Affiliations: [a] Keio University School of Medicine, Tokyo, Japan | [b] AstraZeneca, Macclesfield, UK | [c] Histopathology, Department of Translational Science, Asia & Emerging Markets IMED, AstraZeneca R&D, Shanghai, China
Correspondence:
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Corresponding author: Xiaolu Yin, Histopathology, Department of Translational Science, Asia & Emerging Markets IMED, AstraZeneca R&D, 199 Liangjing Road, Shanghai 201203, China. E-mail:[email protected]
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. AIM: 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. CONCLUSION: BRCA1 expression may be a candidate for a prognostic
biomarker in SOC. Further studies are warranted.
Keywords: BRCA, ovarian cancer, breast cancer, biomarker
