Identification of New Prognostic Markers for Breast Cancer. (PROBREAST)

Identification de Nouveaux Marqueurs Pronostiques Des Cancers du Sein

Candidate markers have been identified thanks to an original approach developed by our research team aiming at detecting ectopic gene expression using public pan-genomic breast cancer data. The same approach had already been used and validated in lung tumors, leukemias and lymphomas. The main objective of the present research is to use tumor samples from patients in a retrospective and prospective cohort to test and validate the relevance of these prognostic markers in breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Conventional treatment protocols of breast cancer

Detailed Description

Following a diagnosis of breast cancer, the most immediate challenges in patient management are the determination of prognosis and the identification of the most appropriate neoadjuvant and adjuvant systemic therapy. Indicators to assess the risk of relapse or metastasis during treatment are still largely insufficient, a situation which does not allow to precisely adjust the treatment, often leading to heavy side effects. In order to minimize the side effects and risks of therapies, it is therefore necessary to discover new markers which would enable us to reliably assess the prognosis of patients diagnosed with breast cancer.

The approach used here for discovering new prognostic markers is based on an original strategy developed by the researchers associated with this project and published in the respective contexts of lung cancer, acute lymphoblastic leukemia and lymphoma. Indeed, genetic abnormalities and deregulation of the systems controlling the expression of specific gene programs not only lead to the abnormal extinction of normally active genes, but is also responsible for the aberrant activation of genes that normally should remain silent. The investigators have recently demonstrated that any type of malignancy is associated with the ectopic expression of these normally silent genes, including genes of the male germline. The in-depth study of these aberrant gene expressions and the search for correlations and associations with the clinical and biological data of the tumors show that the expression of some of these genes and the presence of their products are good indicators of tumor aggressiveness.

The investigators propose here to apply the same approach for the search for new prognostic markers in the case of breast cancer. A prior analysis of breast tumors, of which transcriptome data are publicly available, has identified a number of tissue-specific genes, including the germline and placenta genes, frequently activated in breast cancer. Based on our past observations, our hypothesis is that some of them may directly reflect the level of tumor aggressiveness and could therefore be used as prognostic biomarkers.

The objective of this work will be to look for the prognostic value of these genes by using the samples collected in this cohort of patients to detect their activation and to correlate these aberrant activations with the anatomopathological data of the tumor, as well as to the clinico-biological data and patient follow-up.

• Study Type: Observational
• Enrollment (Anticipated): 1500

Contacts and Locations

• Study Contact: Name: Anne-Cécile PHILIPPE, Dr; Phone Number: +33476766677; Email: ACPhilippe@chu-grenoble.fr
• Study Contact Backup: Name: Emmanuelle JACQUET, Dr; Phone Number: +33476765451; Email: ejacquet1@chu-grenoble.fr

Study Locations

• France
  • Grenoble, France, 38043
    • Recruiting
    • Anne-Cécile PHILIPPE
    • Contact: Anne-Cécile PHILIPPE, Pr; Phone Number: +33(0)4 76 76 66 77; Email: ACPhilippe@chu-grenoble.fr
    • Contact: Emmanuelle JACQUET; Phone Number: +33(0)4 76 76 54 51; Email: ejacquet1@chu-grenoble.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Adult female patients with breast cancer

Description

Inclusion Criteria:

• Adult female patients with breast cancer

Exclusion Criteria:

• Presence of another cancer, excluding basal cell cancers or pre-neoplastic lesions of the cervix.
• Subject under guardianship or subject deprived of liberty
• Impossibility of collecting information on exposure (subjects recently arrived in France, foreign language, etc.)
• Male patients

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study of ectopic gene expression to define new prognostic biomarkers in breast cancer	The overall survival and disease-free survival of patient with breast cancers will be analyzed in terms of gene expression change in order to identify new prognostic biomarkers.	12 years, with evaluation every 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study of response to neoadjuvant treatments of breast cancer assessed from anatomopathological data.	Evaluation of a response rate after neoadjuvant chemotherapy according to RECIST criteria	12 years, with evaluation every 3 years

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: Anne-Cécile PHILIPPE, Dr, University Hospital, Grenoble; Study Director: Mireille MOUSSEAU, Pr, Grenoble Alpes University Hospital

Publications and helpful links

General Publications

• Rousseaux S, Debernardi A, Jacquiau B, Vitte AL, Vesin A, Nagy-Mignotte H, Moro-Sibilot D, Brichon PY, Lantuejoul S, Hainaut P, Laffaire J, de Reynies A, Beer DG, Timsit JF, Brambilla C, Brambilla E, Khochbin S. Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers. Sci Transl Med. 2013 May 22;5(186):186ra66. doi: 10.1126/scitranslmed.3005723.
• Wang J, Mi JQ, Debernardi A, Vitte AL, Emadali A, Meyer JA, Charmpi K, Ycart B, Callanan MB, Carroll WL, Khochbin S, Rousseaux S. A six gene expression signature defines aggressive subtypes and predicts outcome in childhood and adult acute lymphoblastic leukemia. Oncotarget. 2015 Jun 30;6(18):16527-42. doi: 10.18632/oncotarget.4113.
• Le Bescont A, Vitte AL, Debernardi A, Curtet S, Buchou T, Vayr J, de Reynies A, Ito A, Guardiola P, Brambilla C, Yoshida M, Brambilla E, Rousseaux S, Khochbin S. Receptor-Independent Ectopic Activity of Prolactin Predicts Aggressive Lung Tumors and Indicates HDACi-Based Therapeutic Strategies. Antioxid Redox Signal. 2015 Jul 1;23(1):1-14. doi: 10.1089/ars.2013.5581. Epub 2014 Mar 6.
• Emadali A, Rousseaux S, Bruder-Costa J, Rome C, Duley S, Hamaidia S, Betton P, Debernardi A, Leroux D, Bernay B, Kieffer-Jaquinod S, Combes F, Ferri E, McKenna CE, Petosa C, Bruley C, Garin J, Ferro M, Gressin R, Callanan MB, Khochbin S. Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers. EMBO Mol Med. 2013 Aug;5(8):1180-95. doi: 10.1002/emmm.201202034. Epub 2013 Jul 4.
• Reynoird N, Schwartz BE, Delvecchio M, Sadoul K, Meyers D, Mukherjee C, Caron C, Kimura H, Rousseaux S, Cole PA, Panne D, French CA, Khochbin S. Oncogenesis by sequestration of CBP/p300 in transcriptionally inactive hyperacetylated chromatin domains. EMBO J. 2010 Sep 1;29(17):2943-52. doi: 10.1038/emboj.2010.176. Epub 2010 Jul 30.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Anticipated): December 31, 2033
• Study Completion (Anticipated): December 31, 2033

Study Registration Dates

• First Submitted: December 14, 2017
• First Submitted That Met QC Criteria: February 15, 2018
• First Posted (Actual): February 19, 2018

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: biomarkers; Breast cancer; prognostic; response to treatment; ectopic gene expression; expression profile; tissue-specific genes
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 38RC17.172; 2017-A01740-53 (Other Identifier: ID RCB)

Drug and device information, study documents

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