MiR-100 is a predictor of endocrine responsiveness and prognosis in patients with operable luminal breast cancer.

Autor:	Petrelli A; Cancer Molecular Biology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Bellomo SE; Department of Oncology, University of Turin, Torino, Italy., Sarotto I; Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Kubatzki F; Gynaecological Oncology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Sgandurra P; Gynaecological Oncology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Maggiorotto F; Gynaecological Oncology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Di Virgilio MR; Radiology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Ponzone R; Gynaecological Oncology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Geuna E; Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Galizia D; Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Nuzzo AM; Clinical Research Office, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Medico E; Department of Oncology, University of Turin, Torino, Italy; Oncogenomics Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Miglio U; Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Berrino E; Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy; Department of Medical Sciences, University of Turin, Torino, Italy., Venesio T; Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Ribisi S; Cancer Molecular Biology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Provero P; Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino, Italy; Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milano, Italy., Sapino A; Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy; Department of Medical Sciences, University of Turin, Torino, Italy., Giordano S; Cancer Molecular Biology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy; Department of Oncology, University of Turin, Torino, Italy., Montemurro F; Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy. Electronic address: filippo.montemurro@ircc.it.
Jazyk:	angličtina
Zdroj:	ESMO open [ESMO Open] 2020 Oct; Vol. 5 (5), pp. e000937.
DOI:	10.1136/esmoopen-2020-000937
Abstrakt:	Purpose: Overexpression of miR-100 in stem cells derived from basal-like breast cancers causes loss of stemness, induction of luminal breast cancer markers and response to endocrine therapy. We, therefore, explored miR-100 as a novel biomarker in patients with luminal breast cancer. Methods: miR-100 expression was studied in 90 patients with oestrogen-receptor-positive/human-epidermal growth factor receptor 2-negative breast cancer enrolled in a prospective study of endocrine therapy given either preoperatively, or for the treatment of de novo metastatic disease. Response was defined as a Ki67 ≤2.7% after 21±3 days of treatment. The prognostic role of miR-100 expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) breast cancer datasets. Additionally, we explored the correlation between miR-100 and the expression its targets reported as being associated with endocrine resistance. Finally, we evaluated whether a signature based on miR-100 and its target genes could predict the luminal A molecular subtype. Results: Baseline miR-100 was significantly anticorrelated with baseline and post-treatment Ki67 (p<0.001 and 0.004, respectively), and independently associated with response to treatment (OR 3.329, p=0.047). In the METABRIC dataset, high expression of miR-100 identified women with luminal A tumours treated with adjuvant endocrine therapy with improved overall survival (HR 0.55, p<0.001). miR-100 was negatively correlated with PLK1, FOXA1, mTOR and IGF1R expression, potentially explaining its prognostic effect. Finally, a miR-100-based signature developed in patients enrolled in the prospective study outperformed Ki67 alone in predicting the luminal A phenotype. Conclusions: Our findings suggest that miR-100 should be further explored as a biomarker in patients with luminal breast cancer. Competing Interests: Competing interests: FM has received personal speaker’s fees from Roche, Novartis, Pfizer, Pierre Fabre, Eli Lilly, Daiichi Sankyo, Astra Zeneca. EB is the recipient of a Ph.D. fellowship from the Department of Medical Sciences, University of Torino ('Dipartimenti di Eccellenza 2018–2022', Project no. D15D18000410001). (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)
Databáze:	MEDLINE
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