The results of ABCSG 18, a placebo-controlled adjuvant study involving 3,425 post-menopausal breast cancer patients, indicate with surprising clarity that it is easy to reduce treatment-related osteoporosis and bone fractures, which are an adverse side-effect of adjuvant endocrine therapy with aromatase inhibitors, without exposing patients to any additional toxicity. If the human monoclonal antibody denosumab is administered (twice a year by injection) as an adjuvant to this standard therapy, the osteoporosis-related fracture rate drops by 50%. Bone density is also increased and the number of spinal fractures is halved.
"In addition to the unexpectedly clear primary effect of preventing fractures, our data shows that treatment-related fractures are a much greater problem than previously thought," says Michael Gnant, Study Leader, Principal of the University Department of Surgery at MedUni Vienna, Vice-Principal of the Comprehensive Cancer Center (ECC) Vienna and President of the ABCSG. "These data are the by far the most accurate of any published anywhere in the world."
Hence Austria's largest study group ABCSG, which has now been conducting studies successfully for 30 years, is once again at the forefront of global cancer research.
What is also remarkable is that denosumab treatment is equally effective in breast cancer patients with normal bone density and those women who already display osteopenia (reduced bone density). A 6 – 10% increase in bone density was observed in the typical risk areas for osteoporotic fractures – femoral neck, hip and lumbar spine. Gnant expects that these results will lead to a practice change in breast cancer treatment worldwide: "With only two injections per year we can protect our patients from this serious side-effect of cancer treatment – in my opinion, this must very quickly become standard practice throughout Austria."
The results of this ground-breaking breast cancer study were presented to the Annual Meeting of the American Society of Clinical Oncology (ASCO) (the world's major cancer congress) in Chicago on 1 June and simultaneously published in the leading European journal "The Lancet". Its practical significance was outlined today in a press conference held in Vienna.
Osteoporosis and breast cancer – an underestimated problem?
Above all, the new findings provided by this important ABCSG study show that up until now the problem of bone fractures in breast cancer patients has been underestimated. It is not only women showing initial signs of osteopenia who are affected by these fractures but also women displaying completely normal bone density at the start of endocrine cancer treatment. According to ABCSG expert Christian Singer, Vice-Principal of the Breast Health Center at MedUni Vienna (bgz Vienna) and member of the CCC: "If we assume that nearly one tenth of all women with breast cancer, who receive aromatase inhibitor treatment after the menopause, suffer from a detectable bone fracture within three years of diagnosis, that is already a frighteningly high proportion, which clearly shows the importance of the study results."
The largest Austrian breast cancer study to date investigated the adjuvant administration of 60mg of denosumab by subcutaneous injection every six months. "At this dosage it is practically free from side-effects – such a favourable efficacy/side-effect profile is rare in the field of cancer treatment," says Singer, referring to the advantages of adjuvant therapy.
Apart from the fact that it would save the health system money, the primary advantage of this treatment is that it would help to maintain quality of life for patients. There is little doubt that the significant results of this ABCSG study will lead to a relevant change in cancer treatment in Austria, which will then be implemented worldwide in the foreseeable future.
Service: The Lancet
"Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial"
Michael Gnant, Georg Pfeiler, Peter C Dubsky, Michael Hubalek, Richard Greil, Raimund Jakesz, Viktor Wette, Marija Balic, Ferdinand Haslbauer, Elisabeth Melbinger, Vesna Bjelic-Radisic, Silvia Artner-Matuschek, Florian Fitzal, Christian Marth, Paul Sevelda, Brigitte Mlineritsch, Günther G Steger, Diether Manfreda, Ruth Exner, Daniel Egle, Jonas Bergh, MD, Franz Kainberger, Susan Talbot, Douglas Warner, Christian Fesl, Christian F Singer, on behalf of the Austrian Breast and Colorectal Cancer Study Group.