Adjuvant Bisphosphonates May Reduce Bone Recurrence and Breast Cancer Mortality in Postmenopausal Women
In a patient-level meta-analysis reported in The Lancet by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), adjuvant bisphosphonate treatment in early breast cancer was associated with a reduced risk of bone recurrence and breast cancer mortality, with the benefit limited to women who were postmenopausal at the start of treatment.
Study Details
The meta-analysis included data on 18,766 women, including 18,206 in trials of 2 to 5 years of bisphosphonate treatment, with a median follow-up of 5.6 woman-years, 3,453 first recurrences, and 2,106 subsequent deaths. Analysis used intention-to-treat log-rank methods to yield bisphosphonate group vs control group (open label or placebo, with no bisphosphonate) first-event rate ratios (RRs; P values are two-sided).
Reduced Risks in Postmenopausal Women
Overall, bisphosphonate treatment was associated with modest reductions in the risk of recurrence (RR = 0.94, P = .08), distant recurrence (RR = 0.92, P = .03), and breast cancer mortality (RR = 0.91, P = .04) and a more definite reduction in the risk for bone recurrence (RR = 0.83, P = .004).
There was no apparent effect of bisphosphonate treatment on any outcome among premenopausal women.
Among 11,767 postmenopausal women, bisphosphonate treatment was associated with significant reductions in the risk of recurrence (RR = 0.86, P = .002), distant recurrence (RR = 0.82, P = .0003), bone recurrence (RR = 0.72, P = .0002), and breast cancer mortality (RR = 0.82, P = .002). The heterogeneity of benefit in bone recurrence, the outcome with the greatest evidence of benefit, was of borderline significance by menopausal status (P = .06); significant by age (P = .03); and nonsignificant by bisphosphonate class, treatment schedule, estrogen receptor status, nodal status, tumor grade, or concomitant chemotherapy.
Bisphosphonate treatment was not associated with a reduced risk of distant recurrence at extra-osseous sites, locoregional recurrence, or contralateral breast cancer overall or in the postmenopausal subgroup. No differences were observed in non–breast cancer mortality. Bisphosphonate treatment was associated with a reduced risk of bone fractures (RR = 0.85, P = .02).
The investigators concluded: “Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival, but there is definite benefit only in women who were postmenopausal when treatment began.”
The study was funded by Cancer Research UK, Medical Research Council. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
