Trends in Survival and Mortality of "Early" Metastatic Breast Cancer in Northern Italy Following the Introduction of Targeted Therapies.

BACKGROUND/OBJECTIVES: In high-income settings, the incidence of metastatic breast cancer (MBC) at diagnosis has declined, reflecting the impact of effective screening and therapeutic advances. This study examined long-term trends in MBC incidence, mortality, and survival in a province of North Italy, an area characterized by high screening participation and broad access to modern systemic treatments. METHODS: All invasive breast cancer cases (n = 10,966) diagnosed between 2000 and 2022 were retrieved from the Reggio Emilia Cancer Registry (population: 532,000). Metastatic cases were defined "early" if distant metastases occurred within six months of diagnosis. Mortality trends were assessed using joinpoint regression to estimate annual percentage changes (APCs). One-, three-, and five-year survival probabilities were calculated, with follow-up through December 2024. RESULTS: Overall, 511 cases (4.7%) were "early" metastatic breast cancers at diagnosis. This proportion declined from 6.4% in 2000-2003 to 3.8% in 2019-2022. One-year mortality decreased from 38.4% to 26.7% (APC = -6.6; 95% CI -13.1 to -0.5), and two-year mortality from 54.5% to 34.9% (APC = -7.3; 95% CI -12.3 to -1.4) after 2017. One- and three-year survival increased from 63% to 66% and from 39% to 42%, respectively, while five-year survival improved from 21% to 30%. CONCLUSIONS: Over more than two decades, the incidence of MBC at diagnosis and early mortality both declined, accompanied by improved survival. These trends temporally coincide with the widespread adoption of targeted therapies and sustained high screening coverage, suggesting a possible combined contribution of early detection and advances in precision medicine to the observed outcomes.