Ki67 measured after neoadjuvant chemotherapy for primary breast cancer

Clin Cancer Res. 2013 Aug 15;19(16):4521-31. doi: 10.1158/1078-0432.CCR-12-3628. Epub 2013 Jun 27.

Abstract

Purpose: The value of Ki67 measured on residual disease after neoadjuvant chemotherapy is not sufficiently described.

Experimental design: Participants of the GeparTrio study with primary breast cancer randomly received neoadjuvant response-guided [8 cycles TAC (docetaxel/doxorubicin/cyclophosphamide) in responding and TAC-NX (vinorelbine/capecitabine) in nonresponding patients] or conventional (6 cycles TAC) chemotherapy according to interim response assessment. Ki-67 levels were centrally measured immunohistochemically after neoadjuvant treatment if tumor tissue was available. Here, we analyze 1,151 patients having a pathologic complete response (pCR; n, 484), or residual disease with low (0-15%), intermediate (15.1-35%), or high (35.1-100%) posttreatment Ki67 levels in 488, 77, and 102 patients, respectively.

Results: Patients with high posttreatment Ki67 levels showed higher risk for disease relapse (P < 0.0001) and death (P < 0.0001) compared with patients with low or intermediate Ki67 levels. Patients with low Ki67 levels showed a comparable outcome to patients with a pCR (P = 0.211 for disease-free and P = 0.779 for overall survival). Posttreatment Ki67 levels provided more prognostic information than pretreatment Ki67 levels or changes of Ki67 from pre- to posttreatment. Information on pCR plus posttreatment Ki67 levels surmount the prognostic information of pCR alone in hormone-receptor-positive disease [hazard ratios (HR), 1.82-5.88] but not in hormone-receptor-negative disease (HR: 0.61-1.73). Patients with conventional and response-guided treatment did not show a different distribution of posttreatment Ki67 (P = 0.965).

Conclusions: Posttreatment Ki67 levels provide prognostic information for patients with hormone-receptor-positive breast cancer and residual disease after neoadjuvant chemotherapy. Levels were not prognostic for outcome after response-guided chemotherapy. High posttreatment Ki67 indicates the need for innovative postneoadjuvant treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / therapy
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Treatment Outcome
  • Tumor Burden
  • Young Adult

Substances

  • Ki-67 Antigen