Prolactin Receptor and Breast Diseases

Study Overview
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Brief Summary
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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
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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. 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. 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. in a third time we will try to determinate whether a constitutive activation of PRLR leads to enhanced occurrence of benign / malign transitions.

Official Title
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Characterization and Implication of Prolactin Receptor Mutants in Human Breast Diseases

Conditions
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Benign Breast Disease, Breast Cancer

Intervention / Treatment
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* Biological: blood collection for hormonal status analysis
* Procedure: breast Biopsy or surgery
* Genetic: blood collection
* Other: ultrasonography (pelvis and breast), bone mineral density


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>benign breast diseases | Biological: blood collection for hormonal status analysis<br>* for hormonal status analysis<br>Procedure: breast Biopsy or surgery<br>* breast Biopsy or surgery<br>Genetic: blood collection<br>* blood collection for prlR gene sequencing<br>Other: ultrasonography (pelvis and breast), bone mineral density<br>* ultrasonography (pelvis and breast), bone mineral density<br>|
| 2<br>breast cancer | Biological: blood collection for hormonal status analysis<br>* for hormonal status analysis<br>Procedure: breast Biopsy or surgery<br>* breast Biopsy or surgery<br>Genetic: blood collection<br>* blood collection for prlR gene sequencing<br>Other: ultrasonography (pelvis and breast), bone mineral density<br>* ultrasonography (pelvis and breast), bone mineral density<br>|
| 3<br>control | Biological: blood collection for hormonal status analysis<br>* for hormonal status analysis<br>Genetic: blood collection<br>* blood collection for prlR gene sequencing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sequencing of PRLR |  | at inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast diseases,, human mutation,, prolactin receptor;, breast cancer