Vicini Frank, Shah Chirag, Mittal Karuna, Abraham Jame, Kruse Megan, Weinmann Sheila, Leo Michael, Rabinovitch Rachel, Wärnberg Fredrik, Whitworth Pat W, Czerniecki Brian J, Shivers Steven C, Bremer Troy
Michigan Healthcare Professionals, Farmington Hills, MI.
Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Clin Breast Cancer. 2025 Feb;25(2):e152-e158.e1. doi: 10.1016/j.clbc.2024.08.016. Epub 2024 Sep 4.
A subpopulation of women with ductal carcinoma in situ (DCIS) remains at risk for in-breast recurrence (IBR) following breast-conserving surgery (BCS) and radiation therapy (RT). The NSABP B-43 trial evaluated the role of concurrent RT and trastuzumab in patients with HER2-positive DCIS but did not reach the prespecified endpoint. We hypothesized that a 7-gene biosignature (DCISionRT) with its Residual Risk subtype (RRt) could identify 2 groups of HER2(3+) patients with significantly different IBR risks after BCS plus RT.
All patients with HER2(3+) DCIS (n = 178) treated with BCS plus RT were selected from a combined multinational patient cohort. Treatment decisions were neither randomized nor strictly rules-based. Biosignature testing was performed on all patients and stratified with previously defined groups: (1) Combined Low Risk group (DS ≤ 2.8) and Elevated Risk group (DS > 2.8) without RRt or (2) Residual Risk subtype. Kaplan-Meier analysis was used to compute IBR curves.
Sixty-three percent of HER2(3+) patients (113/178) were classified into the Residual Risk subtype. These patients had significantly higher 10-year rates of IBR compared to the nonresidual risk group (16.2% vs. 1.6%, P = .01). The Residual Risk subtype had more nuclear grade 3 disease (87% vs. 63%, P < .001), but age, size, and grade were not associated with IBR rate (P = NS) on univariate and multivariable analysis. Only the Residual Risk group was associated with IBR (P = .05) in multivariate analysis.
The 7-gene biosignature with RRt identified a subset of HER2(3+) patients with greater IBR rates following BCS and RT beyond traditional clinical and pathologic features. Consideration of therapies to reduce these elevated IBR rates should be evaluated, including the incorporation of HER2-targeted therapy.
保乳手术（BCS）和放射治疗（RT）后，原位导管癌（DCIS）女性亚群仍有乳腺内复发（IBR）风险。NSABP B - 43试验评估了同步放疗和曲妥珠单抗在HER2阳性DCIS患者中的作用，但未达到预定终点。我们假设一种7基因生物标志物（DCISionRT）及其残留风险亚型（RRt）可以识别两组HER2(3+)患者，其在BCS加RT后的IBR风险显著不同。
所有接受BCS加RT治疗的HER2(3+) DCIS患者（n = 178）均选自一个跨国联合患者队列。治疗决策既非随机也非严格基于规则。对所有患者进行生物标志物检测，并按先前定义的组进行分层：（1）无RRt的联合低风险组（DS≤2.8）和高风险组（DS>2.8），或（2）残留风险亚型。采用Kaplan - Meier分析计算IBR曲线。
63%的HER2(3+)患者（113/178）被归类为残留风险亚型。与非残留风险组相比，这些患者的10年IBR发生率显著更高（16.2%对1.6%，P = 0.01）。残留风险亚型有更多的核3级疾病（87%对63%，P < 0.001），但在单因素和多因素分析中，年龄、大小和分级与IBR发生率无关（P = 无显著性差异）。在多因素分析中，只有残留风险组与IBR相关（P = 0.05）。
具有RRt的7基因生物标志物识别出了一组HER2(3+)患者，其在BCS和RT后的IBR发生率高于传统临床和病理特征所提示的情况。应评估降低这些升高的IBR发生率的治疗方法，包括纳入HER2靶向治疗。
