Abstract P3-07-15: Prosigna® subtype correlation is a strong predictor of response to neoadjuvant chemotherapy (NAC) in early breast cancer (EBC) study
Authors: R Chica Parrado, B Jiménez-Rodríguez, P Sánchez Rovira, M Álvarez, L Vicioso, AI Fernandez, V de Luque, M José Lozano, E Villar, I Zarcos, C Ramírez, C González-Hermoso, A Jeiranian, N Dowidar, C Schaper, W Buckingham, S Ferree, N Ribelles, I Rodrigo, AP Prat, E Alba
Journal: Cancer Research (2016)

Abstract Background: Prosigna's ROR score was demonstrated as a strong predictor of response to NAC in a representative cohort of EBC patients including HR+/HER2- N0-N1 patients.1 Given that the ROR score is partially derived from the correlation of the tumor's expression profile to that of the four prototypical intrinsic subtypes, we determined the relative strength of the association between each subtype correlation and the likelihood of response to NAC. Methods: We analyzed 294 FFPE breast cancer samples from pts treated with NAC (anthracyclines and taxanes) in a multi-center Spanish cohort. The Prosigna Assay was performed on the NanoString nCounter® Dx Analysis System at HU Virgen de la Victoria de Málaga/CIMES-UMA. Pathologic complete response (pCR) was used as the primary endpoint for this study and was determined using the Miller and Payne scoring criteria. Results: Mean patient age in this population was 50 (±11yr). Apart from targeted therapy, all patients received a standard neoadjuvant treatment regimen consisting of 8-12 cycles of anthracyclines and taxanes. 58% of patients were HR+/HER2- while 24% were classified as HER2+ and 18% were TNBC patients. Of the 311 pts samples previously tested, subtype correlation data was available for 294. Overall subtype concordance between IHC and Prosigna was 72% (K=0.66). The overall pCR rate in this population was 24.9%. Prosigna subtype breakdown in the full study population was 60 Luminal A, 118 Luminal B, 69 HER2-enriched and 47 Basal-like with response rates of 7.2%, 7.2%, 46.2% and 57.4%, respectively. We found that in all study populations, subtype correlation was a strong predictor of response to NAC. Tumors with expression profiles that correlated well with the Luminal prototypical centroids were found to be largely unresponsive to NAC (Luminal A Odds ratio=0.074 per unit increase, p&amp;lt;0.0001; Luminal B Odds ratio=0.059 per unit increase, p&amp;lt;0.0001). Conversely, higher HER2E and Basal-like correlations were associated with increased probability of response (HER2E Odds ratio=11.2 per unit increase, p&amp;lt;0.0001; Basal-like Odds ratio=9.0 per unit increase, p&amp;lt;0.0001). Increased proliferation-score (p-score) was also associated with increased probability of response to NAC (Odds ratio=3.43 per unit increase, p&amp;lt;0.0001). Conclusions: In a representative cohort of breast cancer patients, both the magnitude of the subtype correlation to the prototypical centroids as well as p-score, as determined by the Prosigna Assay, were strong predictors of response to NAC. This data underlines the importance of molecular testing for optimal systemic therapy indications in EBC. 1Rodriguez B, Lavado Fernandez A, Ribelles N, et al. Prosigna (PAM50) to predict response to neoadjuvant chemotherapy (NAC) in HR+/HER2- early breast cancer (EBC) patients. J Clin Oncol 33, 2015 (suppl; abstr 11049). Citation Format: Chica Parrado R, Jiménez-Rodríguez B, Sánchez Rovira P, Álvarez M, Vicioso L, Fernandez AI, de Luque V, José Lozano M, Villar E, Zarcos I, Ramírez C, González-Hermoso C, Jeiranian A, Dowidar N, Schaper C, Buckingham W, Ferree S, Ribelles N, Rodrigo I, Prat AP, Alba E. Prosigna® subtype correlation is a strong predictor of response to neoadjuvant chemotherapy (NAC) in early breast cancer (EBC) study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-15.