Breast cancer is one of the most prevalent cancers among women, accounting for 30% of all female malignancies.1 Neoadjuvant trastuzumab combined with pertuzumab has been shown to significantly prolong the survival of patients. However, it may also lead to adverse events (AEs) in a subset of patients. Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease. Sjögren disease (SjD) represents the predominant extrahepatic disorder associated with PBC. The coexistence of PBC and SjD may predispose patients to a greater likelihood of developing or experiencing more severe outcomes.2 This case report describes severe liver AEs induced by trastuzumab and pertuzumab in a 61-year-old woman with HER2-positive breast cancer. Immune suppressive therapy including baricitinib successfully enabled the patient to finish the anti-HER2 therapy without recurrence of AEs. The patient, a 61-year-old woman with PBC (diagnosed in 2021; antinuclear antibodies (ANA) 1:320, and anti-M2 antibody 598.30 RU/mL) and SjD (diagnosed in 2021; xerostomia, and anti-Ro52 autoantibody+), managed with ursodeoxycholic acid (UDCA) and hydroxychloroquine since 2021, had prednisone and cyclosporine added in 2023 for a SjD flare characterized by lip hyperpigmentation and tooth loss. In July 2023, she developed left chest mass and was diagnosed with HER2+ breast cancer (cT1N1M0, stage IIA) by ultrasound-guided core needle biopsy and breast magnetic resonance imaging. On July 27, 2023, the patient commenced chemotherapy of docetaxel 140 mg, trastuzumab 392 mg, and pertuzumab 840 mg. Simultaneously, all rheumatology medications were discontinued except for UDCA. During four chemotherapy cycles (July–October 2023), she exhibited progressive decline in total protein and albumin (Alb) levels (from 39.8 to 33.3 g/L), alongside persistent elevations in direct bilirubin(DBil) (8–11.7 μmol/L), gamma-glutamyl transferase (GGT) (44–61 U/L), and alkaline phosphatase (ALP) (113–158 U/L). On November 8, 2023, before her admission for a planned left breast cancer excision, she presented with abdominal distension. Ultrasound showed severe ascites (maximum depth 13.0 cm; Figure 1Ba). Laboratory investigations revealed hypoalbuminemia (Alb 28.5 g/L); elevated GGT (157 U/L), ALP (58 U/L), and DBil (10.8 μmol/L); and prolonged activated partial thromboplastin time (37.6 seconds). Clinical evaluation supported a diagnosis of treatment-induced autoimmune hepatic decompensation resembling PBC and systemic autoimmune involvement. She received furosemide for diuresis, and hepatoprotective and choleretic agents for hepatic AEs. Subsequently, her ascites improved significantly (Figure 1Bb and c), enabling a left-modified radical mastectomy (November 24, 2023). Post surgery, she had re-examinations for SjD and autoimmune liver antibodies (ANA 1:640, anti-M2 antibody 447.58 RU/mL, and anti-Ro52 autoantibody+). She resumed glucocorticoids, cyclosporine, hydroxychloroquine, and hepatoprotective agents to tolerate subsequent anti-HER2 therapy. A T helper cell subset analysis was performed, revealing that the proportions of Th1, Th2, and Th17 cells were all elevated (Figure 1A). By January 2024, a follow-up ultrasound showed hepatic cirrhosis, splenomegaly, and a small volume of ascites (Figure 1 Bd). After initiation of hepatoprotective therapy with monoammonium glycyrrhizinate and cysteine, the ascites was completely resolved (Figure 1Be). Repeat T helper cell subset analysis (June 2024) revealed normalization of all previously elevated parameters (Figure 1A). In August 2024, cyclosporine was replaced with baricitinib due to hypertension, enabling completion of anti-HER2 therapy (August 25, 2024). She remains on immunosuppressive therapy containing baricitinib. Her latest follow-up in July 2025 showed stable condition across all parameters (Alb 39.8 g/L) without recurrent ascites. Although severe hepatic AEs from anti-HER2 therapy are rare, this case highlights a serious event in a patient with predisposing autoimmune conditions.3 Following four cycles of anti-HER2 therapy, this patient developed severe ascites, hypoalbuminemia, elevated cholestatic enzymes, and cholestasis. These symptoms significantly improved after drug discontinuation and initiation of symptomatic management, suggesting that this severe hepatotoxicity represented drug-related AEs. Upon binding to HER2, trastuzumab and pertuzumab elicit antibody-dependent cellular cytotoxicity, mediating tumor cell lysis via natural killer (NK) cells.4 Furthermore, HER2-targeted therapy has been shown to increase CD4+ T cell levels.5 The patient's significant post-AE elevation in T helper cell subsets confirmed immune dysregulation from excessive activation. She responded favorably to baricitinib, a selective JAK1/JAK2 inhibitor that suppresses cytokine signaling (eg, interleukin-2 IL-2, IL-6, and IL-12), thereby inhibiting NK cell function and T helper cell differentiation to mitigate dysregulation and enable therapy completion. In general, baricitinib is also a safe and effective drug for managing AE associated with trastuzumab and pertuzumab, but long-term clinical observation and cohort studies are required to confirm its efficacy. Close monitoring and early intervention are critical to managing potential AEs and ensuring treatment continuity. The authors would like to acknowledge all those who contributed to this manuscript for their participation. All authors contributed to at least one of the following manuscript preparation roles: conceptualization AND/OR methodology, software, investigation, formal analysis, data curation, visualization, and validation AND drafting or reviewing/editing the final draft. As corresponding author, Dr He confirms that all authors have provided the final approval of the version to be published and takes responsibility for the affirmations regarding article submission (eg, not under consideration by another journal), the integrity of the data presented, and the statements regarding compliance with institutional review board/Declaration of Helsinki requirements. Disclosure form. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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Li et al. (Thu,) studied this question.