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A Tyrosine Kinase Expression Signature Predicts the Post-Operative Clinical Outcome in Triple Negative Breast Cancers
Open AccessArticle

Should Tumor Infiltrating Lymphocytes, Androgen Receptor, and FOXA1 Expression Predict the Clinical Outcome in Triple Negative Breast Cancer Patients?

1
Functional Biomorphology Laboratory, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, Italy
2
Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola (FC), Italy
3
Pathology Department, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, Italy
4
Medical Oncology Unit, IRCCS-Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, Italy
5
Department of Biomedical Sciences and Human Oncology, University of Bari ‘Aldo Moro’ of Bari, 70124 Bari, Italy
*
Authors to whom correspondence should be addressed.
Contributed equally.
Cancers 2019, 11(9), 1393; https://doi.org/10.3390/cancers11091393
Received: 7 August 2019 / Revised: 28 August 2019 / Accepted: 9 September 2019 / Published: 18 September 2019
(This article belongs to the Special Issue New Insights into Breast and Endometrial Cancer)
Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. TILs have a strong prognostic role in triple negative breast cancer (TNBC). Little is known about the interaction with the androgen receptor (AR) and forkhead box A1 (FOXA1). We analyzed the relationships between TIL levels, AR, and FOXA1 expression and their clinical significance in TNBC patients. Further, we investigated their interaction with other biomarkers like programmed cell death ligand-1 (PD-L1), breast cancer type 1 susceptibility protein (BRCA1), poly (ADP-Ribose) polymerase 1 (PARP1), and Na+/H+ exchanger regulatory factor 1 (NHERF1). The expression of the proteins was evaluated by immunohistochemistry in 124 TNBC samples. TILs were performed adhering to International TILs Working Group 2014 criteria. Cox proportional hazards models were also used to identify risk factors associated with poor prognosis. Multivariate analysis identified TILs as independent prognostic factor of disease free survival (DFS; p = 0.045). A Kaplan–Meyer analysis revealed that the patients with high TILs had a better DFS compared to patients with low TILs (p = 0.037), and the phenotypes TILs−/AR+ and TILs−/FOXA1− had a worse DFS (p = 0.032, p = 0.001 respectively). AR was associated with FOXA1 expression (p = 0.007), and the tumors FOXA1+ presented low levels of TILs (p = 0.028). A poor DFS was observed for AR+/FOXA1+ tumors compared to other TNBCs (p = 0.0117). Low TILs score was associated with poor patients’ survival, and TILs level in combination with AR or FOXA1 expression affected patient’s clinical outcome. In addition, AR+/FOXA1+ phenotype identified a specific subgroup of TNBC patients with poor prognosis. These data may suggest new ways of therapeutic intervention to support current treatments. View Full-Text
Keywords: TILs; TNBC; AR; FOXA1; prognosis TILs; TNBC; AR; FOXA1; prognosis
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MDPI and ACS Style

Mangia, A.; Saponaro, C.; Vagheggini, A.; Opinto, G.; Centonze, M.; Vicenti, C.; Popescu, O.; Pastena, M.; Giotta, F.; Silvestris, N. Should Tumor Infiltrating Lymphocytes, Androgen Receptor, and FOXA1 Expression Predict the Clinical Outcome in Triple Negative Breast Cancer Patients? Cancers 2019, 11, 1393.

AMA Style

Mangia A, Saponaro C, Vagheggini A, Opinto G, Centonze M, Vicenti C, Popescu O, Pastena M, Giotta F, Silvestris N. Should Tumor Infiltrating Lymphocytes, Androgen Receptor, and FOXA1 Expression Predict the Clinical Outcome in Triple Negative Breast Cancer Patients? Cancers. 2019; 11(9):1393.

Chicago/Turabian Style

Mangia, Anita; Saponaro, Concetta; Vagheggini, Alessandro; Opinto, Giuseppina; Centonze, Matteo; Vicenti, Chiara; Popescu, Ondina; Pastena, Maria; Giotta, Francesco; Silvestris, Nicola. 2019. "Should Tumor Infiltrating Lymphocytes, Androgen Receptor, and FOXA1 Expression Predict the Clinical Outcome in Triple Negative Breast Cancer Patients?" Cancers 11, no. 9: 1393.

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