The large, randomized TAM-01 clinical trial demonstrated that 5 mg daily of tamoxifen for 3 years halved the risk for recurrence of breast intraepithelial neoplasia—atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), and lobular carcinoma in situ—in women after surgery and reduced the risk for new contralateral breast cancer by 75% compared with placebo.
The reduction in the risk for recurrent or new breast cancer is in line with results achieved with the use of tamoxifen 20 mg daily for 5 years, which has been the standard treatment (with or without radiation) in this setting.
“Tamoxifen 20 mg per day has troublesome side effects, including endometrial cancer, deep-vein thrombosis, and menopausal symptoms, which pose a barrier to adherence for prevention. We hypothesized that a much lower dose given for shorter duration was as effective as, and less toxic, than standard tamoxifen,” said lead investigator Andrea De Censi, MD, Director, Medical Oncology Unit, National Hospital E.O. Ospedali Galliera, Genoa, Italy, at the 2018 San Antonio Breast Cancer Symposium.
“Our data show that in a randomized trial, low-dose tamoxifen was effective…without causing significant serious adverse events or any increase in menopausal symptoms,” he said. “Therefore, we strongly believe that these data are practice-changing.”
The study randomized 500 women with atypical ductal hyperplasia, DCIS, or lobular carcinoma in situ after surgery, with or without radiation, to low-dose tamoxifen for 3 years or to placebo. The patients were seen every 3 months and had an annual mammogram.
“We did not compare it with 20 mg per day of tamoxifen, because the cost would be prohibitive on our limited budget from nonprofits and the government,” Dr De Censi explained.
The TAM-01 Study Results
At a median follow-up of 5 years, 14 (5.5%) of the 253 patients in the low-dose tamoxifen arm versus 28 (11.3%) of the 247 patients in the placebo arm had breast cancer recurrence or new breast cancer. Thus, low-dose tamoxifen reduced the risk for new or recurring disease by 52% compared with placebo.
Among patients with a contralateral breast cancer recurrence or new disease, 3 of the 14 women in the tamoxifen arm and 12 of the 28 women in the placebo arm had invasive breast cancer, and 11 and 18 women, respectively, had breast intraepithelial neoplasia.
“The decrease in contralateral breast cancer events was based on only 15 events, so we need to be cautious,” Dr De Censi stated.
A total of 12 serious adverse events were reported in the low-dose tamoxifen arm versus 16 events in the placebo arm. Only 1 deep-vein thrombosis or pulmonary embolism occurred in each arm, and 1 case of endometrial cancer was reported in the low-dose tamoxifen arm.
Low-dose tamoxifen did not substantially increase tamoxifen-associated side effects. Based on patient self-reports, an increase in hot flashes in the tamoxifen group versus the placebo group was of borderline significance, “amounting to about 1 extra hot flash per day,” Dr De Censi said. No differences were found between the treatment arms in the rates of vaginal dryness, painful sexual intercourse, and musculoskeletal events.
“Our results have external validity and are generalizable. Tamoxifen 10 mg every other day is applicable in clinical practice from tomorrow on,” Dr De Censi stated, adding that tamoxifen is available in 10-mg tablets only. “You can cut the tablet in half starting tomorrow,” he told listeners.
“I would definitely give lower doses of tamoxifen to the ADH [atypical ductal hyperplasia] and LCIS [lobular carcinoma in situ] patients, and if I have a DCIS patient who is not tolerating the 20-mg dose, I would be extremely happy to give that patient 5 mg per day,” said Virginia Kaklamani, MD, Leader, Breast Cancer Program, UT Health San Antonio M.D. Anderson Cancer Center, San Antonio, TX, who commented on the study.