Adjuvant Bisphosphonates Improve Breast Cancer Survival, Reduce Bone Recurrence in Postmenopausal Women With Early Disease


Key Points

  • A large meta-analysis evaluated adjuvant bisphosphonate therapy in over 22,000 women with early breast cancer.
  • In postmenopausal women, bisphosphonate therapy was associated with fewer bone recurrences and reduced breast cancer deaths; no effect was observed in premenopausal women.
  • These findings may change practice in the adjuvant treatment of postmenopausal women with early breast cancer.

Adjuvant use of bisphosphonates reduced the risk of bone recurrence by 34% and the risk of breast cancer death by 17% in postmenopausal women with early breast cancer in a large meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). The potentially practice-changing findings were presented at the 2013 San Antonio Breast Cancer Symposium by Robert Coleman, MD, of University of Sheffield, United Kingdom (Abstract S4-07)

Adjuvant bisphosphonates achieved reductions in bone recurrence and breast cancer deaths in postmenopausal women regardless of estrogen receptor status, nodal status, and whether or not they received chemotherapy. However, no effects on disease outcome were observed in premenopausal women.

“These results are striking in postmenopausal women," said Peter Ravdin, MD, Co-Director of the San Antonio Breast Cancer Symposium, who was not involved in this study. Dr. Ravdin is director of the Breast Health Clinic at the Cancer Therapy & Research Center (CTRC) of The University of Texas Health Science Center at San Antonio. Dr. Ravdin indicated that he believed bisphosphonates should be considered in clinical treatment guidelines for early breast cancer.

“In addition to the 17% reduction in breast cancer-related mortality, adjuvant bisphosphonates led to an absolute reduction of 3.4% in all-cause mortality,” Dr. Coleman stated.

Large Meta-Analysis

The meta-analysis was prompted by evidence from previous trials suggesting that bisphosphonates reduce distant metastases, predominantly in bone, and this effect is largely confined to postmenopausal women. The individual patient meta-analysis was based on 36 randomized controlled trials comparing adjuvant use of a bisphosphonate vs no bisphosphonate or placebo; a total of 22,982 women were enrolled in these trials.

Seven of the trials compared clodronate vs no bisphosphonate or placebo, and 29 evaluated aminobisphosponates. Two-thirds of women on aminobisphosphonates were taking zoledronic acid, about one-quarter received ibandronate, and 11% received other agents in this class.

Significant Reductions for Postmenopausal Women

Among all women no significant difference was observed in the 10-year rate of all breast cancer recurrences or distant recurrences, including recurrence in bone.

However, among 11,306 postmenopausal women (including women age > 55 if menopausal status unknown), bisphosphonates achieved a highly significant difference in distant recurrence, with rates of 18.4% in women on bisphosponates vs 21.9% in those taking no bisphosphonates (P = .0003), and in bone recurrence, with rates of 5.9% and 8.8%, respectively (P < .00001). No significant effect of bisphosphonates was observed on non-bone recurrence.

Among postmenopausal women, the rate of breast cancer mortality was 15.2% for those treated with bisphosphonates vs 18.3% for those not receiving bisphosphonates (P = .004), and the rate of all-cause mortality was 21.5% vs 23.8%, respectively (P = .007).

Dr. Coleman has provided expert testimony for Novartis and receives honoraria from Amgen.

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®.