First Prospective Multicenter Italian Study on the Impact of the 21-Gene Recurrence Score in Adjuvant Clinical Decisions for Patients with ER Positive/HER2 Negative Breast Cancer

Oncologist. 2018 Mar;23(3):297-305. doi: 10.1634/theoncologist.2017-0322. Epub 2017 Nov 13.


Background: The Breast DX Italy prospective study evaluated the impact of the 21-gene recurrence score (RS) result on adjuvant treatment decisions for patients with early breast cancer.

Materials and methods: Nine centers (two Hub and seven Spoke centers of the Veneto Oncology Network) participated. Consecutive patients with estrogen receptor positive, human epidermal growth receptor negative, T1-T3, N0-N1 early breast cancer were prospectively registered; only those meeting protocol-defined clinicopathological "intermediate risk" criteria were eligible for the RS test. Pre-RS and post-RS physicians' treatment recommendations and treatment actually received were collected.

Results: A total of n = 124 N0 and n = 126 N1 patients underwent the RS assay. The majority had Grade 2 tumors (71%); median age was 55 years, median tumor size was 16 mm, and median Ki67 expression was 20%. Patients enrolled at Hub centers presented higher-risk features. The distribution of RS results was <18 (60.8%), 18-30 (32.4%), and >30 (6.8%). The indication before RS was hormonal therapy (HT) alone in 52% of cases. An indication before RS of chemotherapy (CT)+HT was more frequent for patients with N1 versus N0 tumors (57% vs. 39%, p = .0035) and for patients enrolled at Hub versus Spoke centers (54% vs. 36%, p = .007).The overall rate of change in treatment decision was 16% (n = 40), mostly from CT+HT to HT (n = 30). According to nodal status, rate of change in treatment decision was 12% for the N0 cohort and 20% for the N1 cohort. The proportion of patients recommended to CT+HT was significantly reduced from before to after RS (48% to 40%, p < .0016), especially in the N1 cohort (57% to 45%, p = .0027) and at Hub centers (54% to 44%, p = .001).

Conclusion: Despite frequent indication of HT before RS, the use of the RS assay further contributed to sparing CT, especially for patients with N1 tumors and at Hub centers.

Implications for practice: This study shows that, although a high proportion of patients were recommended to receive endocrine treatment alone before knowing the recurrence score (RS) assay, the RS test further contributed in sparing chemotherapy for some of these patients, especially in case of the N1 stage or for patients enrolled at referral centers. These data highlight the need for further work in collaboration with health authorities and companies in order to define strategies for the implementation of the use of RS testing in clinical practice in the Italian setting.


背景.乳腺 DX 意大利前瞻性研究评估了21基因复发评分(RS)结果对早期乳腺癌患者的辅助治疗决策的影响


结果.总共124名N0患者和126名N1患者接受了复发评分法。大多数有2级肿瘤(71%);平均年龄为55岁, 中位肿瘤大小为16 mm, 中位Ki67表达为20%。在Hub中心入组的患者表现出更高风险特征。复发评分结果的分布为:<18(60.8%)、18‐30(32.4%)及>30(6.8%)。复发评分前的使用情况是在52%的病例中仅使用激素治疗(HT)。对于在化疗(CT)+ HT的复发评分前的使用情况, N1肿瘤患者较N0肿瘤患者相比更频繁(57% vs. 39%, p=0.0035), Hub中心入组的患者较Spoke中心入组的患者更频繁(54% vs. 36%, p=0.007)

治疗决策的总体变化率为16%(n=40), 主要来自CT+HT至HT(n=30)。根据淋巴结状态, N0队列的治疗决策变化率为12%, N1队列的治疗决策变化率为20%。推荐CT+ HT的患者比例从复发评分前到复发评分后显著降低(48%至40%, p<0.0016), 特别是在N1队列(57%至45%, p=0.0027)和Hub中心(54%至44%, p=0.001)

结论.尽管在复发评分之前频繁使用激素治疗, 但复发评分法的使用进一步减少了使用化疗, 尤其是对N1肿瘤患者和Hub中心的患者。

对临床实践的启示:这项研究表明, 尽管在知道复发评分(RS)法之前推荐较高比例的患者仅进行内分泌治疗, 但复发评分测试进一步促进了对这些患者中其中一些减少使用化疗, 特别是对N1期肿瘤患者或对在转诊中心入组的患者。这些数据证明, 有必要进一步与卫生主管部门和企业合​​作, 以确定在意大利临床实践中实施复发评分测试应用的策略

Keywords: Adjuvant chemotherapy; Early breast cancer; Estrogen receptor positive; Recurrence score; Treatment change.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Clinical Decision-Making / methods*
  • Female
  • Gene Expression Profiling
  • Humans
  • Italy
  • Lymphatic Metastasis / pathology
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Neoplasm Recurrence, Local / genetics
  • Prospective Studies
  • Receptors, Estrogen / metabolism


  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Receptors, Estrogen