Cell-free plasma markers of breast cancer in young women and women at high risk

Breast cancer in younger women can have an aggressive course. In pre-menopausal women (<50 years in age), mammography has limited value due to higher breast density. Therefore, there is a need for early and accurate detection to improve patient outcomes. The aim of this thesis was to investigate specific microRNAs (miRNAs) and copy number variations (CNVs) in plasma cell free DNA (cfDNA) as circulating biomarkers in the blood of women who have developed breast cancer at a young age (<50 years) and compare results between breast cancer patients and healthy controls. Candidate miRNAs were selected from TaqMan array card data and quantitative realtime polymerase chain reaction (qPCR) was used to investigate miRNA profiles in patient samples and controls. For plasma cfDNA CNV was compared at key chromosome intervals/genes and results compared with matched normal lymphocytes (as a germline DNA control) using both qPCR and droplet digital PCR (ddPCR) techniques. Both markers were compared in a cohort of women from a family history clinic (97) including 53 women from either BRCA1 or BRCA2 family and 44 women with a family and/or personal history of breast cancer as well as 12 healthy controls. MiRNA profiling showed that five miRNAs (mir-26a, mir-27b, mir-130b, mir-324-3p, and mir-181a) might be useful in monitoring women at high-risk due to BRCA mutation, on follow-up after breast cancer surgery. Similarly CNV was identified in cfDNA in five genes (MYC, CDKN2A, CCND1, HER2, and DMXL2) in women who had had previous surgery for BRCA1/ BRCA2 breast cancer, but not in BRCA1/BRCA2 carriers or healthy controls. The circulating biomarkers (miRNAs and gene specific amplification) identified in the plasma may have use in monitoring women with breast cancer due to inherited BRCA mutation after surgery and adjuvant therapy.