Case presentation
A 34-year-old woman presented to our hospital with a mass in her right breast, which she noticed after giving birth to her second child. Breast cancer was diagnosed via core needle biopsy. The tumor was classified as invasive ductal carcinoma, estrogen receptor (ER) positive, progesterone receptor (PgR) positive, and HER2 positive. The timeline of the treatment course is shown in Figure 1. The patient received 8 courses of docetaxel–pertuzumab–trastuzumab therapy (75 mg/m2docetaxel on day 1, 420 mg/kg pertuzumab on day 1, and 6 mg/kg trastuzumab on day 1 every 3 weeks). Subsequently, right total mastectomy and axillary lymph node dissection were performed. The main pathological findings were a residual tumor diameter measuring 53 mm, a number of residual lymph node metastases found in four of 18 nodes, ER and PgR positivity, HER2 negativity, and a histological response to preoperative therapy of grade 1a. Postoperatively, the patient received chemotherapy and endocrine therapy (pertuzumab–trastuzumab, tamoxifen, and a luteinizing hormone-releasing hormone agonist). Magnetic resonance imaging revealed liver metastases. After three courses of trastuzumab emtansine (3.6 mg/kg every 3 weeks), the metastatic lesions had progressed. Subsequently, adriamycin and cyclophosphamide (AC) therapy (60 mg/m2 adriamycin on day 1 and 600 mg/m2 cyclophosphamide on day 1 every 3 weeks) was administered. Considering cardiotoxicity, AC therapy was completed after 11 courses (total adriamycin dose: 495 mg/m2). Thereafter, lapatinib (1250 mg/kg daily) plus capecitabin (3600 mg/kg on days 1–14 every 3 weeks) therapy was administered. After 20 months, the metastatic tumors showed progression (Figure 2a). BRCA genetic testing was performed and a pathogenic variant was detected. The variant using hg19 as the reference genome was BRCA2 : c.9139C>T (p.Gln3047Ter) (Figure 3). Therefore, olaparib (600 mg/kg daily) was administered. The tumor size reduced after olaparib administration (Figure 2b); however, progression of liver metastases was noted after 12 months of olaparib administration (Figure 2c). Repeated biopsy of the liver metastasis revealed an ER-positive, PgR-positive, and HER2-negative tumor. Abemaciclib (150 mg twice daily) plus fulvestrant (500 mg every 4 weeks) therapy was administered. After 8 months, metastatic lesions progressed. Trastuzumab deruxtecan (5.4 mg/kg every 3 weeks) was administered. After 4 months, metastatic lesions progressed; therefore, bevacizumab (10 mg/kg on days 1 and 15 every 4 weeks) plus paclitaxel therapy (90 mg/m2 on days 1, 8, and 15 every 4 weeks) was administered. Cancer genomic profiling (FoundationOne® Liquid CDx) was performed during bevacizumab plus paclitaxel therapy. The sample at the time of surgery was >3 years old, and the amount of specimen at the time of liver biopsy was insufficient; therefore, liquid biopsy was performed. Figure 2d shows computed tomography images of liver metastasis when cancer genomic profiling testing was performed. The variants detected were BRCA2 c.9139C>T (p.Gln3047Ter) and BRCA2 c.9139_9141delinsTAC (p.Gln3047Tyr) mutation, with 48.9% and 0.37% allele frequency, respectively (Figure 3). After 9 months of bevacizumab plus paclitaxel therapy, metastatic lesions progressed; therefore, eribulin was administered (1.1 mg/m2 on days 1 and 8 every 3 weeks). However, after 3 months, metastatic lesions progressed; thus, irinotecan (100 mg/m2 on days 1, 8, and 15 every 5 weeks) was administered. After one course, the patient’s general condition deteriorated, and the policy of best supportive care was adopted; 4 months later, the patient died.