Androgen receptor and ALDH1 expression among internationally diverse patient populations
Jiagge EM, Jibri A, Bensenhaver J, Wicha M, Awuah B, Merajver S, and Newman L. Androgen receptor and ALDH1 expression among internationally diverse patient populations. Cancer Res 2018; 78(13 Suppl):1639.
Background: Population-based incidence rates of breast cancers that are negative for the estrogen receptor (ER), progesterone receptor (PR), HER2/neu triple-negative breast cancer (TNBC) are higher among African American (AA) compared to White American (WA) women, and several studies suggest that TNBC prevalence is increased among selected populations of African patients. The colonial-era transatlantic slave trade resulted in shared ancestry between contemporary AA and Gh populations. The extent to which associations between TNBC are related to East African versus West African ancestry, and whether these associations extend to expression of additional hormone receptors such as androgen receptor (AR) and stem cell markers such as ALDH1, is uncertain, but this research may explain breast cancer disparities between domestic communities within the United States as well as between international population subsets. Methods: We utilized immunohistochemistry to evaluate ER, PR, HER2/neu, AR and ALDH1 expression among White American (n=153), African American (n=76), Ethiopian (Eth)/East African (n=90), and Ghanaian (Gh)/West African (n=286) breast cancers through an IRB-approved international research program. Results: Mean age at breast cancer diagnosis was 43, 49, 60, and 57 years for the Eth, Gh, AA, and WA patients, respectively. Frequency of TNBC was significantly higher for the AA and Gh patients (41% and 54%, respectively) compared to the WA and Eth patients (23% and 15%, respectively; p<0.001). These associations were unchanged when limited to patients age 50 years and younger (47% and 49% for AA and Gh, respectively, versus 18% and 16% for WA and Eth, respectively; p<0.001). Frequency of ALDH1 positivity was also higher for the AA and Gh tumors (32% and 36%, respectively) compared to the WA and Eth tumors (23% and 17%, respectively; p=0.007). Significant differences were also observed for distribution of AR positivity, which was 71%, 55%, 42%, and 50% for the WA, AA, Gh, and Eth cases, respectively (p=0.008). Frequency of ALDH1 expression was numerically higher in the AA, Gh, and Eth TNBC cases compared to the WA TNBC cases, but this was not statistically significant (33%, 41%, and 31%, respectively, versus 18%; p=0.47). Conclusions: Extent of African ancestry appears 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.