title: Clinical significance of pretherapeutic Ki67 as a predictive parameter for response to neoadjuvant chemotherapy in breast cancer: is it equally useful across tumor subtypes?
abstract: BACKGROUND
  Ki67 has been identified as a prognostic and predictive marker for breast cancer and it was suggested that it may contribute to pathologic complete response (pCR) after neoadjuvant chemotherapy. It is unclear whether expression of Ki67 is particularly helpful for prediction of pCR across tumor subtypes.
  
  
  METHODS
  Pretherapeutic Ki67 was evaluated in a series of 121 breast cancer core biopsies. After neoadjuvant chemotherapy, we used postoperative specimens to evaluate the pCR status. Several parameters predictive of pCR were identified using logistic regression analysis. We investigated subgroups defined by estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2, in which predicting pCR with Ki67 might be feasible.
  
  
  RESULTS
  Ki67 was found to be an independent predictor of pCR in multivariate analysis (odds ratio [OR], 3.62; 95% CI, 1.21-10.8). When stratified by ER, the above significance was exclusive to ER-positive tumors (OR, 6.24; 95% CI, 1.40-27.7). Using an receiver-operating characteristic curve, we obtained moderate discriminative accuracy with an area under the curve of 0.7752 for Ki67 prediction of pCR in ER-positive tumors. In subgroup analysis, patients with high Ki67 showed significantly improved pCR rate in luminal-type disease, with a median Ki67 value of 43% in the patients who achieved pCR, versus 29% for those without pCR (P = .018), whereas no associations were observed in other subtypes.
  
  
  CONCLUSIONS
  Our results suggest that stratification according to Ki67 levels might improve predictive significance of the response in hormone-responsive breast cancer. Even in these subtypes assumed to be less chemosensitive, some patients with highly proliferative tumors derive a significant benefit from chemotherapy, and consequently it is important to identify them.
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sueta
authors.affiliation: Department of Molecular-Targeting Therapy for Breast Cancer, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan. Electronic address: ys-yama@triton.ocn.ne.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan.
authors.forename: Toko
authors.initials: T
authors.lastname: Inao
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Ibusuki
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000145:classification* / Q000188:drug therapy* / Q000378:metabolism; D004358:Drug Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen