Ki67 AFTER NEOADJUVANT CHEMOTHERAPY OF BREAST CANCER

Clin Cancer Res. 2013 Jun 27. [Epub ahead of print]

Ki67 measured after neoadjuvant chemotherapy for primary breast cancer.

von Minckwitz G, Schmitt W, Loibl S, Müller BM, Blohmer JU, Sinn B, Eidtmann H, Eiermann W, Gerber B, Tesch H, Hilfich J, Huober J, Fehm T, Barinoff J,Rüdiger T, Erbstößer E, Fasching PA, Karn T, Mueller V, Jackisch C, Denkert C.

Source

Medicine and Research, German Breast Group.

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 non-responding patients) or conventional (6 cycles TAC) chemotherapy according to interim response assessment. Ki67 levels were centrally measured immunohistochemically post-neoadjuvant treatment if tumor tissue was available. We here analyze 1151 patients having a pCR (N=484), or residual disease with low (0-15%), intermediate (15.1-35%), or high (35.1-100%) post-treatment Ki67 levels in 488, 77, and 102 patients, respectively.

RESULTS:

Patients with high post-treatment Ki67 levels showed higher risk for disease relapse (p<.0001) and death (p<.0001) compared to 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). Post-treatment Ki67 levels provided more prognostic information than pre-treatment Ki67 levels or changes of Ki67 from pre- to post-treatment. Information on pCR plus post-treatment Ki67 levels surmounts the prognostic information of pCR alone in hormone-receptor-positive disease (hazard ratios between 1.82 to 5.88) but not in hormone-receptor-negative disease (hazard ratios between 0.61 and 1.73). Patients with conventional and response-guided treatment did not show a different distribution of Ki67 (p=0.965).

CONCLUSIONS:

Post-treatment 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 post-treatment Ki67 indicates the need for innovative post-neoadjuvant treatments.