对于早期乳腺癌保乳手术后患者，大多数需要接受辅助放疗以预防局部和淋巴引流区域的复发。目前，已有不少帮助选择最佳辅助化疗策略的多基因工具，例如21基因、70基因、50基因、12基因。不过，尚无帮助选择最佳辅助放疗策略的多基因工具。
2019年10月16日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表瑞典隆德大学、隆德大学斯科讷医院、哥德堡大学、萨尔格伦斯卡学院临床科学研究所、萨尔格伦斯卡医院、加拿大皮尔斯＋冯＋斯佩尔斯基因组学、破译生物科学、美国密歇根大学、旧金山加利福尼亚大学（通常被误译为加州大学旧金山分校）的研究报告，探讨了预测早期乳腺癌保乳手术后是否需要加强局部区域治疗的临床基因组放疗分类法。
该研究对SweBCG91放疗研究保乳手术后被随机分配接受全乳放疗或不放疗的淋巴结阴性乳腺癌患者原发肿瘤临床分级和多基因转录组进行了分析。首先根据三个可以公开获得的患者队列数据，建立新的分类法，即辅助放疗强化分类法ARTIC，其中包括27个基因和患者年龄，随后对SweBCG91放疗研究748例患者的局部区域复发进行了独立验证。此外，对于预测SweBCG91放疗研究患者的放疗获益能力，与已经公布的8种多基因谱进行比较。
结果，对于接受放疗的患者，ARTIC评分较高与较低相比，10年局部区域复发风险高3.4倍（风险比：3.4，95%置信区间：2.0～5.9，P<0.001），并且可以预测放疗获益（交互作用P=0.005）。
放疗与不放疗相比：
ARTIC评分较低的患者：10年局部区域复发风险低67%（风险比：0.33，95%置信区间：0.21～0.52，P<0.001，10年累计局部区域复发率：6%比21%）
ARTIC评分较高的患者：10年局部区域复发风险低27%（风险比：0.73，95%置信区间：0.44～1.2，P=0.23，10年累计局部区域复发率：25%比32%）
相比之下，已经发表的8种多基因谱都无法预测SweBCG91放疗研究患者能否获益于放疗。
因此，该研究结果表明，ARTIC可以预测放疗获益较大的女性，以及局部区域复发风险较高的女性，对于这些女性，全乳放疗效果不充分，故有必要加强治疗策略，例如肿瘤部位（瘤床）追加放疗，并且可能应该考虑引流区域淋巴结放疗。据我们所知，ARTIC是第一个对患者随机分配接受或不接受放疗的III期临床研究证实可以预测放疗获益的分类法。
对此，美国埃默里大学癌症研究所乳腺癌中心发表同期述评：ARTIC的意义——这是否形势改变的开始？
J Clin Oncol. 2019 Oct 16. [Epub ahead of print]
Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer.
Sjostrom M, Chang SL, Fishbane N, Davicioni E, Zhao SG, Hartman L, Holmberg E, Feng FY, Speers CW, Pierce LJ, Malmstrom P, Ferno M, Karlsson P.
Lund University, Lund, Sweden; Skane University Hospital, Lund, Sweden; PFS Genomics, Vancouver, Canada; Decipher Biosciences, Vancouver, Canada; University of Michigan Medical School, Ann Arbor, MI; Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden; University of California San Francisco, San Francisco, CA.
PURPOSE: Most patients with early-stage breast cancer are treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) to prevent locoregional recurrence (LRR). However, no genomic tools are used currently to select the optimal RT strategy.
METHODS: We profiled the transcriptome of primary tumors on a clinical grade assay from the SweBCG91-RT trial, in which patients with node-negative breast cancer were randomly assigned to either whole-breast RT after BCS or no RT. We derived a new classifier, Adjuvant Radiotherapy Intensification Classifier (ARTIC), comprising 27 genes and patient age, in three publicly available cohorts, then independently validated ARTIC for LRR in 748 patients in SweBCG91-RT. We also compared previously published genomic signatures for ability to predict benefit from RT in SweBCG91-RT.
RESULTS: ARTIC was highly prognostic for LRR in patients treated with RT (hazard ratio [HR], 3.4; 95% CI, 2.0 to 5.9; P < .001) and predictive of RT benefit (Pinteraction = .005). Patients with low ARTIC scores had a large benefit from RT (HR, 0.33 [95% CI, 0.21 to 0.52], P < .001; 10-year cumulative incidence of LRR, 6% v 21%), whereas those with high ARTIC scores benefited less from RT (HR, 0.73 [95% CI, 0.44 to 1.2], P = .23; 10-year cumulative incidence of LRR, 25% v 32%). In contrast, none of the eight previously published signatures were predictive of benefit from RT in SweBCG91-RT.
CONCLUSION: ARTIC identified women with a substantial benefit from RT as well as women with a particularly elevated LRR risk in whom whole-breast RT was not sufficiently effective and, thus, in whom intensified treatment strategies such as tumor-bed boost, and possibly regional nodal RT, should be considered. To our knowledge, ARTIC is the first classifier validated as predictive of benefit from RT in a phase III clinical trial with patients randomly assigned to receive or not receive RT.
PMID: 31618132
DOI: 10.1200/JCO.19.00761
J Clin Oncol. 2019 Oct 16. [Epub ahead of print]
Implications of ARTIC: Is This the Beginning of a Climate Change?
Torres MA.
Glenn Family Breast Center, Winship Cancer Institute, Emory University, Atlanta, GA.
PMID: 31618130
DOI: 10.1200/JCO.19.02100
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