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Androgen receptor splice variant-7 in breast cancer: clinical and pathologic correlations

Donna C Ferguson1, Douglas A Mata1, Timothy Ky Tay1

  • 1Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|October 1, 2021
PubMed

Insights

Androgen receptor splice variant-7 (AR-V7) is present in 9.7% of breast cancer (BC) cases. Positive AR immunohistochemistry and apocrine morphology may indicate AR-V7 testing is warranted.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Androgen receptor (AR) inhibitor therapy is an emerging treatment for AR-positive breast cancer (BC).
  • AR splice variant-7 (AR-V7) confers resistance to AR inhibitor therapy in prostate cancer and is hypothesized to impact BC treatment.
  • The prevalence and clinical significance of AR-V7 in BC are not well-established.

Purpose of the Study:

  • To determine the prevalence of AR-V7 in a large cohort of primary and metastatic breast cancer.
  • To identify clinicopathologic features associated with AR-V7 positivity in BC.
  • To evaluate AR-V7 as a potential predictive biomarker for AR antagonist therapy in BC.

Main Methods:

  • Targeted RNA sequencing (MSK-Fusion) was used to detect AR-V7 in 196 primary and metastatic/recurrent BC samples.
  • Targeted DNA sequencing (MSK-IMPACT) was performed on a subset of samples.
  • Immunohistochemistry (IHC) for AR and assessment of tumor morphology (apocrine features) were correlated with AR-V7 status.

Main Results:

  • AR-V7 was detected in 9.7% (19/196) of the BC cohort.
  • AR-V7 positivity was associated with positive AR IHC (100%) and apocrine morphology (42.1% vs. 3.4% in AR-V7 negative cases, P < 0.00001).
  • AR-V7 was found in various BC subtypes, including ER-/PgR-/HER2-negative (18%), ER-positive/HER2-negative (3.7%), and HER2-positive (15.4%) BC. AR-V7 was also detected in primary tumors and in patients without prior endocrine therapy.

Conclusions:

  • Positive AR IHC and apocrine morphology are potential indicators for AR-V7 testing in BC.
  • AR-V7 is present in a subset of primary and metastatic BC, suggesting its potential role in treatment resistance.
  • Further assessment of AR-V7 as a predictive biomarker for AR antagonist therapy in BC clinical trials is encouraged.

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