Stage IV Breast Cancer Incidence and Survival, 2010-2021

Importance: Trends in the incidence of de novo stage IV breast cancer in the general population and in the percentage with stage IV disease remain underreported. Objectives: To evaluate the incidence, percentage, and survival of people with de novo stage IV breast cancer diagnosed from 2010 through 2021. Design, Setting, and Participants: This population-based cohort study used data from the Surveillance, Epidemiology, and End Results program to identify all individuals diagnosed with de novo invasive breast cancer between January 1, 2010, and December 31, 2021. No exclusion criteria were applied. Data analyses were conducted from January 2024 to June 2025. Main Outcomes and Measures: Age-adjusted incidence rates of breast cancer and annual percentage changes (APC) from 2010 through 2021 were calculated. Among the diagnosed breast cancers, the yearly percentage of stage IV disease was also calculated. Changes in overall survival (OS) were evaluated for patients with stage IV breast cancer using multivariable Cox proportional hazards regression models stratified by tumor subtype. Results: Of 761 471 breast cancer diagnoses (median [IQR] age at diagnosis, 60 [50-70] years; 99.2% female), 43 934 (5.8%) were stage IV. Stage IV incidence increased from 9.5 (95% CI, 9.2-9.9) cases per 100 000 females in 2010 to 11.2 (95% CI, 10.9-11.6) cases per 100 000 females in 2021, an APC of 1.2% (95% CI, 0.8%-1.6%). The incidence of stages I to III disease also increased, from 163.0 (95% CI, 161.6-164.4) cases per 100 000 females in 2010 to 177.4 (95% CI, 176.1-178.8) cases per 100 000 females in 2021. Stage IV incidence increased across all tumor subtypes, with an APC of 2.0% (95% CI, 1.5%-2.6%) for hormone receptor (HR)-positive/ERBB2-negative, 1.6% (95% CI, 0.2%-2.9%) for HR-positive/ERBB2-positive, 1.3% (95% CI, -0.1%-2.7%) for HR-negative/ERBB2-positive, and 2.7% (95% CI, 1.4%-4%) for triple-negative disease. Stage IV incidence increased statistically significantly across all age groups and numerically across all racial groups. Among males, there was a statistically significant increase in stage IV incidence, with an APC of 3.7% (95% CI, 1.0%-6.5%). The percentage of stage IV diagnoses increased statistically significantly from 2010 through 2021 in each tumor subtype: 4.4% to 95.4% for HR-positive/ERBB2-negative, 8.1% to 91.6% for HR-positive/ERBB2-positive, 10.4% to 89.4% for HR-negative/ERBB2-positive disease, and 6.7% to 92.9% for triple-negative breast cancer. For each successive year, OS among patients diagnosed with stage IV improved, with adjusted hazard ratios of 0.99 (95% CI, 0.98-0.99) for HR-positive/ERBB2-negative, 0.97 (95% CI, 0.95-0.99) for HR-positive/ERBB2-positive, and 0.97 (95% CI, 0.94-0.99) for HR-negative/ERBB2-positive; changes for triple-negative breast cancer were not statistically significant (AHR, 0.99 [95% CI, 0.97-1.01]; P = .33). Conclusions and Relevance: In this cohort study of individuals with stage IV breast cancer, incidence increased significantly overall, across ages, and for both sexes from 2010 through 2021. The percentage of individuals with stage IV vs stages I to III diagnoses also increased. Although OS improved, research is warranted to determine factors contributing to increased incidence, including potential changes in natural history of breast cancer, disease screening, and incidence and mortality of other conditions.