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

Abstract

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.