Abstract PO4-06-02: Frequency of presentation and outcomes of stage IV breast cancer over the past decade: a population-based study
Authors: Avila Jorge , Leone Julieta , Tayob Nabihah , Vallejo Carlos , Hassett Michael , Lin Nancy , Tolaney Sara , Leone Jose 
Published: May 2024

Abstract
Background: Over the past decade, there have been major advances for the treatment of patients (pts) with metastatic breast cancer (MBC). For pts with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative MBC, newer treatments include CDK 4/6 inhibitors among other targeted therapies; for HER2+ MBC, we have seen the development of antibody-drug conjugates (ADC) and other anti-HER2 agents; and for triple-negative breast cancer (TNBC) options include immunotherapy, ADCs, and PARP inhibitors. The aims of this study were to evaluate time trends in clinical characteristics, frequency of presentation and outcomes of pts with stage IV breast cancer over the past decade.
Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) program, we identified pts diagnosed with breast cancer between 2010-2020. Pts required to have known HR and HER2 status and known stage at diagnosis. We described the proportion of stage IV disease overall for each tumor subtype and evaluated trends in the proportion of stage IV over time. Outcomes were evaluated by breast cancer-specific survival (BCSS) using Kaplan-Meier. Among stage IV pts, we conducted multivariable cox models to assess changes in BCSS over time, stratified by tumor subtype and adjusted for age at diagnosis, race and ethnicity, sex, tumor grade, histology, surgery, radiation therapy, chemotherapy, sites of distant metastases, marital status, median household income, rurality and US region. We evaluated overall survival as a secondary endpoint.
Results: We included 443,631 pts of whom 24,788 (5.59%) had stage IV disease at diagnosis. Pts with stage IV breast cancer had a median age of 61 years and a median follow up of 57 months (IQR 28 – 89 months). When compared to stage I-III, stage IV pts were more often of Black race (10.4% for stage I-III vs 15.7% for stage IV), less often married (56.7% vs 43.5%, respectively) and less often HR+/HER2- (74.1% vs 59.9%, respectively); all p &lt; 0.001. Among pts with stage IV, the frequency of each metastatic site at initial diagnosis was: bone 66.45%, lung 30.47%, liver 25.79%, and brain 7.9%. Across all years (2010-2020), the proportion of stage IV disease varied significantly by tumor subtype: 4.6% in HR+/HER2-, 8.5% in HR+/HER2+, 11.3% in HR-/HER2+, and 7.1% in TNBC; p &lt; 0.001. The proportion of stage IV increased modestly during 2010-2020 in HR+/HER2- tumors (4.6% in 2010 to 5.1% in 2020, p for trend = 0.01), in HR-/HER2+ (10% in 2010 to 13.7% in 2020, p for trend &lt; 0.001), and in TNBC (6.9% in 2010 to 7.8% in 2020, p for trend = 0.001). No significant difference was observed in the proportion of stage IV over time in HR+/HER2+ (p for trend = 0.76). Rate of BCSS at 5 years was: 32.51% for HR+/HER2-, 43.92% for HR+/HER2+, 37.28% for HR-/HER2+, and 10.97% for TNBC; p &lt; 0.001. In adjusted Cox models, BCSS improved significantly over time for each additional year in HR+/HER2- (adjusted Hazard Ratio [HzR] 0.982, p = 0.01), in HR+/HER2+ (adjusted HzR 0.945, p &lt; 0.001), and in HR-/HER2+ (adjusted HzR 0.959, p = 0.03). The improvement in BCSS over time in TNBC was not significant (adjusted HzR 0.982, p = 0.15). Overall survival results were similar to those of BCSS both in 5-year rates as well as Cox model results.
Conclusions: In this population-based study, we saw that the proportion of pts presenting with de-novo stage IV varied significantly by tumor subtype, being as low as 4.6% in HR+/HER2- and as high as 11.3% in HR-/HER2+ disease. These proportions have unfortunately increased over time in most subtypes, highlighting a need for additional research to identify the reasons behind these trends. BCSS improved significantly over time in HR+/HER2- and in both HER2+ subtypes, coinciding with a time period of important therapeutic advances. TNBC remains a highly unmet medical need and further follow up is needed to assess the impact of newer treatments.
Citation Format: Jorge Avila, Julieta Leone, Nabihah Tayob, Carlos Vallejo, Michael Hassett, Nancy Lin, Sara Tolaney, Jose Leone. Frequency of presentation and outcomes of stage IV breast cancer over the past decade: a population-based study [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 PO4-06-02.