Identifying predictors of treatment response and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-negative breast cancer: the NEOENDO translational study
- Author(s)
- Schettini, F; Brasó-Maristany, F; Pascual, T; Lorman-Carbó, N; Nucera, S; Bergamino, M; Galván, P; Conte, B; Seguí, E; García Fructuoso, I; Gómez Bravo, R; Rodríguez, AB; Martínez-Sáez, O; Chic, N; Vidal, M; Adamo, B; González-Farre, B; Sanfeliu, E; Cebrecos, I; Mensión, E; Oses, G; Locci, M; Mollà, M; Ganau, S; Jares, P; Vidal-Sicart, S; Muñoz, M; Prat, A;
- Details
- Publication Year 2024-11-27,Volume 9,Issue #12,Page 103989
- Journal Title
- ESMO Open
- Publication Type
- Research article
- Abstract
- BACKGROUND: Predictors of response to neoadjuvant chemotherapy (NACT) and endocrine therapy (NET) in hormone receptor-positive (HoR+)/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) are required. Also, pathological and molecular changes induced by both strategies and their impact on patients' outcomes have not been reported so far. PATIENTS AND METHODS: In a cohort of 186 patients with early-stage HoR+/HER2-negative BC treated with NACT or NET, we assessed the association of baseline main clinicopathological features and PAM50 gene expression (GE), intrinsic subtypes (IS) and risk-of-relapse (ROR-P) score with pathological outcomes according to treatment strategy. Molecular NACT/NET-induced changes were described and compared, along with their associations with event-free survival (EFS). Comparison of the two cohorts after propensity score matching (PSM) was used as sensitivity analysis. Molecular changes were confirmed in cell lines. RESULTS: NACT was associated with higher rates of residual cancer burden (RCB)-0/I than NET in the overall population (38.2% versus 13.5%, P < 0.001) and after PSM (P = 0.036). PAM50 non-luminal IS were the only independent and positive predictor of RCB-0/I (P = 0.024) in the NACT cohort, while MMP11 messenger RNA levels were the only independent and negative predictor (P = 0.014) in the NET cohort. Both treatments shifted the tumor types toward less aggressive forms (i.e. PAM50 luminal A/normal-like), lowered the risk of recurrence in terms of ROR-P, up-regulated selected immune genes and PAM50 basal-like-related genes/signature and significantly downregulated proliferation-/luminal-/HER2-related genes/signatures, though NACT more than NET. Molecular findings were confirmed after PSM. A net reduction in proliferation-related genes and ROR-P was confirmed in cell lines with chemotherapy and endocrine therapy. Different baseline molecular features associated with diverse kind of responses (ROR-P downstaging, Ki67 reduction or pathological responses) with NACT and NET. Decreasing ROR-P and transitioning the tumor subtype to resemble normal tissue (i.e. PAM50 normal-like) suggested improved EFS. CONCLUSIONS: NACT was more effective in the molecular and dimensional tumor 'downstaging' than NET but baseline molecular features associated with differential responses according to treatment strategy. Examining baseline and post-treatment GE might help tailor more personalized and effective care.
- Publisher
- Elsevier
- Keywords
- Pam50; breast cancer; intrinsic subtypes; molecular downstaging; neoadjuvant chemotherapy; neoadjuvant endocrine therapy
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1016/j.esmoop.2024.103989
- Open Access at Publisher's Site
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Creation Date: 2024-12-19 05:48:13
Last Modified: 2025-01-28 06:44:45