This study is aimed at determining the best nonacid nucleic blood tumor marker panels in terms of sensitivity, specificity, and accuracy in order to detect breast cancer in early stages (I, II, and III) among eligible women for breast cancer screening. PubMed, Web of Science, Embase, Scopus, and Cochrane were systematically reviewed to assess nonacid nucleic blood tumor marker panels’ diagnostic value in women, both healthy and patient (before any anticancer treatment), for detecting breast cancer. A network meta-analysis was carried out using a Bayesian network meta-analysis to estimate combined odd ratio (OR) and 95% CI credible interval for presenting the results. Rankograms plot was drawn to rank the diagnostic value of different panels. Of the 2358 titles initially identified, 9 studies and 8 panels were included in the network meta-analysis. Panels A (MMP-9/TIMP-1) and K (TF1+TF2+TF3) had the highest sensitivity in early stages, as panel A with OR = 11.61 and 95% CI (1.49-102.5) demonstrated a better function than mammography. Panels H (CA 15.3 + IL-18) and A (MMP-9/TIMP-1) had the highest specificity in early stages, but no significant difference with mammography. Panels A (MMP-9/TIMP-1) and H (CA 15.3 + IL-18) had the highest accuracy in early stages, as they significantly exhibited a higher function than mammography with OR = 6.87 and 95% CI (2.07-31.35) as well as OR = 3.44 and 95% CI (1.15-11.07), respectively. Panel A including MMP-9/TIMP-1 in early stages demonstrated a higher diagnostic value for breast cancer than the rest of the panels.

This study aimed to compare the non-acid nucleic blood multi-factor panels together and with mammography in terms of sensitivity, specificity, and accuracy in primary breast cancer detection (I, II, III, and IV). We systematically reviewed studies assessing non-acid nucleic blood tumor markers panels’ diagnostic value in both healthy women and patients (before any anticancer treatment) for the detection of primary breast cancer. Out of the 2358 titles initially identified, 12 studies and 9 panels were included in the network meta-analysis. Panels I (MSA + B2m) and J (GATA3 + E-cadherin) had the highest sensitivity in all stages of primary breast cancer but had no significant difference with mammography. Panels L (MSA + CA15–3) and B (M-CSF + CA15–3) had the highest specificity in all stages compared to other panels but no remarkable difference with mammography. Panels J (GATA3 + E-cadherin) and I (MSA + B2m) respectively had the highest accuracy in primary breast cancer detection but no considerable difference with mammography in terms of accuracy. Panel J, including GATA3 + E-cadherin, demonstrated a higher diagnostic value for primary breast cancer detection (I, II, III, and IV) than the rest of the panels.