The clinical significance of Ki-67 as a marker of prognostic value and chemosensitivity prediction in hormone-receptor-positive breast cancer: a meta-analysis of the published literature

Abstract

Objectives:

Hormone-receptor (HR)-positive breast cancer is associated with a poor response to adjuvant chemotherapy. Thus, it is important to identify HR-positive patients who can benefit from chemotherapy and the Ki-67 index may help to predict chemotherapy efficacy in such populations. However, controversies exist regarding the prognostic and predictive role of Ki-67 and its exact cut-off value in HR-positive patients. Therefore, we conducted this study.

Methods:

The meta-analysis included 4512 patients in five trials. Due to different data formats provided by studies, we classified the trials into two groups to facilitate analysis. Group 1 included the PACS01, USON 01062, and IBCSG VIII and IX trials, while Group 2 included the BCIRG001, USON 01062, and IBCSG VIII and IX trials.

Results:

In Group 1, Ki-67 high patients had a worse prognosis in disease-free survival (DFS) than Ki-67 low counterparts (risk ratio [RR] = 1.62, 95% confidence index [CI] = 1.36–1.94, P < 0.001). In Group 2, Ki-67 high patients had a better prognosis in DFS (RR = 0.53, 95% CI = 0.45–0.61, P < 0.001) and overall survival (OS) (RR = 0.32, 95% CI = 0.25–0.42, P < 0.001). In Ki-67 high patients administered anthracycline/taxane-based chemotherapy, the experimental group (FAC → T, AC → TX) achieved a better DFS than the control group (FAC, AC → T, respectively) (RR = 0.60, 95% CI = 0.39–0.90, P = 0.014). With a cut-off point ≥19%, Ki-67 high patients achieved a worse DFS (RR = 1.49, 95% CI = 1.28–1.72, P < 0.001).

Conclusion:

This study had limitations due to its retrospective nature and the lack of standardized Ki-67 measurement methods. Nevertheless, our findings indicate that Ki-67 high patients have a worse prognosis and may be more sensitive to anthracycline/taxane-based regimens. The ideal Ki-67 cut-off point for predicting chemosensitivity may be a certain value among a range of values ≥19% in HR-positive patients.

Keywords::

• Adjuvant chemotherapy
• Hormone-receptor-positive breast cancer
• Ki-67
• Meta-analysis
• Predictive
• Prognostic

Transparency

Declaration of funding

No current external funding sources for this study.

Declaration of financial/other relationships

Y.L., W.Y., T.Y., Y.D., Z.S., and J.L. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

J.L. is responsible for editorial correspondence and has contributed to the conception and design of the study, the interpretation of data, the revision of the article as well as final approval of the version to be submitted. Y.L. participated in the design of the study, collected and analyzed the data, drafted and revised the article. W.Y. is responsible for editorial correspondence and participated in the design of the study, collected and analyzed the data. T.Y. and Y.D. contributed analysis tools and participated in the design of the study. Z.S. conceived of the study, and participated in its design and coordination. All authors read and approved the final version of the manuscript.