BRCA1/2 pathogenic variant prevalence in Japanese breast cancer is unclear. Here, we analyzed BRCA1/2 pathogenic variant prevalence with a particular focus on age factors, using the Japanese HBOC consortium database. All registered subjects were Japanese individuals who underwent BRCA1/2 genetic testing from January 1996 to July 2017 according to the Japanese HBOC consortium database. Cases were extracted and analyzed for each evaluation item. Overall BRCA1 and BRCA2 pathogenic variant prevalence was 11.2% and 9.0% in the cohort of 2366 proband patients, respectively. The age at onset of breast cancer for patients with BRCA1/2 pathogenic variants was significantly lower than that for patients without a BRCA1/2 pathogenic variant. In both BRCA1/2 patients, ages at onset were not statistically significantly different between two subtype groups (ER-positive vs. TNBC). We analyzed the BRCA1/2 pathogenic variant prevalence among age groups in patients with no family history of breast or ovarian cancer. In the TNBC group, the rate of genetic variants was more frequent among younger patients. Our results demonstrated that early breast cancer onset is associated with a BRCA1/2 pathogenic variant in the Japanese population. Younger TNBC patients were more likely to have a BRCA1/2 pathogenic variant irrespective of a family history of breast or ovarian cancer.

We report an extremely rare case of familial breast cancer with deleterious germline mutations in both BRCA1 and BRCA2 genes, of which, to date, no such case has been reported among Japanese breast/ovarian cancer patients. Genetic testing of the family members indicated that the same double heterozygosity for BRCA1 and BRCA2 genes was transmitted to the paternal cousin, and the same BRCA2 mutation to the younger sister with bilateral breast cancer, younger brother with stomach cancer, and proband's son and daughter without cancer. Immunohistochemical analysis of BRCA protein expression was performed using breast cancer tissues from the proband with double heterozygosity for BRCA1 and BRCA2 genes and from her sibling without BRCA1 mutation but with BRCA2 mutation. There was no staining of either BRCA in the proband and no staining of BRCA2 in the sibling.

A case of breast cancer that metastasized to the cervix 10 years and 8 months after mastectomy is reported. The patient had undergone pancreaticoduodenectomy due to solitary metastasis to the head of the pancreas 4 years previously. The cervical metastasis was associated with abnormal genital bleeding. After pancreaticoduodenectomy the serum levels of CEA, CA15-3 and NCC-ST-439, which are markers of breast cancer, were within normal limits, but the serum level of CA15-3 had increased month by month. The patient had abnormal genital bleeding and presented to the department of gynecology at our hospital. The tumor was in the cervix, bled easily and 2.5x2.0 cm in size on ultrasonography. It was thought to be carcinoma of the cervix, but biopsy revealed the tumor to be an adenocarcinoma pathologically and CA15-3 was immunohistochemically demonstrated in the resected specimen, similar to lobular carcinoma of the breast. Abdominal CT scan revealed involvement of the ovaries and uterus, prompting hysterectomy with bilateral oophorectomy. After discharge, she received chemoendocrine therapy. However, she subsequently died due to peritoneal carcinomatosis.

We report a case of malignant melanoma of unknown primary origin presenting metastasis in various organs as well as intraluminal gallbladder bleeding due to gallbladder metastasis. A 58-year-old woman was diagnosed with stage IV metastatic malignant melanoma. Because she exhibited acute cholecystitis and hemobilia due to malignant melanoma of the gallbladder, laparoscopic cholecystectomy was performed to relieve the symptoms. The resected gallbladder specimen showed a pedunculated black mass indicating malignant melanoma. Pathologic examination and immunohistochemical analysis revealed malignant melanoma of the gallbladder. Only a few cases of gallbladder malignant melanoma presenting hemobilia have been reported; here we present our case, including the experience of multidisciplinary treatment.