Inferred Immune-Cell Activity Is an Independent Predictor of HER2-Negative Breast Cancer Prognosis and Response to Paclitaxel-Based Therapy in the GeparSepto Trial
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Inferred Immune-Cell Activity Is an Independent Predictor of HER2-Negative Breast Cancer Prognosis and Response to Paclitaxel-Based Therapy in the GeparSepto Trial. / Fasching, Peter A; Szeto, Christopher; Denkert, Carsten; Benz, Stephen; Weber, Karsten; Spilman, Patricia; Budczies, Jan; Schneeweiss, Andreas; Stickeler, Elmar; Schmatloch, Sabine; Jackisch, Christian; Karn, Thomas; Sinn, Hans Peter; Warm, Mathias; van Mackelenbergh, Marion; Rabizadeh, Shahrooz; Schem, Christian; Heinmöller, Ernst; Mueller, Volkmar; Marmé, Frederik; Soon-Shiong, Patrick; Nekljudova, Valentina; Untch, Michael; Loibl, Sibylle.
In: CLIN CANCER RES, Vol. 29, No. 13, 05.07.2023, p. 2456-2465.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Inferred Immune-Cell Activity Is an Independent Predictor of HER2-Negative Breast Cancer Prognosis and Response to Paclitaxel-Based Therapy in the GeparSepto Trial
AU - Fasching, Peter A
AU - Szeto, Christopher
AU - Denkert, Carsten
AU - Benz, Stephen
AU - Weber, Karsten
AU - Spilman, Patricia
AU - Budczies, Jan
AU - Schneeweiss, Andreas
AU - Stickeler, Elmar
AU - Schmatloch, Sabine
AU - Jackisch, Christian
AU - Karn, Thomas
AU - Sinn, Hans Peter
AU - Warm, Mathias
AU - van Mackelenbergh, Marion
AU - Rabizadeh, Shahrooz
AU - Schem, Christian
AU - Heinmöller, Ernst
AU - Mueller, Volkmar
AU - Marmé, Frederik
AU - Soon-Shiong, Patrick
AU - Nekljudova, Valentina
AU - Untch, Michael
AU - Loibl, Sibylle
N1 - ©2023 The Authors; Published by the American Association for Cancer Research.
PY - 2023/7/5
Y1 - 2023/7/5
N2 - PURPOSE: Tumor microenvironment (TME) immune markers have been correlated with both response to neoadjuvant therapy and prognosis in patients with breast cancer. Here, immune-cell activity of breast cancer tumors was inferred by expression-based analysis to determine if it is prognostic and/or predictive of response to neoadjuvant paclitaxel-based therapy in the GeparSepto (G7) trial (NCT01583426).EXPERIMENTAL DESIGN: Pre-study biopsies from 279 patients with HER2-negative breast cancer in the G7 trial underwent RNA-seq-based profiling of 104 immune-cell-specific genes to assess inferred Immune Cell Activity (iICA) of 23 immune-cell types. Hierarchical clustering was used to classify tumors as iICA "hot," "warm," or "cold" by comparison of iICA in the G7 cohort relative to that of 1,467 samples from a tumor database established by Nantomics LLC. Correlations between iICA cluster, pathology-assessed tumor-infiltrating lymphocytes (TIL), and hormone receptor (HR) status for pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) were determined.RESULTS: iICA cluster correlated with TIL levels. The highest pCR rates were observed in hot cluster tumors, and those with relatively higher TILs. Greater inferred activity of several T-cell types was significantly associated with pCR and survival. DFS and OS were prolonged in patients with hot or warm cluster tumors, the latter particularly for HR negative tumors, even if TILs were relatively low.CONCLUSIONS: Overall, TIL level better predicted pCR, but iICA cluster better predicted survival. Differences in associations between TILs, cluster, pCR, and survival were observed for HR-positive tumors versus HR-negative tumors, suggesting expanded study of the implication of these findings is warranted.
AB - PURPOSE: Tumor microenvironment (TME) immune markers have been correlated with both response to neoadjuvant therapy and prognosis in patients with breast cancer. Here, immune-cell activity of breast cancer tumors was inferred by expression-based analysis to determine if it is prognostic and/or predictive of response to neoadjuvant paclitaxel-based therapy in the GeparSepto (G7) trial (NCT01583426).EXPERIMENTAL DESIGN: Pre-study biopsies from 279 patients with HER2-negative breast cancer in the G7 trial underwent RNA-seq-based profiling of 104 immune-cell-specific genes to assess inferred Immune Cell Activity (iICA) of 23 immune-cell types. Hierarchical clustering was used to classify tumors as iICA "hot," "warm," or "cold" by comparison of iICA in the G7 cohort relative to that of 1,467 samples from a tumor database established by Nantomics LLC. Correlations between iICA cluster, pathology-assessed tumor-infiltrating lymphocytes (TIL), and hormone receptor (HR) status for pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) were determined.RESULTS: iICA cluster correlated with TIL levels. The highest pCR rates were observed in hot cluster tumors, and those with relatively higher TILs. Greater inferred activity of several T-cell types was significantly associated with pCR and survival. DFS and OS were prolonged in patients with hot or warm cluster tumors, the latter particularly for HR negative tumors, even if TILs were relatively low.CONCLUSIONS: Overall, TIL level better predicted pCR, but iICA cluster better predicted survival. Differences in associations between TILs, cluster, pCR, and survival were observed for HR-positive tumors versus HR-negative tumors, suggesting expanded study of the implication of these findings is warranted.
KW - Humans
KW - Female
KW - Breast Neoplasms/drug therapy
KW - Paclitaxel/therapeutic use
KW - Prognosis
KW - Lymphocytes, Tumor-Infiltrating
KW - Disease-Free Survival
KW - Neoadjuvant Therapy
KW - Receptor, ErbB-2/metabolism
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Tumor Microenvironment/genetics
U2 - 10.1158/1078-0432.CCR-22-2213
DO - 10.1158/1078-0432.CCR-22-2213
M3 - SCORING: Journal article
C2 - 37014668
VL - 29
SP - 2456
EP - 2465
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 13
ER -
