随机安慰剂对照试验低剂量他莫昔芬预防乳腺非浸润性肿瘤复发：TAM-01 研究的 10 年随访。

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

机构信息

IEO-European Institute of Oncology IRCCS, Milan, Italy.

Clinical and Epidemiological Research Unit, University Hospital of Parma, Parma, Italy.

出版信息

J Clin Oncol. 2023 Jun 10;41(17):3116-3121. doi: 10.1200/JCO.22.02900. Epub 2023 Mar 14.

DOI:10.1200/JCO.22.02900

PMID:36917758

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

III 期 TAM-01 试验的 5 年数据显示，对于患有上皮内瘤变（IEN）的女性，每天服用低剂量他莫昔芬 5 毫克，持续 3 年，可使浸润性乳腺癌或导管原位癌（DCIS）的复发率降低 52%，且无安慰剂组的其他不良事件。在此，我们报告了 10 年的结果。

方法

我们随机分配了 500 名接受过手术（伴或不伴放疗）的患有乳腺 IEN（非典型导管增生、小叶原位癌[LCIS]或激素敏感或未知的 DCIS）的女性，接受低剂量他莫昔芬或安慰剂治疗。主要终点是浸润性乳腺癌或 DCIS 的发生率。

结果

TAM-01 人群包括 500 名女性（20%非典型导管增生、11%LCIS 和 69%DCIS）。治疗开始时的平均（±SD）年龄为 54±9 岁，58%的参与者处于绝经后状态。中位随访 9.7 年（IQR，8.3-10.9 年）后，诊断出 66 例乳腺癌（原位癌 15 例；浸润性癌 51 例）：他莫昔芬组 25 例，安慰剂组 41 例（每 1000 人年的年发生率，他莫昔芬组为 11.3，安慰剂组为 19.5；风险比[HR]，0.58；95%CI，0.35 至 0.95；对数秩检验=0.03）。大多数复发为浸润性（77%）和同侧（59%）。关于对侧乳腺癌的发生率，他莫昔芬组有 6 例，安慰剂组有 16 例（HR，0.36；95%CI，0.14 至 0.92；=0.025）。用他莫昔芬治疗预防 1 例乳腺癌事件需要治疗的人数在 5 年内为 22 例，在 10 年内为 14 例。这种益处存在于所有患者亚组中。在 DCIS 队列中，他莫昔芬可使复发率降低 50%，占总人群的 70%（HR，0.50；95%CI，0.28 至 0.91；=0.02）。在延长的随访期间，未报告组间严重不良事件发生率的差异。