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Institute of 286 TP53 pathogenic variants in 107 families with LFS showed that the 50% cumulative cancer onset age was 46 years for male and 31 years for female7). It has been reported that 12.2 % of cases are de novo LFS; therefore, cases without a family history are scattered8). LFS has a wide tumor spectrum, including the so-called ‘core’ LFS cancers: soft-tissue sarcomas, osteosarcomas, adre-nocortical carcinomas, central nervous system tumors, and very-early onset female breast cancer9). Juvenile onset of cancer and multiple onsets and types of cancers in one patient are characteristics of LFS. Clinical guidelines for the management of LFS have been published in various countries, including Japan10).According to a report on the analysis of heredi-tary breast cancer-related genes in Japanese breast cancer patients, the percentage of patients with germline TP53 variants is 3.9%, which is small compared to 72.5% for germline BRCA1/2 vari-ants11). Therefore, LFS is rarely encountered in breast cancer treatment, and it is not easy to make a diagnosis. However, in the treatment of breast cancer, radiation therapy (RTx) is often used concomitantly, and the relative contraindication in this disease should be taken into consideration when making treatment decisions12). This report describes a case of LFS that was suspected by its history and clinical course, despite no LFS-related family history of hereditary tumors, which led to LFS genetic testing.Case reportA 33-year-old woman was diagnosed with distal left femoral osteosarcoma at the age of 16 due to pain in the left knee. She received perioperative chemotherapy and local excision and has had no signs of recurrence until now. At the age of 29, a left breast mass was detected by ultrasound screening and diagnosed as breast cancer. She underwent breast-conserving surgery and sentinel node biopsy, and was diagnosed with pT1bN0M0, Stage I, invasive micropapillary carcinoma (5×4 mm; estrogen receptor [ER] 60%, progesterone receptor [PgR] 90%, human epidermal growth factor receptor 2 [HER2] 3+, Ki67 70%; surgical margin positive at the lateral margin for in situ component). She received weekly paclitaxel+tras-tuzumab, LH-RH agonist, tamoxifen and RTx as 406postoperative therapy. Four years after the surgery for left breast cancer, at the age of 33, calcification of her right breast was detected on mammography. A stereotactic core biopsy was performed and diagnosed as breast cancer, cTisN0M0 Stage 0 (ductal carcinoma in situ [DCIS]). When she was diagnosed with metachronous contralateral breast cancer, a hereditary tumor was suspected and she was referred from her family clinic to our genetic department. Her family history included a maternal grandfather with colorectal cancer at the age of 78 and a paternal uncle with lower leg suspected skin cancer at 50 years (Figure 1). This patient had no obvious LFS-related family history. However, since the patient met Chompret’s criteria (2015, Table 1) with multiple cancers and early-onset breast cancer in the ‘core’ tumors, we performed germline TP53 genetic testing (FALCO Ltd., Kyoto, Japan), with her consent (written informed consent was obtained from the patient.). The genetic test results revealed a pathogenic variant, TP53:c.216dupC (p.Val73ArgfsX76) was found in exon 4 of the gene, and a diagnosis of LFS. The patient was referred to the department of breast surgery through the genetic department for further treatment. At the same time as the right mastectomy, the patient preferred to have a left residual mastectomy because of the positive DCIS margins at the previous surgery and for risk reduc-tion. She underwent bilateral mastectomy and breast reconstruction. The postoperative pathology results were as follows. The right breast cancer was DCIS solid > cribriform type, 3×2×12 mm, NG2, pTisN0M0, Stage 0 (ER-, PgR-, HER2 3+, Ki67 40%). The left breast was assessed in every 1 cm-slice for the entire section, due to the residual mastectomy being for risk reduction. Close to the previous surgical scar, DCIS was found (tumor size: 12×6×20 mm, comedo type, NG2, pTisNxMx), which was considered to be a residual lesion due to its similar histology. Additionally, p53 immunohis-tochemical staining (monoclonal, anti-mouse, clone PAb1801) was negative (Figure 2). Sporadic breast cancer cases in the control group that were in situ breast cancer and of similar subtype also tested negative. Currently, she is receiving endocrine therapy for left breast cancer and will be followed up in our department for 5 years after surgery, including