SAN ANTONIO – A low-dose treatment of tamoxifen – 5 mg daily rather than the conventional 20 mg daily – appears to offer women protection against recurrence of early stage breast cancer and also reduces adverse events that often accompany tamoxifen cancer prevention therapy, researchers reported here.
After a median follow-up of 5.1 years, women diagnosed with breast intraepithelial neoplasia who took 5 mg of tamoxifen for 3 years had 14 breast cancer events compared with 28 events among women in the study who were assigned to placebo (P=0.024), reported Andrea De Censi, MD, director of the medical oncology unit at the National Hospital E.O. Ospedali Galliera – S.C. Oncologia Medica in Genoa, Italy.
“Our phase III TAM-01 study shows that a lower dose of tamoxifen – 5 mg per day given for 3 years – decreases by 52% the risk of a recurrence in women with breast intraepithelial neoplasia – that is, ductal carcinoma in situ (DCIS), lobular carcinoma in situ, and atypical ductal hyperplasia,” De Censi told MedPage Today at the annual San Antonio Breast Cancer Symposium.
The researchers also reported that tamoxifen appeared to be protective systemically. There were 12 breast cancer events in the contralateral breast among the placebo patients compared with three in the patients taking low-dose tamoxifen (P=0.018).
“I think our study is practice changing because we show a great effect that is similar to what was seen with the standard dose in previous trials, but with much lower adverse side effects,” he said. “So the women with this disease can benefit from low-dose tamoxifen – either 10 mg every other day or by cutting the tablets in half, for a dose of 5 mg a day. The most important implication is among the women who are healthy but who may be at risk for breast cancer [that they] may benefit from a lower dose of tamoxifen.”
The study conducted at 14 centers in Italy randomized 253 women to tamoxifen at 5 mg a day and 247 women to placebo. The women were approximately 54 years old; about 45% were premenopausal; 70% were diagnosed with DCIS; two-thirds were diagnosed with hormone-positive disease, while hormone receptor status was unknown for the other women. De Censi said most cases of breast intraepithelial neoplasia are hormone positive; about 84% of the women diagnosed with the disease opted to undergo conservative surgical therapy.
“Breast intraepithelial neoplasia significantly increases a woman’s risk for invasive breast cancer,” he said. “Because they are often driven by the hormone estrogen, treatment commonly includes 5 years of tamoxifen, given at 20 mg per day, after surgery and, if needed, radiotherapy.
“Unfortunately, tamoxifen is associated with an increased risk of endometrial cancer and of venous thromboembolism, and can cause menopausal symptoms that lead to treatment discontinuation,” De Censi noted.
Regarding adverse events, there was a borderline statistically significant increase in hot flashes among patients on tamoxifen compared with placebo (P=0.05), but no significant difference in the daily hot flashes score; no difference in vaginal dryness or pain during intercourse; and no difference between the groups in musculoskeletal pain – a major factor in women discontinuing the use of aromatase inhibitors, often given to postmenopausal women at risk of cancer recurrence.
De Censi said there was one case of endometrial cancer in the tamoxifen group, but none in the placebo group. He noted that in studies with the 20 mg dose of tamoxifen, 2.7 cases of endometrial cancer would have been anticipated in the 3-year period of the study.
The results of the study are generalizable, he said, and should be “applicable in clinical practice from tomorrow.”
The moderator of a press conference at the symposium at which the study was discussed, Virginia Kaklamani, MD, of the University of Texas Health San Antonio, told MedPage Today, “This study did not compare 5 mg with 20 mg, but the data seen here was pretty similar to data with the 20 mg dose as far as protecting against cancer.”
“This is pretty compelling and something I would try in my clinic,” she said. “Whether to go lower than 5 mg is an interesting question, but the reason to stick with 5 mg is mainly pragmatic. The smallest tablets we have are 10 mg, so to split them more than in half would be difficult. So I think that for the time being, 5 mg would seem to be a good dose.”
De Censi and Kaklamani disclosed no relevant relationships with industry.