title: Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients.
abstract: OBJECTIVE
  To evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in patients with locally advanced basal-like breast cancers (BLBCs).
  
  
  METHODS
  Thirty-two BLBC patients receiving NACT with an anthracycline-based regimen plus taxane were included in this study. The immunoreactivities of MGMT, MLH1, MSH2 and BRCA1 before and after NACT were evaluated.
  
  
  RESULTS
  A pCR was obtained in 10 of 32 cases (31%). Cancer-related (P = 0.013) and disease-free (P = 0.023) survival rates were significantly higher in the pCR group than in the non-pCR group. In biopsy samples before NACT, attenuated expression of MGMT, MLH1, MSH2 and BRCA1 was observed in 12/32 (38%), 0/32 (0%), 5/32 (16%) and 28/32 (88%) cases, respectively. On evaluation of pCR, patients' characteristics (patients' age, menopausal status, or clinical and pathological stages) and immunohistochemical patterns, attenuated expression of MGMT was only found to be significantly predictive of a pCR (P = 0.018). Paired biopsy sample before NACT and a surgical tumor material after NACT were available for 19 cases of non-pCR. In these cases, decrease in expression during NACT were more frequently observed for MGMT as compared to MLH1, MSH2 or BRCA1 (P = 0.021).
  
  
  CONCLUSIONS
  MGMT status is a predictive factor for pCR with neoadjuvant anthracycline-based plus taxane combination chemotherapy, which may be helpful in the selection of appropriate NACT for Japanese patients with BLBC.
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nakai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mitomi
authors.forename: Yimit
authors.initials: Y
authors.lastname: Alkam
authors.forename: Atsushi
authors.initials: A
authors.lastname: Arakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
authors.forename: Emi
authors.initials: E
authors.lastname: Tokuda
authors.forename: Mitsue
authors.initials: M
authors.lastname: Saito
authors.forename: Fujio
authors.initials: F
authors.lastname: Kasumi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053843:DNA Mismatch Repair; D015254:DNA Modification Methylases / Q000096:biosynthesis*; D045643:DNA Repair Enzymes / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis*; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000096:biosynthesis*; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes