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TP53 Signature Can Predict Pathological Response From Neoadjuvant Chemotherapy and Is a Prognostic Factor in Patients With Residual Disease

TP53 Signature Can Predict Pathological Response From Neoadjuvant Chemotherapy and Is a... Background:The TP53 signature that predicts the mutation status of TP53 has been shown to be a prognostic factor and predictor of neoadjuvant chemotherapy (NAC) response.Objectives:The current study sought to investigate the utility of the TP53 signature for predicting pathological complete response (pCR) and its prognostic significance among patients with residual disease (RD).Design:The study followed a retrospective cohort study design.Methods:Patients with T1-3/N0-1 from a cohort of those with HER2-negative breast cancer who received NAC were selected. Ability to predict pCR was evaluated using odds ratio, positive and negative predictive values, sensitivity, and specificity. Prognostic factors in the RD group were explored using the Cox proportional hazards model with distant recurrence-free survival (DRFS). Four independent cohorts were used for validation.Results:A total of 333 eligible patients were classified into the TP53 mutant signature (n = 154) and wild-type signature (n = 179). Among the molecular and pathological factors, the TP53 signature had the highest predictive power for pCR. In 4 independent cohorts (n = 151, 85, 104, and 67, respectively), pCR rate in TP53 mutant signature group was significantly higher than that in the wild-type group. Univariate and multivariate analyses on DRFS in the RD group identified the TP53 signature and nodal status as independent prognostic factors, with the former having a better hazard ratio than the latter. After comparing DRFS between 3 groups (pCR, RD/TP53 wild-type signature, and RD/TP53 mutant signature groups), the RD/TP53 mutant signature group showed significantly worse prognosis compared with others. The RD/TP53 wild-type signature group did not exhibit inferior DRFS compared with the pCR group.Conclusion:Our results showed that the TP53 mutant signature can predict pCR and that combining pathological response and TP53 mutant signature allows for the identification of subgroups with truly poor prognosis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Breast Cancer Basic and Clinical Research SAGE

TP53 Signature Can Predict Pathological Response From Neoadjuvant Chemotherapy and Is a Prognostic Factor in Patients With Residual Disease

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Publisher
SAGE
Copyright
© The Author(s) 2023
eISSN
1178-2234
DOI
10.1177/11782234231167655
Publisher site
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Abstract

Background:The TP53 signature that predicts the mutation status of TP53 has been shown to be a prognostic factor and predictor of neoadjuvant chemotherapy (NAC) response.Objectives:The current study sought to investigate the utility of the TP53 signature for predicting pathological complete response (pCR) and its prognostic significance among patients with residual disease (RD).Design:The study followed a retrospective cohort study design.Methods:Patients with T1-3/N0-1 from a cohort of those with HER2-negative breast cancer who received NAC were selected. Ability to predict pCR was evaluated using odds ratio, positive and negative predictive values, sensitivity, and specificity. Prognostic factors in the RD group were explored using the Cox proportional hazards model with distant recurrence-free survival (DRFS). Four independent cohorts were used for validation.Results:A total of 333 eligible patients were classified into the TP53 mutant signature (n = 154) and wild-type signature (n = 179). Among the molecular and pathological factors, the TP53 signature had the highest predictive power for pCR. In 4 independent cohorts (n = 151, 85, 104, and 67, respectively), pCR rate in TP53 mutant signature group was significantly higher than that in the wild-type group. Univariate and multivariate analyses on DRFS in the RD group identified the TP53 signature and nodal status as independent prognostic factors, with the former having a better hazard ratio than the latter. After comparing DRFS between 3 groups (pCR, RD/TP53 wild-type signature, and RD/TP53 mutant signature groups), the RD/TP53 mutant signature group showed significantly worse prognosis compared with others. The RD/TP53 wild-type signature group did not exhibit inferior DRFS compared with the pCR group.Conclusion:Our results showed that the TP53 mutant signature can predict pCR and that combining pathological response and TP53 mutant signature allows for the identification of subgroups with truly poor prognosis.

Journal

Breast Cancer Basic and Clinical Research – SAGE

Published: May 1, 2023

Keywords: Breast cancer; neoadjuvant chemotherapy; biomarker; gene expression profile; TP53 gene

References

  • Breast cancer, cancer fact sheets
  • Preoperative chemotherapy for women with operable breast cancer
    Mieog, JS; van der Hage, JA; van de Velde, CJ
  • Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials
  • Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project protocols B-18 and B-27
    Rastogi, P; Anderson, SJ; Bear, HD
  • Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes
    von Minckwitz, G; Untch, M; Blohmer, JU
  • Adjuvant capecitabine for breast cancer after preoperative chemotherapy
    Masuda, N; Lee, SJ; Ohtani, S
  • Trastuzumab emtansine for residual invasive HER2-positive breast cancer
    von Minckwitz, G; Huang, CS; Mano, MS
  • Adjuvant S-1 plus endocrine therapy for oestrogen receptor-positive, HER2-negative, primary breast cancer: a multicentre, open-label, randomised, controlled, phase 3 trial
    Toi, M; Imoto, S; Ishida, T
  • Effect of mutated TP53 on response of advanced breast cancers to high-dose chemotherapy
    Bertheau, P; Plassa, F; Espié, M
  • TP53 mutations are associated with higher rates of pathologic complete response to anthracycline/cyclophosphamide-based neoadjuvant chemotherapy in operable primary breast cancer
    Wang, Y; Xu, Y; Chen, J
  • Value of TP53 status for predicting response to neoadjuvant chemotherapy in breast cancer: a meta-analysis
    Chen, MB; Zhu, YQ; Xu, JY
  • Breast cancer survival predicted by TP53 mutation status differs markedly depending on treatment
    Ungerleider, NA; Rao, SG; Shahbandi, A
  • TP53 mutations and outcomes in breast cancer: reading beyond the headlines
    Shahbandi, A; Nguyen, HD; Jackson, JG.
  • Prediction of breast cancer prognosis by gene expression profile of TP53 status
    Takahashi, S; Moriya, T; Ishida, T
  • Gene expression signature of TP53 but not its mutation status predicts response to sequential paclitaxel and 5-FU/epirubicin/cyclophosphamide in human breast cancer
    Oshima, K; Naoi, Y; Kishi, K
  • Molecular and clinical features of the TP53 signature gene expression profile in early-stage breast cancer
    Yamaguchi, S; Takahashi, S; Mogushi, K
  • Evaluation of public cancer datasets and signatures identifies TP53 mutant signatures with robust prognostic and predictive value
    Lehmann, BD; Ding, Y; Viox, DJ
  • Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657)
    Esserman, LJ; Berry, DA; Cheang, MC
  • A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer
    Hatzis, C; Pusztai, L; Valero, V
  • The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models
    Shi, L; Campbell, G; Jones, WD
  • A systematic evaluation of multi-gene predictors for the pathological response of breast cancer patients to chemotherapy
    Shen, K; Song, N; Kim, Y
  • Serial expression analysis of breast tumors during neoadjuvant chemotherapy reveals changes in cell cycle and immune pathways associated with recurrence and response
    Magbanua, MJ; Wolf, DM; Yau, C
  • Gene expression-based prediction of neoadjuvant chemotherapy response in early breast cancer: results of the prospective multicenter EXPRESSION trial
    Edlund, K; Madjar, K; Lebrecht, A
  • Regulation of p53 downstream genes
    el-Deiry, WS.
  • p53-regulated transcriptional program associated with genotoxic stress-induced apoptosis
    Kho, PS; Wang, Z; Zhuang, L
  • p53 Dimers associate with a head-to-tail response element to repress cyclin B transcription
    Lipski, R; Lippincott, DJ; Durden, BC
  • Significance of TP53 mutations determined by next-generation “deep” sequencing in prognosis of estrogen receptor-positive breast cancer
    Uji, K; Naoi, Y; Kagara, N
  • Phase II study of preoperative sequential FEC and docetaxel predicts of pathological response and disease free survival
    Toi, M; Nakamura, S; Kuroi, K
  • Docetaxel followed by fluorouracil/epirubicin/cyclophosphamide as neoadjuvant chemotherapy for patients with primary breast cancer
    Iwata, H; Sato, N; Masuda, N
  • Randomized trial of preoperative docetaxel with or without capecitabine after 4 cycles of 5-fluorouracil-epirubicin-cyclophosphamide (FEC) in early-stage breast cancer: exploratory analyses identify Ki67 as a predictive biomarker for response to neoadjuvant chemotherapy
    Ohno, S; Chow, LW; Sato, N