However, among postmenopausal women, bisphosphonate treatment produced a larger reduction in bone recurrence of 28% and also reduced the risk of dying from breast cancer by 18% during the first decade after diagnosis.

The benefit held regardless of the type of bisphosphonate, treatment duration, size of tumor, whether it had spread to the lymph nodes, or whether it was estrogen-receptor (ER) positive. However, bisphosphonate treatment did not reduce the risk of new breast cancers developing in the opposite breast.

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“The meta-analysis was not able to assess adverse effects. However, we know from the individual trials that the only adverse event of importance is osteonecrosis of the jaw with a frequency of 0.1% to 1.5% depending on type and schedule of bisphosphonate. Oral bisphosphonates may be associated with gastrointestinal toxicity and intravenous therapy with fever and myalgia after the initial one to two infusions, but these side effects only infrequently limit patient adherence to treatment.” said the bisphosphonate study’s lead author Professor Robert Coleman, MBBS, MD, FRCP, of the University of Sheffield, in Sheffield, United Kingdom.

He said currently bisphosphonates are mainly used to reduce bone loss and fractures in postmenopausal women and to reduce bone complications in advanced cancer patients.

However, the new analyses showed that adjuvant bisphosphonates in postmenopausal women prevent around a quarter of bone recurrences and one in six of all breast cancer deaths in the first decade of treatment.

“We were expecting the effect on bone recurrence in postmenopausal women but the 18% reduction in risk of breast cancer death was a surprisingly large benefit,” Dr. Coleman told Cancer Therapy Advisor

“Bisphosphonates should now be considered for postmenopausal women as part of standard adjuvant treatment and are being introduced in Europe despite a lack of specific regulatory approval.”

RELATED: Adjuvant Bisphosphonates for Breast Cancer May Reduce Recurrence in Bone, Improve Survival

Lead statistician for both studies Professor Richard Gray of the University of Oxford, in Oxford, United Kingdom, said the studies provide strong evidence that both drugs can help reduce breast cancer mortality in postmenopausal women.

He said about two-thirds of all women with breast cancer are postmenopausal with hormone-sensitive tumors, so they could potentially benefit from both. Gray said the drugs are complementary because the main side effect of AIs is an increase in bone loss and fractures while bisphosphonates reduce bone loss and fractures.


  1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of thee randomised trials. [published online ahead of print July 24, 2015]. The Lancet. doi:10.1016/S0140-6736 (15)60908-4.
  2. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. [published online ahead of print July 24, 2015]. The Lancet. doi:10.1016/S0140-6736 (15)60908.