Search

Glycoprotein non-metastatic B (GPNMB) is a transmembrane protein overexpressed in numerous cancers including triple-negative breast cancers (TNBC). It has been linked to promote cancer aggressiveness and implicated as a novel target for GPNMB-expressing cancers. In current study, we aimed to explore the clinical significance of GPNMB in TNBC. Among 759 specimens, immunohistochemistry (IHC) exhibited GPNMB expressions were variable in different subtypes and significantly higher in TNBC. Kaplan–Meier analysis revealed GPNMB overexpression in TNBC was associated with worse prognosis especially distant metastasis (P = 0.020, HR = 2.515, CI 1.154–5.480). Multivariate analysis showed GPNMB expression was an independent prognostic factor in terms of recurrence and distant metastasis (P = 0.008, HR = 3.22, CI 1.36–7.61; P = 0.017, HR = 3.08, CI 1.22–7.74). In silico analysis showed high mRNA expression of GPNMB was associated with distant metastasis and GPNMB was overexpressed in TNBC. Furthermore, GPNMB positively correlated with epithelial–mesenchymal transition (EMT) regulators, mesenchymal marker vimentin, MMP and integrins. The protein levels of Twist and MMP2 were upregulated by GPNMB overexpression in TNBC cells. GPNMB-enhanced cell invasion was attenuated by broad spectrum MMP inhibitor (GM 6001) and the selective inhibitor of MMP-2 (ARP100). In summary, GPNMB expression is prevalent in TNBC and may be implicated as a prognostic biomarker in patients with TNBC. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to prospectively explore severity and prevalence of chemotherapy-induced peripheral neuropathy (CIPN) and examine the correlation between clinician-assessed (objective) and patient-reported (subjective) CIPN in breast cancer survivors receiving taxane. Methods: This was a prospective, longitudinal study. Purposive sampling was adapted to enroll women newly diagnosed with breast cancer and about to receive taxane. The CIPN was assessed after breast cancer diagnosed and before chemotherapy (T1), before cycle 1 to 4 taxane infusion (T2 to T5), and after chemotherapy completion (T6 to T8). Total Neuropathy Score–clinical version (TNSc), Identification Pain Questionnaire (ID pain), Functional Assessment of Cancer Therapy–Taxane subscale (FACT-Tax), and Peripheral Neuropathy Scale (PNS) were utilized for measuring CIPN. Descriptive statistics, Pearson correlation coefficient, and generalized estimating equation were used to analyze data. Results: A total of 88 participants were included. Both clinician-assessed and patient-reported CIPN gradually increased between T1 and T6 and mildly decreased at T7 and T8. Fifty-five participants (62.5%) experienced CIPN at T8. Weak-to-moderate correlations between subjective and objective CIPN were found at T6 to T8 (r = 0.272–0.533, p < 0.05). The change of TNSc, FACT-Tax, and PNS were significant over time. However, the significant change of neuropathic pain was only found at T6. Conclusion: The change of CIPN prevalence and severity were significant over time in survivors newly diagnosed with breast cancer. Specifically, the severest and highest CIPN was detected at chemotherapy completion. Survivors remained suffering from CIPN 3 months after chemotherapy completion. Besides, mild to moderate correlations between clinician-assessed and patient-reported CIPN were identified. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to perform digital RNA counting to validate a gene expression signature for operable breast cancers initially treated with curative intention, and the risk of recurrence, distant metastasis, and mortality was predicted. Methods: Candidate genes were initially discovered from the coherent genomic and transcriptional alternations from microarrays, and the extended concurrent genes were used to build a risk stratification model from archived formalin-fixed paraffin-embedded (FFPE) tissues with the NanoString nCounter. Results: The extended concurrent genes signature was prognostic in 144 Taiwanese breast cancers (5-year relapse-free survival: 89.8 and 69.4% for low- and high-risk group, log-rank test: P = 0.004). Cross-platform comparability was evidenced from significant and positive correlations for most genes as well as equal covariance matrix across 64 patients assayed for both microarray and digital RNA counting. Discussion: Archived FFPE samples could be successfully assayed by the NanoString nCounter. The purposed signature was prognostic stratifying breast cancer patients into groups with distinct survival patterns, and clinical applicability of the residual risk model was proved. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the leading causes of cancer-related deaths in women, and there is a demand in developing an Asian-based genetic profiling database for breast cancer in improving the treatment response. This study aimed to determine molecular alternations and identify potential therapeutic targets by analyzing the genetic profiling from a cohort of Taiwanese breast cancers using a commercialized next-generation sequencing (NGS) targeted panel.Methods: The study population comprised a broad spectrum of breast cancer patients in Taiwan, including Group 1: planned to receive first-line surgery and followed by adjuvant therapy, or early relapse within three years, Group 2: planned to receive first-line neoadjuvant therapy and followed by surgery, and Group 3: de novo stage IV, or stage IV with recurrence beyond three years. Molecular profiles were determined using Thermo Fisher™ Oncomine™ Comprehensive Assay version 3 (TMO comprehensive assay) from Formalin-Fixed Paraffin-Embedded (FFPE) tissues. Level of actionability was evaluated with the ESMO Scale of clinical actionability of molecular targets (ESCAT).Results: A total of 380 TMO comprehensive assays were conducted on 372 patients, and we presented targeted sequencing analyses of Tier I: alteration-drug match associated with improved outcome in clinical trials including ERBB2 amplification, BRCA1/2 germline mutation, PIK3CA mutation, and NTRK translocation, and Tier II: antitumor activity associated with the matched alteration-drug but lack of prospective outcome data including PTEN loss, ESR1 mutation, AKT1 mutation, and ERBB2 mutation, and Tier III: matched drug-alteration that led to clinical benefit in another tumor type including MDM2 amplification, and ERBB3 mutation. Among them, 249 (66%) showed at least one actionable alternation based on the ESCAT criteria. The most frequent impacted genes (all variants combined within each sample) were PIK3CA (38%), followed by ERBB2 (23%), ESR1 (10%), AKT1 (6%), and BRCA2 (5%), and the remaining rare variants (less than 5% of assayed cohort) were BRCA1 (3%), MDM2 (2.2%), and ERBB3 (1.1%).Conclusion: Targeted sequencing of actionable genes is believed to provide clinical applicability and substantial benefits for Taiwanese breast cancer patients. A valid scale of clinical actionability should be adopted for precision medicine practice under multidisciplinary molecular tumor board. [ABSTRACT FROM AUTHOR]

This study describes the fertility intention and explores factors related to fertility intention in reproductive-age women with breast cancer in Taiwan. In this cross-sectional study, women of childbearing age who had been diagnosed with breast cancer completed a face-to-face survey that included demographic, disease, and symptom-related data, and social support and fertility intention information. The mean fertility intention score among the 223 participants was "medium" (M ± SD = 41.18 ± 12.62). Higher symptom severity, especially for distress, was related to lower fertility intention. Instrumental support from families and friends was positively associated with fertility intention score. Younger women had better fertility intention scores than older women. The Sobel test showed that age mediated menopause and fertility intention. The findings offer the evidence of the needs to control symptoms and provide sufficient instrumental support regarding fertility after completing chemotherapy. [ABSTRACT FROM AUTHOR]

The OlympiAD Phase III study (NCT02000622) established the clinical benefits of olaparib tablet monotherapy (300 mg twice daily) over chemotherapy treatment of physician's choice (TPC) in patients with a germline BRCA1/2 mutation (gBRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who had received ≤2 chemotherapy lines in the metastatic setting. Here, we report pre-specified analyses of data from Asian (China, Japan, Korea and Taiwan) patients in the study. All patients were randomized 2:1 to olaparib tablets (300 mg twice daily) or single-agent chemotherapy TPC (21-day cycles of either capecitabine, eribulin or vinorelbine). The primary endpoint was progression-free survival assessed by blinded independent central review. The prevalence of gBRCAm in the OlympiAD Asian subgroup screened for study recruitment was 13.5%. Patient demographics and disease characteristics of the Asian subgroup (87/302 patients) were generally well balanced between treatment arms. Asian patients in the olaparib arm achieved longer median progression-free survival, assessed by blinded independent central review, versus the chemotherapy TPC arm (5.7 vs 4.2 months; HR = 0.53 [95% CI: 0.29–0.97]), which was consistent with findings in the global OlympiAD study population. Findings on secondary efficacy and safety/tolerability outcome measures in Asian patients were also similar to those observed in the global OlympiAD study population. The OlympiAD study was not powered to detect race-related differences between treatment groups; however, the consistency of our findings with the global OlympiAD study population suggests that previously reported findings are generalizable to Asian patients. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated that upregulation of multiple epidermal growth factor-like domains 11 (MEGF11) gene expression is involved in the mechanism by which recurrence of Triple Negative Breast Cancer (TNBC) occurs. Our aim was to elucidate the role of MEGF11 expression in TNBC cells, both in vitro and in vivo, and in human tissue. Following MEGF11 gene knockdown (∆MEGF11) or over-expression in MDA-MB-231 and MB-468 cells, cell growth and chemokine gene expression were evaluated. In vivo, tumour growth of implanted human TNBC cells and the number of circulating 4T1 mouse tumour cells were measured. There was a significant decrease in cell growth via inhibition of AKT, NF-kB, CREB and AP-1 activation in ∆MEGF11 MDA-MB-231 and 468 cells. This also resulted, in vivo, in a suppression of tumour growth and a decrease in the number of mouse circulating 4T1 breast cancer cells. Surprisingly, overexpression of MEGF11 upregulated the expression of various chemokines and proinflammatory cytokines via AKT activation, but there was no increase in cell proliferation. MEGF11 was found to cross-talk positively with IL-17A signalling. Patients with tumours that over-expressed MEGF11 had a poorer prognosis. We conclude that MEGF11 plays an important role in tumour survival and that overexpression of MEGF11 induces both a cytokine and a chemokine cascade, which will favour the tumour microenvironment in terms of distant metastasis. MEGF11 might be a potential therapeutic target for preventing TNBC recurrence. [ABSTRACT FROM AUTHOR]

Aims: Invasive breast cancer patients with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) scores of 3+ or 2+ with reflex in‐situ hybridisation (ISH) positivity are suitable for anti‐HER2 therapies. The aim of this study is to investigate whether the prognoses between IHC 3+ patients and IHC 2+/ISH+ patients are different. Methods and results: We analysed the clinicopathological information of 886 consecutive cases of HER2‐positive early breast cancer. The influences of the patients' age, cancer stage, hormone receptor status and anti‐HER2 treatment were adjusted using a multivariate Cox regression model. Both HER2 copy numbers and HER2 ISH ratios of the IHC 3+ group were significantly higher than those of the IHC 2+/ISH+ group. The outcomes of IHC 3+ patients were significantly better than those of IHC 2+/ISH+ patients in the univariate and multivariate analyses. HER2 copy numbers of ≥8 represented the best prognostic value, and it was chosen to be the cut‐off value. The reflex ISH for IHC 2+ patients with high HER2 copy numbers (≥8) predicted a better overall survival than that for those with low HER2 copy numbers. Conclusion: HER2 IHC scores and HER2 copy numbers can provide prognostic information for patients with HER2‐positive invasive breast cancer. Both IHC 3+ and IHC 2+ patients with high HER2 copy numbers had a better prognosis. [ABSTRACT FROM AUTHOR]