Supplementary Material for: Factors Associated with the Use of Gene Expression Profiles in Estrogen Receptor-Positive Early-Stage Breast Cancer Patients: A Nationwide Study

<strong><em>Background:</em></strong> Breast cancer guidelines suggest the use of gene expression profiles (GEPs) in estrogen receptor-positive (ER+) breast cancer patients in whom controversy exists regarding adjuvant chemotherapy benefit based on traditional prognostic factors alone. We evaluated the current use of GEPs in these patients in the Netherlands. <b><i>Patients and Methods:</i></b> Primary breast cancer patients treated between January 1, 2011 and December 31, 2014 and eligible for GEP use according to the Dutch national breast cancer guideline were identified in the Netherlands Cancer Registry: ER+ patients &lt;70 years with grade 1 tumors &gt;2 cm or grade 2 tumors 1-2 cm without overt lymph node metastases (pN0-Nmi). Mixed-effect logistic regression analysis was performed to associate characteristics of patients, tumors and hospitals with GEP use. <b><i>Results:</i></b> GEPs were increasingly deployed: 12% of eligible patients received a GEP in 2011 versus 46% in 2014. Lobular versus ductal morphology (OR 0.58, 95% CI 0.47-0.72), pN1mi status (versus pN0, OR 0.52, 95% CI 0.40-0.68), and tumor size (&gt;3 cm vs. &gt;2 cm, OR 0.33, 95% CI 0.14-0.88) were inversely associated with GEP use. High socioeconomic status (SES) (OR 1.32, 95% CI 1.06-1.64) and younger age (OR 0.96/year increasing age, 95% CI 0.95-0.96) were positively associated with GEP use. GEP use per hospital did vary, but no predefined institutional factors remained independently associated with GEP use. <b><i>Conclusion:</i></b> GEP use increased over time and was influenced by patient- and tumor-associated factors as well as by SES.

**背景**：乳腺癌诊疗指南建议，对于仅依靠传统预后因素难以判定辅助化疗获益、存在临床争议的雌激素受体阳性（estrogen receptor-positive, ER+）乳腺癌患者，可采用基因表达谱（gene expression profiles, GEPs）进行辅助评估。本研究针对荷兰地区该类患者中GEPs的临床应用现状展开调查评估。**患者与方法**：本研究从荷兰癌症登记系统中筛选2011年1月1日至2014年12月31日期间接受治疗、且符合荷兰国家乳腺癌诊疗指南GEPs应用指征的原发性乳腺癌患者：即年龄＜70岁、伴＞2cm的1级肿瘤，或伴1~2cm的2级肿瘤且无显性淋巴结转移（pN0-Nmi）的ER+患者。采用混合效应logistic回归分析，探究患者、肿瘤及医院相关特征与GEPs应用的相关性。**结果**：GEPs的临床应用呈逐年上升趋势：2011年符合指征的患者中仅12%接受了GEPs检测，至2014年该比例提升至46%。组织形态为小叶型相较于导管型（比值比OR=0.58，95%置信区间CI=0.47~0.72）、pN1mi分期（相较于pN0，OR=0.52，95%CI=0.40~0.68）以及肿瘤大小＞3cm相较于＞2cm（OR=0.33，95%CI=0.14~0.88）均与GEPs应用呈负相关。高社会经济地位（socioeconomic status, SES）（OR=1.32，95%CI=1.06~1.64）与更年轻的年龄（每增加1岁，OR=0.96，95%CI=0.95~0.96）则与GEPs应用呈正相关。不同医院的GEPs应用率存在差异，但未发现预先设定的机构因素与GEPs应用存在独立相关性。**结论**：GEPs的临床应用随时间推移逐步增加，且受到患者与肿瘤相关特征以及社会经济地位的影响。