Ki67 Expression and Docetaxel Efficacy in Patients With Estrogen Receptor–Positive Breast Cancer

Abstract

PURPOSE The indications of adjuvant chemotherapy for patients with estrogen receptor (ER) -positive breast cancer are controversial. We analyzed the predictive value of Ki67, HER2, and progesterone receptor (PR) expression for the efficacy of docetaxel in patients with ER-positive, node-positive breast cancer. PATIENTS AND METHODS Expression of Ki67, HER2, and PR was measured by immunohistochemistry in tumor samples from 798 patients with ER-positive breast cancer who participated in PACS01, a randomized trial that evaluated the efficacy of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age, tumor size, nodal involvement, treatment arm, and biomarkers. The predictive value of biomarkers was assessed by an interaction test. Disease-free survival (DFS) was the primary end point. Results Ki67, HER2, and PR were expressed in 21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were 81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47 to 1.66; P = .71). CONCLUSION Ki67 expression identifies a subset of patients with ER-positive breast cancer who could be sensitive to docetaxel treatment in the adjuvant setting.

Therapeutic effect of taxanes on metastatic breast cancer of various immunohistochemical subtypes

“…In addition, , taxane yielded the therapeutic effect of RR; 28.3% and TTP; 8.3 months in luminal metastatic breast cancer. The results of the present analysis were not comparable to the numerous previous studies (6)(7)(8), which showed the ineffectiveness of taxane anticancer drugs for operable early luminal breast cancer. Possible causes of the difference in the results of pre-and postoperative taxane treatment for early breast cancer and those of taxane treatment for luminal metastatic breast cancer include the following factors.…”

“…Accordingly, immunohistochemical classification with hormone receptors and human epidermal growth factor receptor 2 (HER2) may be used to estimate the subtype. Luminal A breast cancer was defined to express estrogen receptor (ER) and not express HER2 in the CALGGB 9344 trial (6), express ER and/or progesterone receptor (PgR) with a low Ki67 labeling index (cut-off, 13%) in the BCIRG 001 trial (7), and express ER with a low Ki67 labeling index (cut-off, 20%) in the PACS 01 trial (8). In addition, the St. Gallen International Conference 2011 proposed that breast cancer expressing ER and/or PgR, and negative for HER2 with a Ki67 labeling index of <14%, should be defined as luminal A breast cancer (9).…”

The cell cycle and cancer

“…Notably, many of the neoadjuvant and adjuvant chemotherapeutic interventions approved for clinical use include agents targeting either replicating cells (in S phase) or dividing cells (M phase), and will therefore only be effective against cells progressing through the cell cycle. In support of this concept, in breast cancer, high Ki67 levels appear to predict benefit for an adjuvant taxane regime (M phase agent docetaxel) compared with non-taxane regimes [104,105]. However, although Ki67 has emerged as a prognostic marker of potential interest, its introduction into routine clinical practice has been compromised by conflicting data from meta-analysis studies [106].…”

Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast cancer

“…Our previous study showed that patients whose breast tumors showed low Ki67 expression displayed longer time to progression during first-line endocrine therapy with aromatase inhibitors [21]. On the other hand, randomized clinical studies on adjuvant chemotherapy have retrospectively reviewed data and reported that Ki67 was a predictor of benefit from chemotherapy with endocrine therapy in ER-positive breast cancer [22][23][24]. Therefore, expression levels of Ki67 are involved in biological characteristics of the tumors, including prognosis and response to certain kinds of therapies in ER-positive breast cancer.…”