By Anne Harding
NEW YORK (Reuters Health) - 3/5/2019
"Lowering the dose by three-quarters we can still get very significant reduction of recurrence in women with in situ carcinomas, which comprises ductal carcinoma in situ, lobular carcinoma in situ and atypical ductal hyperplasia," Dr. Andrea DeCensi of Ente Ospedaliero Ospedali Galliera in Genoa, Italy, told Reuters Health by phone.
He noted thatin situ disease accounts for 30% of breast cancers identified by screening mammography.
"The data are practice-changing," he added. "Women with in situ disease can start to take a lower dose because this old drug was not carefully assessed in terms of its minimal effective dose, which happens not rarely. Drug companies are always more interested in looking at the maximum tolerated dose rather than the minimum effective dose."
While tamoxifen is not currently available in a 5-mg tablet, as used in the trial, taking a 10-mg dose every other day or cutting the tablet in half would also be effective, Dr. DeCensi and his colleagues note in the Journal of Clinical Oncology, online April 11.
They randomly assigned 500 women 75 or younger with in situ breast cancers to receive tamoxifen 5 mg or placebo for three years after surgery. During follow-up of a median 5.1 years, 14 neoplastic events occurred in the tamoxifen group, compared to 28 in the placebo group (hazard ratio 0.48; P=0.02).
There were three contralateral breast events with tamoxifen, versus 12 with placebo (HR, 0.25; P=0.02).
Women on tamoxifen reported a small increase in daily hot flashes, but other patient-reported outcomes were similar for the two groups.
Twelve serious adverse events occurred with tamoxifen and 16 occurred in the placebo group, including a deep vein thrombosis and a stage-1 endometrial cancer with tamoxifen and a pulmonary embolism with placebo.
Menopausal symptoms like hot flashes are the main reason women stop taking tamoxifen, Dr. DeCensi said. "By lowering the dose we can retain the benefit while reducing the side effects of tamoxifen."
He added: "Also in the adjuvant setting I think that if a woman taking tamoxifen after invasive breast cancer does not tolerate the full dose, there is the possibility to decrease the dose, because the alternative is to withdraw the treatment."
The next step should be to conduct a clinical trial of lower-dose tamoxifen in women at very high risk of breast cancer, for whom it could offer an alternative to prophylactic surgery, he said.
The Italian Ministry of Health and the Italian Association for Cancer Research funded the study.