Biphosphonates do not reduce breast cancer risk — RCTs

FIT and HORIZON-PFT refute findings of previous meta-analysis

Contrary to observational studies that suggest the positive benefits of biphosphonates on breast cancer given its antitumor and antimetastatic properties, two recently published randomized clinical trials concluded that biphosphonates do not reduce breast cancer risk for postmenopausal women.

Bisphosphonates are commonly prescribed drugs for postmenopausal women, and are indicated for the treatment of osteoporosis. They include agents such as alendronate (Fosamax, Merck), ibandronate (Boniva, Genentech), risedronate (Actonel, sanofi-aventis), and zoledronic acid (Reclast, Novartis).

During the 36th Annual San Antonio Breast Cancer Symposium in December of last year, lead investigator Robert Coleman, MD, professor of oncology at the University of Sheffield in the United Kingdom presented their meta-analysis suggesting that adjuvant bisphosphonate treatment significantly improves breast cancer survival and reduces bone recurrence in postmenopausal women with early breast cancer.

“We have finally defined a new addition to standard treatment,” stated Dr. Coleman during a media briefing.

However, findings of the Fracture Intervention Trial (FIT), and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly–Pivotal Fracture Trial (HORIZON-PFT), both of which were recently published, do not agree with the meta-analysis conclusions of Coleman et al.

For the FIT, 6459 women between ages 55 to 81 were randomized to receive either the biphosphate alendronate or placebo. The HORIZON-PFT, on the other hand, had 7756 women, 65 to 89 years of age, who were randomized to receive zoledronic acid or placebo. The data for both studies came from Asia Pacific, Europe, and North and South America. All enrolled subjects have no history of breast cancer.

After a mean follow up of 3.8 years for the FIT study and 2.8 years for the HORIZON-PFT, the studies showed no significant difference in breast cancer rates with either alendronate and zoledronic acid compared to placebo. The figures of the FIT study are at 1.5 percent (n=46) in the placebo group and 1.8 percent (n=57) in the alendronate group (hazard ratio [HR], 1.24 [95 percent CI, 0.84-1.83]).

The HORIZON-PFT on the other hand, showed a breast cancer rate of 0.8 percent (n=29) in the placebo group and 0.9 percent (n=33) in the zoledronic acid group (HR, 1.15 [95 percent CI, 0.70-1.89]).

The study authors noted that the women from the previous observational studies may have had lower bone densities, lower estradilol levels, and higher globulin levels making them more likely to receive biphosphonates and less likely to develop estrogen-receptor-positive breast cancer in the first place. Jose Martin Punzalan with a JAMA Internal Medicine report

VitalSigns Issue 66 Vol. 3, August 1-31, 2014

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