title: Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast cancer.
abstract: BACKGROUND
  Recent studies have indicated that response to chemotherapy and the prognostic impact of a pathologic complete response (pCR) after neoadjuvant chemotherapy differ among breast cancer subtypes.
  
  
  METHODS
  Women with Stage I to III breast cancer treated with anthracycline and taxane-based neoadjuvant chemotherapy (four cycles of docetaxel every 3 weeks followed by four cycles of FEC every 3 weeks) between 2006 and 2011 were retrospectively analyzed. Trastuzumab was concurrently added to docetaxel for HER2-positive breast cancer. Expression of estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 was examined by immunohistochemistry in pre- and post-treatment specimens. Predictive factors for neoadjuvant chemotherapy and prognosis were analyzed by breast cancer subtype.
  
  
  RESULTS
  Of 64 patients, 30 (47 %) were ER-positive (ER+) HER2-negative (HER2-), including eight as luminal A (Ki67 labeling index (LI) <14 %) and 22 as luminal B (Ki67 LI ≥ 14 %) subtypes, 11 (17 %) were ER+ HER2-positive (HER2+), 12 (19 %) were ER-negative (ER-) HER2+, and 11 (17 %) were ER- HER2-. The clinical response rates were significantly higher in luminal B, ER+ HER2+, and ER- HER2+ subtypes compared with luminal A subtype. Patients whose tumors contained high Ki67 expression effectively responded to neoadjuvant chemotherapy. Ki67 LI was a predictive marker for pCR, and all patients whose tumors achieved pCR are currently disease-free. Furthermore, high Ki67 expression in post-treatment tumors was strongly correlated with poor disease-free and overall survival regardless of subtype.
  
  
  CONCLUSIONS
  It is necessary to establish additional strategies to improve survival for patients whose residual tumors show high Ki67 expression after neoadjuvant chemotherapy.
authors: Breast and Endocrine Surgery, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, Sapporo, 060-8648, Japan.
authors: Tatsuya
authors: T
authors: Yoshioka
authors: Mitsuchika
authors: M
authors: Hosoda
authors: Mitsugu
authors: M
authors: Yamamoto
authors: Kazunori
authors: K
authors: Taguchi
authors: Kanako C
authors: KC
authors: Hatanaka
authors: Emi
authors: E
authors: Takakuwa
authors: Yutaka
authors: Y
authors: Hatanaka
authors: Yoshihiro
authors: Y
authors: Matsuno
authors: Hiroko
authors: H
authors: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; D000077143:Docetaxel; C080625:taxane