title: Low p53 binding protein 1 (53BP1) expression is associated with increased local recurrence in breast cancer patients treated with breast-conserving surgery and radiotherapy.
abstract: OBJECTIVE
  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
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiation Oncology, The Cancer Institute of New Jersey and University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Hanmanth J R
authors.initials: HJ
authors.lastname: Neboori
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Haffty
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.forename: Amal
authors.initials: A
authors.lastname: Aly
authors.forename: Sharad
authors.initials: S
authors.lastname: Goyal
authors.forename: Devora
authors.initials: D
authors.lastname: Schiff
authors.forename: Meena S
authors.initials: MS
authors.lastname: Moran
authors.forename: Ryan
authors.initials: R
authors.lastname: Golhar
authors.forename: Chunxia
authors.initials: C
authors.lastname: Chen
authors.forename: Dirk
authors.initials: D
authors.lastname: Moore
authors.forename: Shridar
authors.initials: S
authors.lastname: Ganesan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D015412:Mastectomy, Segmental; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D000071857:Tumor Suppressor p53-Binding Protein 1; C498301:TP53BP1 protein, human