Clinical trial NCT00842465: Prolactin Receptor and Breast Diseases
Official title: Characterization and Implication of Prolactin Receptor Mutants in Human Breast Diseases
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Benign Breast Disease
Breast Cancer
Keywords: Breast diseases,
human mutation,
prolactin receptor;
breast cancer
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut Pasteur
First posted: 2009-02-12
Enrollment: 735
Sex: FEMALE
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Benign breast diseases(60 simple FA, 71 other breast diseases) Brest Cancer : 132 Control : 525

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sequencing of PRLR
timeFrame: at inclusion
Secondary outcomes:
measure: Breast ultrasonography
timeFrame: at inclusion
measure: Breast MRI
timeFrame: at inclusion
measure: Pelvic ultrasonography
timeFrame: at inclusion
measure: Bone mineral density measurement
timeFrame: at inclusion
measure: Hormonal and metabolic evaluation
timeFrame: at inclusion
measure: Histological analysis of tumoral and peri-tumoral tissues
timeFrame: at surgery
measure: Tumor transcriptome analysis
timeFrame: at surgery
Other outcomes:
Locations:
city: Paris
country: France
facility: Pitié Salpêtrière Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Philippe Touraine, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: