Low p53 binding protein 1 (53BP1) expression is associated with increased local recurrence in breast cancer patients treated with breast-conserving surgery and radiotherapy

Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):e677-83. doi: 10.1016/j.ijrobp.2012.01.089. Epub 2012 Apr 18.

Abstract

Purpose: To investigate whether the expression of p53 binding protein 1 (53BP1) has prognostic significance in a cohort of early-stage breast cancer patients treated with breast-conserving surgery and radiotherapy (BCS+RT).

Methods and materials: A tissue microarray of early-stage breast cancer treated with BCS+RT from a cohort of 514 women was assayed for 53BP1, estrogen receptor, progesterone receptor, and HER2 expression by immunohistochemistry. Through log-rank tests and univariate and multivariate models, the staining profile of each tumor was correlated with clinical endpoints, including ipsilateral breast recurrence-free survival (IBRFS), distant metastasis-free survival (DMFS), cause-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS).

Results: Of the 477 (93%) evaluable tumors, 63 (13%) were scored as low. Low expression of 53BP1 was associated with worse outcomes for all endpoints studied, including 10-year IBRFS (76.8% vs. 90.5%; P=.01), OS (66.4% vs. 81.7%; P=.02), CSS (66.0% vs. 87.4%; P<.01), DMFS (55.9% vs. 87.0%; P<.01), and RFS (45.2% vs. 80.6%; P<.01). Multivariate analysis incorporating various clinico-pathologic markers and 53BP1 expression found that 53BP1 expression was again an independent predictor of all endpoints (IBRFS: P=.0254; OS: P=.0094; CSS: P=.0033; DMFS: P=.0006; RFS: P=.0002). Low 53BP1 expression was also found to correlate with triple-negative (TN) phenotype (P<.01). Furthermore, in subset analysis of all TN breast cancer, negative 53BP1 expression trended for lower IBRFS (72.3% vs. 93.9%; P=.0361) and was significant for worse DMFS (48.2% vs. 86.8%; P=.0035) and RFS (37.8% vs. 83.7%; P=.0014).

Conclusion: Our data indicate that low 53BP1 expression is an independent prognostic indicator for local relapse among other endpoints in early-stage breast cancer and TN breast cancer patients treated with BCS+RT. These results should be verified in larger cohorts of patients to validate their clinical significance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Combined Modality Therapy / methods
  • Disease-Free Survival
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mastectomy, Segmental*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Proteins / metabolism*
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / mortality
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Retrospective Studies
  • Tissue Array Analysis
  • Treatment Outcome
  • Tumor Suppressor p53-Binding Protein 1

Substances

  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Receptors, Estrogen
  • TP53BP1 protein, human
  • Tumor Suppressor p53-Binding Protein 1
  • Receptor, ErbB-2