Adjuvant Bisphosphonates: Winner in Postmenopausal Breast Cancer

Phoebe Starr

February 2014, Vol 5, No 1 - SABCS 2014


San Antonio, TX—Adjuvant bisphosphonates reduce the risk of bone metastases by approximately 33% and improve breast cancer–related survival by 17% in postmenopausal women with early breast cancer, according to a large meta-analysis reported at the 2013 San Antonio Breast Cancer Symposium (SABCS). Bisphosphonates had no effect on premenopausal women in the adjuvant setting.

“Adjuvant bisphosphonates had no significant effect on distant recurrences outside the bone, but the risk reductions in bone recurrence and breast cancer death were similar, regardless of estrogen receptor status, node status, and use/non-use of chemotherapy,” stated Robert E. Coleman, MD, MBBS, Yorkshire Cancer Research Professor of Medical Oncology, University of Sheffield, United Kingdom, who presented the results on behalf of the Early Breast Cancer Trialists’ Collaborative Group.

Dr Coleman emphasized that the results were similar with clodronate and the aminobisphosphonates (65% of patients taking bisphosphonates were receiving zoledronic acid [Zometa]).

Bisphosphonates are thought to work by embedding in bone and interrupting the vicious cycle leading to bone breakdown, Dr Coleman told attendees at the meeting.

The meta-analysis included 36 randomized trials conducted in the past 15 years comparing adjuvant bisphosphonates to placebo or to no bisphosphonate. Overall, 7 trials included oral clodronate and 29 included zoledronic acid.

Data were available for 22,982 patients with breast cancer (17,791 received clodronate or an aminobis­phosphonate); 11,036 women were postmenopausal.

With 10 years of follow-up, adjuvant bisphosphonates had no significant effect on disease recurrences of any type in the overall analysis of all women.
Among postmenopausal women, adjuvant bisphosphonates significantly reduced the risk for distant recurrence (21.9%) versus no bisphosphonate (18.4%) at 10 years (P = .003). This difference was mainly driven by the 10-year reduction in bone recurrence (8.8% vs 5.9%, respectively; P <.001).
Adjuvant bisphosphonates had no effect on mortality; however, among postmenopausal women at 10 years, an absolute reduction of 3.1% was seen in breast cancer mortality, and an absolute reduction of 2.3% in all-cause mortality.

Peter M. Ravdin, MD, PhD, Codirec­tor of the SABCS, and Director, Breast Cancer Program, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, called these results “practice changing.” Dr Ravdin said that the impact of bisphosphonates in the adjuvant setting is comparable to that of chemotherapy and trastuzumab (Herceptin) in HER2-positive women. He was not involved in any of the trials included in the meta-analysis.