Hormonal Receptor Immunochemistry Heterogeneity and 18F-FDG Metabolic Heterogeneity: Preliminary Results of Their Relationship and Prognostic Value in Luminal Non-Metastatic Breast Cancers

Abstract

IntroductionWe aimed to investigate whether 18F-FDG PET metabolic heterogeneity reflects the heterogeneity of estrogen receptor (ER) and progesterone receptor (PR) expressions within luminal non-metastatic breast tumors and if it could help in identifying patients with worst event-free survival (EFS).Materials and methodsOn 38 PET high-resolution breast bed positions, a single physician drew volumes of interest encompassing the breast tumors to extract SUVmax, histogram parameters and textural features. High-resolution immunochemistry (IHC) scans were analyzed to extract Haralick parameters and descriptors of the distribution shape. Correlation between IHC and PET parameters were explored using Spearman tests. Variables of interest to predict the EFS status at 8 years (EFS-8y) were sought by means of a random forest classification. EFS-8y analyses were then performed using univariable Kaplan-Meier analyses and Cox regression analysis. When appropriate, Mann-Whitney tests and Spearman correlations were used to explore the relationship between clinical data and tumoral PET heterogeneity variables.ResultsFor ER expression, correlations were mainly observed with 18F-FDG histogram parameters, whereas for PR expression correlations were mainly observed with gray-level co-occurrence matrix (GLCM) parameters. The strongest correlations were observed between skewness_ER and uniformity_HISTO (ρ = −0.386, p = 0.017) and correlation_PR and entropy_GLCM (ρ = 0.540, p = 0.001), respectively. The median follow-up was 6.5 years and the 8y-EFS was 71.0%. Random forest classification found age, clinical stage, SUVmax, skewness_ER, kurtosis_ER, entropy_HISTO, and uniformity_HISTO to be variables of importance to predict the 8y-EFS. Univariable Kaplan-Meier survival analyses showed that skewness_ER was a predictor of 8y-EFS (66.7 ± 27.2 versus 19.1 ± 15.2, p = 0.018 with a cut-off value set to 0.163) whereas other IHC and PET parameters were not. On multivariable analysis including age, clinical stage and skewness_ER, none of the parameters were independent predictors. Indeed, skewness_ER was significantly higher in youngest patients (ρ = −0.351, p = 0.031) and in clinical stage III tumors (p = 0.023).ConclusionA heterogeneous distribution of ER within the tumor in IHC appeared as an EFS-8y prognosticator in luminal non-metastatic breast cancers. Interestingly, it appeared to be correlated with PET histogram parameters which could therefore become potential non-invasive prognosticator tools, provided these results are confirmed by further larger and prospective studies.

Entropy analysis and grey cluster analysis of multiple indexes of 5 kinds of genuine medicinal materials

“…According to the combustion heat, thermogravimetric parameters, fat content, calcium content, trace element content and ash content, the multi-index comprehensive evaluation systems of five kinds of genuine medicinal materials including Diding, Purslane, straw sandal board, June snow, pine vine rattan were established by entropy method 67 – 72 .…”

Radiomics in Oncological PET Imaging: A Systematic Review—Part 1, Supradiaphragmatic Cancers

“…We screened 32 publications on breast cancer [ 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 ], all employing 18F-FDG. The average number of enrolled patients was 126.8 (range 35–435), 18/32 (56.3%) studies including more than 100 patients; 3 studies (9.3%) were based on prospectively acquired data and 6/32 used an internal independent validation cohort (18.8%).…”

The Role of Histogram-Based Textural Analysis of ¹⁸F-FDG PET/CT in Evaluating Tumor Heterogeneity and Predicting the Prognosis of Invasive Lung Adenocarcinoma

“…According to Hyun et al ( 23 ) lower entropy was independently associated with longer survival in patients with pancreatic ductal adenocarcinoma. In their study on breast cancer, Aide et al ( 13 ) reported that tumors with high entropy and low energy-uniformity have shorter event-free survival, but the log-rank tests reached almost statistical significance. The evidence is insufficient, but all these results suggest that precision medicine will improve with the use of TFs.…”

“…This analysis shows that heterogeneity is quantitated in all tumor areas in 18 F-FDG uptake. With textural analysis, lots of studies have been conducted in various areas, such as benign-malignant distinction ( 7 , 8 ), tumor subtype differentiation ( 9 ), treatment response evaluation ( 10 , 11 ), and prognosis prediction ( 12 , 13 ).…”