Characterizing Breast Cancer in a Population with Increased Prevalence of Triple-Negative Breast Cancer: Androgen Receptor and ALDH1 Expression in Ghanaian Women

Abstract

Introduction Androgen Receptor (AR) is the most commonly-expressed nuclear hormone receptor in breast cancer and may be a marker of response to targeted anti-androgen therapy, a particularly attractive option in the setting of triple negative breast cancer (TNBC). Gene expression studies suggest that AR-positivity may distinguish a luminal/AR TNBC subtype from mesenchymal, stem cell-like, and basal-like subtypes. Furthermore, frequency of TNBC is 2–3-times higher in African American and African compared to White American and European breast cancer pts, yet little is known regarding the distribution of TNBC subtypes in the high-risk African-ancestry populations. We sought to characterize AR expression and TNBC patterns among a series of breast cancers from Ghana, Africa. Methods Formalin-fixed, paraffin-embedded invasive breast cancer specimens from 147 pts treated at a single teaching hospital in Ghana were studied at a comprehensive cancer center in the United States and analyzed for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, ALDH1 and AR expression via immunohistochemistry. Results Median patient age was 45 (range, 28–76yrs). Only 31 cases (21%) were ER-positive, and 14 (10%) were HER2-positive; 89 tumors (61%) were TNBC. For the entire group, 44% were AR-positive and 45% were ALDH1-positive. ER/PR-positive tumors were more likely to be AR-positive compared to ER/PR-negative tumors (87% versus 26%; p<0.0001) but there was no association between ALDH1 and AR expression. Among the TNBC cases, 45% were ALDH1-positive and 24% were AR-positive. ALDH1-positivity versus negativity was associated with AR-positivity within the subset of TNBC tumors (36% versus 14%; p=0.019). Conclusions We confirmed the results of others showing that the majority of African breast cancers are triple-negative. We also found that AR expression is lower than that reported in other populations. Surprisingly, a marker of mammary stem cell expression was found to correlate with AR expression among triple negative tumors in this series, suggesting that novel TNBC subtypes may be identified by studying TNBC patterns among more diverse international populations.

Are There Differences in Androgen Receptor Expression in Invasive Breast Cancer in African (Tanzanian) Population in Comparison With the Caucasian (Italian) Population?

“…Another study evaluated AR expression in Ghanaian BC patients. They found a lower percentage (24%) of AR-positive tumors (defined by ≥10% cutoff) among TN BCs ( 16 ).…”

Current advances in biomarkers for targeted therapy in triple-negative breast cancer

“…Another study examined 147 invasive breast tumors from African patients from Ghana and found an association between the prevalence of ALDH1 expression in TNBC and androgen receptor (AR) expression. 106 AR expressing TNBC cell lines are more sensitive to AR antagonists leading to trials exploring the role of AR antagonists in TNBC. ALDH1 is thus a potential predictive biomarker for AR-targeted therapy in TNBC 107 as well as a likely prognostic marker.…”

Increased sensitivity of African American triple negative breast cancer cells to nitric oxide-induced mitochondria-mediated apoptosis

“…Heterogeneity exists within MCSCs populations, which have high aldehyde dehydrogenase 1 (ALDH1) activity and increased expression of CD44, a cell surface marker [ 39 ]. There are reports of high expression of ALDH1 in breast tumors in women from African origin [ 40 , 41 ]. We found high ALDH1 expression in all the 3 AA TN breast cancer cells examined and NO treatment significantly reduced the expression of ALDH1 in these cells (Fig.…”