Chapter 1 - Definition: Translational and Personalised Medicine, Biomarkers, Pharmacodynamics
Prognostic biomarkers: Treated (A) and untreated patients (placebo or best supportive care) (B). Patients expressing (C) and not expressing (D) the biomarker of interest.
A prognostic marker is measured before treatment and identifies tumour-specific molecular or histopathological characteristics including somatic or germline mutations, changes in DNA methylation, micro-RNA levels, or circulating tumour cells in blood that are associated with long-term outcome or course of a disease. As shown in the figure on the right, for a prognostic biomarker, the probability of survival is related to whether or not the biomarker is expressed. In patients who express the biomarker of interest, survival is similar between treated and untreated patients.
Prognostic biomarkers allow for the selection of patients who need more intensive surveillance or adjuvant therapy. In acute myeloid leukaemia (AML), cytogenetic abnormalities serve as prognostic biomarkers for risk categorisation. Inversions in chromosome 16 as well as translocations between chromosomes 8 and 21 and chromosomes 15 and 17 are associated with a favourable prognosis, while deletions in chromosomes 5 and 7 are associated with an unfavourable prognosis. In multiple myeloma, levels of beta-2 microglobulin and albumin are used as prognostic markers to stage myeloma and to classify patients into favourable, intermediate, or unfavourable overall survival prognoses prior to initiating systemic therapy. In breast cancer, commonly used prognostic markers include tumour size, nodal status, grade, and presence or absence of lymphovascular invasion.
