Supplementary Figures from Subtype-Specific Metagene-Based Prediction of Outcome after Neoadjuvant and Adjuvant Treatment in Breast Cancer
Authors: Callari Maurizio , Cappelletti Vera , D'Aiuto Francesca , Musella Valeria , Lembo Antonio , Petel Fabien , Karn Thomas , Iwamoto Takayuki , Provero Paolo , Daidone Maria Grazia , Gianni Luca , Bianchini Giampaolo 
Published: April 2023

<p>Figure S1: Evaluation of chip bias in the GSE17700 dataset; Figure S2: Definition of a metagene-based ER status classifier; Figure S3: ER status and prognosis. Association with distant metastasis free survival (DMFS) for ER status as originally reported (A) and as defined by our ER status predictor (B) in the PROGNOSTIC dataset; Figure S4: Definition of a metagene-based HER2 status classifier; Figure S5: Follow-up of breast cancer subtypes as defined by our ER and HER2 metagenes in the PROGNOSTIC collection; Figure S6: Workflow for metagene identification and confirmation; Figure S7: Outline of metagene refinement procedure to improve association with patients' outcome; Figure S8: Non cross-validated prognostic value for the CTM in ER-HER2- (A), HER2+ (B), ER-HER2+ (C) and ER+HER2+ subtypes; Figure S9: Refined proliferation metagene in all ER+HER2- samples of the TAM collection (A) and separately for N- (B) and N+ samples (C); Figure S10: Association between ER-related metagene by tertile and risk of distant relapse in the ER+HER2+ subtype of patients treated with endocrine treatment (TAM collection); Figure S11: Combination of ER-related and proliferation metagenes; Figure S12: Logistic regression analysis of CTM in association with treatment response in ER- or HER2+ samples from Horak (left) or Desmedt (right) dataset; Figure S13: Association between CTM by tertile and risk of distant relapse in ER-HER2+ (A) and ER+HER2+ (B) in patients treated with chemotherapy +/- endocrine treatment (CHEMO collection); Figure S14: CTM association with long-term outcome in ER- or HER2+ (left), ER-HER2- (center) or HER2+ (right) samples from Petel dataset; Figure S15: CTM association with long-term outcome in ER- or HER2+ (A) and ER-HER2- samples (B) from Desmedt dataset; Figure S16: Association with long-term outcome according with our CTM in patients with residual disease. ER- or HER2+ (A) or ER-HER2- cases (B) from Desmedt dataset; Figure S17: Prognostic role of immune scores (LCK and Tfh) in ER-HER2- and HER2+ breast cancer patients treated with neoadjuvant chemotherapy. Univariable logistic regression analysis of LCK (A) and Tfh (B) immune scores expression and pCR in patients treated with neoadjuvant chemotherapy. Immune scores expression was categorized in low, intermediate and high by tertiles; Figure S18: Prognostic role of immune scores in ER-HER2- and HER2+ breast cancer patients treated with systemic chemotherapy. (A, B and C) Kaplan-Meier analysis for the association of the LCK immune scores expression by tertiles with 5-year DMFS in chemotherapy treated patients for the subgroup of ER-HER2- and HER2+ (A), ER-HER2- (B) and HER2+ (C). (D, E and F) Kaplan-Meier analysis for the association of the Tfh immune scores expression by tertiles with 5-year DMFS in chemotherapy treated patients for the subgroup of ER-HER2- and HER2+ (D), ER-HER2- (E) and HER2+ (F). Survival differences were evaluated by log-rank test; Figure S19: Reciprocal correlation between our immune metagene (IM), Tcell related signatures (LCK and Tfh), Treg, Macrophages and co-inhibitory immune molecules expressed on T cells (co-in_Tcell) or antigen-presenting cells (co-in_APC) (related signature were derived by Rooney et al); Figure S20: Logistic regression analysis of combined proliferation and ER-related metagenes in association with treatment response in ER+HER2- samples of the Hatzis dataset (left) or Horak dataset (right); Figure S21: Association with long-term outcome for the combined proliferation and ER-related metagenes in ER+HER2- cases from Hatzis (left) and Petel (right) datasets; Figure S22: Association with long-term outcome for the combined proliferation and ER-related metagenes in the subgroup of ER+HER2- patients with residual disease (Hatzis dataset); Figure S23: MBRP performance in HER2- (ER- or ER+) treated patients. Risk groups were defined by combining corresponding low, intermediate and high-risk groups in ER-HER2- and ER+HER2-patients. Kaplan-Meier analysis for the association between these three risk groups with 5-year DMFS in patients treated with chemotherapy (ER-HER2) or chemo-endocrine treatment (ER+HER2-). Survival differences were evaluated by log-rank test;</p>