Abstract A14: Copy number profiling in South African breast cancer patients
Authors: Lupicki Kamil , Elifio-Esposito Selene , Fonseca Aline S. , Mahajan Akanksha , Pereira Silma R. , Langa B , Govender Dhirendra , Panieri Eugenio , Hiss Donavon , Abdul-Rasool S , Cavalli Luciane R. 
Published: December 2017

Introduction: Breast cancer is the most common cancer among South African women, where as in many other Sub-Saharan countries, is the leading cause of female death. Although several risk factors can be attributed to their observed high mortality rate, the biology of their tumors are not extensively investigated; consequently the molecular profiles associated with their disease is poorly characterized.

Main goal: In this study our main goal was to characterize the wide-genomic copy number profile of a group of patients with breast cancer diagnosed at the Groote Schuur Hospital, Cape Town, South Africa and associate with their corresponding clinical-pathological data.

Material and Methods: Twenty-eight specimens of formalin fixed paraffin embedded (FFPE) material from twenty-eight patients with invasive breast cancer were acquired prior to any treatment and with complete clinical annotation from the archives of the Division of Anatomical Pathology, National Health Laboratory Service-Groote Schuur Hospital. The mean age and tumor size of the patients at diagnosis was 48.2±12.9 years and 38.2±14.0 mm, respectively. Most of the tumors were of grade 2 and 3 (39.2% and 37.7%, respectively) and stage III (67.8%). ER and ERBB2 positivity was observed in 57.1% and 53.8% of the patients, respectively. PR status was available for only 21.4% of the patients, out of which 33% (2/6) were positive. Three patients were negative for ER, PR and ERBB2 receptors. Race information was self-reported; 61.4% of the patients were from the Colored group, followed by 19.2% from the White and Black group, which are the three most predominant ethnic groups in South Africa. Array-CGH analysis was performed in microdissected tumor areas using the Agilent 8x60K oligo nucleotide array platform.

Results: The average number of copy number alterations (CNAs) observed in these patients was 8.3±1.2 which was significantly associated with patients' tumor grade (P&lt;0.01). The most frequent cytobands affected were Xp22.33-p21.1 (86.7% of the cases), 6p25.3-p21 (83.3%), 19p13.3-p13.11 (56.7%), 21p11.2-p11.1 (50%) and 16p13.3-p11.2 (43.3%), that except for the 21p region, were observed gained and/or amplified. From these commonly affected cytobands, gains on 6p was significantly associated with tumor grade (P&lt;0.05). No significant association was observed among the average number of CNAs and/or the most frequent cytobands with other clinical-histopathological parameters and/or ethnic groups.

Conclusions: Our results indicated that CNAs occur in South African breast cancer patients, in association with advanced tumor grades, but irrespectively of their ethnic descendance and other factors at diagnosis that are known to influence prognosis. Additional molecular studies, such as ours, that aim to determine the biologic contributions to breast-cancer risk in women in South Africa and other African countries are imperative. The understanding of the genetic determinants that are associated with the etiology of their tumors is a direction towards the reduction of their observed high mortality rates.

Citation Format: Kamil Lupicki, Selene Elifio-Esposito, Aline S. Fonseca, Akanksha Mahajan, Silma R. Pereira, B Langa, Dhirendra Govender, Eugenio Panieri, Donavon Hiss, S Abdul-Rasool, Luciane R. Cavalli. Copy number profiling in South African breast cancer patients [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A14.