Abstract P5-02-39: Efficacy of fulvestrant-based therapies in treating HR-positive, HER2-negative breast cancer with liver metastasis
Authors: Chien Christine , Madak-Erdogan Zeynep , Goel Mahima , Gangidi Suma , Tripathy Debu , Raghavendra Akshara Singareeka 
Published: March 2023

Abstract
Background: Hormone receptor-positive (HR+) metastatic breast cancer (MBC) contributes to nearly 70% of breast cancer-related deaths. The liver is the third most common site for metastasis in breast cancer, and liver involvement has been found to have a poor prognosis. One contributing factor is resistance to hormonal treatments. Furthermore, estrogen receptor alpha gene (ESR1) activating mutations, which are enriched in metastatic tumors of the viscera such as the liver, have been linked specifically to resistance against hormone-blocking therapies. We seek to characterize the efficacy of specific treatment modalities, including hormone therapy, immunomodulators, radiotherapy, chemotherapy, and the role of ESR1 mutations in poor treatment response of MBC with liver metastasis. Methods: We conducted a retrospective matched cohort study of 3388 adults with HR+/HER2- MBC with liver and non-liver involvement, who were treated at MD Anderson Cancer Center from 1997-2021. Patients with liver and non-liver metastasis were matched by age at breast cancer diagnosis, race, BMI, and stage. All patients underwent 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 vs. non-liver metastasis on different treatment regimens. We also evaluated the impact of chemotherapy administered for metastasis. Results: Patients with liver metastasis experienced shorter overall and metastatic survival across all treatment regimens (HR, 1.44; 95% CI 1.34-1.57; P&lt;.001). The addition of targeted therapies to fulvestrant offered a survival benefit over fulvestrant alone in patients with non-liver metastasis. However, this benefit did not extend to the liver metastasis group. Independent of chemotherapy, liver metastasis was found to be a negative prognostic factor. Patients with first metastasis to the liver did not significantly differ in survival when compared to those who developed liver metastasis at a later stage. ESR1 mutations were identified in only a minority of the cohort (4%), but a higher prevalence of liver metastasis was found in patients with ESR1 mutations (49%) vs. the wild type group (45%). Independent of ESR1 status, patients with liver metastasis were found to have worse survival. Conclusion: We found liver metastasis to be a negative prognostic factor in patients with MBC 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.
Citation Format: Christine Chien, Zeynep Madak-Erdogan, Mahima Goel, Suma Gangidi, Debu Tripathy, Akshara Singareeka Raghavendra. Efficacy of fulvestrant-based therapies in treating HR-positive, HER2-negative breast cancer with liver metastasis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-39.