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

Abstract

ImportanceBoth 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresRecurrence score and Ki-67 level.Main Outcomes and MeasuresA 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.ResultsA 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 RelevanceIn 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.

Breast cancer patients participating in the Swiss mammography screening program "donna" exhibit extended survival

“…We found, furthermore, that the proportion of Ki-67 levels was signi cantly higher for BC diagnosed outside the MSP. High Ki-67 levels are associated with higher grading and larger tumor size [18], and correlate to late endocrine resistance [19]. Consequently, we found that the number of mastectomies for cases within the MSP was about half compared to outside the MSP (8.9% vs 17.7%).…”

Breast cancer patients enrolled in the Swiss mammography screening program “donna” demonstrate prolonged survival

“…We found, furthermore, that the proportion of Ki-67 levels is significantly higher for BC diagnosed outside the MSP. High Ki-67 levels are associated with higher grading, larger tumor size [ 19 ] and correlate to late endocrine resistance [ 20 ]. Consequently, we found that the number of mastectomies for cases within the MSP was about half compared to outside the MSP (8.9% vs. 17.7%).…”

Development of a multiparametric model for predicting the response to neoadjuvant chemotherapy in breast cancer

“…We defined the values of estrogen receptor (ER) and progesterone receptor (PR) expression as positive or negative, and a cut-off value of 1% was set ( 30 ). A positive staining area ≤20% was defined as Ki-67 negative, while a positive staining area >20% was defined as Ki-67 positive ( 31 ). The histologic grade of the tumor tissue was assessed using the Bloom Richardson method.…”