Low-Dose Tamoxifen Shows Continued Efficacy in Adjuvant Setting at 10-Year Follow-Up


Long-term data support a de-escalated dose of tamoxifen for certain women with breast intraepithelial neoplasia who are unable to receive the standard dose.

Tamoxifen, at a dose of 5 mg daily (babytam), continued to show a benefit over placebo in reducing the risk of recurrence from invasive breast cancers and ductal carcinoma in situ (DCIS) in women with breast intraepithelial neoplasia in a 10-year follow-up of the TAM-01 trial (NCT01357772). According to investigators, the low risk of death observed with a lower dose support treatment de-escalation in DCIS for women who are intolerant to the standard dose (20 to 40 mg/daily) in the adjuvant setting.

An analysis of the data was presented at the 2022 San Antonio Breast Cancer Symposium (SABCS). At a median follow-up of 9.7 years (range, 8.3-10.9), babytam continued to reduce the incidence of invasive breast cancer or DCIS. The survival curves showed a 42% reduction in overall breast events (breast cancer or DCIS) with babytam compared with placebo (HR, 0.58; 95% CI, 0.35-0.95; P = .028).

Moreover, the rate of ipsilateral breast events was reduced by 32% (HR, 0.68; 95% CI, 0.36-1.28) and a 64% reduction was observed in the rate of contralateral breast events (HR, 0.36; 95% CI, 0.14-0.92). In a cohort of patients with DCIS, the rate of any breast event was reduced by 50% (HR, 0.50; 95% CI, 0.28-0.91; P = .02).

These 10-year data represent “promising results for those concerned about tamoxifen side effects,” Lea Ann Biafora, MS, RN, OCN, CCM, ONN-CG, an SABCS attendee, commented in an email interview with Oncology Nursing News®.

Moreover, according to investigators on the trial, this research signifies an efficacious alternative to treatment cessation in woman for whom the 20-mg daily dose is intolerable. It may also reduce interval cancers in premenopausal women with dense breasts as well as reasonably reduce the risk of invasive breast cancer or DICS in young women with chest radiation and represent an effective treatment for women with BRCA2 mutations or who are moderate penetrance gene carries (PALB2, CHEK2, and ATM).

In 2018, a previous report from the trial showed that at a median of 5 years of follow-up, babytam had reduced the risk of breast events by 62% (HR, 0.48; 95% CI; 0.26-0.92), and the risk of contralateral breast cancer by 76% (HR, 0.24; 95% CI, 0.07-0.87; P = .018).2 Following these data, ASCO updated their guidelines to include babytam for preventive therapy in high-risk lesions,3 and the NCCN recommended babytam after DCIS if patients were either symptomatic or unable to take a full dose.4

TAM-01 enrolled women who had undergone an operation for lobular intraepithelial neoplasia or estrogen receptor (ER)-positive ductal intraepithelial neoplasia of the breast.5 More than 500 participants from 14 different centers in Italy were enrolled and randomly assigned to low-dose tamoxifen or placebo. The protocol included 3 years of treatment at least 7 years of follow-up. Follow-up was defined by a visit and quality-of-life questionnaire every 6 months for 3 years, and a mammogram annually for 10 years.1

Between the babytam and the placebo groups, the percentage of patients who were premenopausal, respectively, were 43% and 40%. In terms of intraepithelial neoplasia, the percentage of patients with atypical ductal hyperplasia was 20% in each group, the rate of lobular carcinoma in situ was 11% vs 10%, respectively, and the rate of DCIS was 69% and 70%.1

A subgroup analysis provided further insight into how the treatment regimen translated to recurrence rates in specific populations at 10-years of follow-up.1

Babytam was associated with a 57% reduced risk in postmenopausal women (HR, 0.43; 95% CI, 0.20-0.91; P = .43); a 62% reduced risk among women with an estradiol level of at least 15.8 pg/mL (HR, 0.38; 95% CI, 0.16-0.92; P = .42); a 74% reduced risk in those with a BMI of 30 kg/m2 or higher (HR, 0.26; 95% CI, 0.07-0.97; P = .74); and a 52% reduced risk in patients who never smoked (HR, 0.48; 95% CI, 0.26-0.91; P = .22). In addition, the treatment yielded an 80% reduced risk with history of mastectomy (HR, 0.20; 95% CI, 0.04-0.97; P = 27) and a 51% reduced risk among those with DCIS (HR, 0.49; 95% CI, 0.27-0.89; P = .28).

An analysis of breast neoplastic events by arm showed patients in the placebo arm had higher incidences of invasive disease (30 vs 21); ipsilateral and contralateral recurrence (39 vs 22); tumors at stages Tis, T1, and T 2-4 (50 vs 21); node-negative and -positive disease (38 vs 23); and luminal, human epidermal growth factor receptor 2–positive, or triple-negative disease (37 vs 21), compared with those who received babytam.

Of note, the rates of adverse events (AEs) were similar between the 2 arms, although patients receiving babytam did report higher rates of other neoplasms (16 vs 9; P = .22) and endometrial polyps (20 vs 13; P = .28). Other AEs which were reported included endometrial cancer (1 vs 0), deep vein thrombosis (1 vs 1), superficial phlebitis (2 vs 0), coronary heart disease (2 vs 2), bone fracture (4 vs 2), and cataracts (5 vs 5). Five patients and 2 patients, respectively, died from other causes, and 1 patient and 2 patients died from breast cancer during the follow-up periods. Other serious adverse events occurred in 3 and 6 patients, respectively.

Study authors noted that there was a limited power for subgroup analysis and interactions in the trial. There was also a lack of a vis-à-vis comparison with 20 mg/d and a noninferiority trial would be poorly accepted because of the toxicities associated with a standard dose.

Lastly, despite the findings presented at the conference, 5-mg tablets are not easily accessible in the market. However, using a 10-mg dose on alternate days is “reasonable” because of the agent’s long half-life.


  1. De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX.
  2. De Censi A, Puntoni M, Guerrieri-Gonzaga A. Randomized placebo controlled trial of low-dose tamoxifen to prevent local and contralateral recurrence in breast intraepithelial neoplasia. J Clin Oncol. 2019;37(19):1629-1637. doi:10.1200/JCO.18.01779.
  3. Visvanathan K, Fabian CJ, Bantug E, et al. Use of endocrine therapy for breast cancer risk reduction: ASCO clinical practice guideline update. J Clin Oncol. 2019;37(33):3152-3165. doi:10.1200/JCO.19.01472.
  4. NCCN. Clinical Practice Guidelines in Oncology. Breast cancer, version 4.2022. Accessed February 15, 2023. https://www.nccn.org/professionals/physician_gls/pdf/breast_blocks.pdf
  5. Trial of low dose tamoxifen in women with breast intraepithelial neoplasia - long term follow-up (TAM-01). ClinicalTrials.gov. Updated September 28, 2022. Accessed February 15, 2022. https://clinicaltrials.gov/ct2/show/NCT01357772
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