The coexistence of a germline BRCA1 mutation and human epidermal growth factor receptor 2 (HER2)-positive breast cancer is rare and represents a distinct clinical and therapeutic challenge. The mechanisms underlying this association remain unclear. The HER2-positive subtype is associated with a more aggressive clinical course, but responds well to targeted anti-HER2 therapy, including trastuzumab. Although trastuzumab therapy is generally well tolerated, rare but potentially serious organ complications may occur. We report the case of a 41-year-old woman with a germline BRCA1 mutation and HER2-positive breast cancer who underwent bilateral mastectomy, removal of the ovaries and systemic treatment including chemotherapy and trastuzumab therapy. During treatment, she developed a marked elevation of liver enzymes consistent with drug-induced liver injury. After initial clinical improvement, she developed acute pancreatitis without biliary or metabolic causes, suggesting possible treatment-related toxicity. The clinical course was further complicated by Clostridioides difficile infection, likely associated with prior antibiotic exposure and immunosuppressive therapy. Following temporary interruption of systemic treatment and supportive management, the patient improved and was able to continue oncological therapy under close biochemical monitoring. This case highlights the potential for rare but serious multi-organ complications during trastuzumab-based therapy. Early recognition and appropriate management of such complications may allow continuation of oncological treatment. The case also emphasizes the need for further research on targeted therapeutic strategies, such as PARP inhibitors, for patients with HER2-positive, BRCA1-mutated breast cancer.
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