Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes

Abstract

HER2+ breast cancer (BC) is an aggressive subtype representing a genetically and biologically heterogeneous group of tumors resulting in variable prognosis and treatment response to HER2-targeted therapies according to estrogen (ER) and progesterone receptor (PR) expression. The relationship with androgen receptors (AR), a member of the steroid hormone’s family, is unwell known in BC. The present study aims to evaluate the prognostic impact of AR expression in HER2+ BC subtypes. A total of 695 BCs were selected and reviewed, AR, ER, PR and HER2 expression in tumor cells were examined by immunohistochemical method, and the SISH method was used in case of HER2 with equivocal immunohistochemical score (2+). A high prevalence of AR expression (91.5%) in BC HER+ was observed, with minimal differences between luminal and non-luminal tumor. According to steroid receptor expression, tumors were classified in four subgroups, including BC luminal and non-luminal HER2+ expressing or not AR. The luminal BC HER2 + AR+ was associated with lower histological grade, lower tumor size, higher PR expression and lower HER2 intensity of expression (2+). Also, the non-luminal tumors AR+ showed lower tumor size and lower prognostic stage but frequently higher grade and higher HER2 intensity of expression (3+). These findings should suggest a different progression of luminal and non-luminal tumors, both expressing AR, and allow us to speculate that the molecular mechanisms of AR, involved in the biology of BC HER2 + AR+, differ in relation to ER and PR expression. Moreover, AR expression may be a useful predictor of prognosis for overall survival (OS) in HER2+ BC subtypes. Our findings suggest that AR expression evaluation in clinical practice could be utilized in clinical oncology to establish different aggressiveness in BC HER2+ subtypes.

Deciphering clinical significance of BCL11A isoforms and protein expression roles in triple-negative breast cancer subtype

“…AR Clone SP107 (Cell-MarqueTM, Rocklin, CA, USA) was used to determine AR expression. IHC and SISH analysis were performed as previously described (Orrù et al 2022 ). BCL11A clone 14B 5 (dilution 1:100, ab19487, AbCam, Cambridge, USA) was used to determine BCL11A expression.…”

Treatments Targeting the Androgen Receptor and Its Splice Variants in Breast Cancer

“…Although AR expression was not significantly associated with DFS (HR 1.20; 95% CI, 0.86-1.69, p = 0.28), OS (HR 1.50; 95% CI, 1.01-2.22 p = 0.04) was worse in the HER2-positive subgroup according to the analyses performed by Bozovic-Spasojevic et al [52]. Therefore, AR expression may be useful for the prognosis of OS for patients with ER-negative and HER2-positive breast cancer [76]. Moreover, the inhibition of AR by antiandrogens such as enzalutamide or by shRNA reduced the cell growth of HER2-positive breast cancer cell lines [77].…”

Surgical Interest of an Accurate Real-World Prediction of Primary Systemic Therapy Response in HER2 Breast Cancers

“…In addition to these predictors usually available in daily clinical practice, there are many others that are still in the research phase: HER2DX, a supervised learning algorithm incorporating tumor size, nodal staging, and four gene expression signatures tracking immune infiltration, tumor cell proliferation, luminal differentiation, the expression of the HER2 amplicon, into a single score [32], the value of tumor-infiltrating lymphocytes (TILs) [35], the oncogene bcl-2 [36], HER2/CEN17 ratio [37], androgen receptor [38], and even Machine Learning with MRI Radiomics [39].…”