Metastatic breast cancer: Patterns of metastasis and novel biomarkers

Breast cancer is a heterogeneous disease and is the leading cause of cancer-related deaths among women, with metastatic disease the principle cause of mortality. In recent years great advances have been made in stratifying breast cancer into a variety of subtypes based on morphological appearance, molecular characteristics and genomic signatures, casting light on the diverse intra-tumour and inter-tumour molecular portrait of the disease. In the era of personalized cancer management, it is imperative to further our understanding of the molecular make-up and clinical behaviour of breast cancer disease so as to tailor treatment and surveillance for recurrence appropriately. In this work we demonstrate the disparate metastatic patterns and outcomes following metastasis of the two major histological subtypes of breast cancer. Furthermore, in a retrospective analysis of metastatic breast cancer patients we identified the initial molecular subtype of primary breast cancer may be different to the subtype of the metastatic disease. This can have significant implications for patient survival and treatment strategies. The development of blood-based biomarkers to expedite earlier detection of breast cancer and of recurrence has been the focus of extensive international research in recent years. Mi(cro)RNAs are small, non-coding RNAs that regulate gene expression and are implicated in a variety of key processes driving both the development of breast cancer metastatic cascade. MiRNAs are stable in circulation and can be quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR). We* identified a variety of miRNAs to potentially distinguish local breast cancer from metastatic breast cancer in the commonest type of breast cancer (Luminal A). This work allowed us to identify and validate selected miRNA on an independent cohort of 74 patients. Two miRNAs (mir-331 and mir-195) showed significantly dysregulation between metastatic disease and local disease and healthy controls. This work sheds further light on the heterogeneity of breast cancer and the diverse patterns and outcomes of metastatic disease, and highlights the potential of blood based miRNA biomarkers to contribute to the evolving management of breast cancer.

Funder

National Breast Cancer Research Institute

Publisher

NUI Galway

Rights

Attribution-NonCommercial-NoDerivs 3.0 Ireland

cbn

Collections

University of Galway Theses (PhD Theses)