Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands; European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium.
Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Ann Oncol. 2022 Mar;33(3):310-320. doi: 10.1016/j.annonc.2021.11.014. Epub 2021 Dec 1.
Adjuvant systemic treatments (AST) reduce mortality, but have associated short- and long-term toxicities. Careful selection of patients likely to benefit from AST is needed. We evaluated outcome of low-risk breast cancer patients of the EORTC 10041/BIG 3-04 MINDACT trial who received no AST.
Patients with estrogen receptor-positive, HER2-negative, lymph node-negative tumors ≤2 cm who received no AST were matched 1 : 1 to patients with similar tumor characteristics treated with adjuvant endocrine therapy (ET), using propensity score matching and exact matching on age, genomic risk (70-gene signature) and grade. In a post hoc analysis, distant metastasis-free interval (DMFI) and overall survival (OS) were assessed by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. Cumulative incidences of locoregional recurrence (LRR) and contralateral breast cancer (CBC) were assessed with competing risk analyses.
At 8 years, DMFI rates were 94.8% [95% confidence interval (CI) 92.7% to 96.9%] in 509 patients receiving no AST, and 97.3% (95% CI 95.8% to 98.8%) in 509 matched patients who received only ET [absolute difference: 2.5%, HR 0.56 (95% CI 0.30-1.03)]. No statistically significant difference was seen in 8-year OS rates, 95.4% (95% CI 93.5% to 97.4%) in patients receiving no AST and 95.6% (95% CI 93.8% to 97.5%) in patients receiving only ET [absolute difference: 0.2%, HR 0.86 (95% CI 0.53-1.41)]. Cumulative incidence rates of LRR and CBC were 4.7% (95% CI 3.0% to 7.0%) and 4.6% (95% CI 2.9% to 6.9%) in patients receiving no AST versus 1.4% (95% CI 0.6% to 2.9%) and 1.5% (95% CI 0.6% to 3.1%) in patients receiving only ET.
In patients with stage I low-risk breast cancer, the effect of ET on DMFI was limited, but overall significantly fewer breast cancer events were observed in patients who received ET, after the relatively short follow-up of 8 years. These benefits and side-effects of ET should be discussed with all patients, even those at a very low risk of distant metastasis.
辅助全身治疗（AST）可降低死亡率，但具有短期和长期毒性。需要仔细选择可能从 AST 中受益的患者。我们评估了 EORTC 10041/BIG 3-04 MINDACT 试验中接受无 AST 的低危乳腺癌患者的结局。
对接受无 AST 的雌激素受体阳性、HER2 阴性、淋巴结阴性肿瘤≤2cm 的患者，根据年龄、基因组风险（70 基因特征）和分级，采用倾向评分匹配和精确匹配，与接受辅助内分泌治疗（ET）的相似肿瘤特征患者进行 1:1 匹配。在事后分析中，通过 Kaplan-Meier 分析评估无远处转移间隔（DMFI）和总生存（OS），通过 Cox 回归分析评估风险比（HR）。采用竞争风险分析评估局部区域复发（LRR）和对侧乳腺癌（CBC）的累积发生率。
8 年时，509 例未接受 AST 治疗的患者中，DMFI 率为 94.8%（95%CI 92.7%至 96.9%），509 例仅接受 ET 治疗的匹配患者中为 97.3%（95%CI 95.8%至 98.8%）[绝对差值：2.5%，HR 0.56（95%CI 0.30 至 1.03）]。未接受 AST 治疗的患者 8 年 OS 率为 95.4%（95%CI 93.5%至 97.4%），仅接受 ET 治疗的患者为 95.6%（95%CI 93.8%至 97.5%）[绝对差值：0.2%，HR 0.86（95%CI 0.53 至 1.41）]，差异无统计学意义。未接受 AST 治疗的患者 LRR 和 CBC 的累积发生率分别为 4.7%（95%CI 3.0%至 7.0%）和 4.6%（95%CI 2.9%至 6.9%），仅接受 ET 治疗的患者为 1.4%（95%CI 0.6%至 2.9%）和 1.5%（95%CI 0.6%至 3.1%）。
在 I 期低危乳腺癌患者中，ET 对 DMFI 的影响有限，但在相对较短的 8 年随访后，观察到接受 ET 的患者发生的乳腺癌事件总体显著减少。即使是在远处转移风险极低的情况下，也应与所有患者讨论 ET 的这些获益和副作用。
