Breast Cancer and Endocrine Therapy
Breast cancer is a major cause of cancer-related deaths in women. Patients with hormone receptor positive breast cancer, representing approximately 70% of all breast cancer cases, are offered endocrine treatment by blocking the oestrogen receptor (ER) with a selective ER modulator such as tamoxifen, or by targeting the oestrogen synthesis using an aromatase inhibitor. Resistance to current anti-hormonal therapies is common and occurs in 30-40% of the patients. Tamoxifen is the most widely used drug for the prevention and treatment of hormone-receptor positive breast cancer. Nevertheless, its clinical effectiveness varies among individuals. Tamoxifen is extensively metabolised by cytochrome P450 (CYP) enzymes, and recent in vivo studies have shown that women with genetically impaired CYP2D6 have reduced production of endoxifen, the main active tamoxifen metabolite. This impairment has been linked to a higher risk of breast cancer recurrence. Despite these observations, the contribution of endoxifen to the overall drug effectiveness of tamoxifen remains uncertain. We use advanced technologies and have developed new liquid chromatography tandem mass spectrometry (LCMSMS)-methods to measure tamoxifen and its metabolites, as well as aromatase inhibitors. With a translational focus, from bedside to lab and vice versa, we use clinical cohorts, including The Prospective Breast Cancer Biobank (PBCB) in Western Norway, in combination with experimental cell models, molecular biology, genomics, imaging and bioinformatics.
Our breast cancer projects are
i. Optimization of endocrine therapy based on pharmacogenomics (tailored therapy) and therapeutic drug monitoring.
ii. Molecular determinants of response to endocrine therapy in breast cancer
iii. Effects of metformin in breast cancer prevention.
iv. Endocrine and paracrine environment in breast cancer.