Validation of late recurrence prediction by gene expression profiles and clinicopathological factors in estrogen receptor-positive breast cancer

Sae Kitano ¹, Ryo Tsunashima ², Chikage Kato ¹

⁰Department of Endocrine and Breast Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan.

Breast Cancer (Tokyo, Japan) +

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June 11, 2024

View abstract on PubMed

Summary

Late recurrence of estrogen receptor-positive breast cancer is better predicted by combining gene expression profiles (42-gene classifier) and clinicopathological factors (Clinical Treatment Score post-5 years). This combined approach aids in identifying high-risk patients for extended hormonal therapy.

Area Of Science

Oncology
Genomics
Biostatistics

Background

The mechanisms driving late recurrence (LR) in estrogen receptor (ER)-positive breast cancer are not fully understood.
Previous research has investigated gene expression profiles and clinicopathological factors independently, limiting a comprehensive understanding of LR.
Identifying reliable predictors for LR is crucial for optimizing treatment strategies in ER-positive breast cancer.

Purpose Of The Study

To evaluate the predictive capability of combining gene expression profiles (42-gene classifier, 42GC) and clinicopathological factors (Clinical Treatment Score post-5 years, CTS5) for late recurrence (LR) in ER-positive breast cancer.
To assess the combined predictive power of 42GC and CTS5 in multiple large patient cohorts.
To determine if incorporating additional factors like 95GC can refine risk stratification for extended hormonal therapy.

Main Methods

Analysis of microarray CEL file data from 28 public global cohorts.
Evaluation of 2,454 patients with ER-positive breast cancer for 42GC.
Assessment of 1,263 patients with complete clinicopathological data for CTS5.

Main Results

The 42-gene classifier (42GC) LR and CTS5 low-risk groups showed a tendency towards LR.
The CTS5 high-risk group exhibited the highest LR rate beyond 5 years.
Combining 42GC LR and CTS5 high-risk groups resulted in the highest LR rate (16.9%), significantly higher than the 42GC non-LR and CTS5 low-risk combination (5.41%).
Inclusion of 95GC potentially reduced the number of patients recommended for extended hormonal therapy by approximately 25%.

Conclusions

Both gene expression profiles (42GC) and clinicopathological factors (CTS5) significantly influence the timing of breast cancer recurrence.
Biological predisposition for LR (CTS5 low-risk) differs from the actual high LR rate observed (CTS5 high-risk).
Patients identified as 42GC LR and CTS5 high-risk should be prioritized for extended hormonal therapy.
The integration of CTS5 and 95GC with 42GC enhances the risk classification accuracy for late recurrence.

Keywords:

42-gene classifier Clinical Treatment Score post-5 years ER-positive breast cancer Extended hormonal therapy Late recurrence