Immune-related Gene Expression Predicts Response to Neoadjuvant Chemotherapy but not Additional Benefit from PD-L1 Inhibition in Women with Early Triple-negative Breast Cancer.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Biomarkers, Tumor
Clinical Trials, Phase II as Topic
Computational Biology
/ methods
Disease Management
Disease Susceptibility
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Immune Checkpoint Inhibitors
/ administration & dosage
Immunity
/ genetics
Middle Aged
Multicenter Studies as Topic
Neoadjuvant Therapy
Neoplasm Staging
Randomized Controlled Trials as Topic
Triple Negative Breast Neoplasms
/ drug therapy
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
received:
31
08
2020
revised:
05
12
2020
accepted:
11
02
2021
pubmed:
18
2
2021
medline:
17
3
2022
entrez:
17
2
2021
Statut:
ppublish
Résumé
We evaluated mRNA signatures to predict response to neoadjuvant PD-L1 inhibition in combination with chemotherapy in early triple-negative breast cancer. Targeted mRNA sequencing of 2,559 transcripts was performed in formalin-fixed, paraffin-embedded samples from 162 patients of the GeparNuevo trial. We focused on validation of four predefined gene signatures and differential gene expression analyses for new predictive markers. Two signatures [GeparSixto signature (G6-Sig) and IFN signature (IFN-Sig)] were predictive for treatment response in a multivariate model including treatment arm [G6-Sig: OR, 1.558; 95% confidence interval (CI), 1.130-2.182; Immune-associated signatures are associated with pCR after chemotherapy, but might be of limited use for the prediction of response to additional immune checkpoint blockade. Gene expressions related to antigen presentation and IFN signaling might be interesting candidates for further evaluation.
Identifiants
pubmed: 33593886
pii: 1078-0432.CCR-20-3113
doi: 10.1158/1078-0432.CCR-20-3113
doi:
Substances chimiques
Biomarkers, Tumor
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2584-2591Informations de copyright
©2021 American Association for Cancer Research.
Références
Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19:40–50.
Adams S, Gatti-Mays ME, Kalinsky K, Korde LA, Sharon E, Amiri-Kordestani L, et al. Current landscape of immunotherapy in breast cancer: a review. JAMA Oncol. 2019;5:1205–14.
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379:2108–21.
Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21:44–59.
Loibl S, Untch M, Burchardi N, Huober J, Sinn B V., Blohmer JU, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019;30:1279–88.
Denkert C, Von Minckwitz G, Brase JC, Sinn BV, Gade S, Kronenwett R, et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015;33:983–91.
Metzger Filho O, Stover DG, Asad S, Ansell PJ, Watson M, Loibl S, et al. Immunophenotype and proliferation to predict for response to neoadjuvant chemotherapy in TNBC: results from BrighTNess phase III study. J Clin Oncol. 2019;37:510–.
Higgs BW, Morehouse CA, Streicher K, Brohawn PZ, Pilataxi F, Gupta A, et al. Interferon gamma messenger RNA Signature in tumor biopsies predicts outcomes in patients with non–small cell lung carcinoma or urothelial cancer treated with durvalumab. Clin Cancer Res. 2018;24:3857–66.
Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. 2015;160:48–61.
Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILS) in breast cancer: recommendations by an International TILS Working Group 2014. Ann Oncol. 2015;26:259–71.
Denkert C, Wienert S, Poterie A, Loibl S, Budczies J, Bago-horvath Z, et al. Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer – results of the ring studies of the International Immuno-oncology Biomarker Working Group. Mod Pathol. 2016;29:1–10.
Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387:1837–46.
Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Albright A, et al. Relationship between immune gene signatures and clinical response to PD-1 blockade with pembrolizumab (MK-3475) in patients with advanced solid tumors. J Immunother Cancer. 2015;3:P80.
Prat A, Navarro A, Paré L, Reguart N, Galván P, Pascual T, et al. Immune-related gene expression profiling after PD-1 blockade in non–small cell lung carcinoma, head and neck squamous cell carcinoma, and melanoma. Cancer Res. 2017;77:3540–50.
Rock KL, Reits E, Neefjes J. Present yourself! By MHC class I and MHC class II molecules. Trends Immunol. 2016;37:724–37.
Sinn BV, Weber KE, Schmitt WD, Fasching PA, Symmans WF, Blohmer JU, et al. Human leucocyte antigen class i in hormone receptor-positive, HER2-negative breast cancer: association with response and survival after neoadjuvant chemotherapy. Breast Cancer Res. 2019;21:1–9.
Criscitiello C, Bayar MA, Curigliano G, Symmans FW, Desmedt C, Bonnefoi H, et al. A gene signature to predict high tumor-infiltrating lymphocytes after neoadjuvant chemotherapy and outcome in patients with triple-negative breast cancer. Ann Oncol. 2018;29:162–9.
Tokunaga R, Zhang W, Naseem M, Puccini A, Berger MD, Soni S, et al. CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation – a target for novel cancer therapy. Cancer Treat Rev. 2018;63:40–7.
Ivashkiv LB. IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy. Nat Rev Immunol. 2018;18:545–58.
Karn T, Denkert C, Weber KE, Holtrich U, Hanusch C, Sinn B V., et al. Tumor mutational burden and immune infiltration as independent predictors of response to neoadjuvant immune checkpoint inhibition in early TNBC in GeparNuevo. Ann Oncol. 2020;31:1216–22.