BRCA1 overexpression and
phosphoinositide 3-kinase (PIK3CA) pathway activation are involved in the resistance to
DNA damaging agents. Thus, we hypothesized that
BRCA1 protein expression and activating PIK3CA mutations are potential
tumor biomarkers for the chemotherapeutic response to
doxorubicin/
cyclophosphamide plus
docetaxel in locally advanced
breast cancer. Informed consent was obtained and clinical, pathological and response data were collected.
BRCA1 protein expression levels were assessed by immunohistochemistry of the archived tissue by two independent pathologists. The PIK3CA mutation status was assessed by nested PCR amplification and
DNA sequencing.
BRCA1 protein levels and the PIK3CA mutation status were correlated with pathological complete response and a partial response or better using the Chi-square test, Fisher's exact test and logistic regression. Of the 136 eligible participants, 59 samples could be analyzed. There was a trend of relatively low levels of
BRCA1 protein achieving a pathological complete response (pCR), although this was not statistically significant [odds ratio (OR)=1.74; p=0.437]. Twenty-eight percent of patients had PIK3CA mutations, but no statistically significant association with pCR (OR=0.977; p=0.971) was noted. Neither
BRCA1 protein levels (OR=1.18; p=0.818) nor PIK3CA mutations (OR=1.03; p=0.971) appeared to be associated with the likelihood of achieving a partial response or better from
neoadjuvant chemotherapy. PIK3CA wild-type mutation status showed a trend towards an increased likelihood of not presenting with inflammatory disease (OR=5.34; p=0.101). In this exploratory study, neither
BRCA1 protein expression levels nor the presence of PIK3CA mutations were significantly associated with
chemotherapy response in locally advanced
breast cancer. However, the relatively small sample size limits the overall interpretation.