Triple-negative breast cancer (TNBC) is considered a poor prognostic subtype and a heterogeneous entity. Its only treatment is chemotherapy. Immunotherapy and antiandrogen therapies are being tested. Androgen receptor (AR) is expressed in up to 53% of TNBC. It is associated with a better disease-free survival and overall survival. The relation between tumor infiltrating lymphocytes (TIL) and AR in urothelial cancers has been assessed, unlike in TNBC.
50 stage I-III TNBC patients diagnosed between 2008 and 2013 were analyzed. Minimum follow-up was 57 months or until death. On these samples fixed in 10% formalin and included in paraffin, the evaluation of the expression of AR, CD20, CD4 and CD8 was performed by immunohistochemistry. AR+ was defined by more than 1% expression. Lymphocytes were evaluated as per the recommendations of the International Expert Consensus. We also analyzed total lymphocytes as high/low if they were over/under 80%. Data was analyzed by SPSS version 23.
Clinical characteristics are as follows: mean age of 61 years old, and postmenopausal 68%. 74% of the patients did not relapse and progression-free survival (PFS) was 95,6 months. Main tumor characteristics were Ki67>20%, 67,3%; T1-T2 88%; high grade 67,4%; lymph node (N) positive 51%. Early stage (stage I-II) was the 80%. High level of lymphocytes (HiL) was present in 70% of them. AR + (26%) was associated with younger patients (p = 0.009), low Ki67 (p = 0.014) and N + (p=0.025). No relation was obtained between AR and TIL, tumor size, grade, stage or survival. CD8+ were more present in AR + (p=0.002) and so the proportion CD4/CD8 (CD8>CD4 in AR+; CD4>CD8 in AR-. p = 0.026) HiL was related with higher Ki67 (p = 0.021) and grade 3 (p = 0.029). However, lower relapse and also lower deaths were observed in those with HiL (15.4% vs 84.6%; 21.4% vs 78.6%). In HiL, percentage of CD8+ was inversely proportional (p = 0.021 mean 27,7%).
High grade tumors and higher Ki67 unleash a higher immune response, protecting from a worse prognosis. CD8+ lymphocytes are associated with AR expression. More studies are needed to understand the relationship between AR and TIL and also the role of AR blockade in TNBC and its role in immune-mediated lysis.
Complejo Asistencial Universitario de León.
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All authors have declared no conflicts of interest.