Genetics and Oncology (part 2.). Fundamentals of personalised medicine in the treatment of breast and ovarian cancer

Individualisation of medical management based on prognostic and predictive markers (personalised medicine) allows customisation of prophylaxis and optimisation of treatment by increasing its efficiency and minimisation of adverse effects. In the case of breast cancer, therapy selection is still based on histopathology and immunohistochemical assessment including analysis of estrogen receptor (ER) expression, progesterone receptor (PgR) expression and over-expression or amplification of receptor tyrosine kinase erbB-2 gene ( ERBB2 aka HER2 ). An additional role, facilitating decision on appli­cation or waiver of chemotherapy in early breast cancer, may be played by panels assessing gene expression within tDNA (tumour DNA, i.e. DNA isolated from tumour cells) and evaluation of concentration of uPA (urokinase-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) in tumour cells. Growing hope surrounds the new, targeted therapies, including: inhibitors of CDK 4/6 (cyclin-dependant kinases 4 and 6), mTOR inhibitors (rapamycin’s mammalian target), inhibitors of poly(ADP-ribose)polymerase(PARP) or inhibitors of PI3K (phosphatidylinositol-4,5-bisphosphate 3-ki­nases). For ovarian cancer, treatment selection is based on assessment of the histopathologic type, malignancy degree, FIGO classification and platinum sensitivity of the tumour. However, the increasing use of PARP inhibitors and angiogenesis inhibitors is noteworthy. In the context of personalised medicine for both these cancers, an important element involves also individualisation of prophylactic and therapeutic recommendations in carriers of germline mutations associated with hereditary cancer syndromes.