The influence of receptor expression and clinical subtypes on baseline [18F]FDG uptake in breast cancer: systematic review and meta-analysis

Abstract

Background To quantify the relationship between [18F]FDG uptake of the primary tumour measured by PET-imaging with immunohistochemical (IHC) expression of ER, PR, HER2, Ki-67, and clinical subtypes based on these markers in breast cancer patients. Methods PubMed and Embase were searched for studies that compared SUVmax between breast cancer patients negative and positive for IHC expression of ER, PR, HER2, Ki-67, and clinical subtypes based on these markers. Two reviewers independently screened the studies and extracted the data. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were estimated by using DerSimonian-Laird random-effects models. P values less than or equal to 5% indicated statistically significant results. Results Fifty studies were included in the final analysis. SUVmax is significantly higher in ER-negative (31 studies, SMD 0.66, 0.56–0.77, P < 0.0001), PR-negative (30 studies, SMD 0.56; 0.40–0.71, P < 0.0001), HER2-positive (32 studies, SMD − 0.29, − 0.49 to − 0.10, P = 0.0043) or Ki-67-positive (19 studies, SMD − 0.77; − 0.93 to − 0.61, P < 0.0001) primary tumours compared to their counterparts. The majority of clinical subtypes were either luminal A (LA), luminal B (LB), HER2-positive or triple negative breast cancer (TNBC). LA is associated with significantly lower SUVmax compared to LB (11 studies, SMD − 0.49, − 0.68 to − 0.31, P = 0.0001), HER2-positive (15 studies, SMD − 0.91, − 1.21 to − 0.61, P < 0.0001) and TNBC (17 studies, SMD − 1.21, − 1.57 to − 0.85, P < 0.0001); and LB showed significantly lower uptake compared to TNBC (10 studies, SMD − 0.77, − 1.05 to − 0.49, P = 0.0002). Differences in SUVmax between LB and HER2-positive (9 studies, SMD − 0.32, − 0.88 to 0.24, P = 0.2244), and HER2-positive and TNBC (17 studies, SMD − 0.29, − 0.61 to 0.02, P = 0.0667) are not significant. Conclusion Primary tumour SUVmax is significantly higher in ER-negative, PR-negative, HER2-positive and Ki-67-positive breast cancer patients. Luminal tumours have the lowest and TNBC tumours the highest SUVmax. HER2 overexpression has an intermediate effect.

Clinical and economic outcomes of adding [18F]FES PET/CT in estrogen receptor status identification in metastatic and recurrent breast cancer in the US

“…[ 18 Age min, max in years 18, 100 [27] Proportion of patients regarding HER2 status HER2-negative 88% [28] HER2-positive 12% [28] Number of lesions per patient (HER2-negative, HER2-positive)…”

“…The variables that affect the incremental cost-effectiveness ratio (ICER) the most were the sensitivity of [ 18 F]FES PET/ CT in mBC patients when biopsy failed or was inconclusive and appropriateness of endocrine therapy in mBC patients when biopsy was not possible, and in rBC patients when [ 18 F]FES PET/CT was used in combination with IHC. The estimated ICER was also sensitive to changes in other clinical inputs, such as discordance rates, and specificity of [ 18 The probabilistic sensitivity analysis (PSA) was conducted with 1000 simulations to test the combined uncertainty and correlation between model parameters simultaneously. Mean…”

“…This compound allows for a minimally invasive yet selective [22] and comprehensive assessment of the whole-body ER-positive tissue status. In the case of multi-metastatic disease, when the standard of care would require only one metastasis to be biopsied, [ 18 F]FES can help to evaluate the ER status of the non-biopsied metastases [17].…”

“…]FES PET/CT indicates 16α-18 F-fluoro-17β-fluoroestradiol with positron emission tomography/computed tomography; AEs, adverse events; CEM, cost-effectiveness model; IHC, immunohistochemistry; HER2, human epidermal growth factor receptor 2; SD, standard deviation; SE, standard error. *Assumption; & calculated https://doi.org/10.1371/journal.pone.0302486.t001…”

“…18 F]FES PET/CT indicates 16α-18 F-fluoro-17β-fluoroestradiol with positron emission tomography imaging/ computed tomography; CEM, cost-effectiveness model; ICER, incremental cost-effectiveness ratio; mBC, metastatic breast cancer; QALYs, quality-adjusted life years; rBC, recurrent breast cancer. https://doi.org/10.1371/journal.pone.0302486.t003 PLOS ONE probabilistic…”