Go Low With Tamoxifen for DCIS

5 MG a Day Is Effective, Says Phase 3 Trial

Nick Mulcahy

December 07, 2018

SAN ANTONIO — Daily use of low-dose (5 mg) tamoxifen (multiple brands) for a shorter-than-usual treatment period (3 years) for patients with ductal carcinoma in situ (DCIS) and other forms of noninvasive breast cancer halved the recurrence of new breast cancer events in comparison with placebo, a new Italian study indicates.

Noninvasive breast cancers are also known as breast intraepithelial neoplasias. Other types, in addition to DCIS, that were included in the randomized, phase 3 TAM-01 clinical trial were lobular carcinoma in situ (LCIS) and atypical ductal hyperplasia (ADH).

Tamoxifen is typically prescribed post surgery at a dosage of 20 mg/day for 5 years for DCIS and these other conditions, said lead study author Andrea De Censi, MD, of the National Hospital EO Ospedali Galliera – SC Oncologia Medica in Genoa, Italy.

Tamoxifen was developed in the 1960s, but the minimal effective dose has never been established, he said during a press briefing here at San Antonio Breast Cancer Symposium (SABCS) 2018, where the study was presented.

De Censi and colleagues hypothesized that a reduced dose and a shorter duration would be effective. That idea was based on a 2003 study from this same Italian group, which showed that 5 mg of tamoxifen was comparable to 20 mg in reducing breast cancer proliferation, as measured by Ki-67 level.

In the new 500-patient trial, 5.5% patients in the low-dose tamoxifen arm (n = 14 of 253) had either experienced disesase recurrence or had new disease, including invasive disease, compared with 11.3% in the placebo arm (n = 28 of 247).

Median follow-up was 5.1 years.

With the low dose, rates of occurrence of two worrisome side effects of tamoxifen — endometrial cancer (which is rare), and deep vein thrombosis (DVT)/pulmonary embolism (PE) — were not different from the rate seen among the patients taking placebo, reported De Censi. Menopausal symptoms, the other common side effect, were not worsened, with the exception of hot flashes, in which the drug had a borderline effect.

Prescribing low-dose tamoxifen involves a twist, De Censi explained. A 5-mg pill is not currently available, so patients need to take a 10-mg pill every other day.

In a press statement at the meeting, De Censi said that the new results are "practice changing."

"Tamoxifen 10 mg every other day is applicable in practice [starting] from tomorrow," he told reporters.

Virginia Kaklamani, MD, of UT Health San Antonio, embraced the idea. She is a codirector of the SABCS and acted as press briefing moderator.

"Looking at these data, especially for the ADH and LCIS patients, I would definitely give lower doses of tamoxifen," she said, explaining that the data were most compelling for those two groups.

She added: "If I have a DCIS patient who is not tolerating tamoxifen at the 20-mg dose, I would be extremely happy to lower it to 5 mg based on these data."

But will patients take the drug? Tamoxifen has a reputation among patients, said Marissa Weiss, MD, a Philadelphia-based radiation oncologist and head of breastcancer.org, a consumer website, who attended the press conference.

Patients have heard too many of the "bad stories" and not enough of the good ones, commented Weiss. "For people to be receptive to this, we almost need to reintroduce it as a new medicine," she said.

For reasons not illuminated by the study, treatment adherence was not high. A total of 64.8% of patients in the tamoxifen arm and 60.7% of patients in the placebo arm did not adhere to the regimen.

More About Adverse Events

De Censi also reported that there were no statistically significant differences between the two arms for an array of menopausal symptoms, such as hot flashes, vaginal dryness, and pain during intercourse.

There were 12 serious adverse events in the low-dose-tamoxifen arm and 16 in the placebo arm.

Serious AEs Tamoxifen Placebo
Endometrial cancer 1 0
DVT or PE 1 1
Other neoplasms 4 6
Heart disease 2 2
Other 3 5
Death 1 2
Total 12 16


"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 per day, we see comparable risk reduction and significantly reduced serious adverse events, respectively," said De Censi in a press statement at the meeting.

The study was supported by the Italian Ministry of Health, the Italian Association for Cancer Research, and the Italian League Against Cancer. Dr De Censi has financial ties with Indena SpA, Roche, Pfizer, Janssen, Novartis, Sanofi-Aventis, Quintiles, Gilead, and MacroGenics. Dr Kaklamani has disclosed no relevant financial relationships.

San Antonio Breast Cancer Symposium (SABCS) 2018: Abstract GS3-01. Presented December 6, 2018.

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