Sturtz Lori A, Melley Jen, Mamula Kim, Shriver Craig D, Ellsworth Rachel E
Clinical Breast Care Project, Henry M, Jackson Foundation for the Advancement of Military Medicine, Windber, PA, USA.
BMC Cancer. 2014 Feb 4;14:62. doi: 10.1186/1471-2407-14-62.
Although diagnosed less often, breast cancer in African American women (AAW) displays different characteristics compared to breast cancer in Caucasian women (CW), including earlier onset, less favorable clinical outcome, and an aggressive tumor phenotype. These disparities may be attributed to differences in socioeconomic factors such as access to health care, lifestyle, including increased frequency of obesity in AAW, and tumor biology, especially the higher frequency of triple negative breast cancer (TNBC) in young AAW. Improved understanding of the etiology and molecular characteristics of TNBC in AAW is critical to determining whether and how TNBC contributes to survival disparities in AAW.
Demographic, pathological and survival data from AAW (n = 62) and CW (n = 98) with TNBC were analyzed using chi-square analysis, Student's t-tests, and log-rank tests. Frozen tumor specimens were available from 57 of the TNBC patients (n = 23 AAW; n = 34 CW); RNA was isolated after laser microdissection of tumor cells and was hybridized to HG U133A 2.0 microarrays. Data were analyzed using ANOVA with FDR <0.05, >2-fold difference defining significance.
The frequency of TNBC compared to all BC was significantly higher in AAW (28%) compared to CW (12%), however, significant survival and pathological differences were not detected between populations. Gene expression analysis revealed the tumors were more similar than different at the molecular level, with only CRYBB2P1, a pseudogene, differentially expressed between populations. Among demographic characteristics, AAW consumed significantly lower amounts of caffeine and alcohol, were less likely to breastfeed and more likely to be obese.
These data suggest that TNBC in AAW is not a unique disease compared to TNBC in CW. Rather, higher frequency of TNBC in AAW may, in part, be attributable to the effects of lifestyle choices. Because these risk factors are modifiable, they provide new opportunities for the development of risk reduction strategies that may decrease mortality by preventing the development of TNBC in AAW.
尽管非洲裔美国女性(AAW)患乳腺癌的诊断率较低,但与白人女性(CW)患乳腺癌相比,具有不同特征,包括发病更早、临床结局较差以及肿瘤表型侵袭性更强。这些差异可能归因于社会经济因素的不同,如获得医疗保健的机会、生活方式(包括AAW中肥胖频率增加)以及肿瘤生物学特性,特别是年轻AAW中三阴性乳腺癌(TNBC)的频率更高。更好地了解AAW中TNBC的病因和分子特征对于确定TNBC是否以及如何导致AAW的生存差异至关重要。
使用卡方分析、学生t检验和对数秩检验分析AAW(n = 62)和CW(n = 98)患有TNBC的人口统计学、病理学和生存数据。57例TNBC患者(n = 23例AAW;n = 34例CW)可获得冷冻肿瘤标本;在对肿瘤细胞进行激光显微切割后分离RNA,并与HG U133A 2.0微阵列杂交。使用FDR<0.05、差异倍数>2定义显著性的方差分析对数据进行分析。
与所有乳腺癌相比,AAW中TNBC的频率(28%)显著高于CW(12%),然而,未检测到不同人群之间存在显著的生存和病理差异。基因表达分析显示肿瘤在分子水平上的相似性高于差异性,只有假基因CRYBB2P1在不同人群之间存在差异表达。在人口统计学特征中,AAW摄入的咖啡因和酒精量显著较低,母乳喂养的可能性较小,肥胖的可能性较大。
这些数据表明,与CW中的TNBC相比,AAW中的TNBC并非一种独特的疾病。相反,AAW中TNBC频率较高可能部分归因于生活方式选择的影响。由于这些风险因素是可改变的,它们为制定降低风险策略提供了新机会,这些策略可能通过预防AAW中TNBC的发生来降低死亡率。