METHODS: We analysed the expression of AR in 97 TNBC cases from Penang General Hospital for a period of 3 years (2014 to 2017). Androgen receptor immunoreactivity was considered positive if ≥ 1% of tumour cells nuclei were stained irrespective of staining intensity.
RESULTS: The prevalence of AR expression in TNBC was 31% (30/97), with the proportion of AR-positive tumour cells ranged from 1% to 90%. These include 23 invasive carcinomas, no special type (NST) and 7 other invasive carcinoma subtypes (papillary, lobular, clear cell and medullary carcinomas). Sixty-seven cases (69%) that showed AR immunonegativity were invasive carcinomas, NST (n=60), clear cell carcinoma (n=1) and metaplastic carcinoma (n=6). Androgen receptor immunoexpression was inversely correlated with tumour grade (p=0.016), but not the tumour stage, tumour size and nodal status.
CONCLUSION: AR is expressed in about one-third of TNBC and loss of AR immunoexpression does not predict adverse clinical outcomes. Larger cohorts for better characterisation of the role of AR immunoexpression in TNBC are warranted.
OBJECTIVE: This study aims to determine the effect of S. crispus active fraction (F3) and its bioactive components on glycolysis in triple-negative breast cancer cells (MDA-MB-231).
METHODS: This study utilizes F3, lutein, β-sitosterol, and stigmasterol to be administered in MDA-MB-231 cells for measurement of antiglycolytic activities through cell poliferation, glucose uptake, and lactate concentration assays. Cell proliferation was assessed by MTT assay of MDA-MB-231 cells after treatment with F3 and its bioactive components lutein, β-sitosterol, and stigmasterol. The IC50 value in each compound was determined by MTT assay to be used in subsequent assays. The determination of glucose uptake activity and lactate concentration were quantified using fluorescence spectrophotometry.
RESULTS: Antiproliferative activities were observed for F3 and its bioactive components, with IC50 values of 100 µg/mL (F3), 20 µM (lutein), 25 µM (β-sitosterol), and 90 μM (stigmasterol) in MDA-MB-231 cells at 48 h. The percentage of glucose uptake and lactate concentration in MDA-MB-231 cells treated with F3, lutein, or β sitosterol were significantly lower than those observed in the untreated cells in a time-dependent manner. However, treatment with stigmasterol decreased the concentration of lactate without affecting the glucose uptake in MDA-MB-231 cells.
CONCLUSION: The antiglycolytic activities of F3 on MDA-MB-231 cells are attributed to its bioactive components.
METHODS: In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 with untreated locally recurrent inoperable or metastatic triple-negative breast cancer using a block method (block size of six) and an interactive voice-response system with integrated web-response to pembrolizumab (200 mg) every 3 weeks plus chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine plus carboplatin) or placebo plus chemotherapy. Randomisation was stratified by type of on-study chemotherapy (taxane or gemcitabine-carboplatin), PD-L1 expression at baseline (combined positive score [CPS] ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Eligibility criteria included age at least 18 years, centrally confirmed triple-negative breast cancer; at least one measurable lesion; provision of a newly obtained tumour sample for determination of triple-negative breast cancer status and PD-L1 status by immunohistochemistry at a central laboratory; an Eastern Cooperative Oncology Group performance status score 0 or 1; and adequate organ function. The sponsor, investigators, other study site staff (except for the unmasked pharmacist), and patients were masked to pembrolizumab versus saline placebo administration. In addition, the sponsor, the investigators, other study site staff, and patients were masked to patient-level tumour PD-L1 biomarker results. Dual primary efficacy endpoints were progression-free survival and overall survival assessed in the PD-L1 CPS of 10 or more, CPS of 1 or more, and intention-to-treat populations. The definitive assessment of progression-free survival was done at this interim analysis; follow-up to assess overall survival is continuing. For progression-free survival, a hierarchical testing strategy was used, such that testing was done first in patients with CPS of 10 or more (prespecified statistical criterion was α=0·00411 at this interim analysis), then in patients with CPS of 1 or more (α=0·00111 at this interim analysis, with partial alpha from progression-free survival in patients with CPS of 10 or more passed over), and finally in the intention-to-treat population (α=0·00111 at this interim analysis). This study is registered with ClinicalTrials.gov, NCT02819518, and is ongoing.
FINDINGS: Between Jan 9, 2017, and June 12, 2018, of 1372 patients screened, 847 were randomly assigned to treatment, with 566 patients in the pembrolizumab-chemotherapy group and 281 patients in the placebo-chemotherapy group. At the second interim analysis (data cutoff, Dec 11, 2019), median follow-up was 25·9 months (IQR 22·8-29·9) in the pembrolizumab-chemotherapy group and 26·3 months (22·7-29·7) in the placebo-chemotherapy group. Among patients with CPS of 10 or more, median progression-free survival was 9·7 months with pembrolizumab-chemotherapy and 5·6 months with placebo-chemotherapy (hazard ratio [HR] for progression or death, 0·65, 95% CI 0·49-0·86; one-sided p=0·0012 [primary objective met]). Median progression-free survival was 7·6 and 5·6 months (HR, 0·74, 0·61-0·90; one-sided p=0·0014 [not significant]) among patients with CPS of 1 or more and 7·5 and 5·6 months (HR, 0·82, 0·69-0·97 [not tested]) among the intention-to-treat population. The pembrolizumab treatment effect increased with PD-L1 enrichment. Grade 3-5 treatment-related adverse event rates were 68% in the pembrolizumab-chemotherapy group and 67% in the placebo-chemotherapy group, including death in <1% in the pembrolizumab-chemotherapy group and 0% in the placebo-chemotherapy group.
INTERPRETATION: Pembrolizumab-chemotherapy showed a significant and clinically meaningful improvement in progression-free survival versus placebo-chemotherapy among patients with metastatic triple-negative breast cancer with CPS of 10 or more. These findings suggest a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic triple-negative breast cancer.
FUNDING: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
METHODS: Patients diagnosed with invasive breast cancer (BC) from 2005 to 2013 at our tertiary institution were included and divided according to race and subtypes. Demographic and clinical information of non-metastatic TNBC patients were analyzed. Log-rank test, univariate and multivariate Cox proportional hazard regression models were used to find associated risk factors related with overall survival (OS) and disease-free survival (DFS).
RESULTS: Among 1227 BC patients, 129 (10.5%) had TNBC. TNBC patients had the worst OS (P: 0.0005) and DFS (P: 0.0016) among the subtypes. However, variations in race did not have any difference in OS or DFS among TNBC patients. Axillary lymph node involvement, invasive lobular histology, larger tumor size, and the presence of lymphovascular invasion (LVI) were factors associated with both poor DFS and OS among TNBC patients.
CONCLUSIONS: Racial variation did not have any impact on the prognosis of the TNBC.
Purpose: To study EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort to determine the possibility of using anti-EGFR combinatorial therapy for this population.
Patients and methods: In this study, we evaluated 58 cases of Malaysian TNBC patient samples for EGFR gene copy number alteration and EGFR protein overexpression using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) methods, respectively.
Results: EGFR protein overexpression was observed in about 30% while 15.5% displayed high EGFR copy number including 5.17% gene amplification and over 10% high polysomy. There is a positive correlation between EGFR protein overexpression and gene copy number and over expression of EGFR is observed in ten out of the 48 low copy number cases (20.9%) without gene amplification.
Conclusion: This study provides the first glimpse of EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort emphasising the need for the nationwide large scale EGFR expression evaluation in Malaysia.