title: Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data.
abstract: BACKGROUND
  Tamoxifen and raloxifene reduce the risk of breast cancer in women at elevated risk of disease, but the duration of the effect is unknown. We assessed the effectiveness of selective oestrogen receptor modulators (SERMs) on breast cancer incidence.
  
  
  METHODS
  We did a meta-analysis with individual participant data from nine prevention trials comparing four selective oestrogen receptor modulators (SERMs; tamoxifen, raloxifene, arzoxifene, and lasofoxifene) with placebo, or in one study with tamoxifen. Our primary endpoint was incidence of all breast cancer (including ductal carcinoma in situ) during a 10 year follow-up period. Analysis was by intention to treat.
  
  
  RESULTS
  We analysed data for 83,399 women with 306,617 women-years of follow-up. Median follow-up was 65 months (IQR 54-93). Overall, we noted a 38% reduction (hazard ratio [HR] 0·62, 95% CI 0·56-0·69) in breast cancer incidence, and 42 women would need to be treated to prevent one breast cancer event in the first 10 years of follow-up. The reduction was larger in the first 5 years of follow-up than in years 5-10 (42%, HR 0·58, 0·51-0·66; p<0·0001 vs 25%, 0·75, 0·61-0·93; p=0·007), but we noted no heterogeneity between time periods. Thromboembolic events were significantly increased with all SERMs (odds ratio 1·73, 95% CI 1·47-2·05; p<0·0001). We recorded a significant reduction of 34% in vertebral fractures (0·66, 0·59-0·73), but only a small effect for non-vertebral fractures (0·93, 0·87-0·99).
  
  
  CONCLUSIONS
  For all SERMs, incidence of invasive oestrogen (ER)-positive breast cancer was reduced both during treatment and for at least 5 years after completion. Similar to other preventive interventions, careful consideration of risks and benefits is needed to identify women who are most likely to benefit from these drugs.
  
  
  BACKGROUND
  Cancer Research UK.
authors: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK. j.cuzick@qmul.ac.uk
authors: Jack
authors: J
authors: Cuzick
authors: Ivana
authors: I
authors: Sestak
authors: Bernardo
authors: B
authors: Bonanni
authors: Joseph P
authors: JP
authors: Costantino
authors: Steve
authors: S
authors: Cummings
authors: Andrea
authors: A
authors: DeCensi
authors: Mitch
authors: M
authors: Dowsett
authors: John F
authors: JF
authors: Forbes
authors: Leslie
authors: L
authors: Ford
authors: Andrea Z
authors: AZ
authors: LaCroix
authors: John
authors: J
authors: Mershon
authors: Bruce H
authors: BH
authors: Mitlak
authors: Trevor
authors: T
authors: Powles
authors: Umberto
authors: U
authors: Veronesi
authors: Victor
authors: V
authors: Vogel
authors: D Lawrence
authors: DL
authors: Wickerham
mesh_terms: D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000517:prevention & control*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D016588:Anticarcinogenic Agents; D020845:Selective Estrogen Receptor Modulators
references: J Bone Miner Res. 2011 Feb;26(2):397-404
references: 20658564
references: Nat Rev Cancer. 2007 Jan;7(1):46-53
references: 17186017
references: N Engl J Med. 2006 Jul 13;355(2):125-37
references: 16837676
references: Cancer Prev Res (Phila). 2012 Jul;5(7):943-51
references: 22581816
references: J Natl Cancer Inst. 2005 Nov 16;97(22):1652-62
references: 16288118
references: Lancet. 2002 Sep 14;360(9336):817-24
references: 12243915
references: Lancet. 1998 May 16;351(9114):1451-67
references: 9605801
references: Recent Results Cancer Res. 2003;163:96-103; discussion 264-6
references: 12903846
references: J Natl Cancer Inst. 2007 Feb 21;99(4):283-90
references: 17312305
references: Lancet. 2003 Jan 25;361(9354):296-300
references: 12559863
references: JAMA. 2006 Jun 21;295(23):2727-41
references: 16754727
references: J Natl Cancer Inst. 2007 May 2;99(9):727-37
references: 17470740
references: J Natl Cancer Inst. 2004 Dec 1;96(23):1751-61
references: 15572757
references: N Engl J Med. 2010 Feb 25;362(8):686-96
references: 20181970
references: J Natl Cancer Inst. 2010 Nov 17;102(22):1706-15
references: 21051656
references: Lancet. 1985 Aug 3;2(8449):282
references: 2862460
references: J Natl Cancer Inst. 1998 Sep 16;90(18):1371-88
references: 9747868
references: Cancer Prev Res (Phila). 2010 Jun;3(6):696-706
references: 20404000
references: N Engl J Med. 2007 Jan 18;356(3):227-36
references: 17229950
references: Breast Cancer Res Treat. 2001 Jan;65(2):125-34
references: 11261828
references: N Engl J Med. 2011 Jun 23;364(25):2381-91
references: 21639806
references: Lancet. 1998 Jul 11;352(9122):98-101
references: 9672274
references: Lancet. 1998 Jul 11;352(9122):93-7
references: 9672273
references: J Natl Cancer Inst. 2007 Feb 21;99(4):272-82
references: 17312304
references: Breast Cancer Res Treat. 2012 Jul;134(1):299-306
references: 22484799