Breast cancer: bisphosphonates reduce skeletal events but not death in women with advanced disease and bone metastases

Clinical bottom line (level 1a)

  1. Women with advanced breast cancer and bone metastases who take bisphosphonates compared with placebo are less likely to have a skeletal event (NNT = 17 at months) , but are not clearly less likely to die.
  2. There is no clear effect on bone metastases in women with advanced breast cancer and no clinically evident bone metastases or women with early breast cancer.
Pavlakis and Stockler: Cochrane Library 2002; 1 : -
Expires June 2004

The study

Systematic review of all randomised controlled trials of
  • Patients: women with early breast cancer or metastatic breast cancer
  • Intervention: bisphosphonates compared with placebo or another bisphosphonate
  • Outcome: skeletal events, death

Articles found in ?all languages using Cochrane Breast Cancer Group including Medline, CENTRAL, Embase, CancerLit, (search terms: detailed in text ) and hand-searching selected journals, conference proceedings and reference lists of retrieved articles. Authors and other bisphosphonate investigators were also contacted.

Selection criteria: by 2 independent reviewers with disagreements resolved by consensus
Appraisal criteria: by 2 independent reviewers with disagreements resolved by consensus: using concealment allocation, blinding, loss to follow-up
Articles excluded if:
  • duplicate papers

19 RCTs found
  • 13 involving 4395 women with advanced breast cancer and existing bone metastases
  • 3 involving 320 women with advanced breast cancer and no clinically evident bone metastases
  • 3 involving 1680 women with early breast cancer
Study results for bone metastases in early breast cancer were found to be significantly heterogeneous.

The evidence

advanced breast cancer and bone metastases: any bisphosphonate v. control
Outcome Time to outcome CER OR
(95% CI)		 NNT
(95% CI)
skeletal event months 694/989
(70.2%)		 0.63
(0.52 to 0.76) 		10
(7 to 17)
death months 624/841
(74.2%)		 0.95
(0.75 to 1.19) 		100
(NNT = 17 to infinity;
NNH = 31 to infinity)

advanced breast cancer and no clinically evident bone metastases: any bisphosphonate v. placebo
Outcome Time to outcome CER OR
(95% CI)		 NNT
(95% CI)
bone metastases months 38/159
(23.9%)		 0.99
(0.59 to 1.66) 		550
(NNT = 12 to infinity;
NNH = 10 to infinity)

early breast cancer: any bisphosphonate v. placebo
Outcome Time to outcome CER OR
(95% CI)		 NNT
(95% CI)
bone metastases months 93/837
(11.1%)		 0.71
(0.51 to 0.98) 		34
(20 to 510)

  • 4 studies assessing iv pamidronate in women with advanced breast cancer and metastases showed a delay in the median time to a first skeletal event.
  • 4/10 studies found a reduction in pain using bisphosphonates.
  • Adverse effects were few. The commonest were fever and asymptomatic hypocalcaemia. Oral clodronate was associated with mild gastrointestinal toxicity.

Citation

  1. Pavlakis N, and Stockler M: bisphosphonates in breast cancer (Cochrane Review). Cochrane Library 2002; 1 : -
Search Terms: from ACP Journal Club other articles noted
Contributor: Chris Ball, June 2002
Reviewer:

Clinical Question.
Patient breast cancer
Intervention or Exposure bisphosphonates
Comparison placebo
Outcome skeletal events, death