# Personalized multifactorial risk assessment in neoadjuvant-treated breast carcinoma

## TL;DR

This study improves the prediction of breast cancer outcomes after neoadjuvant treatment by combining clinical and histopathological factors into a personalized risk assessment tool.

## Contribution

The study introduces a novel interactive tool and heat maps for personalized risk assessment using pre- and post-treatment biomarkers and clinical features.

## Key findings

- Decreased PR expression was associated with a 3.8-fold higher mortality risk and significantly shorter survival.
- Mitotic and apoptotic activity were identified as important but previously overlooked histological features for prognosis.
- A web-based tool (bcnatreccalc.utu.fi) was developed to illustrate combinations of risk factors and disease outcomes.

## Abstract

Due to biological heterogeneity of breast carcinoma, predicting the individual response to neoadjuvant treatment (NAT) is complex. Consequently, there are no comprehensive, generally accepted practices to guide post-treatment follow-up. We present clinical and histopathological criteria to advance the prediction of disease outcome in NA-treated breast cancer.

A retrospective consecutive cohort of 257 NA-treated Finnish breast cancer patients with up to 13-year follow-up and the corresponding tissue samples of pre- and post-NAT breast and metastatic specimen were evaluated for prognostic impacts. All relevant clinical and biomarker characteristics potentially correlated with tumor response to NAT, course of disease, or outcome of breast cancer were included in the statistical analyses.

The results highlight the intensified characterization of distinguished prognostic factors and previously overlooked histological features, e.g., mitotic and apoptotic activity. Particularly, decreased PR indicated 3.8-fold (CI 1.9–7.4, p = 0.0001) mortality risk, and a > 10.5-year shorter survival for the majority, > 75% of patients (Q1). Clinically applicable prognostic factors both preceding and following NAT were identified and compiled into heat maps to quantify mortality and recurrence risks. Combinations of risk factors for aggressive disease were exemplified as an interactive tool (bcnatreccalc.utu.fi) to illustrate the spectrum of disease outcomes.

The results emphasize the value of comprehensive evaluation of conventional patient and biomarker characteristics, especially concerning re-assessment of biomarkers, risk-adapted surveillance, and personalized treatment strategies. Future personalized NA-treatment strategies might benefit from models combining risk-adapted surveillance data and post-NAT re-assessed biomarkers.

The online version contains supplementary material available at 10.1007/s10549-024-07584-4.