HER2 targeted therapy
During 2009, clinicians and scientists at The Royal Marsden led international research into improved treatments for women with a particular subtype of breast cancer that expresses the protein ‘human epidermal growth factor receptor 2’ (HER2).
Professor Stephen Johnston from The Royal Marsden led the trial which showed that the combination of a conventional hormone treatment (letrozole) with the HER2 inhibitor lapatinib significantly improved the outcome for patients with metastatic breast cancer that co-expressed both hormone receptors and HER2.
This concept arose from laboratory studies in The Institute of Cancer Research that demonstrated how lapatinib and letrozole could work together in models of endocrine-resistant breast cancer. This illustrates again how our laboratory research can influence clinical practice.
The results of the clinical trial were published in the Journal of Clinical Oncology, and in early 2010 led to approval of this drug combination as a new standard of care in both the US and Europe.
Translational research
HER2 is involved in the signalling pathways leading to abnormal cancer cell growth, and results in breast cancer that is more aggressive and resistant to conventional hormone- and chemotherapy-based treatments.
Working out the molecular biomarker profile (bar code) represents important translational research that can further refine which patients with HER2+ breast cancer can benefit from a given type of HER2 targeted therapy. The Royal Marsden’s Breast Unit has led the field internationally in aspects of this work.
In 2009 Professor Stephen Johnston reported that the oral HER2 targeted drug lapatinib could be used to treat patients with HER2+ inflammatory breast cancer (IBC) when the antibody therapy Herceptin had stopped working, and that specific biomarker profiles within the tumour could predict those patients who would derive an overall survival benefit from the drug.
In a separate study, Professor Mitch Dowsett led the translational study which investigated HER2 gene amplification in over 2,000 tumours from the international adjuvant Herceptin trial (HERA), again establishing who derives the most benefit.
This ground-breaking type of translational research can help understand how best to use these new therapies in the clinic, both maximising benefit for patients and utilising expensive new therapies most effectively.