# Clinical Significance of Tumor Grade in Triple-Negative Breast Cancer: A Retrospective Cohort Analysis

**Authors:** Neya Ramanan, Mah-noor Malik, Sarang Upneja, Haniya Farooq, Swati Kulkarni, Rasna Gupta, John Mathews, Abdullah Nasser, Alina Bocicariu, Laurice Arayan, Lisa Porter, Bre-Anne Fifield, Rong Luo, Muriel Brackstone, Caroline Hamm

PMC · DOI: 10.3390/biomedicines13051100 · Biomedicines · 2025-05-01

## TL;DR

This study finds that grade 2 triple-negative breast cancer has a higher risk of relapse and death after five years compared to grade 3 tumors.

## Contribution

The study reveals a distinct long-term survival pattern in grade 2 triple-negative breast cancer not previously well characterized.

## Key findings

- Grade 2 TNBC showed higher relapse rates after 5 years compared to grade 3 TNBC.
- Patients with grade 2 TNBC had higher mortality rates after 5 years than those with grade 3 TNBC.

## Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous cancer that lacks estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) proteins. Here, we investigated the prognostic value of grade in patients with TNBC. Methods: This retrospective study analyzed 780 TNBC patients from two large regional cancer programs in Canada. Patients seen between 1 January 2004 and 31 December 2022 were included. Patients with grade 1 tumors and stage IV disease were excluded from analysis. Demographic information regarding the patient, tumor, and treatment were collected. The primary outcomes, relapse-free survival (RFS) and overall survival (OS), were analyzed using the Cox proportional hazards model and max-combo test. Results: For patients with grade 2 TNBC, median RFS was 14.1 years (95% CI, 9.48 to not reached (NR)) while it was not reached for patients with grade 3 tumors. No difference for relapse was identified in the first five years. Beyond 5 years, 4.9% of the patients with grade 2 tumors and 1.6% of those with grade 3 tumors relapsed (p = 0.006). In that same study period, 10.4% of patients with grade 2 tumors and 5.7% of those with grade 3 tumors died (p = 0.03). Conclusion: Grade 2 TNBC was associated with a higher risk of relapse and death after the 5-year mark compared to grade 3 TNBC. This distinct pattern of relapse and survival in grade 2 TNBC, characterized by an increased risk of relapse and mortality after 5 years, warrants confirmatory investigations.

## Linked entities

- **Diseases:** triple-negative breast cancer (MONDO:0005494), breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}
- **Diseases:** Tumor (MESH:D009369), IV disease (MESH:D020432), TNBC (MESH:D064726), death (MESH:D003643)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12109397/full.md

## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12109397/full.md

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Source: https://tomesphere.com/paper/PMC12109397