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Background Estrogen receptor-positive (ER+) metastatic breast cancer (MBC) contributes to nearly 70% of breast cancer-related deaths. Liver metastasis is the third most common site and has been found to carry a poor prognosis. One contributing factor is resistance to available treatments. Meanwhile, estrogen receptor alpha gene (ESR1) activating mutations, which can be enriched in metastatic tumors of the viscera such as the liver, have also been linked to resistance against hormone-blocking agents. We seek to characterize the efficacy of available treatment modalities, including hormone therapy, immunomodulators, and chemotherapy, for MBC with liver disease, and the role of ESR1 mutations in poor treatment response. Methods We conducted a retrospective review of 3388 adults with ER+/HER2- MBC who were treated at a single U. S. cancer center between 1997-2021. All patients received fulvestrant monotherapy or fulvestrant-based combination therapy with CDK4/6 inhibitors, mTOR kinase inhibitors (everolimus), or PI3K inhibitors (alpelisib). We compared the overall and metastatic survival of patients with liver versus non-liver metastasis between different treatment regimens. We also evaluated the impact of chemotherapy administered before or after metastasis. To account for confounders, we included age at first cancer diagnosis, BMI, and stage IV at diagnosis as covariates in our multivariate analyses. Results We identified 1556 (46%) patients in our cohort with liver metastasis. Patients with liver metastasis experienced shorter overall and metastatic survival across all treatment regimens (HR 1.5; CI 1.3-1.6). While fulvestrant-based combination therapies offered a survival benefit over fulvestrant alone in patients with non-liver metastasis, this benefit did not extend to the liver metastasis group. Chemotherapy administered before liver metastasis improved survival, but chemotherapy administered after liver metastasis did not. Patients with first metastasis to the liver did not significantly differ in survival when compared to those who developed liver metastasis later. ESR1 mutations were identified in only a minority of our cohort (4%), but a higher prevalence of liver metastasis was found in patients with ESR1mutations (49% vs. 45% in wild type group). Independent of ESR1 status, patients with liver metastasis were found to have worse survival. Conclusion We find liver metastasis to be a negative prognostic factor in patients with metastatic breast cancer, independent of ESR1 status. While novel fulvestrant-based combination therapies have been promising for MBC, similar survival benefits are not seen in those with liver metastasis. Liver metastasis proves to be aggressive and difficult to treat, and current therapies are insufficient. Presentation: No date and time listed |
