Prolactin Receptor and Breast Diseases (Prolacsein)

Characterization and Implication of Prolactin Receptor Mutants in Human Breast Diseases

Prolactin is known to play an important role in breast development and differentiation. Thus proliferative breast diseases are good models to unravel PRl / PRLR function in proliferative processes.

The aim of this project is to identify and to characterize new mutants of the prolactin receptor gene within cohorts of benign or malign breast diseases with low or high occurrence frequency in human populations

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Benign Breast Disease
• Intervention / Treatment: Biological: blood collection for hormonal status analysis; Procedure: breast Biopsy or surgery; Genetic: blood collection; Other: ultrasonography (pelvis and breast), bone mineral density

Detailed Description

There is currently no known genetic disease linked to prolactin (prl) or its receptor (prlR) in humans. In a previous work, we have identified a new mutation of prolactin receptor that leads to it's constitutive activation and to cell proliferation signalling cascades (i.e. through MAP kinases).

This result suggests that PRLR mutants may have a strong physiopathological impact on breast diseases etiology and/or development and/or evolution.

Based on this, we will pursue the identification of new PRLR mutants in various breast diseases and continue their in vitro functional characterization and then analyse their in vivo consequences on breast tissue samples collected within these women.

1. In a first time we wish to confirm our previous results on multiple fibroadenomas (MFA). The current cohort will be augmented with 30 to 35 new patients each year. We will confirm our in vitro results in vivo with tumoral and peri-tumoral tissue samples.
2. We then wish to extend this study to other rare breast pathologies (i.e. gigantomastia, phyllodies tumors, giant fibroadenomas) and to more common ones (simple fibroadenomas) to demonstrate a link between simple FA and MFA.
3. in a third time we will try to determinate whether a constitutive activation of PRLR leads to enhanced occurrence of benign / malign transitions.

• Study Type: Observational
• Enrollment (Actual): 735

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Pitié Salpêtrière Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Benign breast diseases(60 simple FA, 71 other breast diseases) Brest Cancer : 132 Control : 525

Description

Inclusion criteria :

• benign breast diseases

  • 10 < age < 25 for simple FA
  • 10 < age < 50 for other diseases .no hormonal treatment for at least 3 months if patients took cyproterone acetate; 1 month for other ovaries-interfering hormonal treatment, and 1 week for ovaries-non-interfering hormonal treatments.
  • Signature of the informed consent form (icf) by patients or their legal representative (for patients under age of 18.)

• breast cancer :

  • having a breast cancer with a planned surgery
  • age > 55 years
  • post menopausal with not menopause substitution treatment
  • signature of the icf

• control group :

  • 18 < age < 60
  • signature of the icf

Exclusion criteria :

• no signature or no conformity of the icf
• no social security

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; benign breast diseases	Biological: blood collection for hormonal status analysis; for hormonal status analysis; Procedure: breast Biopsy or surgery; breast Biopsy or surgery; Genetic: blood collection; blood collection for prlR gene sequencing; Other: ultrasonography (pelvis and breast), bone mineral density; ultrasonography (pelvis and breast), bone mineral density
2; breast cancer	Biological: blood collection for hormonal status analysis; for hormonal status analysis; Procedure: breast Biopsy or surgery; breast Biopsy or surgery; Genetic: blood collection; blood collection for prlR gene sequencing; Other: ultrasonography (pelvis and breast), bone mineral density; ultrasonography (pelvis and breast), bone mineral density
3; control	Biological: blood collection for hormonal status analysis; for hormonal status analysis; Genetic: blood collection; blood collection for prlR gene sequencing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sequencing of PRLR	at inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Breast ultrasonography	at inclusion
Breast MRI	at inclusion
Pelvic ultrasonography	at inclusion
Bone mineral density measurement	at inclusion
Hormonal and metabolic evaluation	at inclusion
Histological analysis of tumoral and peri-tumoral tissues	at surgery
Tumor transcriptome analysis	at surgery

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut Pasteur
• Investigators: Principal Investigator: Philippe Touraine, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: January 13, 2009
• First Submitted That Met QC Criteria: February 11, 2009
• First Posted (Estimate): February 12, 2009

Study Record Updates

• Last Update Posted (Estimate): November 25, 2013
• Last Update Submitted That Met QC Criteria: November 21, 2013
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: breast cancer; Breast diseases,; human mutation,; prolactin receptor
• Additional Relevant MeSH Terms: Skin Diseases; Breast Diseases; Fibrocystic Breast Disease
• Other Study ID Numbers: P070608