Breast Cancer Molecular Subtype Prevalence and Commonly Mutated Genes in Triple Negative Breast Cancer in Uganda

Abstract

Breast cancer is the second commonest cancer in women in Uganda, accounting for about 21% of all cancer related mortality in women in Uganda. An estimated 35-36% of all breast cancer patients in Uganda have triple negative breast cancer. Triple negative breast cancer has a worse prognosis than other types of breast cancer. A series of biomarkers in triple negative breast cancer have been shown to have potential therapeutic targets e.g presence of the luminal androgen receptor can be targeted with anti-androgen therapy. However, the molecular profile and the mutation patterns of commonly mutated breast cancer genes have not been described in Uganda. This study, undertook molecular profiling of breast cancer in Uganda using immunohistochemistry and also undertook targeted exome sequencing of the commonly mutated genes in triple negative breast cancer to determine the molecular profile and type of mutations associated with triple negative breast cancer in Uganda. 4.2 Objectives To the molecular subtype prevalence of breast cancer in Uganda and commonly mutated genes in TNBC in Uganda. 4.3 Material and Methods This study was a cross-sectional study that studied women seeking care diagnostic services for breast cancer at the Uganda Cancer Institute from January to December 2020. A total of 252 formalin fixed tissue biopsies were histologically analyzed to confirm a diagnosis of breast cancer. Immunohistochemistry was performed to determine the molecular subtype. A total of 45 cases of TNBC were identified and subjected to targeted exome sequencing. Sequencing was undertaken on 12 genes (BRCA1/2, PIK3CA, TP53, RB1, MYC, RUNX1, GATA3, AKT1, MAP3K1, CDH1, NF1 and CDKN1) using tools from Galaxy suite. Sequences were aligned to the human reference genome GRCh38 to determine presence of mutations if any. 4.4 Results In this study, 30.2% of the women had luminal A breast cancer, 31.0% Luminal B, 12.7% HER2-enriched breast cancer and the percentage of TNBC was 26.2%. Mutations were identified in BRCA1/2, PIK3CA, TP53, RB1, MYC, RUNX1, GATA3, AKT1, MAP3K1, CDH1, NF1 and CDKN1. The most commonly mutated gene was the BRCA2 gene which was mutated in 24.4% of the samples. The most frequent type of mutation was the synonymous single nucleotide variant in 48% of the samples.

4.5 Conclusions Over one quarter of breast cancer patients attending breast cancer care at the UCI have TNBC and about 11 different genes are found mutated in the samples sequenced. Majority of the patients attending care had either Luminal A or Luminal B cancer.

4.6 Recommendations

A broader understanding of the mutational profile of breast cancer in Uganda is required to provide a better understanding of the biology of cancer in Uganda to enable development of new diagnostics and new therapeutics. This information could help in improving adoption and utilization of existing therapies.