Low-Dose Tamoxifen vs Placebo in Preventing Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia


Key Points

  • Tamoxifen at 5 mg/d vs placebo for 3 years significantly reduced the risk of recurrent breast intraepithelial neoplasia.
  • The tamoxifen regimen was associated with a favorable safety profile.

In an Italian phase III study reported in the Journal of Clinical Oncology, DeCensi et al found that tamoxifen at 5 mg/d vs placebo for 3 years reduced the risk of recurrence of breast intraepithelial neoplasia and was associated with limited toxicity. As noted by the investigators, “Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use.”

The double-blind multicenter trial included 500 women aged ≤ 75 years with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ (DCIS). Patients were randomly assigned between November 2008 and March 2015 to receive tamoxifen at 5 mg/d (n = 253) or placebo (n = 247) for 3 years. The primary endpoint was incidence of invasive breast cancer or DCIS.

Reduced Recurrence Risk

The median follow-up was 5.1 years. There were breast neoplastic events in 14 patients in the tamoxifen group vs 28 in the placebo group (11.6 vs 23.9 per 1,000 person-years, hazard ratio [HR] = 0.48, P = .02). The 5-year number needed to treat to prevent 1 neoplastic event was 22. Contralateral breast cancer was observed in 3 vs 12 patients (HR = 0.25, P = .02). In the tamoxifen group, 11 cases were invasive and 3 were DCIS; in the placebo group, 19 cases were invasive and 9 were DCIS.

Adverse Events

Patient-reported outcomes did not differ between the groups, except for increased frequency of daily hot flashes in the tamoxifen group (incidence rate ratio = 1.46, P = .02; mean daily hot flash frequency = 2.1 vs 1.5). No differences in vaginal dryness, pain during sexual intercourse, or musculoskeletal symptoms/arthralgia were observed. Serious adverse events occurred in 12 patients in the tamoxifen group vs 16 patients in the placebo group, including 1 patient with deep-vein thrombosis and 1 patient diagnosed with stage I endometrial cancer in the tamoxifen group, and 1 patient who experienced pulmonary embolism in the placebo group.

The investigators concluded, “Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.”

Andrea DeCensi, MD, of the Division of Medical Oncology, Ente Ospedaliero Ospedali Galliera, Genoa, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and Italian League against Cancer. For full disclosures of the study authors, visit

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