Joined: 08 May 2019
|Posted: Fri Aug 09, 2019 7:05 pm Post subject: Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to
|Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local
Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose.Nolvadex uses
PATIENTS AND METHODS
We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ.
Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen (P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo.
Breast intraepithelial neoplasia, including atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), and ductal carcinoma in situ (DCIS), has a five to 10 times higher risk of developing into invasive breast cancer compared with the general population and accounts for 15% to 25% of breast neoplasms on the basis of screening mammography.1 The natural history of breast intraepithelial neoplasia is heterogeneous. Some forms remain indolent, whereas other forms can progress to life-threatening invasive disease, which has led to controversial issues with regard to its optimal approach.1,2