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Supplemental Material from A PAM50-Based Chemoendocrine Score for Hormone Receptor–Positive Breast Cancer with an Intermediate Risk of Relapse

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posted on 2023-03-31, 19:30 authored by Aleix Prat, Ana Lluch, Arran K. Turnbull, Anita K. Dunbier, Lourdes Calvo, Joan Albanell, Juan de la Haba-Rodríguez, Angels Arcusa, José Ignacio Chacón, Pedro Sánchez-Rovira, Arrate Plazaola, Montserrat Muñoz, Laia Paré, Joel S. Parker, Nuria Ribelles, Begoña Jimenez, Abdul Aziz Bin Aiderus, Rosalía Caballero, Barbara Adamo, Mitch Dowsett, Eva Carrasco, Miguel Martín, J. Michael Dixon, Charles M. Perou, Emilio Alba

Supplemental Methods, Tables and Figures Tables Table S1. CES association with chemotherapy sensitivity (measured as pCR) in the MDACC-based dataset. Table S2. CES association with chemotherapy sensitivity (measured as Residual Cancer Burden [RCB]) in the MDACC-based dataset. Model A. Table S3. CES association with chemotherapy sensitivity (measured as Residual Cancer Burden [RCB]) in the MDACC-based dataset. Model B. Table S4. Univariate association of CES and various signatures with chemotherapy sensitivity in HR+/HER2-negative disease from the MDACC-based dataset. Table S5. Association of CES and PAM50 Proliferation Signature with chemotherapy sensitivity in HR+/HER2-negative disease from the MDACC-based dataset. Table S6. Association of CES and CHEMOPRED Signature with chemotherapy sensitivity in HR+/HER2-negative disease from the MDACC-based dataset. Table S7. Association of CES and the proliferation component of the Genomic Health Index (GHI; OncotypeDX Recurrence Score) with chemotherapy sensitivity in HR+/HER2- negative disease from the MDACC-based dataset. Table S8. Association of CES and Genomic Grade Index (GGI) Signature with chemotherapy sensitivity in HR+/HER2-negative disease from the MDACC-based dataset. Table S9. Association of CES and SET index Signature with chemotherapy sensitivity in HR+/HER2-negative disease from the MDACC-based dataset. Table S10. Association of CES and RCBPRED Signature with chemotherapy sensitivity in HR+/HER2-negative disease from the MDACC-based dataset. Table S11. Association of CES and DLDA30 Signature with chemotherapy sensitivity in HR+/HER2-negative disease from the MDACC-based dataset. Table S12. Association of CES and ROR-P Signature with chemotherapy sensitivity in HR+/HER2-negative disease from the MDACC-based dataset. Table S13. Association of CES and Ki67 by IHC with chemotherapy sensitivity in HR+/HER2-negative disease of the Malaga cohort. 7 Table S14. Association of CES and PAM50 ROR with chemotherapy sensitivity in HR+/HER2-negative disease of the Malaga cohort. Table S15. CES association with endocrine sensitivity in the Marsden dataset (n=103). Table S16. CES association with endocrine sensitivity in the Marsden dataset within HER2-negative disease (n=89). Figures Fig. S1. Association of CES with Miller-Payne following chemotherapy in HR+/HER2- negative disease from the Malaga-based cohort. Fig. S2. CES association with endocrine sensitivity in the Edinburgh dataset (n=120). (A) Tumor volume changes of each patient and response classification. (B) Association of CES and other variables with response (defined as at least 70% reduction by 90 days) in the overall population. (C) Association of CES and other variables with response within HER2-negative disease. Fig. S3. Association of CES with pCR in the combined dataset from the MDACC- and Malaga-based cohorts.

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ARTICLE ABSTRACT

Purpose: Hormone receptor–positive (HR+) breast cancer is clinically and biologically heterogeneous, and subgroups with different prognostic and treatment sensitivities need to be identified.Experimental Design: Research-based PAM50 subtyping and expression of additional genes was performed on 63 patients with HR+/HER2− disease randomly assigned to neoadjuvant multiagent chemotherapy versus endocrine therapy in a phase II trial. The biology associated with treatment response was used to derive a PAM50-based chemoendocrine score (CES). CES's predictive ability was evaluated in 4 independent neoadjuvant data sets (n = 675) and 4 adjuvant data sets (n = 1,505). The association of CES, intrinsic biology, and PAM50 risk of relapse (ROR) was explored across 6,007 tumors.Results: Most genes associated with endocrine sensitivity were also found associated with chemotherapy resistance. In the chemotherapy test/validation data sets, CES was independently associated with pathologic complete response (pCR), even after adjusting for intrinsic subtype. pCR rates of the CES endocrine–sensitive (CES-E), uncertain (CES-U), and chemotherapy-sensitive (CES-C) groups in both data sets combined were 25%, 11%, and 2%, respectively. In the endocrine test/validation data sets, CES was independently associated with response. Compared with ROR, >90% of ROR-low and ROR-high tumors were identified as CES-E and CES-C, respectively; however, each CES group represented >25% of ROR-intermediate disease. In terms of survival outcome, CES-C was associated with poor relapse-free survival in patients with ROR-intermediate disease treated with either adjuvant endocrine therapy only or no adjuvant systemic therapy, but not in patients treated with (neo)adjuvant chemotherapy.Conclusions: CES is a genomic signature capable of estimating chemoendocrine sensitivity in HR+ breast cancer beyond intrinsic subtype and risk of relapse. Clin Cancer Res; 23(12); 3035–44. ©2016 AACR.

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