title: Expression of potential biomarkers associated with homologous recombination repair in patients with ovarian or triple-negative breast cancer.
abstract: BACKGROUND
  Poly(ADP)-ribose polymerase (PARP) inhibitors such as olaparib can induce cell death in cancer cells with homologous recombination (HR) DNA repair deficiencies, such as BRCA1/2 mutations.
  
  
  OBJECTIVE
  To identify prognostic biomarkers of long-term outcomes in cancer patients.
  
  
  METHODS
  Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients. RECIST assessment was used.
  
  
  RESULTS
  Patient demographic data and BRCA1/2 mutation status were unavailable. Most proteins listed previously were detected in > 80% of tissue samples, with BRCA1 expression detected in 60-65%. A potential link between BRCA1 expression and overall survival (M stage adjusted) in SOC patients was observed, but was not statistically significant after multiple testing adjustment. Correlations between other biomarker expression and survival were not observed. In TNBC patients, MDC1 staining was associated with progressive disease, but this was not statistically significant; the analysis did not identify significant correlations between biomarker expression and disease control. Limited event numbers prevented assessment of the prognostic value of BRCA1 in TNBC.
  
  
  CONCLUSIONS
  BRCA1 expression may be a candidate for a prognostic biomarker in SOC. Further studies are warranted.
authors.affiliation: Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nomura
authors.affiliation: Keio University School of Medicine, Tokyo, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Kataoka
authors.affiliation: Keio University School of Medicine, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.affiliation: Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Jinno
authors.affiliation: Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sato
authors.affiliation: AstraZeneca, Macclesfield, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Womack
authors.affiliation: AstraZeneca, Macclesfield, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Wombwell
authors.affiliation: AstraZeneca, Macclesfield, UK.
authors.forename: Darren
authors.initials: D
authors.lastname: Hodgson
authors.affiliation: AstraZeneca, Macclesfield, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: O'Connor
authors.affiliation: AstraZeneca, Macclesfield, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Harbron
authors.affiliation: Histopathology, Department of Translational Science, Asia & Emerging Markets IMED, AstraZeneca R&D, Shanghai, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Yin
mesh_terms: D014408:Biomarkers, Tumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D059767:Recombinational DNA Repair; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: BRCA; biomarker; breast cancer; ovarian cancer