Automated mitotic spindle hotspot counts are highly associated with clinical outcomes in systemically untreated early-stage triple-negative breast cancer

Roberto A Leon-Ferre ¹, Jodi M Carter ², David Zahrieh ³

⁰Mayo Clinic, Rochester, MN, USA. leonferre.roberto@mayo.edu.

Npj Breast Cancer +

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March 30, 2024

View abstract on PubMed

Summary

Automated mitotic spindle hotspot counts predict recurrence and death risk in early-stage triple-negative breast cancer (TNBC) patients not receiving systemic therapy. This biomarker offers prognostic insights independent of traditional factors.

Area Of Science

Oncology
Pathology
Biomarker Discovery

Background

Operable triple-negative breast cancer (TNBC) presents a high risk of recurrence and mortality.
Current prognostic factors like tumor size and nodal status are insufficient for precise risk stratification.
Novel biomarkers are needed to identify TNBC subsets with favorable prognoses, potentially enabling treatment de-escalation.

Purpose Of The Study

To evaluate the prognostic value of fully automated mitotic spindle hotspot (AMSH) counts in early-stage TNBC patients.
To determine if AMSH counts predict recurrence-free survival (RFS) and overall survival (OS) independently of established clinical factors.
To validate AMSH counts in independent patient cohorts.

Main Methods

Utilized a convolutional neural network to quantify AMSH counts from digitized whole slide images of TNBC tumors.
Analyzed the association of AMSH counts with RFS and OS in two distinct cohorts of systemically untreated early-stage TNBC patients.
Performed multivariable analysis controlling for tumor size, nodal status, and tumor-infiltrating lymphocytes (TILs).

Main Results

AMSH counts were significantly associated with both RFS and OS in the Mayo Clinic cohort (p < 0.0001).
Each 10-point increase in AMSH counts correlated with a 16% higher risk of RFS events and a 7% higher risk of death.
Findings were successfully corroborated in an independent cohort from Radboud UMC, confirming the prognostic utility of AMSH.

Conclusions

Fully automated mitotic spindle hotspot counts provide significant prognostic information for early-stage TNBC patients.
AMSH counts are independent predictors of recurrence and survival, outperforming traditional factors like tumor size, nodal status, and TILs.
Validated AMSH counts may guide future de-escalation strategies for systemic therapy in select TNBC patients.