Metastatic Recurrence of Breast Cancer by Stage and Molecular Profile: A Population‐Based Study Among Italian Women

Background: This study aims to estimate the long-term risk of metastatic recurrence (MR) among Italian women with breast cancer (BC) by period, age, stage, and surrogate molecular profile. Methods: Data on 59,968 women below age 75 years diagnosed in 1997–2017 with stage I-III BC from 7 population-based Italian cancer registries were analyzed. We used a novel modeling method, based on an illness–death process coupled with a mixture cure model, to estimate relative survival and MR risks up to 15 years after BC diagnosis according to calendar period, age, stage, and profile. Results: The risk of MR for the entire cohort at 15 years decreased from 20.6% in 1997–2006 to 12.3% in 2007–2017, when MR risk within 15 years was 3.0% for stage I, 16.0% for stage II, and 42.7% for stage III. The conditional risk of MR decreased with time since diagnosis, with stage I–III triple-negative BC having a higher risk of developing MR in the first 5 years regardless of age (16.0% at age 15–54 years and 18.3% at 55–74 years), but < 1% once they survived for 5 years without recurrence. In contrast, hormone receptor-positive BC had a lower but persisting risk of MR of about 6% for both age groups in the first 10 years, halving to about 3% in the following 5 years after diagnosis. Conclusions: This study provides a population-based estimate of the long-term risk of MR for women with BC by major prognostic factors. These findings may help in tailoring follow-up strategies through informative risk stratification.