Abstract
Background: Triple negative breast cancer (TNBC) is an aggressive subtype of with ill-defined therapeutic targets. Androgen receptor (AR) expression ranged from 32-53% in different reports presenting emerging biomarker in TNBC. Tumor-infiltrating lymphocytes (TIL) play an important prognostic and predictive value in TNBC. The relationship between AR, TIL and clinical behavior is still not fully understood. Methods: Thirty-six TNBC patients were retrospectively selected from a cohort of 800 patients diagnosed in 2012. Clinico-demographic data were collected. Formalin-fixed, paraffin embedded tissue specimens were evaluated for AR (+ ve if ≥ 1% expression), CD3, CD20, CD4, CD8 with IHC. Stromal TIL were quantified following the TIL Working Group recommendations. Lymphocyte-predominant breast cancer (LPBC) are defined as stromal TILs of ≥ 50%. Results: The mean age was 52.5 years and 27.8% were ≥60 years. The majority of patients (58.3%) were invasive duct carcinoma (IDC), while IDC with medullary features and invasive lobular carcinoma were 22% and 14% respectively. Grade III tumors were 52.8%. Stage III, IV were 54.3%, 8.6% respectively and N+ve were 77%. Seven patients of the total (19.4%) were AR+ve. TIL were assessed in 31 patients where LPBC was 32.3%. Median TIL was 15% and 33% (p = 0.07) and CD20 was 7% and 18% (p = 0.01) in AR+ve and AR-ve respectively. Mean CD3 was 93.3% and 80.6% (p = 0.007) and CD8 was 80.8% and 75% (p = 0.41) in AR+ve and AR-ve respectively. Majority of patients ≥60 years (66.7%) were lymphocyte deficient (TIL˂50%). CD8 was significantly lower in stage III/IV vs I/II (p = 0.04). LPBC type was significantly lower in N+ve vs N-ve patients (p = 0.03). Significant positive correlation presented between CD8 and CD3 (p˂0.001) while significant negative correlation presented between CD20 and CD3 (p = 0.03) and CD4 and CD8 (p = 0.04). Non statistically significant increased median OS in AR+ve vs AR-ve (44 vs 40 months, p = 0.84). Conclusions: The present study show that T cell marker (CD3) was more predominant in AR+ve TNBC. Older patients and N+ve were lymphocyte deficient (TIL˂50%). More studies are needed to focus on the clinical impact of the relation between AR and TIL in TNBC. Legal entity responsible for the study: Hagar Elghazawy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Highlights
Therapies targeting HER2 amplification are a success of modern oncology, yet resistance to these agents remains a major challenge
Inflammatory breast cancer (IBC) patient samplesdemonstrated a near absence of nuclear SMAD3 expression in the primary tumors from (P < 0.001) and a further reduction of SMAD3 staining intensity was observed in tumor emboli (P 1⁄4 0.019)
Integration of gene and protein expressiondata revealed that a substantial fraction of the IBC signature genes correlated with SMAD3 and these genes (i.e. 21/24; P < 0.001) are indicative of attenuated SMAD3 signaling in IBC
Summary
Therapies targeting HER2 amplification are a success of modern oncology, yet resistance to these agents remains a major challenge. Results: Fourteen genes, highly enriched for positive or negative selection after T-DM1 or DM1 treatment, were selected to assess the impact of individual knockout on TDM1 sensitivity This confirmed the role of the putative lysosomal DM1 transporter SLC46A3, in T-DM1 resistance, and identified a set of genes potentially involved in TDM1 activity. This study aimed to evaluate the predictive and prognostic role of ADRB2 expression as a biomarker in HER2þ breast cancer patients. Breast cancer treatment often involves the use of paclitaxel to target tumor cells; some patients do not respond to treatment and would be better treated with an alternative drug. Methods: A genome-wide RNAi screen was performed with MDA-MB-231 tumor xenografts in female NOD/SCID mice This allowed the identification of enriched and depleted shRNA sequences that theoretically target paclitaxel sensitivity and resistance genes, respectively. The screen identified 40 potential novel paclitaxel response genes in breast cancer
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