Dysfunctional mismatch repair in patients with early triple-negative breast cancer
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María Muñiz-Castrillo [1] ; Noel Blaya Boluda [3] ; Esmeralda García-Torralba [3] ; Paula Jiménez-Fonseca [1] ; Carmen González del Rey [1] ; Milagros Balbín [1] ; Ginés Luengo-Gil [2] ; Francisco Ayala de la Peña [3] ; Emilio Esteban González [1] ; Alberto Carmona-Bayonas [3]
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[1] Hospital Universitario Central de Asturias
Hospital Universitario Central de Asturias
Oviedo, España
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[2] Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca
Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca
Murcia, España
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[3] Department of Medical Oncology, Hospital Universitario Morales Meseguer (HUMM), Murcia, Spain
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- Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 27, Nº. 10, 2025, págs. 3924-3937
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
Background While mismatch repair (MMR) deficiency is well-characterized in several cancers, its role in triple-negative breast cancer (TNBC) remains unclear. We comprehensively assessed MMR in early-stage TNBC, examining its prevalence, clinical correlations, prognostic value, relationship with microsatellite instability (MSI), and patterns of intratumoral heterogeneity.
Methods Two early-stage TNBC cohorts were investigated for germline mutations using next-generation sequencing, protein expression by immunohistochemistry, and MSI status through molecular detection. Associations with clinicopathological characteristics and survival were examined. Results were validated using The Cancer Genome Atlas (TCGA) data.
Results Among 259 patients, MMR deficiency was observed in 8.2%, all showing PMS2 loss, while 2 germline PMS2 mutations (2.7%) were detected. At the somatic level, 35.8% showed heterogeneous MMR expression, more frequently in earlier stages (IA-IIA 41.4% vs. IIB-III 22.4%, p=0.04) and smaller tumors (cT1–2 39.1% vs. cT3–4 18.5%, p=0.01).
MMR status showed no significant associations with other clinicopathological variables or survival. No MSI was detected in MMR-deficient cases. The 5-year recurrence rate was 16.0% (95% CI 10.0–24.0) for MMR-intact, 20.0% (95% CI 4.5–43.0) for MMR-deficient, and 17.9% (95% CI 9.8–28.1) for heterogeneous tumors (p=0.75). Pathological complete response to neoadjuvant chemotherapy was similar across MMR status groups. These findings were consistent with analyses using TCGA data.
Conclusion MMR system shows a low rate of alterations in TNBC, with its deficiency being infrequent and not correlated with MSI. Although MMR system isolated evaluation may not be justified in early-stage TNBC due to its limited clinical impact, its inclusion in multigene panels should be further considered.
