Androgen Receptor and ALDH1 Expression Among Internationally Diverse Patient Populations

Abstract

PurposePopulation-based incidence rates of breast cancers that are negative for estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2/neu (triple-negative breast cancer [TNBC]) are higher among African American (AA) compared with white American (WA) women, and TNBC prevalence is elevated among selected populations of African patients. The extent to which TNBC risk is related to East African versus West African ancestry, and whether these associations extend to expression of other biomarkers, is uncertain.MethodsWe used immunohistochemistry to evaluate estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2/neu, androgen receptor and aldehyde dehydrogenase 1 (ALDH1) expression among WA (n = 153), AA (n = 76), Ethiopian (Eth)/East African (n = 90), and Ghanaian (Gh)/West African (n = 286) patients with breast cancer through an institutional review board–approved international research program.ResultsMean age at diagnosis was 43, 49, 60, and 57 years for the Eth, Gh, AA, and WA patients, respectively. TNBC frequency was higher for AA and Gh patients (41% and 54%, respectively) compared with WA and Eth patients (23% and 15%, respectively; P < .001) Frequency of ALDH1 positivity was higher for AA and Gh patients (32% and 36%, respectively) compared with WA and Eth patients (23% and 17%, respectively; P = .007). Significant differences were observed for distribution of androgen receptor positivity: 71%, 55%, 42%, and 50% for the WA, AA, Gh, and Eth patients, respectively (P = .008).ConclusionExtent of African ancestry seems to be associated with particular breast cancer phenotypes. West African ancestry correlates with increased risk of TNBC and breast cancers that are positive for ALDH1.

Receptor-Defined Breast Cancer in Five East African Countries and Its Implications for Treatment: Systematic Review and Meta-Analysis

“…Our PubMed search identified 319 publications after eliminating duplicates (Fig 1 ). After all exclusions, we had 21 eligible articles with the following distribution: Ethiopia = 4, 21 , 22 , 31 , 32 Kenya = 8, 23 , 33 - 39 Rwanda = 1, 9 Tanzania = 4, 40 - 43 and Uganda = 4. 44 - 47 Although 36 articles had receptor data, 13 articles were excluded because of identical or overlapping samples 48 - 60 and two did not meet study criteria.…”

“… 27 Yet, one study found a higher proportion of ER+ BC among Ethiopian women compared with African American and Ghanaian women despite their younger mean age (42.7 years compared with 60.2 and 49.3 for African Americans and Ghanaians, respectively). 31 …”

Lack of Androgen Receptor Expression Selects for Basal-Like Phenotype and Is a Predictor of Poor Clinical Outcome in Non-Metastatic Triple Negative Breast Cancer

“…Only two previous studies have examined the expression of AR and ALDH1 in TNBCs. However, they did not report the relevance of AR and ALDH1 with clinical outcome (34,35). This may be due to challenges associated with collection of long-term clinical follow-up data from developing countries.…”

Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells

“…Limited therapeutic options are available for TNBC patients and consequently can result in aggressive metastatic disease, with greater mortality rates in African American (AA) women, relative to Caucasian-American (33,34). This health disparity may arise due to diagnosis at later stages of the disease (35) or a predisposed racially distinct genetic or epigenetic profile (36,37) with a propensity toward an overactive oncogenic p38 MAPK, Wnt/β-catenin, IGF2/ERbeta signaling axis (38)(39)(40). Additional factors to a health disparity arising in AA women regarding TNBC include vitamin D deficiencies (41) socioeconomic factors, later stage diagnosis, obesity, or even breast feeding patterns (42)(43)(44).…”