Abstract
The Androgen Receptor (AR) has recently garnered a lot of attention as a potential biomarker and therapeutic target in hormone-dependent cancers, including breast cancer. However, several inconsistencies exist within the literature as to which subtypes of breast cancer express AR or whether it can be used to define its own unique subtype. Here, we analyze 1246 invasive breast cancer samples from the Cancer Genome Atlas and show that human breast cancers that have been subtyped based on their HER2, ESR1, or PGR expression contain four clusters of genes that are differentially expressed across all subtypes. We demonstrate that Sox10 is highly expressed in approximately one-third of all HER2/ESR1/PGR-low tumors and is a candidate biomarker of the triple-negative subtype. Although AR expression is acquired in many breast cancer cases, its expression could not define a unique subtype. Despite several reports stating that AR expression is acquired in HER2/ESR1/PGR triple-negative cancers, here we show that a low percentage of these cancers express AR (~20%). In contrast, AR is highly expressed in HER2-positive or ESR1/PGR-positive cancers (> 95%). Although AR expression cannot be used as an independent subtype biomarker, our analysis shows that routine evaluation of AR expression in tumors which express HER2, ESR1 and/or PGR may identify a unique subset of tumors which would benefit from anti-androgen based therapies.
Highlights
Breast cancer is the most common cancer in women, accounting for approximately 25% of all reported carcinomas worldwide [1]
Androgen Receptor (AR) expression cannot be used as an independent subtype biomarker, our analysis shows that routine evaluation of AR expression in tumors which express Human Epidermal Growth Factor Receptor-2 (HER2), Estrogen Receptor 1 (ESR1) and/or Progesterone Receptor (PGR) may identify a unique subset of tumors which would benefit from anti-androgen based therapies
To provide further evidence for the lack of AR expression in the triple-negative breast cancers (TNBC) subtype, we utilized our hierarchical clustering of patient samples based on HER2, ESR1, PGR and SOX10 and assessed the expression of AR across each patient (Figure 7)
Summary
Breast cancer is the most common cancer in women, accounting for approximately 25% of all reported carcinomas worldwide [1]. ESR1 and PGR-positive breast cancers make up the Luminal A (Ki-67-negative) and Luminal B (Ki-67positive) subtypes [2,3,4,5]. The Luminal A and B subtypes are the most common, accounting for approximately 65% of all breast cancer cases [4]. The HER2-positive subtype is characterized by overexpression and amplification of HER2 with a prevalence of approximately 25% and a poor prognosis due to its association with highly metastatic breast cancers [4, 7,8,9]. The monoclonal antibody, Trastuzumab (Herceptin), in combination with chemotherapy is currently the best form of treatment for HER2-positive breast cancers [10]
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