Stage IV Breast Cancer Incidence and Survival, 2010-2021
Key Takeaways
- The share of invasive breast cancers diagnosed as stage IV increased modestly from 5.6% in 2010 to 6.0% in 2021.
- Incidence increases were observed across subtype and demographic strata, although the magnitude varied between groups.
- Overall survival improved over time for HR-positive/ERBB2-negative, HR-positive/ERBB2-positive, and HR-negative/ERBB2-positive disease, while triple-negative disease did not show a significant time trend; breast cancer-specific survival showed a similar pattern.
This retrospective, population-based cohort used the SEER 17 registry database for all invasive breast cancer diagnoses from January 1, 2010, through December 31, 2021. No exclusion criteria were applied, and in situ cases were not included. The cohort comprised 761,471 diagnoses, including 43,934 stage IV cases, which represented 5.8% of the total. These data supported the incidence, stage distribution, and survival analyses.
The full cohort had a median age of 60 years, and 99.2% of patients were female. Among patients with stage IV disease, the median age was 63 years, with 45.7% aged 65 years or older and 18.4% younger than 50 years. Compared with patients with stage I to III disease, those with stage IV disease were more often non-Hispanic Black, less often married, and more often in lower income groups. These baseline differences framed the time trend analyses.
Overall female age-adjusted stage IV incidence increased with an annual percentage change of 1.2% and a 95% CI of 0.8% to 1.6%. The proportion of invasive breast cancers presenting as stage IV also rose, with P<.001 for trend. Age-adjusted subtype-specific annual percentage changes were 2.0% for HR-positive and ERBB2-negative, 1.6% for HR-positive and ERBB2-positive, 1.3% for HR-negative and ERBB2-positive, and 2.7% for triple-negative disease. The steepest age increase occurred in patients younger than 40 years at 3.1%, and the highest race and ethnicity estimate was 3.4% in non-Hispanic Asian and Pacific Islander individuals. Among males, age-adjusted stage IV incidence increased from 0.12 to 0.20 per 100,000, with an annual percentage change of 3.7%. Sensitivity analyses excluding 2020 and 2021 showed a similar female trend, with an annual percentage change of 1.0% from 2010 to 2019. The increases were broad across strata, although the magnitude was not uniform.
Among patients with stage IV disease, median follow-up was 63 months, with an interquartile range of 31 to 99 months. During follow-up, 28,888 deaths occurred, including 25,317 deaths attributed to breast cancer. Adjusted overall survival improved over successive years for HR-positive and ERBB2-negative disease, with an adjusted hazard ratio of 0.99, for HR-positive and ERBB2-positive disease at 0.97, and for HR-negative and ERBB2-positive disease at 0.97. Triple-negative disease did not show a significant time trend, with an adjusted hazard ratio of 0.99 and P=.33. Five-year overall survival was 30.6%, 41.3%, 35.5%, and 10.3% across those subtypes, respectively, and breast cancer-specific survival followed a similar pattern. Survival gains were not observed for triple-negative disease.
The investigators said the rising incidence and modestly higher stage IV share may reflect broader population-level influences. They identified screening, diagnostic timing, and other factors as areas for further investigation, without establishing them as explanations. Important limits included absent data on screening use, adherence, obesity, alcohol use, breastfeeding, and hormone use, along with no capture of recurrent metastatic disease. Incomplete biomarker or testing data contributed to unknown categories, and SEER may not generalize beyond the US settings it covers. Pandemic-era disruption may have affected patterns in 2020 and 2021, and multiple comparisons could have yielded some false-positive findings. Across 2010 through 2021, increasing stage IV presentation and subtype-specific survival gains were observed in parallel in US registry data.