Survival among patients with untreated metastatic breast cancer.
Authors: Plichta Jennifer Kay , Thomas Samantha M. , Sammons Sarah , McDuff Susan G.R. , DiLalla Gayle , Kimmick Gretchen Genevieve , Hwang Eun-Sil Shelley 
Published: June 2021

1095

Background: Treatments for metastatic breast cancer (MBC) have significantly improved survival for patients who receive treatment, yet data describing the prognosis for untreated patients is lacking. Therefore, we sought to assess the survival outcomes of patients with de novo MBC who did not receive treatment. Methods: Adults with MBC at diagnosis (clinical M1 or pathologic M1) were selected from the NCDB (2010-2016) and stratified based on receipt of treatment (treated = received at least one treatment; untreated = received no treatments). Differences between patient groups were tested using Chi-square tests for categorical variables and t-tests for continuous variables. Overall survival (OS) was estimated using the Kaplan-Meier method for the overall cohort and stratified by select patient and/or disease characteristics, and groups were compared with log-rank tests. Cox Proportional Hazards models were used to identify factors associated with OS in the untreated MBC subgroup. Results: Of the 53,240 patients with de novo MBC, the median age was 61y (IQR 52-71), and the majority had a comorbidity score of 0 (81.2%). Within this cohort, 49,040 (92.1%) received at least one treatment (treated) and 4,200 (7.9%) had no documented treatments (untreated). Untreated patients were more likely to be older (median 68y vs 61y, p < 0.001) and have higher comorbidity scores (p < 0.001). Patients with untreated MBC were more likely to have triple negative disease (17.8% vs 12.6%), and a higher disease burden (≥2 metastatic sites: 38.2% untreated vs 29.2% treated, p < 0.001). The median unadjusted OS in the untreated subgroup was 2.5mo vs 36.4mo in the treated subgroup (p < 0.001). For those who survived at least 1mo post-diagnosis, the median unadjusted OS in the untreated subgroup was 6.9mo vs 37.3mo in the treated subgroup (p < 0.001), which increased to 18.6mo and 40.3mo for those who survived at least 3mo post-diagnosis (p < 0.001). In the untreated population, unadjusted OS varied by breast cancer subtype (median 3.8mo for HR+/HER2-, vs 2.6mo for HER2+, vs 2.1mo for triple negative, p < 0.001) and number of metastatic sites (4.1mo for 1 site, vs 1.8mo for 2 sites, vs 1.1mo for 3 sites, vs 1.2mo for ≥4 sites, p < 0.001). After adjustment, variables associated with a worse OS in the untreated cohort included older age, higher comorbidity scores, higher tumor grade, and triple negative (vs HR+/HER2-) tumor subtype (all p < 0.05), while the number of metastatic sites was not associated with survival; these same findings were also noted when the analysis was limited to those who survived at least 1mo post-diagnosis. Conclusions: Patients with de novo MBC who do not receive treatment are more likely to be older, present with comorbid conditions, and have clinically aggressive disease. Similar to those who do receive treatment, survival in an untreated population is associated with select patient and disease characteristics. However, the prognosis for untreated MBC is dismal.