Incidence and Risk Factors for Development of Portal Hypertension and Sinusoidal Liver Injury Associated with T-DM1 in HER2-Positive Breast Cancer.
Authors
Affiliations (10)
Affiliations (10)
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. [email protected].
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
- Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea.
- Interdisciplinary Program of Bioengineering, Seoul National University, Seoul, Korea.
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. [email protected].
- Department of Genomic Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. [email protected].
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
Abstract
While an association between trastuzumab emtansine (T-DM1) and development of portal hypertension has been suggested, clinical studies on the incidence and risk factors remain limited. HER2-positive breast cancer patients treated with T-DM1 as adjuvant or palliative therapy were retrospectively enrolled. The composite endpoint of portal hypertension and sinusoidal liver injury was defined as development of splenomegaly and at least one among gastroesophageal varices, spontaneous portosystemic shunt, or portal hypertensive ascites; or biopsy-confirmed sinusoidal obstruction syndrome. Splenomegaly was defined as ≥50% increase in spleen volume, measured from CT images using a deep learning algorithm and reviewed by an independent radiologist. Univariable and multivariable analyses identified potential risk factors. A total of 173 patients (median age: 53 (28-80)) were analyzed. Patients received a median of 14 (2-18) T-DM1 cycles in the adjuvant (n=62) and 11 (2-84) in the palliative setting (n=111). Portal hypertension and sinusoidal liver injury occurred in 31 (17.9%) (adjuvant; 11.3%, palliative; 21.6%), splenomegaly in 86 (49.7%) patients (adjuvant; 32.3%, palliative; 59.5%). Eight cases (4.6%) of liver-related T-DM1 discontinuation and 5 cases (2.9%) of significant liver-related complications were identified (4 variceal bleeding, one portosystemic encephalopathy). Age at T-DM1 treatment ≥60 years (OR 2.7, p=0.027), cumulative dose ≥55 mg/kg (OR 2.7, p=0.029), and baseline platelet count ≤150 × 109/L (OR 12.7, p=0.008) were identified as potential risk factors; however, the latter two associations should be interpreted with caution because the cumulative-dose association likely reflects prolonged T-DM1 exposure and the association observed for low baseline platelet count was derived from a very small subgroup of six patients. Portal hypertension and sinusoidal liver injury are clinically significant in patients receiving T-DM1, warranting careful monitoring, especially in those with older age, low baseline platelet count, and prolonged T-DM1 exposure.