Troester Melissa A, Sun Xuezheng, Allott Emma H, Geradts Joseph, Cohen Stephanie M, Tse Chiu-Kit, Kirk Erin L, Thorne Leigh B, Mathews Michelle, Li Yan, Hu Zhiyuan, Robinson Whitney R, Hoadley Katherine A, Olopade Olufunmilayo I, Reeder-Hayes Katherine E, Earp H Shelton, Olshan Andrew F, Carey Lisa A, Perou Charles M
Department of Epidemiology, Lineberger Comprehensive Cancer Center; Department of Pathology and Lab Medicine, Department of Nutrition (EHA), and Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC; Dana Farber Cancer Institute, Harvard University, Boston, MA; Center for Clinical Cancer Genetics, Global Health Department of Medicine, The University of Chicago, Chicago, IL.
J Natl Cancer Inst. 2018 Feb 1;110(2):176-82. doi: 10.1093/jnci/djx135.
African American breast cancer patients have lower frequency of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative disease and higher subtype-specific mortality. Racial differences in molecular subtype within clinically defined subgroups are not well understood.
Using data and biospecimens from the population-based Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified 980 invasive breast cancers using RNA expression-based PAM50 subtype and recurrence (ROR) score that reflects proliferation and tumor size. Molecular subtypes (Luminal A, Luminal B, HER2-enriched, and Basal-like) and ROR scores (high vs low/medium) were compared by race (blacks vs whites) and age (≤50 years vs > 50 years) using chi-square tests and analysis of variance tests.
Black women of all ages had a statistically significantly lower frequency of Luminal A breast cancer (25.4% and 33.6% in blacks vs 42.8% and 52.1% in whites; younger and older, respectively). All other subtype frequencies were higher in black women (case-only odds ratio [OR] = 3.11, 95% confidence interval [CI] = 2.22 to 4.37, for Basal-like; OR = 1.45, 95% CI = 1.02 to 2.06, for Luminal B; OR = 2.04, 95% CI = 1.33 to 3.13, for HER2-enriched). Among clinically HR+/HER2- cases, Luminal A subtype was less common and ROR scores were statistically significantly higher among black women.
Multigene assays highlight racial disparities in tumor subtype distribution that persist even in clinically defined subgroups. Differences in tumor biology (eg, HER2-enriched status) may be targetable to reduce disparities among clinically ER+/HER2- cases.
非裔美国乳腺癌患者激素受体阳性(HR+)/人表皮生长因子受体2(HER2)阴性疾病的发生率较低,但亚型特异性死亡率较高。临床定义亚组内分子亚型的种族差异尚未完全了解。
利用基于人群的卡罗来纳乳腺癌研究(CBCS)3期(2008 - 2013年)的数据和生物样本,我们使用基于RNA表达的PAM50亚型和反映增殖及肿瘤大小的复发(ROR)评分对980例浸润性乳腺癌进行分类。通过卡方检验和方差分析,比较种族(黑人与白人)和年龄(≤50岁与>50岁)的分子亚型(管腔A型、管腔B型、HER2富集型和基底样型)及ROR评分(高与低/中)。
各年龄段黑人女性管腔A型乳腺癌的发生率在统计学上显著较低(黑人中年轻和年长女性分别为25.4%和33.6%,白人中分别为42.8%和52.1%)。黑人女性所有其他亚型的发生率较高(基底样型:仅病例比值比[OR]=3.11,95%置信区间[CI]=2.22至4.37;管腔B型:OR = 1.45,95% CI = 1.02至2.06;HER2富集型:OR = 2.04,95% CI = 1.33至3.13)。在临床HR+/HER2-病例中,管腔A型亚型较少见,黑人女性的ROR评分在统计学上显著较高。
多基因检测突出了肿瘤亚型分布中的种族差异,即使在临床定义的亚组中这种差异依然存在。肿瘤生物学差异(如HER2富集状态)可能是可靶向的,以减少临床ER+/HER2-病例之间的差异。