Abstract

Abstract Background: The LAR subtype of triple negative breast cancer (TNBC) was defined using the Vanderbilt genomic signature in cell lines. The characteristics of this population remain unclear. Methods: We collected the clinicopathological, molecular and imaging characteristics of the LAR population who were enrolled in the ARTEMIS trial, a prospective trial to treat women with TNBC to receive neoadjuvant anthracycline therapy followed by experimental arms based on biomarker versus taxane. The ultrasonography-based response assessment was performed at baseline, after 2 and 4 cycles of anthracycline chemotherapy. The Vanderbilt genomic signature was used to classify the TNBC into the basal-like 1, basal-like 2, immunomodulatory, mesenchymal, mesenchymal stem-like and luminal androgen receptor (LAR) subtypes. The clinical data for this analysis included age, race, menopausal status, TNM stage and BRCA mutation status. Pathological and molecular characteristics included histologic subtype, nuclear grade, Ki67, vimentin expression, androgen receptor (AR) immunohistochemical (IHC) nuclear staining, stromal tumor infiltrating lymphocytes (TIL) percentage and residual cancer burden (RCB) at surgery. Results: Total 28 patients with the LAR signature were analyzed. The characteristics are showed in the table: AgeRaceno. (%)Clinical Stageno. (%)AR IHC StainingBRCA Mutationno. (%)Median (yr)55White19 (68)IA1 (4)Median (%)52No mutation16 (57)Distribution(%)no. (%)Asian3 (11)IIA6 (21)Distribution (%)no(%)Mutation present018-402 (7)Black2 (7)IIB10 (36)<259 (32)VUS1 (4)41-6012 (43)Hispanic3 (11)IIIA6 (21)25-505 (18)Test not indicated6 (21)>6014 (50)American Indian1 (3)IIIB051-751 (3,5)Unknown5 (18)IIIC5 (18)76-10012 (43)Not available1 (3,5)Menopauseno. (%)Histologic subtypeno. (%)Ki67Stromal TILno. (%)Vimentin expressionno. (%)Postmenopausal23 (82)IDC24 (87)Median (%)40<5%10 (36)< 1%24 (85)Perimenopausal2 (7)ILC2 (7)Distribution (%)no. (%)5% - <50 %16 (57)≥1%3 (11)Premenopausal3 (11)Apocrine Carcinoma1 (3)<205 (18)≥50%1 (3,5)N/A1 (4)Metaplastic carcinoma1 (3)≥2013 (46)N/A1 (3,5)N/A10 (36)T stageno. (%)Lymph node involvementno. (%)Nuclear gradeno. (%)Tumor reduction (%)no. (%)RCBno(%)T1c3 (11)Yes22 (79)11 (4)≥ 7012 (43)pCR-111 (39)T213 (46)No6 (21)26 (21)< 7014 (50)2-315 (54)T311 (39)321 (75)N/A2 (7)N/A2 (7)T41 (4)Experimental armno. (%)Enzalutamide8 (29)Atezolizumab4 (14)None16 (57) Relevant characteristics are: median age of 55 years, 82% postmenopausal, 89% breast tumor size > 2cm, 79% with lymph node involvement, no BRCA mutation detected, 75% nuclear grade III, 46% with Ki67 ≥ 20%, median AR IHC staining of 52%, 85% vimentin expression of <1%, 93% had stromal TIL <50%, 39% RCB 0-1 and 54% RCB 2-3. We found that 43% had ≥ 70% reduction in size after 4 cycles of AC. Univariate and multivariate analysis using characteristics did not reveal contributing factor to the RCB. Conclusion: The LAR subgroup harbors unique characteristics that require further confirmation in larger cohorts. Citation Format: James Crespo, Seth Sahil, Elizabeth Ravenberg, Lei Huo, Kenneth Hess, Lumarie Santiago, Beatriz Adrada, Gaiane Rauch, Damodaran Senthil, Rashmi Murthy, Jennifer Litton, Debu Tripathy, Naoto Ueno, Stacy Moulder, Bora Lim. Characterization of the LAR subtype triple negative breast cancer population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1409.

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