Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Thyroid and Breast Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School, Shanghai, China.
Front Endocrinol (Lausanne). 2021 Nov 2;12:759338. doi: 10.3389/fendo.2021.759338. eCollection 2021.
The 21-gene assay recurrence score (RS) provides additional information on recurrence risk of breast cancer patients and prediction of chemotherapy benefit. Previous studies that examined the contribution of the individual genes and gene modules of RS were conducted mostly in postmenopausal patients. We aimed to evaluate the gene modules of RS in patients of different ages.
A total of 1,078 estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients diagnosed between January 2009 and March 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were included. All patients were divided into three subgroups: Group A, ≤40 years and premenopausal ( = 97); Group B, >40 years and premenopausal ( = 284); Group C, postmenopausal ( = 697). The estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of the variance tests were conducted for RS and its constituent modules.
In patients >40 years, RS had a strong negative correlation with its estrogen module ( = -0.76 and -0.79 in Groups B and C) and a weak positive correlation with its invasion module ( = 0.29 and 0.25 in Groups B and C). The proliferation module mostly contributed to the variance in young patients (37.3%) while the ER module contributed most in old patients (54.1% and 53.4% in Groups B and C). In the genetic high-risk (RS >25) group, the proliferation module was the leading driver in all patients ( = 0.38, 0.53, and 0.52 in Groups A, B, and C) while the estrogen module had a weaker correlation with RS. The impact of ER module on RS was stronger in clinical low-risk patients while the effect of the proliferation module was stronger in clinical high-risk patients. The association between the RS and estrogen module was weaker among younger patients, especially in genetic low-risk patients.
RS was primarily driven by the estrogen module regardless of age, but the proliferation module had a stronger impact on RS in younger patients. The impact of modules varied in patients with different genetic and clinical risks.
21 基因检测复发评分（RS）为乳腺癌患者提供了复发风险的额外信息，并预测了化疗的获益。此前的研究主要在绝经后患者中对 RS 的单个基因和基因模块的贡献进行了研究。我们旨在评估不同年龄患者的 RS 基因模块。
共纳入 2009 年 1 月至 2017 年 3 月上海交通大学乳腺癌数据库中诊断为雌激素受体（ER）阳性和人表皮生长因子受体 2（HER2）阴性的 1078 例乳腺癌患者。所有患者分为三组：A 组，≤40 岁且绝经前（n = 97）；B 组，>40 岁且绝经前（n = 284）；C 组，绝经后（n = 697）。采用 RS 的雌激素、增殖、侵袭和 HER2 模块评分来描述各自的分子特征。对 RS 及其组成模块进行 Spearman 相关性和方差分析。
在>40 岁的患者中，RS 与雌激素模块呈强负相关（B 组和 C 组分别为-0.76 和-0.79），与侵袭模块呈弱正相关（B 组和 C 组分别为 0.29 和 0.25）。增殖模块主要影响年轻患者（37.3%），而 ER 模块主要影响老年患者（B 组和 C 组分别为 54.1%和 53.4%）。在遗传高危（RS >25）组中，增殖模块在所有患者中都是主要驱动因素（A、B 和 C 组分别为 0.38、0.53 和 0.52），而雌激素模块与 RS 的相关性较弱。ER 模块对 RS 的影响在临床低危患者中更强，而增殖模块在临床高危患者中更强。RS 与雌激素模块之间的关联在年轻患者中较弱，尤其是在遗传低危患者中。
无论年龄大小，RS 主要由雌激素模块驱动，但在年轻患者中，增殖模块对 RS 的影响更强。不同遗传和临床风险患者的模块影响不同。
