Gene Expression-Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial.
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Biomarkers, Tumor
/ genetics
Breast Neoplasms
/ diagnosis
Chemotherapy, Adjuvant
/ methods
Clinical Decision-Making
/ methods
Datasets as Topic
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Mastectomy
Middle Aged
Neoadjuvant Therapy
/ methods
Neoplasm Staging
Oligonucleotide Array Sequence Analysis
Patient Selection
Predictive Value of Tests
Prognosis
Prospective Studies
Treatment Outcome
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:
15 04 2021
15 04 2021
Historique:
received:
08
07
2020
revised:
20
11
2020
accepted:
01
02
2021
pubmed:
6
2
2021
medline:
15
3
2022
entrez:
5
2
2021
Statut:
ppublish
Résumé
Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT. We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts ( A 20-gene classifier established in the EXPRESSION cohort using a Youden index-based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer. The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts.
Identifiants
pubmed: 33542080
pii: 1078-0432.CCR-20-2662
doi: 10.1158/1078-0432.CCR-20-2662
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
2148-2158Informations de copyright
©2021 American Association for Cancer Research.
Références
Burstein HJ, Curigliano G, Loibl S, Dubsky P, Gnant M, Poortmans P, et al. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019. Ann Oncol. 2019;30:1541–57.
Ditsch N, Untch M, Thill M, Muller V, Janni W, Albert US, et al. AGO recommendations for the diagnosis and treatment of patients with early breast cancer: update 2019. Breast Care. 2019;14:224–45.
Spring LM, Fell G, Arfe A, Sharma C, Greenup R, Reynolds KL, et al. Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin Cancer Res. 2020;26:2838–48.
Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, et al. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer-the evaluating treatment with neoadjuvant abraxane (ETNA) trial: a randomized phase 3 clinical trial. JAMA Oncol. 2018;4:302–8.
Iwata H, Sato N, Masuda N, Nakamura S, Yamamoto N, Kuroi K, et al. Docetaxel followed by fluorouracil/epirubicin/cyclophosphamide as neoadjuvant chemotherapy for patients with primary breast cancer. Jpn J Clin Oncol. 2011;41:867–75.
Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, et al. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016;17:345–56.
von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Eng J Med. 2012;366:299–309.
von Minckwitz G, Kummel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, et al. Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst. 2008;100:552–62.
Ayers M, Symmans WF, Stec J, Damokosh AI, Clark E, Hess K, et al. Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol. 2004;22:2284–93.
Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Elledge R, et al. Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet. 2003;362:362–9.
Farmer P, Bonnefoi H, Anderle P, Cameron D, Wirapati P, Becette V, et al. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med. 2009;15:68–74.
Hatzis C, Pusztai L, Valero V, Booser DJ, Esserman L, Lluch A, et al. A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer. JAMA. 2011;305:1873–81.
Hess KR, Anderson K, Symmans WF, Valero V, Ibrahim N, Mejia JA, et al. Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol. 2006;24:4236–44.
Lee JK, Coutant C, Kim YC, Qi Y, Theodorescu D, Symmans WF, et al. Prospective comparison of clinical and genomic multivariate predictors of response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res. 2010;16:711–8.
Liedtke C, Hatzis C, Symmans WF, Desmedt C, Haibe-Kains B, Valero V, et al. Genomic grade index is associated with response to chemotherapy in patients with breast cancer. J Clin Oncol. 2009;27:3185–91.
Naoi Y, Kishi K, Tanei T, Tsunashima R, Tominaga N, Baba Y, et al. Prediction of pathologic complete response to sequential paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide therapy using a 70-gene classifier for breast cancers. Cancer. 2011;117:3682–90.
Rodriguez AA, Makris A, Wu MF, Rimawi M, Froehlich A, Dave B, et al. DNA repair signature is associated with anthracycline response in triple negative breast cancer patients. Breast Cancer Res Treat. 2010;123:189–96.
Sota Y, Naoi Y, Tsunashima R, Kagara N, Shimazu K, Maruyama N, et al. Construction of novel immune-related signature for prediction of pathological complete response to neoadjuvant chemotherapy in human breast cancer. Ann Oncol. 2014;25:100–6.
Tabchy A, Valero V, Vidaurre T, Lluch A, Gomez H, Martin M, et al. Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer. Clin Cancer Res. 2010;16:5351–61.
Thuerigen O, Schneeweiss A, Toedt G, Warnat P, Hahn M, Kramer H, et al. Gene expression signature predicting pathologic complete response with gemcitabine, epirubicin, and docetaxel in primary breast cancer. J Clin Oncol. 2006;24:1839–45.
Tsunashima R, Naoi Y, Kagara N, Shimoda M, Shimomura A, Maruyama N, et al. Construction of multi-gene classifier for prediction of response to and prognosis after neoadjuvant chemotherapy for estrogen receptor positive breast cancers. Cancer Lett. 2015;365:166–73.
Turner N, Forcato M, Nuzzo S, Malorni L, Bicciato S, Di Leo A. A multifactorial ‘Consensus Signature’ by in silico analysis to predict response to neoadjuvant anthracycline-based chemotherapy in triple-negative breast cancer. NPJ Breast Cancer. 2015;1:15003.
Schmidt M, Hellwig B, Hammad S, Othman A, Lohr M, Chen Z, et al. A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors. Clin Cancer Res. 2012;18:2695–703.
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.
Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H, et al. The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res. 2008;68:5405–13.
Boulware MJ, Subramanian VS, Said HM, Marchant JS. Polarized expression of members of the solute carrier SLC19A gene family of water-soluble multivitamin transporters: implications for physiological function. Biochem J. 2003;376:43–8.
Chou SJ, Tole S. Lhx2, an evolutionarily conserved, multifunctional regulator of forebrain development. Brain Res. 2019;1705:1–14.
Deneka A, Korobeynikov V, Golemis EA. Embryonal Fyn-associated substrate (EFS) and CASS4: the lesser-known CAS protein family members. Gene. 2015;570:25–35.
Dunbier AK, Ghazoui Z, Anderson H, Salter J, Nerurkar A, Osin P, et al. Molecular profiling of aromatase inhibitor-treated postmenopausal breast tumors identifies immune-related correlates of resistance. Clin Cancer Res. 2013;19:2775–86.
Flynn MJ, Hartley JA. The emerging role of anti-CD25 directed therapies as both immune modulators and targeted agents in cancer. Br H Haematol. 2017;179:20–35.
Hsu HM, Chu CM, Chang YJ, Yu JC, Chen CT, Jian CE, et al. Six novel immunoglobulin genes as biomarkers for better prognosis in triple-negative breast cancer by gene co-expression network analysis. Sci Rep. 2019;9:4484.
Hummler E. Epithelial sodium channel, salt intake, and hypertension. Curr Hypertens Rep. 2003;5:11–8.
Kim SJ, Schätzle S, Ahmed SS, Haap W, Jang SH, Gregersen PK, et al. Increased cathepsin S in Prdm1(-/-) dendritic cells alters the T(FH) cell repertoire and contributes to lupus. Nat Immunol. 2017;18:1016–24.
Nieuwenhuis J, Adamopoulos A, Bleijerveld OB, Mazouzi A, Stickel E, Celie P, et al. Vasohibins encode tubulin detyrosinating activity. Science. 2017;358:1453–6.
Nowinska K, Ciesielska U, Piotrowska A, Jablonska K, Partynska A, Paprocka M, et al. MCM5 expression is associated with the grade of malignancy and Ki-67 antigen in LSCC. Anticancer Res. 2019;39:2325–35.
Praefcke GJK. Regulation of innate immune functions by guanylate-binding proteins. Int J Med Microbiol. 2018;308:237–45.
Ramkumar A, Jong BY, Ori-McKenney KM. ReMAPping the microtubule landscape: how phosphorylation dictates the activities of microtubule-associated proteins. Dev Dyn. 2018;247:138–55.
Rhie SK, Yao L, Luo Z, Witt H, Schreiner S, Guo Y, et al. ZFX acts as a transcriptional activator in multiple types of human tumors by binding downstream of transcription start sites at the majority of CpG island promoters. Genome Res. 2018;28:310–20.
Schreiber M, Weigelt M, Karasinsky A, Anastassiadis K, Schallenberg S, Petzold C, et al. Inducible IL-7 hyperexpression influences lymphocyte homeostasis and function and increases allograft rejection. Front Immunol. 2019;10:742.
Wang X, Zhang T, Zhang S, Shan J. Prognostic values of F-box members in breast cancer: an online database analysis and literature review. Biosci Rep. 2019;39:BSR20180949.
Wu RY, Kong PF, Xia LP, Huang Y, Li ZL, Tang YY, et al. Regorafenib promotes antitumor immunity via inhibiting PD-L1 and IDO1 expression in melanoma. Clin Cancer Res. 2019;25:4530–41.
Sato Y. The vasohibin family: a novel family for angiogenesis regulation. J Biochem. 2013;153:5–11.
Harris LN, Ismaila N, McShane LM, Hayes DF. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline summary. J Oncol Pract. 2016;12:384–9.
Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25–32.
Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. Pembrolizumab for early triple-negative breast cancer. New Eng J Med. 2020;382:810–21.
Yu K, Sang QA, Lung PY, Tan W, Lively T, Sheffield C, et al. Personalized chemotherapy selection for breast cancer using gene expression profiles. Sci Rep. 2017;7:43294.