Figure S5 from A Prognostic Model Based on PAM50 and Clinical Variables (PAM50MET) for Metastatic Hormone Receptor–positive HER2-negative Breast Cancer

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posted on 2023-03-31, 22:08 authored by Aleix Prat, Yi-Hsuan Tsai, Tomás Pascual, Laia Paré, Barbara Adamo, Maria Vidal, Fara Brasó-Maristany, Patricia Galván, Jan Christoph Brase, Vanessa Rodrik-Outmezguine, Stephen Johnston, Eva Ciruelos, Joel S. Parker

<p>Survival outcomes based on the PAM50MET score in the BOLERO-2 trial according to non-visceral versus visceral disease. (A) Progression-free survival of PAM50MET in patients with non-visceral disease. (B) Overall survival of PAM50MET in patients with non-visceral disease. (C) Progression-free survival of PAM50MET in patients with visceral disease. (D) Overall survival of PAM50MET in patients with visceral disease.</p>

Funding

Instituto de Salud Carlos III

Breast Cancer Research Foundation

Breast Cancer Now

European Union's Horizon 2020 and innovation programme

Fundació la Maratóde TV3

History

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DOI - Is supplement to A Prognostic Model Based on PAM50 and Clinical Variables (PAM50MET) for Metastatic Hormone Receptor–positive HER2-negative Breast Cancer

ARTICLE ABSTRACT

Predicting prognosis in HR+/HER2− metastatic breast cancer (MBC) might be clinically useful; however, no validated prognostic biomarkers exist in this setting to date. In phase III, EGF30008 trial, 484 patients with HER2− MBC who received letrozole and placebo or lapatinib were selected. PAM50 data, ECOG performance status, visceral disease, number of metastasis, biopsy type, and age were evaluated. A progression-free survival (PFS) Cox model was evaluated. The final model (PAM50MET) with a prespecified cutoff was validated in patients (n = 261) with HR+/HER2− advanced breast cancer (aBC) from BOLERO-2 (phase III trial that evaluated exemestane and placebo or everolimus). In EGF30008, prognostic models with PAM50 plus clinical variables yielded higher C-index values versus models with only PAM50 or clinical variables. The PAM50MET model combined 21 variables: 2 PAM50 subtypes, basal signature, 14 genes, and 4 clinical variables. In EGF30008, the optimized cutoff was associated with PFS [HR = 0.37; 95% confidence interval (CI), 0.29–0.47; P < 0.0001] and overall survival (OS; HR = 0.37; 95% CI, 0.27–0.51; P < 0.0001). The median (months; 95% CI) PFS and OS were 22.24 (19.0–24.9) and not reached in PAM50MET-low versus 9.13 (8.15–11.0) and 33.0 (28.0–40.0) in PAM50MET-high groups, respectively. In BOLERO-2, the PAM50MET-low was associated with better PFS (HR = 0.72; 95% CI, 0.53–0.96; P = 0.028) and OS (HR = 0.51; 95% CI, 0.35–0.69; P < 0.0001). The median (months) (95% CI) PFS and OS were 6.93 (5.57–11.0) and 36.9 (33.4–NA) in PAM50MET-low versus 5.23 (4.2–6.8) and 23.5 (20.2–28.3) in PAM50MET-high groups, respectively. PAM50MET is prognostic in HR+/HER2− MBC, and further evaluation might help identify candidates for endocrine therapy only or novel therapies.