In The Lancet, the Early Breast Cancer Trialists’ Collaborative Group11 presents a meta-analysis of randomised trials of bisphosphonates as adjuvant systemic therapy for breast cancer.

This meta-analysis is comprised of individual patient data derived from randomised adjuvant bisphosphonate trials in breast cancer done over the past 20 years.
The analysis received data on 18?766 women (18?206 in randomised trials of 2–5 years of adjuvant bisphosphonate vs control), with a median follow-up of 5·6 years, 3453 first recurrences, and 2106 deaths.

For all patients, there were borderline significant reductions with the addition of bisphosphonates at 10 years for distant recurrence (20·4% vs 21·8%, rate ratio [RR]=0·92, 95% CI 0·85–0·99; 2p=0·03), bone recurrence (7·8% vs 9·0%, RR=0·83, 0·73–0·94; 2p=0·004), breast cancer mortality (16·6% vs 18·4%, RR=0·91, 0·83–0·99; 2p=0·04), and all-cause mortality (20·8% vs 22·3%, RR=0·92, 0·85–1·00; 2p=0·06).

In postmenopausal women, there were highly significant reductions with the addition of bisphosphonates at 10 years for bone recurrence (6·6% vs 8·8%, RR=0·72, 0·60–0·86; 2p=0·0002) and for breast cancer mortality (14·7% vs 18·0%, RR=0·82, 0·73–0·93; 2p=0·002).

This benefit was independent of the type of bisphosphonate, the schedule of bisphosphonate administration, the oestrogen receptor status of the primary tumour, the presence of axillary lymph node involvement, and the use of concomitant systemic chemotherapy.

There was no reduction in the incidence of contralateral breast cancer or in the risk of metastasis to non?osseous sites. In the 13?341 women with available fracture data, bisphosphonates reduced the risk of fracture from 7·3% to 6·3% (RR=0·85, 0·75–0·97; 2p=0·02).

This landmark report on breast cancer treatment should lead to widespread adoption of bisphosphonates as a standard of care for the adjuvant therapy of early-stage breast cancer in postmenopausal women. The absolute reduction in the risk of breast cancer death at 10 years with the use of bisphosphonates in postmenopausal women (3·3%) is similar to the benefit seen with anthracycline polychemotherapy versus non-anthracycline polychemotherapy.

Bisphosphonates, in one form or another, are generic and relatively inexpensive in most parts of the world. The toxic effects of these agents are relatively mild (i.e., gastrointestinal upset, arthralgias, and very uncommon osteonecrosis of the jaw).

All bisphosphonates appear to be effective, as long as they are given for at least 2 years. Given their low cost, relatively low toxicity, and overall survival benefit, widespread use of adjuvant bisphosphonates for postmenopausal breast cancer has great potential to reduce mortality from this disease further.

G Mohan.