Prognostic value of androgen receptor expression in triple negative breast carcinomas: personal experience and comments on a review about "Triple-negative breast cancer: treatment challenges and solutions" by Collignon et al.

Dear editor

Recently, we read with great interest the review by Collignon et al entitled “Triple-negative breast cancer: treatment challenges and solutions”,1 which appeared in the last issue of Breast Cancer: Targets and Therapy. In this article, the authors extensively reviewed studies concerning the opportunity to identify triple negative breast carcinoma (TNBC) subtypes by newly proposed markers, taking into account their biological heterogeneity on the light of clinical implications.

It is well known that TNBC represents ~15% of all breast cancers and they are distinguished by the lack of expression of the estrogen and progesterone receptor using immunohistochemistry (IHC) and by the lack of overexpression and/or amplification of HER2 obtained using IHC and/or fluorescence in situ hybridization.1 The clinicopathological characteristics of this subtype include tumors of large size, highly undifferentiated, high proliferative index, central necrosis, multiple apoptotic cells, and high-positive lymph nodes.

However, utilizing gene expression profiling of TNBC, a luminal androgen receptor subtype has been identified among others.2 Moreover, a recent systematic meta-analysis of 19 different studies showed that the expression of androgen receptor (AR) is a favorable prognostic marker, providing the rationale for the development of a Phase II study with bicalutamide, a nonsteroidal antiandrogen in the treatment of metastatic TNBC-AR positive (NCT00468715).3 In relation to this hypothesized role of AR, we would report herein our previous immunohistochemical experience in a cohort of TNBC.4 In detail, we have found AR immunopositivity (IHC >10%) in 26.6% of TNBC cases; moreover, both univariate and multivariate analyses showed that AR is significantly associated with overall survival, representing an independent variable able to identify a TNBC subtype.4 These data further confirm the significantly positive correlation between AR expression and favorable survival in TNBC patients since higher AR expression predicted a better relapse-free survival in patients with chemoresistant TNBC, as reported elsewhere.5

In light of the abovementioned studies, we fully agree with the suggestion of Collignon et al1 regarding the block of AR pathway as promising approach in the treatment of patients with the luminal AR subtype of TNBC. In fact, this new targeted therapy shows potential advantages,6 although more additional studies are needed to be validated in order to acquire a prognostic/predictive significance of AR in TNBC. However, the documented inverse correlation between low AR expression and high Ki67 rate has been significantly correlated with a shorter overall survival and a more aggressive disease in TNBC.4 Therefore, our data suggest that an immunohistochemical tissue approach by the combination of AR expression and Ki-67 status might be a useful prognostic marker in TNBC in order to subclassify the risk of these patients.

Dear editor

Thank you for having shared with us your interesting experience concerning the determination of the androgen receptor status, the inverse correlation between KI67 and androgen receptor expression, and the potential prognostic implications. Your results are in line with previous work published in this field and further highlights that additional research in this subgroup of triple negative breast cancer is definitively needed. In particular, we hope that specific treatments will allow us to do a major step forward in the treatment of a subgroup of patients presenting with triple negative breast cancer. Unfortunately, the results currently available with antiandrogen therapy, although promising, represent rather a very small step forward. Further research is also needed in order to evaluate if standard immunohistochemistry techniques can be an alternative to androgen-related gene signatures for the identification of patients presenting better outcome after antiandrogen therapy.