of Androgen Receptor Expression in Breast Cancer With or Without BRCA Mutation

Study Overview
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Brief Summary
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Androgen Receptor is extensively expressed in BRCA and its role in the disease may differ depending upon molecular subtypes and stages. Androgen Receptor (AR) may act as an antagonist of estrogen receptor α (ERα), in ERα induced effect, whereas in the absence of estrogens, AR may act as an agonist, of ERα- promoting tumor. Thus, depending on the BRCA micro-environment, both agonists and antagonists of the AR have been suggested for therapeutic approaches.

Detailed Description
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The rate of AR positivity in breast cancer is about 60% to 80%. Biologically the AR pathway has cross talk with several other key signaling pathway, including the PI3K/Akt/mTOR and MAPK Pathways, and with other receptor, including estrogen receptor and human epidermal growth factor receptor-2. In clinical trials in patients with breast cancer, AR targeted therapies such as AR agonists, AR antagonists, PARP inhibitors, and PI3K inhibitors have shown promising results. The use of AR targeted therapies in conjunction with other agent has been investigated for overcoming resistance to AR focused treatments. Thus, the value of AR positivity as a prognostic marker has not been identified. Several retrospective clinical studies have shown that AR might be a prognostic or predictive factor in breast cancer. BRCA1 mutation accounts for the progress of hereditary breast cancers and is in connection with unique clinicopathological characteristics compared with sporadic breast cancers. The database is still evolving and newer mutation and their significance is being found every day. Also, there were several limitations to these previous studies. First, the cut-off for AR positivity was arbitrary. In most of the studies, the cut-off points were 1% or 10% and weren't enough to predict carcinoma survival. Moreover, quite 90% of the studies were conducted in non-Asian regions. Most of the studies involving Asian patients studied the prognostic role of AR in TNBC patients, with inconclusive results. There are only a few studies from Indian continents and none has correlated the AR expression with BRCA. After the written inform consent in case of fresh recruitment the blood will be collected and tissue blocks will be obtained, use of already available blocks of patients who earlier participated in another study is also proposed. (a) Samples will be stored for DNA study and will be frozen in liquid nitrogen and stored at -80 °C until further processing. (samples will store in 10% formalin at room temperature (RT) for Immunohistochemistry

Official Title
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Clinico-pathological Study of Androgen Receptor Expression in Breast Cancer With or Without BRCA Mutation

Conditions
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Breast Cancer

Intervention / Treatment
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* Diagnostic Test: Androgen receptor status and BRCA mutation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histology proven cases of breast cancer Exclusion Criteria: Patients with prior treatment Pregnant and lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Breast Cancer<br>Patients with histologically proven breast cancer | Diagnostic Test: Androgen receptor status and BRCA mutation<br>* Androgen receptor status by IHC and germ line BRCA mutation<br>|
| Benign breast disease<br>Patients with benign breast diseases undergoing surgical resection | Diagnostic Test: Androgen receptor status and BRCA mutation<br>* Androgen receptor status by IHC and germ line BRCA mutation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Receptor expression | Androgen receptor expression and its correlation with molecular subtypes of breast cancer | 6 months | 
| BRCA1 and BRCA2 mutations | BRCA mutations and its correlation with molecular subtypes of breast cancer | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AR and BRCA | Correlation of Androgen receptor expression with BRCA mutation | 6 months |