SABCS 2018: Low-Dose Tamoxifen in Reducing Recurrence and New Disease for Patients With Breast Intraepithelial Neoplasia
Treatment with a low dose of tamoxifen (5 mg/d), compared with placebo, decreased the risk of disease recurrence and new disease for women who had been treated with surgery following a diagnosis of breast intraepithelial neoplasia. Moreover, it did not cause more serious adverse events, according to data from the randomized, phase III TAM-01 clinical trial presented by De Censi et al at the 2018 San Antonio Breast Cancer Symposium (Abstract GS3-01).
“Breast intraepithelial neoplasia is a term for a group of noninvasive conditions in which abnormal cells are found in the breast, including ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), and atypical ductal hyperplasia (ADH),” said 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. “These conditions significantly increase a woman’s risk for invasive breast cancer. Because they are often driven by the hormone estrogen, treatment commonly includes 5 years of tamoxifen, given at 20 mg/d, after surgery and, if needed, radiotherapy.”
Dr. De Censi continued, “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. Our data show that in a randomized trial, low-dose tamoxifen was effective at reducing the risk of breast cancer development and recurrence for women with DCIS, LCIS, and ADH, and it did not cause significant serious adverse events or any increase in menopausal symptoms. Therefore, we strongly believe that these data are practice-changing.”
Study Findings
Dr. De Censi and colleagues randomly assigned 500 women with DCIS, LCIS, and ADH who had been treated with surgery and, if needed, radiotherapy, to be treated with either low-dose tamoxifen or placebo. Treatment continued for 3 years, and patients were seen by the research team every 6 months and had a mammogram annually.
After a median follow-up of 5.1 years, 14 (5.5%) of the 253 patients in the low-dose tamoxifen arm and 29 (11.3%) of the 247 patients in the placebo arm had disease recurrence or new disease. These data led the researchers to calculate that low-dose tamoxifen reduced the risk of recurrence or new disease by 52%.
Among the patients who had a recurrence or new disease in the opposite breast, 3 of the 14 in the low-dose tamoxifen arm had invasive breast cancer and 11 had breast intraepithelial neoplasia. In the placebo arm, 10 had invasive breast cancer and 18 had breast intraepithelial neoplasia.
There were 12 serious adverse events among the patients in the low-dose tamoxifen arm and 16 among those in the placebo arm. There was one case of endometrial cancer among the patients in the low-dose tamoxifen arm and none among those in the placebo arm. There was one venous thromboembolism in the tamoxifen arm and one pulmonary embolism in the placebo arm. There were no significant differences between the two arms in reporting of menopausal symptoms such as hot flashes, vaginal dryness, and pain during intercourse.
Context and Limitations
“When we compare our low-dose tamoxifen data with results from the NSABP B-24 and NSABP-P1 trials of tamoxifen given at 20 mg/d, we see comparable risk reduction and significantly reduced serious adverse events, respectively,” said Dr. De Censi.
According to Dr. De Censi, the main limitation of the study is that treatment adherence was only 64.8% and 60.7% in the tamoxifen and placebo arms, respectively. He also said that if compliance to treatment had been higher, he would have expected to see a greater benefit of tamoxifen. Dr. De Censi also mentioned that currently, tamoxifen is only available in 10-mg tablets, but prior studies conducted by the researchers have shown that 10 mg every other day are as effective as 5 mg/d at reducing recurrence.
Disclosure: This study was supported by the Italian Ministry of Health, the Italian Association for Cancer Research, and the Italian League Against Cancer. See the study authors’ full disclosures at sabcs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
