Ki-67 and breast cancer prognosis: does it matter if Ki-67 level is examined using preoperative biopsy or postoperative specimen?

Purpose This study aimed to identify the association between Ki-67 level and the prognosis of patients with breast cancer, regardless of the timing of Ki-67 testing (using preoperative biopsy vs. postoperative specimen). Methods A total of 4177 patients underwent surgery between January 2008 and December 2016. Immunohistochemical Ki-67 levels, using either preoperative (1673) or postoperative (2831) specimens, were divided into four groups using cutoff points of 10%, 15%, and 20%. Results Groups with higher-Ki-67 levels, in both the pre- and postoperative periods, showed significantly larger tumor size, higher grade, more frequent hormone receptor-negativity and human epidermal growth factor receptor 2 overexpression, and active adjuvant treatments than groups with lower-Ki-67 levels. High-Ki-67 levels were also significantly associated with poor survival, irrespective of the timing of specimen examination. Conclusion Despite the problems associated with Ki-67, Ki-67 level is an important independent prognostic factor, regardless of the timing of Ki-67 testing, i.e., preoperative or postoperative testing.

Predictive Value of Serum Aurora A, Thymidine Kinase 1, and HER3/ErbB3 in Breast Cancer Patients Before Neoadjuvant Treatment

Further personalization is needed to improve the outcomes of breast cancer treatment. It is necessary to find new inexpensive and easily evaluated predictive markers. In this study, we determined serum level of Aurora A (AURKA), thymidine kinase 1 (TK1) and human epidermal growth factor receptor type 3 (HER3) by enzyme immunoassay ELISA. We collected peripheral blood sera of 119 women with breast cancer before neoadjuvant treatment and the control group of 47 randomly selected healthy women. After treatment we analyzed clinical data: age, initial TNM stage, tumor receptors expression: estrogen (ER), progesterone (PGR), epidermal growth factor receptor type 2 (HER2), Ki67, histological malignancy grade, biological subtype, and response to neoadjuvant treatment in residual cancer burden (RCB) classification. Pathologic complete response (PCR) was achieved in 41 patients (34.45%). In univariate analysis patients with higher AURKA levels were more likely to obtain PCR (p=0.039). In multivariate analysis we used the logit regression model with PCR as the dependent. The effect of AURKA concentration ≥4.75 ng / mL on the chance of achieving PCR was found (OR: 3.5; 95%CI: 1.2-10.1; p = 0.023). Other significant PCR factors included: node status (OR: 0.503; 95% CI: 0.263-0.965; p = 0.039), negative PGR expression (OR: 0.104; 95% CI: 0.038-0.284; p < 0.001), and Ki67 >20% (OR: 5.44; 95% CI: 1.24-23,9; p < 0.025). There was no significance in marker concentrations and clinical features nor between breast cancer patients and control group. The outcomes suggest that serum AURKA level is a potential PCR prediction marker in neoadjuvant breast cancer treatment. Further studies are needed to confirm our observations.

A Comparative Pharmacokinetic Study to Evaluate the Bioequivalence and Safety of A Humanized Recombinant Monoclonal Antibody Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with the Reference Herceptin in Healthy Chinese Subjects

Purpose:This study aimed to evaluate the safety, tolerability, pharmacokinetics and bioequivalence of a test humanized recombinant monoclonal antibody targeting Human Epidermal Growth Factor receptor 2 (HER-2) with the reference Herceptin®.Materials and methods:The trial consists of two parts (part I and part II). Part I was an open-label, sequential-cohort dose-escalation study, QLHER2 (test) was intravenous infusion at single doses escalating from 0.2 to 6 mg/kg (0.2, 1, 2, 4 and 6mg/kg) and Herceptin(reference) 4 mg/kg in 16 healthy subjects, to evaluated the safety, tolerability and pharmacokinetics of QLHER2. Part II was a randomized, double-blind, parallel-group study to evaluate the bioequivalence of QLHER2 and Herceptin in 60 subjects.Results:Following a 1.5-h intravenous infusion of single ascending doses of QLHER2 (1, 2, 4, or 6 mg/kg) In part I, Cmax and Tmax were 19.43-120.01 μg/mL and 68.91-157.87 h, respectively. AUC0-t and CL were 1.91-34.21 h*μg/mL and 0.54-0.12 ml/h/kg, indicating decreased clearance at higher doses, with a greater than proportional increase in the AUC0-t , and the t1/2 was 68.91-157.87 h. In part II, Plasma concentrations appeared to be comparable between QLHER2 and Herceptin over the 70-day sampling period and the QLHER2/Herceptin ratio of the Cmax and AUC0-t was 105.90% (90% CI: 95.69-117.26) and 95.79% (90% CI: 87.74-106.40%), respectively.Conclusion:The 90% CIs of the Cmax and AUC0-t for QLHER2/Herceptin ratio were within the range of 80.0-125.00% indicated that QLHER2 was bioequivalent to Herceptin. The results supported for further evaluation of QLHER2.Trial registration number: ChiCTR2000041577 and ChiCTR2100041802Date of registration: December 30,2020 and January 5, 2021