Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
BMC Cancer. 2023 Sep 14;23(1):865. doi: 10.1186/s12885-023-11291-6.
Radiotherapy (RT) following breast-conserving surgery (BCS) is mainly used to decrease the rate of ipsilateral breast tumor recurrence (IBTR) in women with breast ductal carcinoma in situ (DCIS). Recent studies have demonstrated that low-dose tamoxifen significantly reduces IBTR in breast DCIS. Here, we aim to determine whether the administration of low-dose tamoxifen is non-inferior to RT in preventing IBTR in patients with low-risk characteristics of breast DCIS.
METHODS/DESIGN: This is a prospective, international, open-label, randomized, non-inferiority trial. Patients with low-risk clinicopathologic features (> 40 years old, low risk of breast cancer susceptibility gene (BRCA) 1 and BRCA2 mutations, mammographically detected unicentric and non-mass lesions, low- or intermediate-grade without comedo or necrosis, measuring < 2.5 cm with margins ≥ 3 mm, and estrogen receptor-positive status) of DCIS who underwent BCS will be randomized at a 1:1 ratio to either receive tamoxifen (5 mg/day) for 5 years or undergo RT with conventional fractions (50 Gy in 25 fractions) or hypofractionations (40.05 Gy in 15 fractions). Randomization will be stratified by the Taiwan Breast Cancer Consortium. As approximately 5% of patients cannot tolerate the side effects of low-dose tamoxifen and will receive RT, we estimate that 405 patients will be randomized to a low-dose tamoxifen arm and 405 patients to the RT arm, according to a non-inferiority margin within 5% of IBTR difference and 90% β-power noticing non-inferiority. The primary endpoints are breast tumor recurrence, including ipsilateral, regional, contralateral, and distant recurrence of breast DCIS or invasive cancer. The secondary endpoints are overall survival and adverse effects of RT and tamoxifen. Translational studies will also be conducted for this trial.
This is the first non-inferiority trial on breast DCIS. This study will provide an important recommendation for clinical physicians on whether to use low-dose adjuvant tamoxifen for patients with low-risk breast DCIS who do not want to receive adjuvant RT.
ClinicalTrials.gov, ID: NCT04046159, Registered on April 30, 2019.
保乳手术后的放射治疗（RT）主要用于降低乳腺导管原位癌（DCIS）女性同侧乳房肿瘤复发（IBTR）的发生率。最近的研究表明，低剂量他莫昔芬显著降低了 DCIS 中的 IBTR。在这里，我们旨在确定在具有低危特征的乳腺 DCIS 患者中，给予低剂量他莫昔芬是否不劣于 RT 预防 IBTR。
方法/设计：这是一项前瞻性、国际、开放标签、随机、非劣效性试验。接受保乳手术的低危临床病理特征（>40 岁，乳腺癌易感基因 1 和 BRCA2 突变低风险，乳腺 X 线照相检测到单中心和非肿块病变，低-或中等级别无粉刺或坏死，<2.5cm 且边缘≥3mm，雌激素受体阳性）的 DCIS 患者将按 1:1 的比例随机分为接受他莫昔芬（5mg/天）治疗 5 年或接受常规分割 RT（50Gy/25 次）或适形分割 RT（40.05Gy/15 次）。随机分组将按台湾乳腺癌联盟进行分层。由于约 5%的患者无法耐受低剂量他莫昔芬的副作用，并且将接受 RT，我们估计根据 5%的 IBTR 差异和 90%β-功率的非劣效性界限，将有 405 名患者被随机分配到低剂量他莫昔芬组，405 名患者被分配到 RT 组。主要终点是乳腺肿瘤复发，包括同侧、区域、对侧和远处乳腺 DCIS 或浸润性癌的复发。次要终点是总生存和 RT 和他莫昔芬的不良反应。该试验还将进行转化研究。
这是第一项关于乳腺 DCIS 的非劣效性试验。这项研究将为临床医生提供重要建议，即对于不想接受辅助 RT 的低危乳腺 DCIS 患者，是否使用低剂量辅助他莫昔芬。
ClinicalTrials.gov，ID：NCT04046159，注册于 2019 年 4 月 30 日。
