International Validation of a Staging Model for de novo Metastatic Breast Cancer

Abstract Background Given the heterogeneity in outcomes for de novo metastatic breast cancer (dnMBC), a staging system was recently developed that refines prognostic estimates for patients presenting with distant metastases (JCO 2023;10:2546). This staging model was developed using the National Cancer Database and stratified patients into 4 subgroups, termed IVA, IVB, IVC, and IVD based on 3-year overall survival (OS): IVA >70%, IVB 50-70%, IVC 25-< 50%, and IVD < 25%; the primary factors affecting higher stage grouping were negative for ER, PR, and HER2 expression and a higher number of involved organ sites. Here, we aim to validate this model using an international data set. Methods Data for dnMBC patients were obtained from the Netherlands Cancer Registry (NCR, hosted by IKNL), Epidemiological Strategy and Medical Economics (ESME) by Unicancer, British Columbia Cancer (BCCan), Instituto Nacional de Cancerología, México (INCan), and Grupo Español de Investigación en Cáncer de Mama (GEICAM); the diagnosis years included varied by organization (range 2002-2021). Stage groups were assigned based on previously published criteria, defined by T-category, grade, ER, PR, HER2, histology, organ system site of metastases (bone-only, brain-only, visceral), and number of organ systems involved. For each cohort, followup time and OS were estimated using the reverse Kapan-Meier and Kaplan-Meier method, respectively. Median rates were estimated across all cohorts by weighting on cohort sample size or number at risk. Cox proportional hazards models were used to estimate the association of stage with OS after adjustment for age at diagnosis (treatment data not available for all cohorts). For the ESME cohort, a subgroup multivariable analysis was used to estimate the association of stage with OS after adjustment for age, local (surgery or radiotherapy) and first line systemic treatments. Results The final validation cohort was comprised of N=11,199 patients from 5 international organizations: n=5063 (45.2%, IKNL), n=4139 (37.0%, ESME), n=774 (6.9%, BCCan), n=757 (6.8%, INCan), and n=466 (4.2% GEICAM). Median followup across all cohorts was 77.5 months (95% CI 74.3-80.2). Median followup (in months) for the IKNL, ESME, BCCan, INCan, and GEICAM cohorts was 45.3 (95% CI 43.6-47.1), 77.5 (95% CI 74.3-80.2), 105.0 (95% CI 95.9-106.5), 93.0 (95% CI 86.5-102.1), and 49.5 (95% CI 46.5-53.4), respectively. Patients were stratified into stage groups: IVA, n=603 (5.4%); IVB, n=5704 (50.9%); IVC, n=3356 (30.0%); IVD, n=1536 (13.7%). For all cohorts combined, the weighted average OS rates consistently decreased with increasing stage group; similar findings were noted for individual cohorts (all p< 0.001; Table). On multivariable subgroup analysis including age at diagnosis, stage group was significantly associated with OS, and the risk of death increased with increasing stage (all p< 0.001; Table). On multivariable subgroup analysis for n=4139 patients (ESME cohort), stage group remained significantly associated with OS [IVA: reference; IVB: HR 1.51 (95% CI 1.17-1.93); IVC: HR 2.11 (95% CI 1.64-2.72); IVD: HR 3.60 (95% CI 2.75-4.70)] after adjusting for age and treatment. Conclusions These findings provide external validation of the previously published staging guidelines for dnMBC. This may guide future revisions of the AJCC staging guidelines for patients with dnMBC and provide patients and providers valuable information in planning therapy and goals of care as they approach the end-of-life. Table. Citation Format: Jennifer Plichta, Samantha Thomas, Sabine Siesling, Linda de Munck, Amélie Lusque, Thomas Grinda, Lovedeep Gondara, Stephen Chia, Paula Cabrera-Galeana, Nancy Reynoso-Noverón, Sara López-Tarruella, Isabel Álvarez López, Stephen Edge, Gabriel Hortobagyi. International Validation of a Staging Model for de novo Metastatic 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 PO4-18-01.