AR negative triple negative or “Quadruple Negative” breast cancers in African American women have an enriched basal and immune signature

Melissa B Davis, Shweta Tripathi, Raymond Hughley, Qinghua He, Sejong Bae, Balasubramanyam Karanam, Rachel Martini, Lisa Newman, Windy Colomb, William Grizzle, Clayton Yates

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

There is increasing evidence that Androgen Receptor (AR) expression has prognostic usefulness in Triple negative breast cancer (TNBC), where tumors that lack AR expression are considered “Quadruple negative” Breast Cancers (“QNBC”). However, a comprehensive analysis of AR expression within all breast cancer subtypes or stratified by race has not been reported. We assessed AR mRNA expression in 925 tumors from The Cancer Genome Atlas (TCGA), and 136 tumors in 2 confirmation sets. AR protein expression was determined by immunohistochemistry in 197 tumors from a multi-institutional cohort, for a total of 1258 patients analyzed. Cox hazard ratios were used to determine correlations to PAM50 breast cancer subtypes, and TNBC subtypes. Overall, AR-negative patients are diagnosed at a younger age compared to AR-positive patients, with the average age of AA AR-negative patients being, 49. AA breast tumors express AR at lower rates compared to Whites, independent of ER and PR expression (p<0.0001). AR-negative patients have a (66.60; 95% CI, 32–146) odds ratio of being basal-like compared to other PAM50 subtypes, and this is associated with an increased time to progression and decreased overall survival. AA “QNBC” patients predominately demonstrated BL1, BL2 and IM subtypes, with differential expression of E2F1, NFKBIL2, CCL2, TGFB3, CEBPB, PDK1, IL12RB2, IL2RA, and SOS1 genes compared to white patients. Immune checkpoint inhibitors PD-1, PD-L1, and CTLA-4 were significantly upregulated in both overall “QNBC” and AA “QNBC” patients as well. Thus, AR could be used as a prognostic marker for breast cancer, particularly in AA “QNBC” patients.

Original languageEnglish (US)
Article numbere0196909
JournalPloS one
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2018

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Androgen Receptors
African Americans
breast neoplasms
Breast Neoplasms
Tumors
neoplasms
Triple Negative Breast Neoplasms
Neoplasms
Transforming Growth Factor beta3
androgen receptors
Genes
Atlases
odds ratio
immunohistochemistry
Hazards
protein synthesis
Immunohistochemistry
Odds Ratio
Genome
Messenger RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

AR negative triple negative or “Quadruple Negative” breast cancers in African American women have an enriched basal and immune signature. / Davis, Melissa B; Tripathi, Shweta; Hughley, Raymond; He, Qinghua; Bae, Sejong; Karanam, Balasubramanyam; Martini, Rachel; Newman, Lisa; Colomb, Windy; Grizzle, William; Yates, Clayton.

In: PloS one, Vol. 13, No. 6, e0196909, 01.06.2018.

Research output: Contribution to journalArticle

Davis, MB, Tripathi, S, Hughley, R, He, Q, Bae, S, Karanam, B, Martini, R, Newman, L, Colomb, W, Grizzle, W & Yates, C 2018, 'AR negative triple negative or “Quadruple Negative” breast cancers in African American women have an enriched basal and immune signature', PloS one, vol. 13, no. 6, e0196909. https://doi.org/10.1371/journal.pone.0196909
Davis, Melissa B ; Tripathi, Shweta ; Hughley, Raymond ; He, Qinghua ; Bae, Sejong ; Karanam, Balasubramanyam ; Martini, Rachel ; Newman, Lisa ; Colomb, Windy ; Grizzle, William ; Yates, Clayton. / AR negative triple negative or “Quadruple Negative” breast cancers in African American women have an enriched basal and immune signature. In: PloS one. 2018 ; Vol. 13, No. 6.
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abstract = "There is increasing evidence that Androgen Receptor (AR) expression has prognostic usefulness in Triple negative breast cancer (TNBC), where tumors that lack AR expression are considered “Quadruple negative” Breast Cancers (“QNBC”). However, a comprehensive analysis of AR expression within all breast cancer subtypes or stratified by race has not been reported. We assessed AR mRNA expression in 925 tumors from The Cancer Genome Atlas (TCGA), and 136 tumors in 2 confirmation sets. AR protein expression was determined by immunohistochemistry in 197 tumors from a multi-institutional cohort, for a total of 1258 patients analyzed. Cox hazard ratios were used to determine correlations to PAM50 breast cancer subtypes, and TNBC subtypes. Overall, AR-negative patients are diagnosed at a younger age compared to AR-positive patients, with the average age of AA AR-negative patients being, 49. AA breast tumors express AR at lower rates compared to Whites, independent of ER and PR expression (p<0.0001). AR-negative patients have a (66.60; 95{\%} CI, 32–146) odds ratio of being basal-like compared to other PAM50 subtypes, and this is associated with an increased time to progression and decreased overall survival. AA “QNBC” patients predominately demonstrated BL1, BL2 and IM subtypes, with differential expression of E2F1, NFKBIL2, CCL2, TGFB3, CEBPB, PDK1, IL12RB2, IL2RA, and SOS1 genes compared to white patients. Immune checkpoint inhibitors PD-1, PD-L1, and CTLA-4 were significantly upregulated in both overall “QNBC” and AA “QNBC” patients as well. Thus, AR could be used as a prognostic marker for breast cancer, particularly in AA “QNBC” patients.",
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AU - Karanam, Balasubramanyam

AU - Martini, Rachel

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AU - Yates, Clayton

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