Four RCTs were included in the review and meta-analysis (466 patients). Random sequence generation seemed adequate across all of the trials; allocation concealment and double blinding of participants, personnel and outcome assessment were each reported by three trials. No evidence for missing data was found; all trials were assessed as having a low risk of bias for selective reporting, although study protocols were not always available. Other potential sources of bias were reported.
Compared with untreated control groups, a statistically significant lower risk of gynaecomastia was found with tamoxifen at three months (RR 0.06, 95% CI 0.01 to 0.43; one trial), six months (RR 0.10, 95% CI 0.05 to 0.22; two trials) and nine to 12 months (RR 0.17, 95% CI 0.09 to 0.31; two trials). No substantial statistical heterogeneity was shown (Ι² values all 0%). Similar results were shown for risk of breast pain at three months (RR 0.09, 95% CI 0.03 to 0.24, two trials; Ι²=74%), six months (RR 0.06, 95% CI 0.02 to 0.17; two trials; Ι²=27%) and nine to 12 months (RR 0.13, 95% CI 0.06 to 0.27; two trials; Ι²=0%). A random-effects sensitivity analysis demonstrated a similarly lower risk of breast pain at three months with tamoxifen versus controls (RR 0.10, 95% CI 0.01 to 0.90).
After a median of 12 months, tamoxifen (20mg daily) showed a statistically significant benefit over anastrozole (1mg/day) for the prevention of gynecomastia (RR 0.22, 95% CI 0.08 to 0.58; one trial) and breast pain (RR 0.25, 95% CI 0.10 to 0.64; two trials; Ι²=0%). Similar results for prevention of gynecomastia (RR 0.24, 95% CI 0.09 to 0.65; one trial) and breast pain (RR 0.20, 95% CI 0.06 to 0.65) were shown when tamoxifen (10mg daily) was compared with radiotherapy at six months.
Statistically significant differences favouring tamoxifen to control groups were found for the treatment of breast events at three months (one trial) and improvement of symptoms related to gynaecomastia, breast pain or both at nine months (one trial). Radiotherapy in one trial (a single fraction of 12Gy) significantly increased the risk of nipple erythema and skin irritation, when compared with tamoxifen, but the events were resolved after a median of four weeks. No other significant differences related to adverse events were found (four trials); further detail was reported in the paper.