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Somatic mutations of triple-negative breast cancer: a comparison between Black and White women.

三阴性乳腺癌的体细胞突变: 黑人和白人女性的比较。

  • 影响因子:3.45
  • DOI:10.1007/s10549-020-05693-4
  • 作者列表:"Omilian AR","Wei L","Hong CC","Bandera EV","Liu S","Khoury T","Ambrosone CB","Yao S
  • 发表时间:2020-07-01
Abstract

PURPOSE:Understanding the contribution of tumor genome biology to racial disparities of triple-negative breast cancer (TNBC) is important for narrowing the cancer mortality gap between Black and White women. METHODS:We evaluated tumor somatic mutations using targeted sequencing of a customized panel of 151 genes and 15 copy number variations (CNVs) within a population of 133 TNBC patients, including 71 Black and 62 White women. RESULTS:The overall mutational burden between Black and White women with TNBC was not significantly different, with a median of 5 somatic changes per patient (point mutations and CNVs combined) for the customized panel (range 1-31 for Blacks vs. 1-26 for Whites; p = 0.76). Of the 151 genes examined, none were mutated at a significantly higher frequency in Black than in White cases, whereas two genes were mutated at a higher frequency in White cases-PIK3CA and NCOR1. No significant difference in the frequency of CNVs was observed between Black and White women with TNBC in our study population. CONCLUSION:Of gene mutations and CNVs in TNBC tumors from Black and White women, only PIK3CA and NCOR1 had significantly different, although slight, frequencies by race. These results indicate that overall differences observed in the mutation spectra between Black and White women with breast cancer are likely due to the differential distributions of breast cancer subtypes by race.

摘要

目的: 了解肿瘤基因组生物学对三阴性乳腺癌 (TNBC) 种族差异的贡献对于缩小黑人和白人女性之间的癌症死亡率差距很重要。 方法: 我们在 151 例 TNBC 患者群体中,使用定制的 133 个基因和 15 个拷贝数变异 (CNVs) 的测序来评价肿瘤体细胞突变。包括 71 名黑人和 62 名白人妇女。 结果: 患有 TNBC 的黑人和白人女性之间的总体突变负担没有显著差异,每个患者的体细胞变化中位数为 5 (点突变和 CNVs 合并) 对于自定义面板 (范围 1-31 为黑人 vs. 1-26 为白人; P = 0.76)。在检测的 151 个基因中,没有一个基因在黑色病例中的突变频率显著高于白色病例,而两个基因在白色 cases-PIK3CA 和 ncor1 中的突变频率更高。在我们的研究人群中,TNBC 的黑人和白人女性之间未观察到 CNVs 频率的显著差异。 结论: 在黑人和白人女性 TNBC 肿瘤的基因突变和 CNVs 中,只有 PIK3CA 和 NCOR1 在种族上有显著差异,尽管频率轻微。这些结果表明,在黑人和白人女性乳腺癌患者的突变谱中观察到的总体差异可能是由于乳腺癌亚型按种族的差异分布。

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影响因子:2.87
发表时间:2020-01-31
来源期刊:Bioscience reports
DOI:10.1042/BSR20192546
作者列表:["Chen X","Theobard R","Zhang J","Dai X"]

METHODS::RAD50 is commonly depleted in basal-like breast cancer with concomitant absence of INPP4B and several tumor suppressors such as BRCA1 and TP53. Our previous study revealed that INPP4B and RAD50 interact and such an interaction is associated with breast cancer survival at the transcriptional, translational and genomic levels. In the present study, we explored single nucleotide polymorphisms (SNPs) of these two genes that have synergistic effects on breast cancer survival to decipher mechanisms driving their interactions at the genetic level. The Cox's proportional hazards model was used to test whether SNPs of these two genes are interactively associated with breast cancer survival, following expression quantitative trait loci (eQTL) analysis and functional investigations. Our study revealed two disease-associating blocks, each encompassing five and two non-linkage disequilibrium linked SNPs of INPP4B and RAD50, respectively. Concomitant presence of any rare homozygote from each disease-associating block is synergistically prognostic of poor breast cancer survival. Such synergy is mediated via bypassing pathways controlling cell proliferation and DNA damage repair, which are represented by INPP4B and RAD50. Our study provided genetic evidence of interactions between INPP4B and RAD50, and deepened our understandings on the orchestrated genetic machinery governing tumor progression.

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影响因子:3.29
发表时间:2020-01-31
来源期刊:BMC cancer
DOI:10.1186/s12885-020-6534-z
作者列表:["Soliman H","Shah V","Srkalovic G","Mahtani R","Levine E","Mavromatis B","Srinivasiah J","Kassar M","Gabordi R","Qamar R","Untch S","Kling HM","Treece T","Audeh W"]

METHODS:BACKGROUND:Increased usage of genomic risk assessment assays suggests increased reliance on data provided by these assays to guide therapy decisions. The current study aimed to assess the change in treatment decision and physician confidence based on the 70-gene risk of recurrence signature (70-GS, MammaPrint) and the 80-gene molecular subtype signature (80-GS, BluePrint) in early stage breast cancer patients. METHODS:IMPACt, a prospective, case-only study, enrolled 452 patients between November 2015 and August 2017. The primary objective population included 358 patients with stage I-II, hormone receptor-positive, HER2-negative breast cancer. The recommended treatment plan and physician confidence were captured before and after receiving results for 70-GS and 80-GS. Treatment was started after obtaining results. The distribution of 70-GS High Risk (HR) and Low Risk (LR) patients was evaluated, in addition to the distribution of 80-GS compared to IHC status. RESULTS:The 70-GS classified 62.5% (n = 224/358) of patients as LR and 37.5% (n = 134/358) as HR. Treatment decisions were changed for 24.0% (n = 86/358) of patients after receiving 70-GS and 80-GS results. Of the LR patients initially prescribed CT, 71.0% (44/62) had CT removed from their treatment recommendation. Of the HR patients not initially prescribed CT, 65.1% (41/63) had CT added. After receiving 70-GS results, CT was included in 83.6% (n = 112/134) of 70-GS HR patient treatment plans, and 91.5% (n = 205/224) of 70-GS LR patient treatment plans did not include CT. For patients who disagreed with the treatment recommended by their physicians, most (94.1%, n = 16/17) elected not to receive CT when it was recommended. For patients whose physician-recommended treatment plan was discordant with 70-GS results, discordance was significantly associated with age and lymph node status. CONCLUSIONS:The IMPACt trial showed that treatment plans were 88.5% (n = 317/358) in agreement with 70-GS results, indicating that physicians make treatment decisions in clinical practice based on the 70-GS result. In clinically high risk, 70-GS Low Risk patients, there was a 60.0% reduction in treatment recommendations that include CT. Additionally, physicians reported having greater confidence in treatment decisions for their patients in 72% (n = 258/358) of cases after receiving 70-GS results. TRIAL REGISTRATION:"Measuring the Impact of MammaPrint on Adjuvant and Neoadjuvant Treatment in Breast Cancer Patients: A Prospective Registry" (NCT02670577) retrospectively registered on Jan 27, 2016.

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