A Cochrane review [Abstract] 1 included 44 studies. In patients with advanced breast cancer and bone metastases (9 studies, 2810 women), bisphosphonates reduced the risk of developing a skeletal event by 14% , increased the time to skeletal event, and reduced bone pain compared with placebo or no bisphosphonates T1.
| Outcome (Follow-up 12 months to 24 months) | Relative effect(95% CI) | Risk with placebo/observation | Risk with intervention - bisphosphonates (95% CI) | №of participants(studies) Quality of evidence |
|---|---|---|---|---|
| Skeletal-related event | RR 0.86(0.78 to 0.95) | 640 per 1000 | 550 per 1000(499 to 608) | 2810(9) High |
| Median time to a skeletal-related event | Median ratio 1.43 (1.29 to 1.58) | 4.9 to 14.9 months | 8.7 to 20.8 months | 2810(9) High |
| Overall survival (Risk of death) | RR 1.01(0.91 to 1.11) | 575 per 1000 | 581 per 1000(523 to 638) | 1935(7) Moderate |
| Bone pain(Brief Pain Inventory,VAS and other validated or unvalidated scales | - | Bone pain was significantly reduced compared to placebo (in 6 out of 11 studies) and was reduced inon-significantly in another 3 studies | 3297(11) Moderate | |
In postmenopausal women with early breast cancer bisphosphonates reduced the incidence of bone metastases and increased overall survival. However this was a post-hoc subgroup analysis.
American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario) guideline update 2 recommens that adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients' risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy.
A Cochrane network meta-analysis [Abstract] 3 included 47 trials (n=35163). 70 of 1000 participants with no treatment/placebo had fractures. Treatment (16 trials,n=19492) with clodronate or ibandronate decreased the number of fractures compared to no treatment/placebo (42 of 1000; RR 0.60, 95% CI 0.39 to 0.92; 40 of 1000; RR 0.57, 95% CI 0.38 to 0.86, respectively, high certainty). Denosumab or zoledronic acid decreased fractures (51 of 1000; RR 0.73, 95% CI 0.52 to 1.01; 55 of 1000; RR 0.79, 95% CI 0.56 to 1.11, respectively, moderate certainty), as well as and risedronate (39 of 1000; RR 0.56, 95% CI 0.15 to 2.16, moderate certainty). 920 of 1000 participants with no treatment/placebo survived overall. There was little to no difference regarding overall survival with treatment (17 trials, n=30991) compared to no treatment/placebo (low certainty): clodronate (924 of 1000; HR 0.95, 95% CI 0.77 to 1.17), denosumab (927 of 1000; HR 0.91, 95% CI 0.69 to 1.21), ibandronate (915 of 1000; HR 1.06, 95% CI 0.83 to 1.34) and zoledronic acid (925 of 1000; HR 0.93, 95% CI 0.76 to 1.14).
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