Do Bisphosphonates Protect Against Breast Cancer?
San Antonio, TX – The use of oral bisphosphonates may protect against the development of invasive breast cancer, according to a new analysis of data on over 150,000 women in the Women’s Health Initiative (WHI). In an age-adjusted analysis, women who reported using oral bisphosphonates at the start of the study were 29% less likely to develop invasive breast cancer over 7.8 years of follow-up, compared with the women who said they did not take the drugs (P <.0001). More than 90% of the women were taking alendronate (Fosamax). Rowan Chlebowski, MD, PhD, medical oncologist, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, reported the results at the 32nd Annual San Antonio Breast Cancer Symposium.
The new research builds on a study published in The New England Journal of Medicine earlier this year showing that the addition of zoledronic acid (Zometa) to adjuvant endocrine therapy improves disease-free survival rates in premenopausal patients with estrogen-responsive early breast cancer (Gnant H, et al, N Engl J Med, 2009;360:679-91). Preclinical and animal research has suggested that bisphosphonates may help fight cancer in a variety of ways: inducing apoptosis, reducing angiogenesis, or stimulating memory T cells, Dr Chlebowski said. This provided rationale for the study.
Using Women's Health Initiative data, Dr Chlebowski and colleagues compared breast cancer rates in 2816 women who reported using oral bisphosphonates at the start of the study with rates for 151,952 women who reported they did not take the drugs. In the unadjusted analysis, there were 4.38 cases of invasive breast cancer per 1000 women not taking the drugs over the course of a year, compared with 3.29 cancers per 1000 women taking the drugs.
To adjust for the effect of potential bone mineral density differences among bisphosphonate users and non-users on the rate of cancer occurrence, the researchers used patients’ hip fracture scores. The hip fracture score is a published, validated algorithm developed in the WHI cohort that takes into account 11 clinical factors evident in all WHI participants and calculates a 5-year probability of hip fracture. “Since bisphosphonates are prescribed for women with low bone mineral density and low bone mineral density has been associated with higher breast cancer incidence, it’s important to correct for that,” Dr Chlebowski explained. SABCS Abstract 21.
Also at the meeting, a case-controlled study involving more than 4000 postmenopausal women provided supportive evidence for a protective effect with bisphosphonates. Data were reported by Gad Rennert, MD, Carmel Medical Center and Technion-Israel Institute of Technology, Haifa, Israel. He said women in the study who had breast cancer were 29% less likely to have taken oral bisphosphonates for at least 1 year than women who did not have breast cancer (hazard ratio, 0.71; confidence interval, 0.57- 0.90). SABCS Abstract 27.
The two observational studies used different methodologies to arrive at the same basic result, adding to the strength of the findings, said Indiana University's Theresa Guise, MD, who moderated a news briefing on the findings. Several ongoing randomized clinical trials evaluating the impact of oral and intravenous bisphosphonates on the development of contralateral breast cancer may “provide confirmation of these observational cohort studies within a year or two,” Dr Chlebowski said.