GlaxoSmithKline has announced for the first time final results from a prospective study that demonstrated that lapatinib decreases tumourigenic stem cells in primary breast cancers of women receiving neoadjuvant treatment. These data were highlighted in an oral presentation at the 6th European Breast Cancer Conference (EBCC-6).
Despite advances in the detection and treatment of metastatic breast cancer, mortality remains high due, in part, to the emergence of therapy-resistant cancer cells. Recent research has identified a specific subset of tumour cells with the unique capacity to proliferate and form new tumours, referred to as tumourigenic stem cells. Therefore, the possibility arises of using anti-stem cell therapy to prevent breast cancer occurring, as opposed to merely treating the symptoms of the disease.
"The results from this study are exciting," said Jenny Chang, MD, medical director, Breast Care Centre, Associate Professor of Medicine, Baylor College of Medicine, Houston, Texas and lead investigator on this study. "Over time, resistance to chemotherapy builds and this is highly problematic in clinical practice. The genes that trigger molecular pathways involved in chemoresistance, tumour formation and malignant cell self-renewal are all linked to this specific group of tumorigenic breast cancer cells. New therapies that decrease or inhibit the action of these stem cells are vitally important - if these precursors to tumour formation are not targeted, in essence any subsequent treatments are of limited value".
45 patients with locally advanced ErbB2 over-expressing breast cancer, received lapatinib before surgery, initially as a single agent for the first six weeks, followed by a combination of lapatinib plus weekly trastuzumab and three-weekly docetaxel for 12 weeks. Biopsies were taken at time of diagnosis and after six weeks of lapatinib, and assessed for tumourigenic cells.
Results showed significant tumour regression in primary tumours after only six weeks of single agent lapatinib. Unlike treatment with chemotherapy, lapatinib decreased tumorigenic breast cancer stem cells from 10.6 per cent to 4.7 per cent. The pathologic complete response rate following combination treatment (lapatinib plus trastuzumab and docetaxel) was 63 per cent.
"These data have gone some way towards answering a number of questions in current breast cancer knowledge," said Dr Steven Stein, vice president, oncology medicine development centre, GlaxoSmithKline. "For example, stem cell research may bring us closer towards understanding why, in some women, breast cancer can return after lying dormant for many years following full remission. We are encouraged by the data from this study and are committed to further investigations".
Lapatinib is the first oral, small molecule dual targeted therapy that works by getting inside the cancer cell to inhibit both ErbB1 (EGFR) and ErbB2 (HER2), two receptor proteins which are responsible for tumour growth. This novel mechanism of action is a new way to treat breast cancer.