A 7-Gene Biosignature for Ductal Carcinoma in situ of the Breast Identifies Subpopulations of HER2-positive Patients With Distinct Recurrence Rates After Breast-Conserving Surgery and Radiation Therapy.

IF 2.9 3区医学 Q2 ONCOLOGY

Clinical breast cancer Pub Date : 2024-09-04 DOI:10.1016/j.clbc.2024.08.016

Frank Vicini, Chirag Shah, Karuna Mittal, Jame Abraham, Megan Kruse, Sheila Weinmann, Michael Leo, Rachel Rabinovitch, Fredrik Wärnberg, Pat W Whitworth, Brian J Czerniecki, Steven C Shivers, Troy Bremer

{"title":"A 7-Gene Biosignature for Ductal Carcinoma in situ of the Breast Identifies Subpopulations of HER2-positive Patients With Distinct Recurrence Rates After Breast-Conserving Surgery and Radiation Therapy.","authors":"Frank Vicini, Chirag Shah, Karuna Mittal, Jame Abraham, Megan Kruse, Sheila Weinmann, Michael Leo, Rachel Rabinovitch, Fredrik Wärnberg, Pat W Whitworth, Brian J Czerniecki, Steven C Shivers, Troy Bremer","doi":"10.1016/j.clbc.2024.08.016","DOIUrl":null,"url":null,"abstract":"Purpose: 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.Patients and methods: 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.Results: 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.Conclusion: 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.","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical breast cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.clbc.2024.08.016","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusion: 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.

查看原文本刊更多论文

乳腺原位导管癌的 7 基因生物特征可识别 HER2 阳性患者亚群，这些患者在接受保乳手术和放疗后的复发率各不相同。

目的：在接受保乳手术（BCS）和放疗（RT）后，一部分患有导管原位癌（DCIS）的女性仍面临乳房内复发（IBR）的风险。NSABP B-43 试验评估了同期 RT 和曲妥珠单抗在 HER2 阳性 DCIS 患者中的作用，但未达到预设终点。我们假设，7 个基因生物特征（DCISionRT）及其残余风险亚型（RRt）可以识别出 BCS 加 RT 后 IBR 风险显著不同的两组 HER2(3+) 患者：所有接受BCS加RT治疗的HER2(3+) DCIS患者（n = 178）都是从一个多国联合患者队列中挑选出来的。治疗决定既不是随机的，也不是严格基于规则的。对所有患者进行了生物特征检测，并按之前定义的组别进行了分层：(1) 联合低风险组（DS ≤ 2.8）和高风险组（DS > 2.8），无 RRt 或 (2) 残余风险亚型。采用卡普兰-梅耶尔分析法计算IBR曲线：63%的HER2(3+)患者（113/178）被归入残余风险亚型。与非残余风险组相比，这些患者的10年IBR率明显更高（16.2% vs. 1.6%，P = .01）。残余风险亚型有更多的核3级疾病（87% vs. 63%，P < .001），但在单变量和多变量分析中，年龄、大小和分级与IBR率无关（P = NS）。在多变量分析中，只有残余风险组与IBR相关（P = .05）：结论：具有 RRt 的 7 基因生物特征确定了 HER2(3+)患者的一个子集，该子集在 BCS 和 RT 后的 IBR 率高于传统的临床和病理特征。应考虑采用哪些疗法来降低这些升高的IBR率，包括纳入HER2靶向疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical breast cancer 医学-肿瘤学

CiteScore

5.40

自引率

3.20%

发文量

174

审稿时长

48 days

期刊介绍： Clinical Breast Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of breast cancer. Clinical Breast Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of breast cancer. The main emphasis is on recent scientific developments in all areas related to breast cancer. Specific areas of interest include clinical research reports from various therapeutic modalities, cancer genetics, drug sensitivity and resistance, novel imaging, tumor genomics, biomarkers, and chemoprevention strategies.