Cancer Epidemiol Biomarkers Prev. 2022 Jan;31(1):124-131. doi: 10.1158/1055-9965.EPI-21-0661. Epub 2021 Nov 04.

TP53 Pathway Function, Estrogen Receptor Status, and Breast Cancer Risk Factors in the Carolina Breast Cancer Study.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Amber N Hurson, Mustapha Abubakar, Alina M Hamilton, Kathleen Conway, Katherine A Hoadley, Michael I Love, Andrew F Olshan, Charles M Perou, Montserrat Garcia-Closas, Melissa A Troester

PMID: 34737209 DOI: 10.1158/1055-9965.EPI-21-0661

Abstract

BACKGROUND: TP53 and estrogen receptor (ER) both play essential roles in breast cancer development and progression, with recent research revealing cross-talk between TP53 and ER signaling pathways. Although many studies have demonstrated heterogeneity of risk factor associations across ER subtypes, associations by TP53 status have been inconsistent.

METHODS: This case-case analysis included incident breast cancer cases (47% Black) from the Carolina Breast Cancer Study (1993-2013). Formalin-fixed paraffin-embedded tumor samples were classified for TP53 functional status (mutant-like/wild-type-like) using a validated RNA signature. For IHC-based TP53 status, mutant-like was classified as at least 10% positivity. We used two-stage polytomous logistic regression to evaluate risk factor heterogeneity due to RNA-based TP53 and/or ER, adjusting for each other and for PR, HER2, and grade. We then compared this with the results when using IHC-based TP53 classification.

RESULTS: The RNA-based classifier identified 55% of tumors as TP53 wild-type-like and 45% as mutant-like. Several hormone-related factors (oral contraceptive use, menopausal status, age at menopause, and pre- and postmenopausal body mass index) were associated with TP53 mutant-like status, whereas reproductive factors (age at first birth and parity) and smoking were associated with ER status. Multiparity was associated with both TP53 and ER. When classifying TP53 status using IHC methods, no associations were observed with TP53. Associations observed with RNA-based TP53 remained after accounting for basal-like subtype.

CONCLUSIONS: This case-case study found breast cancer risk factors associated with RNA-based TP53 and ER.

IMPACT: RNA-based TP53 and ER represent an emerging etiologic schema of interest in breast cancer prevention research.

©2021 The Authors; Published by the American Association for Cancer Research.

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Publication Types

• Journal Article

Grant support

• U01 CA179715/CA/NCI NIH HHS/United States
• U54 CA156733/CA/NCI NIH HHS/United States
• P30 ES010126/ES/NIEHS NIH HHS/United States
• F31 CA257388/CA/NCI NIH HHS/United States
• P50 CA058223/CA/NCI NIH HHS/United States
• R01 CA253450/CA/NCI NIH HHS/United States
• Z99 CA999999/ImNIH/Intramural NIH HHS/United States