P3-04-01: Molecular Characterization of African Breast Cancer; Results from a Large Tissue Microarray Study.
Authors: Shaaban A , Hatfield A , Omoniyi Esan GO , Komolafe AO , Daramola A , Pathak D , D'Cruz N , Alizadeh Y , Lewis P , Titloye NA 
Published: June 2012

Introduction: Breast cancer in African women has been understudied for decades. Evidence derived mainly from studies on African-American women, supports that tumours of black women are biologically different and more aggressive than those occurring in the white population. Of the 4 main taxonomic groups of breast cancer, basal tumours are more represented in those women. In the present state of knowledge, very little is known about the biology and molecular profile of breast cancer in Africa. The aim of this study was to test the hypothesis that the molecular profile of African breast cancer is distinct from its Western counterpart. This was achieved by collecting a large cohort of breast carcinomas from an indigenous African population for phenotypical characterization and testing for expression of potential predictive and prognostic markers.

Methods: Breast tumours were collected via collaboration with five centres in Nigeria (the most populous country in Africa) and assembled into tissue microarrays (TMAs). All tumours were reviewed by a specialist breast pathologist following the Royal College of Pathologists (RCPath) guidelines to confirm diagnosis, type, grade and nodal status. Patients age, tumour size and clinical data, where available, were collected from the original pathology reports and case notes. Representative tumour areas were selected and marked for TMA construction. TMA sections were stained for a range of markers including hormone receptors (ERα, ERβ, PR, AR), cyclin D, HER2, Ki67, bcl2, basal (CK5/6, CK14) and luminal cytokeratins (CK18, 19).

Results: A total of 830 tumours were assembled into TMAs. The mean age at diagnosis was 47.69yrs with 58% of patients presenting under the age of 50. Only 8.5% of tumours were of grade 1. Most tumours (87%) were of ductal no special type, followed by lobular and metaplastic carcinomas. The majority of the tumours were ERα, PR and HER2 negative (77%, 80% and 81% respectively). The triple negative tumours were the predominant phenotype (55.6%). Luminal A type tumours comprised 24.3% followed by the HER2 positive (13.9%) and luminal B tumours (6.2%). The differences of all those parameters were statistically highly significant (p&lt;0.001). Most tumours expressed ERß including 75% of those that were ERα/PR negative. A large proportion of the tumours (22%) were of the basal phenotype of which two thirds were also triple negative. Over half of the triple negative tumours were also node positive.

Hierarchal cluster analysis showed the basal tumours dendrogram to comprise two groups; one showing clustering of ***ERα/PR/HER2 and the second showing clustering of ERß with CK5 and CK14.

Conclusion: To our knowledge, this is largest and most comprehensive study of African breast cancer to date. Our data confirms the hypothesis that African breast cancer is biologically distinct and shows remarkable differences in histological type, grade, hormone receptors & HER2 status when compared with breast cancer in white women. The early age at presentation, predominance of high grade and triple negative, but not necessarily basal phenotype, may explain the poor prognosis and requires tailoring treatment strategies to target this unique profile.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-04-01.