Use of Selective Estrogen Receptor Modulators in the Prevention of Breast Cancer: An Overview of the Randomized Trials.
Authors: Cuzick J. 
Published: December 2010

Jack Cuzick on behalf of the SERM Chemoprevention of Breast Cancer Overview Group.Background: We carried out an overview of trials using a SERM (tamoxifen, raloxifene or lasofoxifene) as prophylactic agent against breast cancer.Materials and Methods: Individual patient data were collected from trials comparing a SERM, either tamoxifen or raloxifene, to placebo. In addition, aggregate data were available for one trial comparing lasofoxifene to placebo. Follow up was restricted to the first 10 years.Results: A total of 54,555 patients from 7 different placebo controlled trials have been included, of which four trials evaluated tamoxifen, two raloxifene and one lasofoxifene.Overall these trials showed a reduction of 37% (95% CI 29-43; p&lt;0.001) in breast cancer incidence. The reduction was larger in the first 5 years of follow-up (41%, [32-48]; p&lt;0.001) than in the years 5-10 (25% reduction, [7-39]; p=0.007). When the analysis was restricted to invasive breast cancer, incidence was decreased by 38% (30-46; p&lt;0.001) after 10 years of follow-up (42% [33-50]; p&lt;0.001 and 29% [11-43]; p=0.003 for 0-5 years and 5-10 years of follow-up, resp.). There was a non-significant increase in estrogen receptor (ER) negative invasive cancers (hazard ratio (HR) 1.20 [0.94-1.54], p=0.14) but the incidence of ER positive cancers was decreased by 50% (42-57; p&lt;0.001).A substantial heterogeneity (p = 0.1) between the trials was observed for DCIS: overall, there was a significant decrease in DCIS incidence (28% [6-46]; p=0.02) but this is mainly due to the results from NSABP-P1 and IBIS-I trials, which are the biggest trials and heavily influenced the overall effect.There was an increase in rates of endometrial cancer only in the tamoxifen trials (HR 2.18 [1.39-3.42]; p=0.001). This effect was observed during the first five years of follow-up (HR 2.85 [1.66-4.88]; p&lt;0.001) but not in the years 5-10 (HR 0.95 [0.37-2.42]; p=0.91).The incidence of deep vein thrombosis, pulmonary embolism or retinal vein thrombosis was increased with all SERMs (OR 1.72 [1.46-2.03]; p&lt;0.001). Overall there was an 11% reduction in fractures (odds ratio (OR) 0.89 [0.84-0.95]; p&lt;0.001); a more specific analysis of osteoporotic sites will be carried out. The incidence of hysterectomy was increased with tamoxifen (OR 1.70 [1.51-1.93]; p&lt;0.001) and lasofoxifene (OR 1.52 [1.05-2.20]; p=0.03) but not with raloxifene (OR 0.97 [0.75-1.27]; p=0.84). There was no effect of SERMs on death from breast cancer, overall mortality, colorectal, ovarian or other cancers, stroke, transient ischemic attack or myocardial infarction.A detailed analysis according to age, HRT use and other factors is ongoing and a full description of the results will be provided. Data from the STAR P-2 data, directly comparing raloxifene to tamoxifen, will also be included in the final version.Discussion:We have found that for all SERMs the incidence of ER+ breast cancer was reduced both during treatment and after its completion, but there was a small non-significant increase in ER negative tumours. The effect of SERMs on preventing DCIS was less clear and could be treatment dependent.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 905.