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Ki-67, 21-Gene Recurrence Score, Endocrine Resistance, and Survival in Patients With Breast Cancer

Authors
 Janghee Lee  ;  Young-Jin Lee  ;  Soong June Bae  ;  Seung Ho Baek  ;  Yoowon Kook  ;  Yoon Jin Cha  ;  Jong Won Lee  ;  Byung Ho Son  ;  Sei Hyun Ahn  ;  Hee Jin Lee  ;  Gyungyub Gong  ;  Joon Jeong  ;  Sae Byul Lee  ;  Sung Gwe Ahn 
Citation
 JAMA NETWORK OPEN, Vol.6(8) : e2330961, 2023-08 
Journal Title
JAMA NETWORK OPEN
Issue Date
2023-08
MeSH
Breast ; Breast Neoplasms* / drug therapy ; Breast Neoplasms* / genetics ; Cohort Studies ; Female ; Humans ; Ki-67 Antigen ; Middle Aged ; Neoplasm Recurrence, Local / genetics
Abstract
Importance: Both high 21-gene recurrence score (RS) and high Ki-67 level are poor prognostic factors in patients with estrogen receptor (ER)-positive ERBB2-negative (ER+/ERBB-) breast cancer; however, a discrepancy between the 2 has been noted. Survival differences according to these 2 biomarkers are not well known.

Objective: To assess the associations between RS and Ki-67 expression and between Ki-67 expression and recurrence-free survival in patients with ER+/ERBB- breast cancer with low RS.

Design, setting, and participants: This cohort study included women treated for ER+/ERBB2- breast cancer who underwent the 21-gene RS test from March 2010 to December 2020 in 2 hospitals in Korea.

Exposures: Recurrence score and Ki-67 level.

Main outcomes and measures: A Cox proportional hazards regression model was used to examine the association of Ki-67 with recurrence-free survival (RFS), while a binary logistic regression model was used to examine the association between Ki-67 and secondary endocrine resistance. High Ki-67 expression was defined as 20% or greater, and low genomic risk as an RS of 25 or less. Secondary endocrine resistance was defined as breast cancer recurrence that occurred after at least 2 years of endocrine therapy and during or within the first year after completing 5 years of adjuvant endocrine therapy.

Results: A total of 2295 female patients were included (mean [SD] age, 49.8 [9.3] years), of whom 1948 (84.9%) were in the low genomic risk group and 1425 (62.1%) had low Ki-67 level. The median follow-up period was 40 months (range, 0-140 months). The RS and Ki-67 level had a moderate correlation (R = 0.455; P < .001). Of the patients with low Ki-67 level, 1341 (94.1%) had low RS, whereas 607 of 870 patients with high Ki-67 level (69.8%) had low RS. In patients with low RS, the RFS differed significantly according to Ki-67 level (low Ki-67, 98.5% vs high Ki-67, 96.5%; P = .002). Among the 1807 patients with low genomic risk who did not receive chemotherapy, high Ki-67 level was independently associated with recurrence (hazard ratio, 2.51; 95% CI, 1.27-4.96; P = .008). Recurrence after 3 years differed significantly according to Ki-67 level (low Ki-67, 98.7% vs high Ki-67, 95.7%; P = .003), whereas recurrence within 3 years did not differ (low Ki-67, 99.3% vs high Ki-67, 99.3%; P = .90). In addition, Ki-67 was associated with secondary endocrine resistance in patients with low RS who did not receive chemotherapy (odds ratio, 2.49; 95% CI, 1.13-5.50; P = .02).

Conclusions and relevance: In this cohort study of patients with ER+/ERBB2- breast cancer, a moderate correlation was observed between Ki-67 and RS, and high Ki-67 level in patients with low genomic risk was associated with increased risk of secondary endocrine resistance.
Files in This Item:
T202305059.pdf Download
DOI
10.1001/jamanetworkopen.2023.30961
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kook, Yoonwon(국윤원)
Bae, Soong June(배숭준) ORCID logo https://orcid.org/0000-0002-0012-9694
Baek, Seung Ho(백승호)
Ahn, Sung Gwe(안성귀) ORCID logo https://orcid.org/0000-0002-8778-9686
Jeong, Joon(정준) ORCID logo https://orcid.org/0000-0003-0397-0005
Cha, Yoon Jin(차윤진) ORCID logo https://orcid.org/0000-0002-5967-4064
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196301
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