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

## TL;DR

This study estimates the long-term risk of breast cancer recurrence in Italian women, showing how it varies by stage, age, and molecular profile.

## Contribution

A novel modeling method combining an illness-death process and mixture cure model was used to estimate metastatic recurrence risks.

## Key findings

- The 15-year metastatic recurrence risk decreased from 20.6% in 1997–2006 to 12.3% in 2007–2017.
- Triple-negative breast cancer had a higher early recurrence risk, but low risk after 5 years of no recurrence.
- Hormone receptor-positive breast cancer showed a lower but persistent recurrence risk over time.

## Abstract

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.

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.

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.

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.