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. 2026 Jan;15(1):e71492.
doi: 10.1002/cam4.71492.

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

Fabiola Giudici  1 , Sara De Vidi  1 , Stefano Guzzinati  2 , Federica Toffolutti  1 , Silvia Francisci  3 , Angela B Mariotto  4 , Alessandra Ravaioli  5 , Laura Botta  6 , Roberta De Angelis  7 , Ettore Bidoli  1 , Fabio Falcini  5 , Antonella Puppo  8 , Lucia Mangone  9 , Maria Michiara  10 , Mario Fusco  11 , Anna Clara Fanetti  12 , Alessandra Andreotti  2 , Riccardo Capocaccia  13 , Diego Serraino  1 , Luigino Dal Maso  1 ; AIRTUM working group
Collaborators, Affiliations

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

Fabiola Giudici et al. Cancer Med. 2026 Jan.

Abstract

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.

Keywords: breast cancer; metastatic recurrence; mixed cure model; relative survival.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Relative survival (●) and corresponding model‐based estimates (lines) for Italian breast cancer patients diagnosed in 1997–2017 by stage, age group, and period.
FIGURE 2
FIGURE 2
Risk of metastatic recurrence for Italian breast cancer patients diagnosed in 1997–2017 by stage, age group, and period.
FIGURE 3
FIGURE 3
Risk of metastatic recurrence for Italian breast cancer patients diagnosed in 2003–2012 by stage, age group, and surrogate molecular profile.
FIGURE 4
FIGURE 4
Conditional probabilities of metastatic recurrence risk for Italian breast cancer patients diagnosed in 2003–2012 by stage, age group, and surrogate molecular profile.
See this image and copyright information in PMC

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