Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia

Authors: DeCensi et. al.
Source: NEJM doi: 10.1200/JCO.18.01779

Tamoxifen is a selective estrogen receptor (ER) modulator and is used in the treatment of hormone positive breast cancer. Tamoxifen is also used for the prevention of breast cancer in women who are at higher risk based on hyperplasia or increased growth of cells on prior biopsies. Typically, tamoxifen is used in younger women who have not yet gone through menopause. However, tamoxifen is not without risk. The most serious adverse side effects of tamoxifen are blood clots and endometrial cancer. Tamoxifen also can affect quality of life as some women experience menopause-like symptoms such as hot flashes and difficulty with intercourse. Due to these lifestyle side effects, there is a significant percent of patients who stop tamoxifen therapy despite known benefits.

One recent study revealed 21% of women stopped their therapy within a year of diagnosis and 35% stopped by 3.5 years. The study sought to evaluate whether a lower dose of tamoxifen yielded sufficient outcomes with potentially fewer side effects. A lower dose of tamoxifen (5 mg) was compared to the conventional 20 mg to determine effectiveness in reducing breast cancer recurrence without experiencing significant adverse side effects. This was a Phase 3 trial of tamoxifen 5 mg per day for three years in women less than 75 years old, who had prior hormone-sensitive hyperplasia. Women were seen every six months and had a mammogram and transvaginal ultrasound for surveillance. The primary outcomes of the study were looking at development of invasive breast cancer or ductal carcinoma in situ (DCIS).

Five hundred women were included in the study with an average age of 54 years. After an average of 5.1 years of follow-up, there were 14 events of breast cancer in the tamoxifen group and 28 breast cancer events in the placebo group. There were 12 serious adverse events in the tamoxifen group and 16 in the placebo group. There was a slight increase of daily frequency of participant-reported hot flashes in the tamoxifen group compared to the placebo group, but the average hot flash score was not different between the two.

So what does this mean for women who are recommended tamoxifen therapy? Tamoxifen at 5 mg per day for three years can halve the recurrence of hormone-sensitive breast cancer. In these women on tamoxifen 5 mg per day, adverse events were not significantly different than the placebo group. The effect of tamoxifen 5 mg per day is similar to 20 mg per day seen in prior studies. In comparing this data to prior studies, the risk of blood clots and endometrial cancer was 2.5 times lower with the 5 mg per day dose compared to the 20 mg per day dose. Therefore, for some women a lower dose of tamoxifen may be able to deliver similar results in reducing the risk of breast cancer with fewer side effects. This option may not be available for women who previously had breast cancer, but this is an option to discuss with your physician if you are recommended to start tamoxifen therapy for risk reduction therapy.