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TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases.

Publication ,  Journal Article
Williams, LA; Butler, EN; Sun, X; Allott, EH; Cohen, SM; Fuller, AM; Hoadley, KA; Perou, CM; Geradts, J; Olshan, AF; Troester, MA
Published in: NPJ Breast Cancer
2018

Mutations in tumor suppressor TP53 have been inconsistently linked to breast cancer risk factors and survival. Immunohistochemistry (IHC) staining, a primary clinical means of TP53 mutation determination, only detects mutations that facilitate protein accumulation (e.g., missense mutations). RNA-based pathway methods capture functional status and may aid in understanding the role of TP53 function in racial disparities of breast cancer. TP53 status was assessed among invasive breast cancer cases from the Carolina Breast Cancer Study (CBCS) (2008-2013) using IHC and an established RNA-based TP53 signature (CBCS and The Cancer Genome Atlas (TCGA)). Frequency of TP53 status (IHC, RNA-based) was estimated in association with tumor characteristics, PAM50 intrinsic subtype, age, and race using relative frequency differences (RFDs) and 95% confidence intervals (95% CI) as the measure of association. Approximately 60% of basal-like tumors were TP53 protein positive (IHC), while nearly 100% were TP53 mutant-like (RNA). Luminal A tumors had low frequency of TP53 positivity (IHC: 7.9%) and mutant-like status (RNA: 1.7%). Mutant-like TP53 (RNA) was strongly associated with age ≤50 years, high tumor grade, advanced stage of disease, large tumor size, and basal-like and HER2 intrinsic subtypes. Black race was strongly associated with TP53 mutant-like status (RNA) (RFD: 24.8%, 95% CI: 20.5, 29.0) even after adjusting for age, grade, stage (RFD: 11.3%; 95% CI: 7.6, 15.0). Associations were attenuated and non-significant when measured by IHC. IHC-based TP53 status is an insensitive measurement of TP53 functional status. RNA-based methods suggest a role for TP53 in tumor prognostic features and racial disparities.

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Published In

NPJ Breast Cancer

DOI

ISSN

2374-4677

Publication Date

2018

Volume

4

Start / End Page

13

Location

United States

Related Subject Headings

  • 4202 Epidemiology
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Williams, L. A., Butler, E. N., Sun, X., Allott, E. H., Cohen, S. M., Fuller, A. M., … Troester, M. A. (2018). TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases. NPJ Breast Cancer, 4, 13. https://doi.org/10.1038/s41523-018-0067-5
Williams, Lindsay A., Ebonee N. Butler, Xuezheng Sun, Emma H. Allott, Stephanie M. Cohen, Ashley M. Fuller, Katherine A. Hoadley, et al. “TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases.NPJ Breast Cancer 4 (2018): 13. https://doi.org/10.1038/s41523-018-0067-5.
Williams LA, Butler EN, Sun X, Allott EH, Cohen SM, Fuller AM, et al. TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases. NPJ Breast Cancer. 2018;4:13.
Williams, Lindsay A., et al. “TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases.NPJ Breast Cancer, vol. 4, 2018, p. 13. Pubmed, doi:10.1038/s41523-018-0067-5.
Williams LA, Butler EN, Sun X, Allott EH, Cohen SM, Fuller AM, Hoadley KA, Perou CM, Geradts J, Olshan AF, Troester MA. TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases. NPJ Breast Cancer. 2018;4:13.

Published In

NPJ Breast Cancer

DOI

ISSN

2374-4677

Publication Date

2018

Volume

4

Start / End Page

13

Location

United States

Related Subject Headings

  • 4202 Epidemiology
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences