Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment

Abstract

Background: The pathological complete response (pCR) after neoadjuvant chemotherapy is a surrogate marker for a favorable prognosis in breast cancer patients. Factors capable of predicting a pCR, such as the proliferation marker Ki67, may therefore help improve our understanding of the drug response and its effect on the prognosis. This study investigated the predictive and prognostic value of Ki67 in patients with invasive breast cancer receiving neoadjuvant treatment for breast cancer. Methods: Ki67 was stained routinely from core biopsies in 552 patients directly after the fixation and embedding process. HER2/neu, estrogen and progesterone receptors, and grading were also assessed before treatment. These data were used to construct univariate and multivariate models for predicting pCR and prognosis. The tumors were also classified by molecular phenotype to identify subgroups in which predicting pCR and prognosis with Ki67 might be feasible. Results: Using a cut-off value of > 13% positively stained cancer cells, Ki67 was found to be an independent predictor for pCR (OR 3.5; 95% CI, 1.4, 10.1) and for overall survival (HR 8.1; 95% CI, 3.3 to 20.4) and distant diseasefree survival (HR 3.2; 95% CI, 1.8 to 5.9). The mean Ki67 value was 50.6 ± 23.4% in patients with pCR. Patients without a pCR had an average of 26.7 ± 22.9% positively stained cancer cells.

Integrated tumor identification and automated scoring minimizes pathologist involvement and provides new insights to key biomarkers in breast cancer

“…16 Nevertheless, it is also known that Ki67 score can be predictive of neoadjuvant chemotherapy response, 29 and mean Ki67 labeling indices have been found to be higher in patients with a pathological complete response after neoadjuvant chemotherapy; this has led to the hypothesis that there may be a high cutoff above which prognosis is better than in patients with lower Ki67 values. 30 As all patients within the cohort in this study received anthracycline-based chemotherapy, 8 our findings that high Ki67 values within the ER-negative subgroup are significantly associated with better overall survival lends tentative support to this hypothesis, and warrants further investigation. In any case, the fact that the 'correct' interpretation of Ki67 may take on opposing roles depending upon the treatment and molecular subtype of the cancer may shed some further light on why it has proven so difficult to establish a standardized approach to Ki67 evaluation with a single accepted methodology and cutoff value, 16,24 as the best cutoff found within each study is highly dependent upon the makeup of the cohort.…”

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

“…Recent studies have shown that the so called "Luminal A" subtype-characterized by low histological grade, low proliferation as measured by Ki67, high hormone receptor status, and negative HER2 status-was less responsive to chemotherapy, and that no preferable chemotherapy regimen could be defined for treatment of this subtype [2,10]. The potential usefulness of Ki67 in predicting response and long-term outcome has been explored by assessing preand post-treatment levels of Ki67 expression in neoadjuvant chemotherapy studies [11][12][13][14]. There is a general theory that biomarkers for rate of proliferation can predict responsiveness to systemic therapy, with highly proliferative tumors being more chemotherapy responsive.…”

Ki67 Index in Breast Cancer: Correlation with Other Prognostic Markers and Potential in Pakistani Patients

“…Conversely patients with tumors that have a very high level of proliferation have a better response to chemotherapy (Bottini et al, 2005). Furthermore this marker could help select patients who are unable to benefit from chemotherapy, such as those with HER2neu-negative and hormone receptorpositive tumors with low proliferation (Fasching et al, 2011).…”