Association between TP53 mutation and high 21-gene recurrence score in estrogen receptor-positive/HER2-negative breast cancer

Jung Hwan Ji; Soong June Bae; Kyungsoo Kim; Chihhao Chu; Kyung-A Lee; Yoonjung Kim; Jee Hung Kim; Joon Jeong; Sung Gwe Ahn

doi:10.1038/s41523-022-00384-3

Association between TP53 mutation and high 21-gene recurrence score in estrogen receptor-positive/HER2-negative breast cancer

NPJ Breast Cancer. 2022 Feb 16;8(1):19. doi: 10.1038/s41523-022-00384-3.

Authors

Jung Hwan Ji^{1

2}, Soong June Bae^{1

2}, Kyungsoo Kim², Chihhao Chu^{1

2}, Kyung-A Lee³, Yoonjung Kim³, Jee Hung Kim^{2

4}, Joon Jeong^{1

2}, Sung Gwe Ahn^{5

6}

Affiliations

¹ Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
² Institute for Breast Cancer Precision Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
³ Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁴ Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁵ Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. ASG2004@yuhs.ac.
⁶ Institute for Breast Cancer Precision Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. ASG2004@yuhs.ac.

Abstract

We investigated the association between TP53 mutation and 21-gene recurrence score (RS) in ER-positive/HER2-negative breast cancer (BC) using data from 141 patients who underwent TP53 sequencing and Oncotype DX^® tests. We detected TP53 mutations in 18 (12.8%) patients. Most patients with TP53 mutation had a high 21-gene RS (≥26). The average 21-gene RS was higher in TP53 mutant tumors. Multivariate analysis showed that mutated TP53 is an independent factor for a high 21-gene RS. Mutated TP53 remained closely associated with high 21-gene RS in patients with low pathological risk (n = 103). In the ER⁺/PR⁺/HER2-negative subset (n = 356) of The Cancer Genome Atlas, the non-luminal A intrinsic subtype was more prevalent in the group with mutant TP53. mRNA levels of p53-regulated senescence gatekeeper and cell cycle-related genes were increased in BC with mutated TP53. Mutational analysis of TP53 helped identify endocrine-resistant tumors.