MicroRNAs and Prognosis in Breast Cancer (BREMIR)

MicroRNAs Methylation and Expression Profiling for Identification of Breast Cancer Patients at High Risk to Develop Distant Metastases

Mono-centric, observational retrospective and prospective study, designed for breast cancer patients to identify novel miRNA based biomarker able to predict metastases development in breast cancer patients.

Study Overview

• Status: Completed
• Conditions: Breast Cancer Female; Metastases Breast
• Intervention / Treatment: Diagnostic test: miRNA targeted analysis on breast cancer tissues; Diagnostic test: miRNA profiling of breast cancer tissues; Diagnostic test: miRNA targeted analysis on plasma samples

Detailed Description

The potential role of miRNAs will be studied as a predictor of metastases development. miRNAs expression and miRNAs promoter methylation will be evaluated in surgically removed specimens obtained from breast cancer patients at diagnosis. Relevant miRNAs will be first identified by analysing a retrospective breast cancer cohort including at least and subsequently validated on a prospective cohort.

• Study Type: Observational
• Enrollment (Actual): 1432

Contacts and Locations

Study Locations

• Italy
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
      • Casa Sollievo Della Sofferenza IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Retrospective Cohort: 260 patients diagnosed with breast cancer of any histological type that underwent surgery for breast cancer from 2004 to 2014. For all this subjects fresh frozen specimen collected at the time of surgery are available for DNA and/or RNA extraction.

Prospective cohort: 1072 individuals were enrolled in this study from December 2014 to December 2019: 972 patients were affected by breast cancer, 100 patients showed benign breast lesions. For all this subjects fresh frozen specimen and/or FFPE sample at diagnosis, together with a plasma sample collected at the time of surgery are available for DNA and/or RNA extraction. For invasive breast cancer at least two plasma samples were colleted at surgery and after surgery. A third plasma sample is being collected at the eventual progression.

Description

Retrospective Cohort

Inclusion Criteria:

Tissue samples from breast cancer cases diagnosed from 2004 to 2014 for which informed consent for tumour banking and complete clinicopathological and follow up data were available.

Exclusion Criteria:

Pre-surgery neoadjuvant treatment for breast cancer with chemotherapy, lapatinib, trastuzumab, letrozole, anastrozole, exemestane or tamoxifen.

Other cancers diagnosed in the last five years.

Prospective Cohort:

Inclusion Criteria:

Ability to provide written informed consent; Age greater than 18 years; Histological diagnosis of Breast disease; First diagnosis of Breast Cancer; Syncronous distant metastasis absent.

Exclusion Criteria:

Stage IV breast cancer; Pre-surgery neoadjuvant treatment for breast cancer with chemotherapy, lapatinib, trastuzumab, letrozole, anastrozole, exemestane or tamoxifen; Other cancers diagnosed in the last five years; Alteration of mental status, dementia, or any psychiatric condition that might impair the ability to consciously sign the informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Retrospective; Identification in a retrospective cohort of a miRNA panel associated with the development of distant metastases.The retrospective cohort consists of tumor and normal tissue obtained from breast cancer patients, stored at -80°C at the Laboratory of Oncology. Of these samples, 360 met the inclusion criteria.	Diagnostic test: miRNA targeted analysis on breast cancer tissues; Total RNA is extracted from tissue sample and selected miRNA quantified by PCR based relative quantification method (QPCR) with a standard curve.; Diagnostic test: miRNA profiling of breast cancer tissues; Selected samples from the retrospective cohort are profiled for miRNA expression by using GeneChip® miRNA 4.0 Array.
Prospective; The association between miRNA expression and the clinical course of the disease identified in the retrospective cohort, is being confirmed in an independent prospective cohort. Both normal and tumor tissues of the patients, as well as plasma collected before surgery and at each follow-up time point, is being analyzed. Based on the annual number of surgeries performed at the Breast Surgery Unit, we initially estimated that the prospective cohort would consist of about 500 patients recruited over three years. Since the project was extended for additional two years the actual number of subject recruited was 972. In addition plasma sample for 100 breast benign condition was also collected as controls.	Diagnostic test: miRNA targeted analysis on breast cancer tissues; Total RNA is extracted from tissue sample and selected miRNA quantified by PCR based relative quantification method (QPCR) with a standard curve.; Diagnostic test: miRNA targeted analysis on plasma samples; miRNAs extracted from plasma samples are analysed by QPCR and/or ddPCR .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of metastases development	Identification of miRNAs associated with the risk to develop distant metastases.	evaluation 5 and 10 years after diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Identification of miRNAs associated with the risk of cancer specific death	evaluation 5 and 10 years after diagnosis

Collaborators and Investigators

• Sponsor: Casa Sollievo della Sofferenza IRCCS

Publications and helpful links

General Publications

• Barbano R, Pasculli B, Rendina M, Fontana A, Fusilli C, Copetti M, Castellana S, Valori VM, Morritti M, Graziano P, Luigi C, Coco M, Picardo F, Mazza T, Evron E, Murgo R, Maiello E, Esteller M, Fazio VM, Parrella P. Stepwise analysis of MIR9 loci identifies miR-9-5p to be involved in Oestrogen regulated pathways in breast cancer patients. Sci Rep. 2017 Mar 27;7:45283. doi: 10.1038/srep45283.
• Pasculli B, Barbano R, Fontana A, Biagini T, Di Viesti MP, Rendina M, Valori VM, Morritti M, Bravaccini S, Ravaioli S, Maiello E, Graziano P, Murgo R, Copetti M, Mazza T, Fazio VM, Esteller M, Parrella P. Hsa-miR-155-5p Up-Regulation in Breast Cancer and Its Relevance for Treatment With Poly[ADP-Ribose] Polymerase 1 (PARP-1) Inhibitors. Front Oncol. 2020 Aug 12;10:1415. doi: 10.3389/fonc.2020.01415. eCollection 2020.
• Pasculli B, Barbano R, Rendina M, Fontana A, Copetti M, Mazza T, Valori VM, Morritti M, Maiello E, Graziano P, Murgo R, Fazio VM, Esteller M, Parrella P. Hsa-miR-210-3p expression in breast cancer and its putative association with worse outcome in patients treated with Docetaxel. Sci Rep. 2019 Oct 17;9(1):14913. doi: 10.1038/s41598-019-51581-3.
• Fontana A, Barbano R, Dama E, Pasculli B, Rendina M, Morritti MG, Melocchi V, Castelvetere M, Valori VM, Ravaioli S, Bravaccini S, Ciuffreda L, Graziano P, Maiello E, Copetti M, Fazio VM, Esteller M, Bianchi F, Parrella P. Combined analysis of miR-200 family and its significance for breast cancer. Sci Rep. 2021 Feb 3;11(1):2980. doi: 10.1038/s41598-021-82286-1.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2014
• Primary Completion (Actual): October 28, 2018
• Study Completion (Actual): November 28, 2019

Study Registration Dates

• First Submitted: August 9, 2024
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): August 15, 2024
• Last Update Submitted That Met QC Criteria: August 13, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: prognosis; microRNA; risk prediction
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Breast Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: BREMIR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No