Abstract Background: CDK4/6 inhibitors revolutionized the treatment of hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (MBC), significantly improving outcomes. In premenopausal patients, their combination with ovarian suppression and endocrine therapy is the standard of care in the first-line. In patients with extensive liver metastases with a great treatment response, rare but clinically relevant complications such as pseudocirrhosis can occur. Recognizing this radiological mimic of cirrhosis is essential to avoid misdiagnosis with disease progression and ensure appropriate management. Methods: We describe a case of pseudocirrhosis in a 43-year-old premenopausal woman with HR+/HER2- MBC and high hepatic tumor burden at diagnosis, who experienced a robust response to first-line treatment. Results: This patient was diagnosed in August 2022 with grade 3 invasive breast carcinoma of no special type, ER 98%, PR 2%, HER2-negative, Ki-67 85%, and extensive liver involvement. Treatment was initiated with tamoxifen plus abemaciclib, transitioning to letrozole following GnRH agonist. Molecular testing revealed no somatic or germline mutations. She experienced radiologic complete response, with only a solitary liver lesion progression in February 2025, which was treated with stereotatic body radiotion therapy. In July 2025, routine labs revealed elevated liver enzymes without clinical symptoms. Laboratory tests showed: ALT 60 (Reference value - RV: 13-35); AST 43 (RV:15-37), GGT 510 (RV55), ALP 232 (RV: 46-116). Comprehensive evaluation excluded viral, autoimmune, or drug-induced hepatitis, and imaging suggested morphologic features of cirrhosis, without any evidence of disease progression. Despite imaging findings, the patient had no signs of portal hypertension or liver failure. The diagnosis of pseudocirrhosis has been done and started with ursodeoxycholic acid 300 mg BID and vitamin E 800 mg daily to avoid its progression. She continues on first-line treatment, with stable disease and some improvement in liver enzymes. Discussion: Pseudocirrhosis refers to radiologic changes in the liver—such as capsular retraction, nodularity, and caudate lobe hypertrophy—mimicking true cirrhosis, but without histologic confirmation of fibrosis. It has been reported most frequently in breast cancer, particularly in patients with hepatic metastases undergoing chemotherapy. While the exact mechanism is unclear, proposed explanations include extensive tumor regression leading to capsular retraction, nodular regenerative hyperplasia, desmoplastic reaction, and hepatocellular injury due to oxidative stress from rapid tumor lysis. Despite resembling chronic liver disease radiographically, pseudocirrhosis often lacks clinical features of decompensated cirrhosis, making the correct diagnosis crucial. Importantly, up to 75% of women with metastatic breast cancer may exhibit some degree of liver contour irregularity on imaging, underscoring the need for oncologists to correlate radiologic changes with treatment history and clinical context. Conclusion: This case highlights pseudocirrhosis as a rare but important differential diagnosis in patients with extensive liver metastases responding to systemic therapy. Awareness of this entity can prevent misinterpretation of imaging as disease progression or cirrhosis and help guide appropriate management without unnecessary treatment changes. Citation Format: M. C. Gouveia, R. Borges, P. Zanuncio, B. Zucchetti. Pseudocirrhosis Following Great Response to CDK4/6 Inhibitor and Endocrine Therapy in a Premenopausal Patient With HR+/HER2- Metastatic Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-08.
Gouveia et al. (Tue,) studied this question.