The Role of Ki-67 in HR+/HER2- Breast Cancer: A Real-World Study of 956 Patients

Abstract

Objective

This study determined the cut-off value of Ki-67 expression and discussed the interaction between Ki-67 and histological grade, further explored the prognostic role of Ki-67 in hormone receptor-positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer;.

Materials and Methods

We assessed the Ki-67 expression of 956 patients with HR+/HER2 breast cancer diagnosed in the General Hospital of Ningxia Medical University from 2015 to 2019 by immunohistochemistry (IHC), The disease-free survival (DFS) was defined as the time from postoperative to the first local recurrence, distant metastasis or death of the disease. The follow-up by means of inpatient or outpatient medical records and telephone.

Results

22.5% was used as the cut-off for low/high Ki-67 expression in HR+/HER2- breast cancer. Compared with the value of 14%, which is commonly used in clinic at present, the consistency of the two values is moderate (Kappa = 0.484, P<0.001). The expression of Ki-67 was increased with the grade. (Median: G1:10%; G2:20%; G3:40%. Mean: G1:13%; G2:23%; G3:39%, P <0.001). Survival analysis was based on all patients for a median of 51 months (24–89 months), 63 cases had recurrence or metastasis during the follow-up, which 21 cases had low expression of Ki-67 and 42 cases had high expression. The patients with Ki-67 ≥ 22.5% had a 2.969 higher risk of early recurrence and metastasis than the patients with Ki-67 < 22.5%. There were 4 cases of local recurrence, 7 cases of regional lymph node metastasis, and 52 cases of distant metastasis in all patients, the common distant metastases were bone, liver, and lung, and rare metastases were adrenal gland, bone marrow, and pericardium.

Conclusion

In HR+/HER2- breast cancer, patients with Ki-67 > 22.5% have a worse prognosis and are more likely to have early recurrence and metastasis.

Keywords:

• Ki-67
• breast cancer
• cut-off value
• histological grade
• recurrence and metastasis

Abbreviations

HR, Hormone receptor; HER2, Human epidermal growth factor receptor; DFS, Disease-free survival; ER, Estrogen receptor; PR, Progesterone receptor; FISH, Fluorescence in situ hybridization; AJCC, American Joint Committee on Cancer.

Data Sharing Statement

Available upon request to [email protected].

Ethical Statement

This study approval was granted by the Ethics Committee of the General Hospital of Ningxia Medical University (No: KYLL-2021- 610). This study was conducted in accordance with the Declaration of Helsinki. The lead researcher was presenting the purpose of the study, the benefit, and the risk of the procedure taken by the research participant to the ethical committee board prior to approval. Each research participant was given detailed information regarding the purpose, benefit, and risk of the study. Each research participant signed an informed consent form before participating in the study.

Acknowledgment

The authors thank all the patients who agreed to participate in this study and the pathologist and surgical residents who helped carry out this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All authors declare that they have no competing interests in this work.

Additional information

Funding

This project is supported by the “Newly enrolled Master training” project of the General Hospital of Ningxia Medical University (NO.YKDZY2022013).