in his right lower leg at 17 years of age. However, the father had not undergone genetic testing or cancer surveillance and did not disclose his family history of LFS with his wife (the patient’s mother). Consequently, the child did not undergo cancer screening. A cancer gene panel test of the patient’s peripheral blood and brain tumor tissue revealed a pathogenic TP53 variant, c.1041delC (p.L348fs*22), previously confirmed in the paternal lineage, leading to a definitive diagnosis of LFS. This case highlights the importance of understanding the significant psychological burden faced by fathers with LFS and underscores the critical need to initiate cancer screening tests immediately after a child’s birth.

　 BRCA1 and BRCA2 are widely known to predisposing genes of hereditary breast and ovarian syndrome (HBOC). Recently, BRCA1/2has a clinical relevance with esophageal, gastric and biliary tract cancers, in addition to well established four cancers (breast, ovary, prostate and pancreas)1).　This fact let us recognize again that males are also involved in this cancer predisposition syndrome as well as females. Though the clinical importance of HBOC is widely recognized, we can find less literatures concerning male HBOC, and surveillance guidelines for these newly associated gastrointestinal cancers have not been established. 　The case involves a 77-year-old man, detected a left breast mass in a follow-up imaging study after the surgery of his esophageal cancer. Further examination led to a diagnosis of left breast cancer, and he underwent surgery. Besides the patient had a history of male breast, esophageal, and prostate cancer, he also had a family history of breast cancer and ovarian cancer in his sisters. BRCA1/2 genetic testing revealed a pathogenic variant in BRCA2 gene. This case illustrates a male patient with BRCA2 pathogenic variant who developed three HBOC-associated cancers and includes a review of literatures discussing factors contributing to the development of multiple cancers.

　The cancer support center in Nagano Red Cross Hospital provides seamless support from attending outpatient visits for genomic medicine consultations to facilitating visits to an Outpatient Service for Cancer Genomic Medicine. Since our designation as an Affiliated Hospital for Cancer Genomic Medicine in 2019, we had been requesting Expert Panel reviews from Core Hospital or Designated Hospital (from September 2020) for Cancer Genomic Medicine and providing result explanations after receiving the Expert Panel reports. With the new designation system for Affiliated Hospitals for Cancer Genomic Medicine Capable of Conducting Expert Panels starting in 2024, we intensified our efforts to establish an in-house Expert Panel system. In November 2024, we received designation of Affiliated Hospitals for Cancer Genomic Medicine Capable of Conducting Expert Panels from the Ministry of Health, Labour and Welfare and began operating our own Expert Panel. As a result, we have successfully reduced the turnaround time for Expert Panel reports and improved intra-hospital coordination.