Evaluating MRNA Expression Levels As a Predictor of Response to Endocrine Therapy in ER+ Breast Cancer

Overview

Journal Front Pharmacol

Date 2019 Feb 12

PMID 30740056

Citations 10

Authors

Julie A Vendrell

Jerome Solassol

Balazs Gyorffy

Paul Vilquin

Marta Jarlier

Caterina F Donini

Laurent Gamba

Thierry Maudelonde

Philippe Rouanet

Pascale A Cohen

Affiliations

Soon will be listed here.

Abstract

is a candidate oncogene with a wide variety of deleterious functions in breast cancer. Here, we aimed at investigating in a pilot prospective study the association between mRNA expression levels and the clinical response to neoadjuvant endocrine therapy (ET) in postmenopausal ER-positive (ER+) breast cancer patients. Core surgical biopsy samples before treatment initiation and post-treatment were obtained from 68 patients, and Ki-67 values measured by immunohistochemistry (IHC) were used to identify responders ( = 59) and non-responders ( = 9) after 4 months of ET. We report for the first time that high mRNA expression level measured by RT-qPCR in the initial tumor samples (pre-treatment) is associated with poor response to neoadjuvant ET. Indeed, the clinical positive response rate in patients with low expression levels was significantly higher than that in those with high expression levels ( = 0.027). Additionally, a retrospective analysis evaluating expression levels in primary breast tumor of ER+/HER2-/LN0 breast cancer patients treated with adjuvant ET enabled the identification of poorer responders prone to earlier relapse ( = 0.013), while did not retain any prognostic value in the ER+/HER2-/LN0 breast cancer patients who did not receive any treatment. Altogether, these data suggest that expression might be predictive of clinical response to ET.

Citing Articles

Characterization of breast cancer tumors in older patients who show de novo resistance to endocrine therapy.

Ishizuka Y, Horimoto Y, Yuan M, Ueki Y, Onagi H, Saeki H Sci Rep. 2024; 14(1):32116.

PMID: 39738567 PMC: 11686229. DOI: 10.1038/s41598-024-83895-2.

Gene Copy Number as a Marker of Response to Standard Therapy Drugs According to ERα Status in Breast Cancer.

Rangel N, Sanchez I, Valbuena D, Rondon-Lagos M Breast Cancer (Dove Med Press). 2024; 16:127-139.

PMID: 38505863 PMC: 10950081. DOI: 10.2147/BCTT.S445753.

Dimethyl fumarate inhibits ZNF217 and can be beneficial in a subset of estrogen receptor positive breast cancers.

Sharma T, Zhang Y, Zigrossi A, Cravatt B, Kastrati I Breast Cancer Res Treat. 2023; 201(3):561-570.

PMID: 37477798 DOI: 10.1007/s10549-023-07037-4.

Non-Coding RNAs Modulating Estrogen Signaling and Response to Endocrine Therapy in Breast Cancer.

Treeck O, Haerteis S, Ortmann O Cancers (Basel). 2023; 15(6).

PMID: 36980520 PMC: 10046587. DOI: 10.3390/cancers15061632.

The Intricate Interplay between the ZNF217 Oncogene and Epigenetic Processes Shapes Tumor Progression.

Fahme P, Ramadan F, Le D, Nguyen Thi K, Ghayad S, Hussein N Cancers (Basel). 2022; 14(24).

PMID: 36551531 PMC: 9776013. DOI: 10.3390/cancers14246043.

References

Dowsett M, Smith I, Ebbs S, Dixon J, Skene A, Griffith C . Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence-free survival. Clin Cancer Res. 2005; 11(2 Pt 2):951s-8s. View

Dowsett M, Smith I, Ebbs S, Dixon J, Skene A, AHern R . Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst. 2007; 99(2):167-70. DOI: 10.1093/jnci/djk020. View

Ellis M, Tao Y, Luo J, AHern R, Evans D, Bhatnagar A . Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst. 2008; 100(19):1380-8. PMC: 2556704. DOI: 10.1093/jnci/djn309. View

Gyorffy B, Schafer R . Meta-analysis of gene expression profiles related to relapse-free survival in 1,079 breast cancer patients. Breast Cancer Res Treat. 2008; 118(3):433-41. DOI: 10.1007/s10549-008-0242-8. View

Chia Y, Ellis M, Ma C . Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool. Br J Cancer. 2010; 103(6):759-64. PMC: 2966629. DOI: 10.1038/sj.bjc.6605845. View

Ellis M, Suman V, Hoog J, Lin L, Snider J, Prat A . Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline.... J Clin Oncol. 2011; 29(17):2342-9. PMC: 3107749. DOI: 10.1200/JCO.2010.31.6950. View

Vendrell J, Thollet A, Nguyen N, Ghayad S, Vinot S, Bieche I . ZNF217 is a marker of poor prognosis in breast cancer that drives epithelial-mesenchymal transition and invasion. Cancer Res. 2012; 72(14):3593-606. DOI: 10.1158/0008-5472.CAN-11-3095. View

Charehbili A, Fontein D, Kroep J, Liefers G, Mieog J, Nortier J . Neoadjuvant hormonal therapy for endocrine sensitive breast cancer: a systematic review. Cancer Treat Rev. 2013; 40(1):86-92. DOI: 10.1016/j.ctrv.2013.06.001. View

Nguyen N, Vendrell J, Poulard C, Gyorffy B, Goddard-Leon S, Bieche I . A functional interplay between ZNF217 and estrogen receptor alpha exists in luminal breast cancers. Mol Oncol. 2014; 8(8):1441-57. PMC: 5528595. DOI: 10.1016/j.molonc.2014.05.013. View

10.

Polley M, Leung S, Gao D, Mastropasqua M, Zabaglo L, Bartlett J . An international study to increase concordance in Ki67 scoring. Mod Pathol. 2015; 28(6):778-86. DOI: 10.1038/modpathol.2015.38. View

11.

Turnbull A, Arthur L, Renshaw L, Larionov A, Kay C, Dunbier A . Accurate Prediction and Validation of Response to Endocrine Therapy in Breast Cancer. J Clin Oncol. 2015; 33(20):2270-8. DOI: 10.1200/JCO.2014.57.8963. View

12.

Marous M, Bieche I, Paoletti X, Alt M, Razak A, Stathis A . Designs of preoperative biomarkers trials in oncology: a systematic review of the literature. Ann Oncol. 2015; 26(12):2419-28. DOI: 10.1093/annonc/mdv378. View

13.

Rugo H, Vidula N, Ma C . Improving Response to Hormone Therapy in Breast Cancer: New Targets, New Therapeutic Options. Am Soc Clin Oncol Educ Book. 2016; 35:e40-54. DOI: 10.1200/EDBK_159198. View

14.

Focke C, Decker T, van Diest P . Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours. Histopathology. 2016; 69(5):849-861. DOI: 10.1111/his.13007. View

15.

Ellis M, Suman V, Hoog J, Goncalves R, Sanati S, Creighton C . Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance). J Clin Oncol. 2017; 35(10):1061-1069. PMC: 5455353. DOI: 10.1200/JCO.2016.69.4406. View

16.

Bellanger A, Donini C, Vendrell J, Lavaud J, Machuca-Gayet I, Ruel M . The critical role of the ZNF217 oncogene in promoting breast cancer metastasis to the bone. J Pathol. 2017; 242(1):73-89. DOI: 10.1002/path.4882. View

17.

Iwamoto T, Katagiri T, Niikura N, Miyoshi Y, Kochi M, Nogami T . Immunohistochemical Ki67 after short-term hormone therapy identifies low-risk breast cancers as reliably as genomic markers. Oncotarget. 2017; 8(16):26122-26128. PMC: 5432244. DOI: 10.18632/oncotarget.15385. View

18.

Morigi C . Highlights from the 15th St Gallen International Breast Cancer Conference 15-18 March, 2017, Vienna: tailored treatments for patients with early breast cancer. Ecancermedicalscience. 2017; 11:732. PMC: 5406222. DOI: 10.3332/ecancer.2017.732. View

19.

Rimm D, Leung S, McShane L, Bai Y, Bane A, Bartlett J . An international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer. Mod Pathol. 2018; 32(1):59-69. DOI: 10.1038/s41379-018-0109-4. View

20.

Iwata H, Masuda N, Yamamoto Y, Fujisawa T, Toyama T, Kashiwaba M . Validation of the 21-gene test as a predictor of clinical response to neoadjuvant hormonal therapy for ER+, HER2-negative breast cancer: the TransNEOS study. Breast Cancer Res Treat. 2018; 173(1):123-133. PMC: 6394785. DOI: 10.1007/s10549-018-4964-y. View