Ding Yuan Chun, Steele Linda, Warden Charles, Wilczynski Sharon, Mortimer Joanne, Yuan Yuan, Neuhausen Susan L
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Department of Cellular and Molecular Biology, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Oncotarget. 2019 Jan 4;10(2):198-208. doi: 10.18632/oncotarget.26559.
Molecular subtypes of triple negative breast cancer (TNBC) are associated with variation in survival and may assist in treatment selection. However, the association of patient race or ethnicity with subtypes of TNBC and clinical outcome has not been addressed. Using nCounter Gene Expression Codesets, we classified TNBCs into subtypes: basal-like immune-activated (BLIA), basal-like immunosuppressed (BLIS), luminal androgen receptor (LAR), and mesenchymal (MES) in 48 Hispanic, 12 African-American, 21 Asian, and 34 White patients. Mean age at diagnosis was significantly associated with subtype, with the youngest mean age (50 years) in MES and the oldest mean age (64 years) in LAR ( < 0.0005). Subtype was significantly associated with tumor grade ( = 0.0012) and positive lymph nodes ( = 0.021), with a marginally significant association of tumor stage ( = 0.076). In multivariate Cox-proportional hazards modeling, BLIS was associated with worst survival and LAR with best survival. Hispanics had a significantly higher proportion of BLIS (53%, = 0.03), whereas Asians had a lower proportion of BLIS (19%, = 0.05) and a higher proportion of LAR (38%, = 0.06) compared to the average proportion across all groups. These differences in proportions of subtype across racial and ethnic groups may explain differences in their outcomes. Determining subtypes of TNBC facilitates understanding of the heterogeneity of the TNBCs and provides a foundation for developing subtype-specific therapies and better predictors of TNBC prognosis for all races and ethnicities.
三阴性乳腺癌（TNBC）的分子亚型与生存率差异相关，可能有助于治疗选择。然而，患者种族或民族与TNBC亚型及临床结局之间的关联尚未得到探讨。我们使用nCounter基因表达编码集，将48名西班牙裔、12名非裔美国人、21名亚洲人和34名白人患者的TNBC分为以下亚型：基底样免疫激活型（BLIA）、基底样免疫抑制型（BLIS）、腔面雄激素受体型（LAR）和间充质型（MES）。诊断时的平均年龄与亚型显著相关，MES亚型的平均年龄最小（50岁），LAR亚型的平均年龄最大（64岁）（P<0.0005）。亚型与肿瘤分级（P = 0.0012）和阳性淋巴结（P = 0.021）显著相关，与肿瘤分期的关联具有边际显著性（P = 0.076）。在多变量Cox比例风险模型中，BLIS与最差生存率相关，LAR与最佳生存率相关。与所有组的平均比例相比，西班牙裔患者中BLIS的比例显著更高（53%，P = 0.03），而亚洲人中BLIS的比例较低（19%，P = 0.05），LAR的比例较高（38%，P = 0.06）。不同种族和民族间亚型比例的这些差异可能解释了它们结局的差异。确定TNBC的亚型有助于理解TNBC的异质性，并为开发亚型特异性疗法以及为所有种族和民族提供更好的TNBC预后预测指标奠定基础。
