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

Androgen receptor splice variant-7 in breast cancer: Clinical and pathologic correlations Journal Article

Authors:	Ferguson, D. C.; Mata, D. A.; Tay, T. KY.; Traina, T. A.; Gucalp, A.; Chandarlapaty, S.; D'Alfonso, T. M.; Brogi, E.; Mullaney, K.; Ladanyi, M.; Arcila, M. E.; Benayed, R.; Ross, D. S.
Article Title:	Androgen receptor splice variant-7 in breast cancer: Clinical and pathologic correlations
Abstract:	Androgen receptor (AR) inhibitor therapy is a developing treatment for AR-positive breast cancer (BC) with ongoing clinical trials. AR splice variant-7 (AR-V7) is a truncated variant of AR that leads to AR inhibitor therapy resistance in prostate cancer; recent studies have identified AR-V7 in BC and theorized that AR-V7 can have a similar impact. This study assessed the prevalence and clinicopathologic features associated with AR-V7 in a large BC cohort. BC samples were evaluated by MSK-Fusion targeted RNAseq for AR-V7 detection and MSK-IMPACT targeted DNAseq, including triple-negative tumors with no driver alteration and estrogen receptor-positive/ESR1 wildtype tumors progressing on therapy. Among 196 primary and metastatic/recurrent cases (196 RNAseq, 194DNAseq), 9.7% (19/196) were AR-V7 positive and 90.3% (177/196) AR-V7 negative. All AR-V7 positive BC were AR-positive by immunohistochemistry (19/19). The prevalence of AR-V7 by receptor subtype (N = 189) was: 18% (12/67) in ER-/PgR-/HER2-negative BC, 3.7% (4/109) in ER-positive/HER2-negative BC, and 15.4% (2/13) in HER2-positive BC; AR-V7 was detected in one ER-positive/HER2-unknown BC. Apocrine morphology was observed in 42.1% (8/19) of AR-V7 positive BC and 3.4% (6/177) AR-V7 negative BC (P < 0.00001). Notably, AR-V7 was detected in 2 primary BC and 7 metastatic/recurrent BC patients with no prior endocrine therapy. We conclude that positive AR IHC and apocrine morphology are pathologic features that may indicate testing for AR-V7 is warranted in both primary and metastatic BC in the appropriate clinical context. The study findings further encourage the assessment of AR-V7 as a predictive biomarker for AR antagonist benefit in ongoing clinical BC trials.
Keywords:	estrogen; tumors; expression
Journal Title:	Modern Pathology
Volume:	35
Issue:	3
ISSN:	0893-3952
Publisher:	Nature Research
Date Published:	2022-03-01
Start Page:	396
End Page:	402
Language:	English
ACCESSION:	WOS:000702222900002
DOI:	10.1038/s41379-021-00924-5
PROVIDER:	wos
PMCID:	PMC8863633
PUBMED:	34593966
Notes:	Article -- Source: Wos