RESUMO
Background: The circulating tumor DNA (ctDNA) diagnostic accuracy for detecting phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations in breast cancer (BC) is under discussion. We aimed to compare plasma and tissue PIK3CA alterations, encompassing factors that could affect the results. Methods: Two reviewers selected studies from different databases until December 2020. We considered BC patients with matched tumor tissue and plasma ctDNA. We performed meta-regression and subgroup analyses to explore sources of heterogeneity concerning tumor burden, diagnostic technique, sample size, sampling time, biological subtype, and hotspot mutation. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the related area under the curve (AUC) were elaborated for the overall population and each subgroup. Results: The pooled analysis was carried out on 25 cohorts for a total of 1966 patients. The overall ctDNA sensitivity and specificity were 0.73 (95% CI: 0.70-0.77) and 0.87 (95% CI: 0.85-0.89). The AUC was 0.93. Pooled concordance, negative predictive value and positive predictive value values were 0.87 (95% CI: 0.82-0.92), 0.86 (95% CI: 0.81-0.90), and 0.89 (95% CI: 0.81-0.95) with pooled PLR, NLR, and DOR of 7.94 (95% CI: 4.90-12.86), 0.33 (95% CI: 0.25-0.45), and 33.41 (95% CI: 17.23-64.79), respectively. The pooled results consistently favored next-generation sequencing (NGS)- over polymerase chain reaction-based methodologies. The best ctDNA performance in terms of sensitivity, specificity, and AUC (0.85, 0.99, and 0.94, respectively) was observed in the low-time sampling subgroup (⩽18 days between tissue and plasma collection). Meta-regression and subgroup analyses highlighted sampling time as a possible major cause of heterogeneity. Conclusions: These findings reliably estimate the high ctDNA accuracy for the detection of PIK3CA mutations. A ctDNA-first approach for the assessment of PIK3CA mutational status by NGS may accurately replace tissue tumor sampling, representing the preferable strategy at diagnosis of metastatic BC in patients who present with visceral involvement and at least two metastatic lesions, primarily given low clinical compliance or inaccessible metastatic sites.
RESUMO
The restriction of proteins, amino acids or sugars can have profound effects on the levels of hormones and factors including growth hormone, IGF-1 and insulin. In turn, these can regulate intracellular signaling pathways as well as cellular damage and aging, but also multisystem regeneration. Both intermittent (IF) and periodic fasting (PF) have been shown to have both acute and long-term effects on these hormones. Here, we review the effects of nutrients and fasting on hormones and genes established to affect aging and cancer. We describe the link between dietary interventions and genetic pathways affecting the levels of these hormones and focus on the mechanisms responsible for the cancer preventive effects. We propose that IF and PF can reduce tumor incidence both by delaying aging and preventing DNA damage and immunosenescence and also by killing damaged, pre-cancerous and cancer cells.