Abstract PO5-06-13: Impact of Therapy on Sites of Metastases in Triple Negative Breast Cancer

Abstract Background: Metastatic triple negative breast cancer (TNBC) is a diverse disease with the propensity to spread to visceral organs and the central nervous system (CNS). While systemic chemotherapy is commonly used, there is a growing utilization of immune checkpoint inhibitors (ICI) and antibody drug conjugates (ADC). However, few studies have examined the impact of specific therapies on individual metastatic sites, limiting clinical guidance for solitary metastases. Objective: This study aimed to evaluate the efficacy of various systemic therapies in TNBC patients with lung, liver, and CNS metastases. Methods: We analyzed data from the Dallas Metastatic Breast Cancer Study, a retrospective cohort study that includes all patients with metastatic breast cancer treated at a single academic medical center and identified 52 TNBC patients with visceral and CNS metastases diagnosed between 2009 and 2021. We correlated the site of metastasis with and treatment response, which was assessed based on imaging findings using RECIST 1.1 criteria. Results and Discussion: The median age at diagnosis of visceral metastatic disease was 52 years. Of the patients, 60% presented with de novo metastatic disease, while 40% experienced disease recurrence. The most prevalent metastatic sites were the lung (n=28), CNS (n=28), and liver (n=9). Among patients with detectable circulating tumor DNA, the most prevalent gene mutations in lung metastases were TP53 (36%), PTEN (13%), and PIK3R1 (10%). In liver metastases, TP53 (53%) and BRCA1 (15%) mutations were the most frequently observed. Similarly, in CNS metastases, TP53 (40%) and BRCA1 (13%) mutations were again most frequently detected. The notable frequency of TP53 mutations indicates the necessity for further investigations to explore potential differences in treatment approaches for patients with these mutations. The median overall survival (OS) was 14.43 months ±15.53, with the longest survival observed in patients with lung metastases (15 months), followed by liver metastases (6 months) and CNS metastases (5 months). Patients with involvement of a single visceral or CNS site had a mean OS of 15.80±18.19 months, whereas those with two sites of involvement had a mean OS of 13.08±10.18 months. Patients with metastases in all three sites had a mean OS of 8.33±8.50 months. Treatment modalities varied among patients. For liver metastases, chemotherapy (n=6), ICI (n=2), ADC (n=1), radiation therapy (n=2), and surgery (n=1) were administered. Lung metastases were treated with chemotherapy (n=26), ICI (n=4), ADC (n=5), radiation therapy (n=4), and surgery (n=1). CNS metastases were managed with chemotherapy (n=14), ICI (n=2), ADC (n=1), radiation therapy (n=21), and surgery (n=4). Systemic therapy for liver metastases resulted in stable disease (75%) and progressive disease (25%). In lung metastases, it led to stable disease (56%), partial response (23%), complete response (13%), and progressive disease (8%). CNS metastases treated with systemic therapy demonstrated stable disease (86%) and progressive disease (14%). The most commonly used systemic therapy was paclitaxel. Immunotherapy achieved a partial response (60%), stable disease (20%), and progressive disease (20%) in metastatic lesions. Treatment with ADCs resulted in stable disease (43%), partial response (29%), and progressive disease (29%). Compared to lung metastases, liver and CNS metastases exhibited lower response rates and overall survival. CNS metastases were less likely to receive systemic therapies, indicating a need for improvement. These findings highlight the importance of personalized treatment strategies tailored to individual metastatic sites in TNBC. Citation Format: Hannah Chang, Pallavi Dev, Luise Froessl, Shao-Po Huang, Christine Hodgdon, Julia Maues, Isaac Chan. Impact of Therapy on Sites of Metastases in Triple Negative Breast Cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-13.