title: USP-11 as a predictive and prognostic factor following neoadjuvant therapy in women with breast cancer.
abstract: OBJECTIVE
  USP-11, a member of the ubiquitin-specific protease family, has emerged as an essential regulator of double-strand break repair. Few studies have shown that silencing USP-11 led to hypersensitivity to poly(ADP-ribose) polymerase inhibition, ionizing radiation, and DNA-damaging agents. We sought to examine the predictive and prognostic relevance of USP-11 in patients treated with neoadjuvant systemic therapy (NST) for breast cancer.
  
  
  METHODS
  Fifty-six women who were treated with NST for breast cancer between 1999 and 2004 were included in the study. The Kaplan-Meier product-limit method was used to estimate disease-free survival and overall survival rates. Logistic regression models were fit to determine the associations between USP-11 status, pathological complete response (pCR), and survival.
  
  
  RESULTS
  Sixteen patients (29%) had high-USP-11-expressing tumors, and 40 (71%) patients had low-USP-11-expressing tumors. No significant differences were observed in pCR rates with respect to USP-11 status. At a median follow-up of 7.4 years, 33 patients (59%) experienced a disease recurrence or death. Patients with high-USP-11-expressing tumors had a higher risk of recurrence (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.51-9.93; P = 0.005) and death (OR, 6.03; 95% CI, 2.00-18.17; P = 0.001) than those with low-USP-11-expressing tumors. Patients who did not achieve a pCR had an increased risk of recurrence (OR, 5.16; 95% CI, 1.16-23.07; P = 0.03).
  
  
  CONCLUSIONS
  Our data indicate that USP-11 is not a predictor of a pCR after anthracycline-taxane-containing NST for breast cancer. Low USP-11 expression was independently correlated with better survival outcomes.
authors: Departmentsof Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Soley
authors: S
authors: Bayraktar
authors: Angelica M
authors: AM
authors: Gutierrez Barrera
authors: Diane
authors: D
authors: Liu
authors: Lajos
authors: L
authors: Pusztai
authors: Jennifer
authors: J
authors: Litton
authors: Vicente
authors: V
authors: Valero
authors: Kelly
authors: K
authors: Hunt
authors: Gabriel N
authors: GN
authors: Hortobagyi
authors: Yun
authors: Y
authors: Wu
authors: Fraser
authors: F
authors: Symmans
authors: Banu
authors: B
authors: Arun
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D013869:Thiolester Hydrolases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: C101359:USP11 protein, human; D013869:Thiolester Hydrolases