Throughout the world there are now two studies on the subject of “Bone health and cancer” – one of which was recently completed by the Austrian study group ABCSG (which has now been conducting studies successfully for 30 years), after running for more than 10 years with sensational findings that are likely to bring about a practice-change in the treatment of breast cancer. A total of 3,425 patients suffering from hormone receptor positive breast cancer took part in this breast cancer study, which is the largest ever conducted in Austria, being recruited between December 2006 and July 2013. Currently the standard treatment for postmenopausal women suffering from hormone receptor positive breast cancer is aromatase inhibitors. However, these have a negative impact on bone density and thus significantly increase the risk of osteoporosis. In turn this is associated with bone fractures and considerably impaired quality of life.
The placebo-controlled, double-blind adjuvant study ABCSG 18 has now shown that this treatment-related long-term effect can be reduced by 50%, if the human monoclonal antibody denosumab is administered in addition to endocrine therapy (92 fractures as against 176 in the placebo arm, Hazard Ratio = 0.50). Without adding any toxicity, the subcutaneous administration of 60 mg of denosumab twice a year halves the number of clinical fractures, increases bone density in the spine by 10%, in the hip by around 8% and in the femoral neck by 6%. “At the very least, our data must affect day-to-day practice, because now, with just two injections a year and without any additional burden, we are able to spare our patients a serious long-term effect of cancer treatment,” says Michael Gnant, ABCSG Chairman, Director of the University Department of Surgery at MedUni Vienna, Vice Principal of the Comprehensive Cancer Center (CCC) Vienna and head of the ABCSG 18 study, to sum up the significance of the study results.
This long-awaited data will be presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO, 29.5.-2.6.) in Chicago, which thousands of cancer experts are expected to attend. “It is a groundbreaking finding and even we were surprised by how unequivocal it was,” says Gnant speaking about the data. “The world of oncology is once again looking to Austria with anticipation.”
ABCSG 18: Austria worked to the bone
Nearly all Austrian cancer centers and a few Swedish centers have been involved in this project, in addition to numerous resident radiologists, who performed regular bone density measurements on the study participants. A total of 65 centers with several hundred doctors were involved in the study, in order to eliminate the dreaded side-effect of cancer treatment, namely osteoporosis. ABCSG 18 was funded by the international pharmaceutical company Amgen.
Studies show that 16% of all postmenopausal breast cancer patients develop osteoporosis and display a significant reduction in bone density five years after treatment with aromatase inhibitors. The incidence of fractures is much higher in these women and these fractures heal poorly so that, apart from health-economics considerations, they severely restrict the patients’ quality of life. ABCSG 18 clearly proves that the adjuvant administration of denosumab improves bone health in postmenopausal breast cancer patients and halves the risk of fractures.
Healthy bones and cancer – no longer a contradiction
The IgG2 anti-RANKL antibody denosumab has a similar effect to bisphosphonate, which is used to treat osteoporosis. ABCSG 18 investigated whether the beneficial effect on bone density also occurs if no changes have yet taken place, i.e. can it also be given to healthy patients to reduce the risk of treatment-related osteoporosis. Postmenopausal patients with hormone receptor positive breast cancer were 1:1 randomized in the study. The primary endpoint was the time period from randomization to the first clinical fracture (with the exception of fractures of the skull, face, fingers and toes, since these are rarely associated with osteoporosis). The secondary endpoints included changes in bone density and spinal fractures.
In bone metabolism, denosumab imitates the effects of osteoprotegerin, a protein for increasing bone density and a capturing receptor for RANKL (Receptor Activator of Nuclear Factor-kappaB Ligand). This protein converts pre-osteoclasts, that is to say precursor cells, into osteoclasts, thereby increasing the activity of these cells that are responsible for the breakdown of bone, which leads to osteoporosis.
Comprehensive Cancer Center Vienna
The Comprehensive Cancer Centre (CCC) Vienna belonging to MedUni Vienna and Vienna General Hospital provides a network for all professionals from these two institutions who treat cancer patients, conduct cancer research and are active in teaching and education in this field. Christoph Zielinski, Chairman of the University Department of Internal Medicine I and Principal of the Department of Oncology, also heads up the CCC. (www.ccc.ac.at)