Abstract GS2-09: The single-arm confirmatory trial of tamoxifen alone without surgery for low-risk DCIS of the breast with ER-positive HER2-negative (LORETTA trial: JCOG1505)

Abstract Background: The frequency of ductal carcinoma in situ (DCIS) has increased due to the screening program. The standard treatment for DCIS is still resection. A prospective study of no surgery for low grade DCIS showed positive outcomes in 2024. However, due to the short observation period, no surgery therapy is not even a recommended treatment option. Methods: The LORETTA trial (Low-risk DCIS with Endocrine Therapy Alone-TAM; JCOG1505) is a single-arm confirmatory trial of endocrine therapy alone for estrogen receptor positive, low-risk DCIS. The study population were women seeking treatment for DCIS at one of the JCOG Breast Cancer Study Group institutions in Japan. Eligible participants were 40 and over age with low-risk DCIS defined as nuclear grade (NG) 1 or 2 without comedo necrosis, estrogen receptor positive, HER2-negative on core biopsy without microinvasive or invasive cancer. The maximum tumor diameter does not exceed 25 mm with no finding of invasive cancer on all imaging (MMG, US, and MRI). Tamoxifen (TAM) 20 mg/day is mandatory without surgery in all patients. The primary endpoint was 5-year cumulative incidence proportion of ipsilateral invasive cancer (CIPIC). The secondary endpoints include contralateral breast disease-free survival, overall survival (OS), surgical proportion/timing, and safety. The analysis assumed a 5 year CIPIC threshold of 7% and an expected of 2.5%, with a one-sided α of 2.5% and 95% power. A total of 340 patients was required. The efficacy of TAM alone without surgery is considered confirmed when the upper limit of the 95% confidence interval is less than or equal to 7%. Results: From Jul 2017 to Jan 2024, 341 pts were enrolled. In Jan 2025, early termination was recommended by DSMC as interim monitoring showed 5Y CIPIC exceeded 7%. Median follow up is 36 (range: 0-80.4) months. The patient’s characteristics: median age 53 (range: 40-85) years, PS 0/1:340/1, NG1/2:238/103, PgR 0/weak/strong: 11/17/313, HER2 0/1/2: 66/186/76, pre/post menopause: 162/173. Among 341 pts, 18 pts were found to have ipsilateral invasive cancer. 5Y CIPIC is 9.8% (95% confidence interval CI:5.2-16.1%). In the subgroup analysis, imaging-defined tumor diameter was associated with the occurrence of invasion: MMG (p=0.0278), US (p=0.0433), MRI (p=0.0530). No significant association with NG, HER2, PgR, or age. Contralateral breast disease-free survival: 97.5% (4 patients). 5Y OS: 98.8% (2 deaths, unrelated). Surgical proportion: 9.7% (33/341); 5Y surgery-free survival: 82%. Grade ≥3 adverse events occurred in 3.8% of patients. Conclusion: The primary endpoint did not meet the predefined threshold. However, the incidence of ipsilateral invasive breast cancer and the surgical proportion were low at 5 years. TAM alone without surgery therapy might be an option in carefully selected low-risk DCIS with ER-positive HER2-negtaive. Citation Format: H. Iwata, C. Kanbayashi, T. Toyama, A. Yoshimura, T. Sakai, Y. Bando, K. Watanabe, K. Terata, T. Morimoto, E. Tokunaga, T. Sangai, M. Kitahara, T. Kuwayama, A. Matsui, T. Fujisawa, F. Hara, R. Kajikawa, T. Shibata, K. Sasaki, T. Shien.The single-arm confirmatory trial of tamoxifen alone without surgery for low-risk DCIS of the breast with ER-positive HER2-negative (LORETTA trial: JCOG1505) abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS2-09.