Aalders K C, Kuijer A, Straver M E, Slaets L, Litiere S, Viale G, Van't Veer L J, Glas A M, Delorenzi M, van Dalen T, Tryfonidis K, Piccart M J, Cardoso F, Rutgers E J
Medical Department, European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
Department of Surgery, Diakonessenhuis Utrecht, Utrecht, The Netherlands; Department of Radiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Eur J Cancer. 2017 Jul;79:98-105. doi: 10.1016/j.ejca.2017.03.034. Epub 2017 May 3.
In multifocal breast cancer, guidelines recommend basing adjuvant systemic treatment decisions on characteristics of the largest lesion, disregarding multifocality as an independent prognosticator. We assessed the association between multifocal disease and both the 70-gene signature (70-GS), and distant metastasis-free survival (DMFS) in clinical low-risk breast cancer patients enrolled in the European Organisation for Research and Treatment of Cancer 10041/BIG 03-04 Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy (MINDACT) trial.
The analysed population consisted of enrolled patients in the MINDACT trial with clinical low-risk disease, defined by a modified Adjuvant! Online cut-off for the 10-year risk of recurrent disease or death. Eligibility criteria of MINDACT dictate that patients with multifocal disease could be included if the different lesions had similar pathological characteristics. The presence of multifocal disease was deducted from the case report form (CRF)-question for sum of diameter for all invasive tumour foci. Clinicopathological characteristics and gene expression of patients with unifocal and multifocal (largest lesion) disease were compared. Subsequently, the association between multifocal disease and the 70-GS was evaluated as well as the association between multifocality and 5-year DMFS.
The study included 3090 clinical low-risk patients with unifocal and 238 patients with multifocal disease. Apart from a higher prevalence of lobular tumours (21.8% versus 10.8%, by local pathology), we did not observe differences in baseline characteristics between multifocal and unifocal tumours. Patients with multifocal tumours were more likely to be at high genomic risk as compared to patients with unifocal tumours (22.7% versus 17.3%, odds ratio [OR] 1.45, 95% confidence interval [CI] 1.02-2.07, P = 0.038). We did not find a significant association between tumour focality and DMFS (97.1% for unifocal versus 96.9% for multifocal, hazard ratio [HR] = 1.55, 95% CI 0.68-3.46, P = 0.172), nor a signal for a potential interaction between the prognostic effect of the 70-GS and focality of the tumour regarding DMFS.
In the group of clinical low-risk MINDACT patients, multifocal tumours were more likely to have a high-risk 70-GS profile compared to unifocal tumours. We did not observe a significant interaction between multifocality and the 70-GS with respect to survival without distant metastasis in these patients.
在多灶性乳腺癌中，指南建议根据最大病灶的特征来制定辅助性全身治疗决策，而不将多灶性视为独立的预后因素。我们在欧洲癌症研究与治疗组织10041/BIG 03 - 04微阵列研究（针对腋窝淋巴结阴性和1至3个阳性淋巴结疾病可能避免化疗（MINDACT）试验）中，评估了多灶性疾病与70基因标志物（70-GS）以及远处无转移生存期（DMFS）之间的关联。
分析人群包括MINDACT试验中符合临床低风险疾病的入组患者，临床低风险疾病由改良的Adjuvant! Online复发疾病或死亡10年风险切点定义。MINDACT的纳入标准规定，如果不同病灶具有相似的病理特征，多灶性疾病患者也可纳入。多灶性疾病的存在是从病例报告表（CRF）中所有浸润性肿瘤病灶直径总和的问题中推断出来的。比较了单灶性和多灶性（最大病灶）疾病患者的临床病理特征和基因表达。随后，评估了多灶性疾病与70-GS之间的关联以及多灶性与5年DMFS之间的关联。
该研究纳入了3090例临床低风险单灶性疾病患者和238例多灶性疾病患者。除小叶肿瘤的患病率较高外（根据局部病理，分别为21.8%和10.8%），我们未观察到多灶性和单灶性肿瘤之间基线特征的差异。与单灶性肿瘤患者相比，多灶性肿瘤患者更有可能处于高基因组风险（分别为22.7%和17.3%，比值比[OR]1.45，95%置信区间[CI]1.02 - 2.07，P = 0.038）。我们未发现肿瘤灶性与DMFS之间存在显著关联（单灶性为97.1%，多灶性为96.9%，风险比[HR]=1.55，95%CI 0.68 - 3.46，P = 0.172），也未发现70-GS的预后效应与肿瘤灶性在DMFS方面存在潜在相互作用的信号。
在临床低风险的MINDACT患者组中，与单灶性肿瘤相比，多灶性肿瘤更有可能具有高风险的70-GS特征。在这些患者中，我们未观察到多灶性与70-GS在远处无转移生存方面存在显著相互作用。
