Alterations in circulating miRNA levels following early-stage estrogen receptor-positive breast cancer resection in post-menopausal women.

INTRODUCTION: Circulating microRNAs (miRNAs) exhibit remarkable stability and may serve as biomarkers in several clinical cancer settings. The aim of this study was to investigate changes in the levels of specific circulating miRNA following breast cancer surgery and evaluate whether these alterations were also observed in an independent data set. METHODS: Global miRNA analysis was performed on prospectively collected serum samples from 24 post-menopausal women with estrogen receptor-positive early-stage breast cancer before surgery and 3 weeks after tumor resection using global LNA-based quantitative real-time PCR (qPCR). RESULTS: Numbers of specific miRNAs detected in the samples ranged from 142 to 161, with 107 miRNAs detectable in all samples. After correction for multiple comparisons, 3 circulating miRNAs (miR-338-3p, miR-223 and miR-148a) exhibited significantly lower, and 1 miRNA (miR-107) higher levels in post-operative vs. pre-operative samples (p<0.05). No miRNAs were consistently undetectable in the post-operative samples compared to the pre-operative samples. Subsequently, our findings were compared to a dataset from a comparable patient population analyzed using similar study design and the same qPCR profiling platform, resulting in limited agreement. CONCLUSIONS: A panel of 4 circulating miRNAs exhibited significantly altered levels following radical resection of primary ER+ breast cancers in post-menopausal women. These specific miRNAs may be involved in tumorigenesis and could potentially be used to monitor whether all cancer cells have been removed at surgery and/or, subsequently, whether the patients develop recurrence

Scatter plots.

<p>Scatter plots showing the corresponding expression levels of (A) miR-148a, (B) miR-223, (C) miR-338-3p and (D) miR-107 for the paired pre- and post resection samples for each early-stage breast cancer patient (n = 24).</p

Significantly deregulated miRNAs after surgery using two different normalization approaches.

<p>MiRNAs in bold are regulated in the same direction using both normalization methods. Paired student's t-test (p<0.05).</p

Circulating microRNAs differentially expressed in the serum of patients with early-stage breast cancer before tumor resection compared to ∼3 weeks post-surgery.

<p>MiRNAs in bold pass Bonferroni correction.</p

Top 28 candidate miRNAs from our current study compared in Cookson et al. dataset using two alternative normalization methods.

<p>MiRNAs in bold are changed after surgery in both studies using at least one normalization method.</p>†<p>1-sided as reported by Cookson et al.</p><p>*only 6 months after surgery.</p>‡<p>Pass Bonferroni correction. ns: not significant.</p

Correlation between circulating cell‐free PIK3CA tumor DNA levels and treatment response in patients with PIK3CA‐mutated metastatic breast cancer

Liquid biopsies focusing on the analysis of cell‐free circulating tumor DNA (ctDNA) may have important clinical implications for personalized medicine, including early detection of cancer, therapeutic guidance, and monitoring of recurrence. Mutations in the oncogene, PIK3CA, are frequently observed in breast cancer and have been suggested as a predictive biomarker for PI3K‐selective inhibitor treatment. In this study, we analyzed the presence of PIK3CA mutations in formalin‐fixed, paraffin‐embedded, metastatic tissue and corresponding ctDNA from serum of patients with advanced breast cancer using a highly sensitive, optimized droplet digital PCR (ddPCR) assay. We found 83% of patients with PIK3CA mutation in the metastatic tumor tissue also had detectable PIK3CA mutations in serum ctDNA. Patients lacking the PIK3CA mutation in corresponding serum ctDNA all had nonvisceral metastatic disease. Four patients with detectable PIK3CA‐mutated ctDNA were followed with an additional serum sample during oncological treatment. In all cases, changes in PIK3CA ctDNA level correlated with treatment response. Our results showed high concordance between detection of PIK3CA mutations in tumor tissue and in corresponding serum ctDNA and suggest that serum samples from patients with advanced breast cancer and ddPCR may be used for PIK3CA mutation status assessment to complement imaging techniques as an early marker of treatment response

Severity and 90-day survival of SARS-CoV-2 infection among patients with haematological disorders

Severity and 90-day survival of SARS-CoV-2 infection among patients with haematological disorder