Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study

• Published in: Journal of clinical oncology Vol. 41; no. 17; pp. 3116 - 3121
• Main Authors: Lazzeroni, Matteo, Puntoni, Matteo, Guerrieri-Gonzaga, Aliana, Serrano, Davide, Boni, Luca, Buttiron Webber, Tania, Fava, Marianna, Briata, Irene M, Giordano, Livia, Digennaro, Maria, Cortesi, Laura, Falcini, Fabio, Serra, Patrizia, Avino, Franca, Millo, Francesco, Cagossi, Katia, Gallerani, Elisa, De Simone, Alessia, Cariello, Anna, Aprile, Giuseppe, Renne, Maria, Bonanni, Bernardo, DeCensi, Andrea
• Format: Journal Article
• Language: English
• Published: United States 10-06-2023
• Subjects: Antineoplastic Agents, Hormonal; Breast Neoplasms - pathology; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating - pathology; Female; Follow-Up Studies; Humans; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - prevention & control; Tamoxifen
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.22.02900

Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results.
We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS.
The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen
19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank
= .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92;
= .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91;
= .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period.
Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.