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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: Androgen receptor status and BRCA mutation

Detailed Description

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

• Study Type: Observational
• Enrollment (Actual): 231

Contacts and Locations

Study Locations

• India
  • UP
    • Varanasi, UP, India, 221005
      • Banaras Hindu University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients with breast cancer and benign breast diseases

Description

Inclusion Criteria:

• Histology proven cases of breast cancer

Exclusion Criteria:

• Patients with prior treatment
• Pregnant and lactating women

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Breast Cancer; Patients with histologically proven breast cancer	Diagnostic test: Androgen receptor status and BRCA mutation; Androgen receptor status by IHC and germ line BRCA mutation
Benign breast disease; Patients with benign breast diseases undergoing surgical resection	Diagnostic test: Androgen receptor status and BRCA mutation; Androgen receptor status by IHC and germ line BRCA mutation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Banaras Hindu University
• Investigators: Principal Investigator: Manoj Pandey, MS, PhD, Banaras Hindu University

Publications and helpful links

General Publications

• Anand A, Singh KR, Kumar S, Husain N, Kushwaha JK, Sonkar AA. Androgen Receptor Expression in an Indian Breast Cancer Cohort with Relation to Molecular Subtypes and Response to Neoadjuvant Chemotherapy - a Prospective Clinical Study. Breast Care (Basel). 2017 Jul;12(3):160-164. doi: 10.1159/000458433. Epub 2017 Jun 16.
• Vidula N, Yau C, Wolf D, Rugo HS. Androgen receptor gene expression in primary breast cancer. NPJ Breast Cancer. 2019 Dec 10;5:47. doi: 10.1038/s41523-019-0142-6. eCollection 2019.
• Zhang L, Fang C, Xu X, Li A, Cai Q, Long X. Androgen receptor, EGFR, and BRCA1 as biomarkers in triple-negative breast cancer: a meta-analysis. Biomed Res Int. 2015;2015:357485. doi: 10.1155/2015/357485. Epub 2015 Jan 28.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): July 1, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: May 31, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: August 9, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens
• Other Study ID Numbers: BRAR1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: On request
• IPD Sharing Time Frame: 3 months
• IPD Sharing Access Criteria: on request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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