Promising breast cancer prevention drug 'weakens bones'
The drug exemestane, which is used to treat breast cancer and is also in trials to prevent the disease developing in postmenopausal women, significantly worsens age-related bone loss, according to a study from Canada.
The findings, published in The Lancet Oncology, suggest that the cancer-protective effects of the drug need to be weighed against the risk of bone fracture, and that any women prescribed the drug to prevent breast cancer in the future will need to be carefully monitored for bone effects.
Exemestane - also called Aromasin - is a type of hormonal therapy called an aromatase inhibitor and is used to treat oestrogen-receptor-positive breast cancer in women who have been through the menopause.
The drug works by blocking the production of oestrogen, which fuels the growth this type of cancer.
Clinical trials are being carried out to assess whether exemestane is also effective at preventing breast cancer in postmenopausal women at high risk of developing the disease.
Concerns have been raised about the effects of aromatase inhibitors on bone loss and increased fracture risk, but previous studies were conducted against a comparison with tamoxifen, a treatment with known beneficial effects on bone in postmenopausal women.
Preliminary research suggested that exemestane might cause less bone loss than other aromatase inhibitors and could even stimulate bone formation.
In this latest work, Dr Angela Cheung and colleagues from the University Health Network, Toronto, studied women from the MAP.3 trial in order to measure the effect of exemestane on bone-mineral density (BMD) and structure in postmenopausal women.
The trial is looking at the effect of exemestane at preventing breast cancer in more than 4,500 healthy postmenopausal women with a family history of breast cancer.
Study results published last year showed that exemestane reduced the risk of developing breast cancer by 65 per cent compared with placebo.
In the latest analysis, 351 women without osteoporosis were included, 176 given exemestane and 175 given placebo.
After two years of treatment, women given exemestane had a significant loss of BMD at the distal tibia and distal radius, common sites for fractures related to osteoporosis.
Cortical thickness (the tissue that usually makes up the outer shell of bone) and area had also declined by almost eight per cent compared with a one per cent decline in the placebo group over the two-year period.
The study found that exemestane substantially affected the loss of cortical bone compared with trabecular - spongy - bone. This finding is important because 80 per cent of fractures in old age are caused by greater loss of cortical (rather than trabecular) bone and account for most disability.
Dr Cheung, said: "Exemestane worsens age-related decreases in bone mineral density by about three times, even in the setting of adequate calcium and vitamin D intake."
In conclusion, the authors said: "Women considering exemestane for the primary prevention of breast cancer should weigh their individual risks and benefits. For women taking exemestane, regular bone monitoring plus adequate calcium and vitamin D supplementation are important."
They added: "Long-term studies are needed to assess the effect of our findings on fracture risk."
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: "Exemestane is not routinely used as a breast cancer prevention drug, as we don't have enough information about its risks and benefits, but it is being tested in clinical trials.
"For women already given these types of hormone drugs to prevent their breast cancer coming back doctors already look out for the bone-weakening effects, and if suitable, prescribe drugs to strengthen the bones. This new study shows that monitoring of women treated with exemestane and other similar drugs is really important.
"Cancer Research UK is supporting a breast cancer prevention trial - IBIS-II - with another aromatase inhibitor called anastrozole. Results from this study, and the longer-term follow up of exemestane, will be important to measure the protective effects and side effects of the aromatase inhibitors."
Professor Jack Cuzick, a Cancer Research UK epidemiologist based at Queen Mary, University of London, said: "In IBIS -II we measure bone density before starting trial medication and if it is low we recommend use of bisphosphonates at the same time. Our initial studies have shown that this will actually increase bone density even when given with an aromatase inhibitor."
Copyright Press Association 2012
- Cheung, A. et al. (2012). Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomised controlled trial. Lancet Oncology DOI: 10.1016/S1470-2045(11)70389-8