Characterizing Breast Cancer in a Population with Increased Prevalence of Triple-Negative Breast Cancer: Androgen Receptor and ALDH1 Expression in Ghanaian Women.
BACKGROUND
The androgen receptor (AR) is a commonly-expressed hormone receptor in breast cancer and may be a marker of response to targeted anti-androgen therapy, a particularly attractive option for triple-negative breast cancer (TNBC). Gene expression studies suggest that ARs may distinguish a luminal/AR TNBC subtype from stem cell-like subtypes. TNBC frequency is two to three times higher in African American and African breast cancers compared with White American and European breast cancers, yet little is known regarding TNBC subtypes in high-frequency African-ancestry populations. We evaluated ARs and the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) among breast cancers from Ghana, Africa.


METHODS
Overall, 147 formalin-fixed, paraffin-embedded invasive breast cancers from the Komfo Anoyke Teaching Hospital in Ghana were studied at the University of Michigan, and analyzed immunohistochemically for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, ALDH1, and AR expression.


RESULTS
The median age of patients was 45 years. Only 31 cases (21 %) were ER-positive, and 14 (10 %) were HER2-positive; 89 (61 %) were TNBCs. 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 with ER/PR-negative tumors (87 vs. 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 was associated with AR positivity within the subset of TNBC (36 vs. 14 %; p = 0.019).


CONCLUSIONS
We confirmed other studies showing a high frequency of TNBC in Africa. Surprisingly, ALDH1 was found to correlate with AR expression among TNBC, suggesting that novel TNBC subtypes may exist among populations with African ancestry.
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Erica
E
Proctor
Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Kelley M
KM
Kidwell
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.|Department of Surgery, Komfo Anoyke Teaching Hospital, Kumasi, Ghana.|Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Evelyn
E
Jiagge
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.|Division of Surgical Oncology, University of Michigan Health Systems, Ann Arbor, MI, USA.|Breast Care Center, University of Michigan, Comprehensive Cancer Center, Ann Arbor, MI, USA.
Jessica
J
Bensenhaver
Department of Oncology, Komfo Anoyke Teaching Hospital, Kumasi, Ghana.
Baffour
B
Awuah
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Kofi
K
Gyan
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Kathy
K
Toy
Department of Surgery, Komfo Anoyke Teaching Hospital, Kumasi, Ghana.
Joseph Kwaku
JK
Oppong
Department of Surgery, Komfo Anoyke Teaching Hospital, Kumasi, Ghana.
Ishmael
I
Kyei
Department of Surgery, Komfo Anoyke Teaching Hospital, Kumasi, Ghana.
Francis
F
Aitpillah
Department of Oncology, Komfo Anoyke Teaching Hospital, Kumasi, Ghana.
Ernest
E
Osei-Bonsu
Department of Pathology, Komfo Anoyke Teaching Hospital, Kumasi, Ghana.
Ernest
E
Adjei
Department of Oncology, Komfo Anoyke Teaching Hospital, Kumasi, Ghana.
Michael
M
Ohene-Yeboah
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Robert Newman
RN
Brewer
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Linda Ahenkorah
LA
Fondjo
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.|Department of Pathology, Komfo Anoyke Teaching Hospital, Kumasi, Ghana.
Osei
O
Owusu-Afriyie
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Breast Care Center, University of Michigan, Comprehensive Cancer Center, Ann Arbor, MI, USA.
Max
M
Wicha
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Breast Care Center, University of Michigan, Comprehensive Cancer Center, Ann Arbor, MI, USA.
Sofia
S
Merajver
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.|Breast Care Center, University of Michigan, Comprehensive Cancer Center, Ann Arbor, MI, USA.
Celina
C
Kleer
Department of Surgery, University of Michigan, Ann Arbor, MI, USA. lanewman@umich.edu.|Division of Surgical Oncology, University of Michigan Health Systems, Ann Arbor, MI, USA. lanewman@umich.edu.|Breast Care Center, University of Michigan, Comprehensive Cancer Center, Ann Arbor, MI, USA. lanewman@umich.edu.
Lisa
L
Newman
D000328:Adult; D000080924:Aldehyde Dehydrogenase 1 Family; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000453:epidemiology; D018275:Carcinoma, Lobular / Q000737:chemistry* / Q000453:epidemiology; D005260:Female; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D008875:Middle Aged; D015995:Prevalence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011944:Receptors, Androgen / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D050697:Retinal Dehydrogenase / Q000032:analysis*; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry* / Q000453:epidemiology
D000080924:Aldehyde Dehydrogenase 1 Family; D007527:Isoenzymes; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D050697:Retinal Dehydrogenase; C510223:ALDH1A1 protein, human; C508053:ERBB2 protein, human