This study showed that increased SUVRmax of the psoas muscle is correlated with shorter DFS in patients with breast cancer. The multivariate analysis with covariates of the TN stage, ER/PR/HER2 status, surgical protocol, SUVRmean, and SUVRmax revealed that N3 stage was an independent prognostic factor. Mastectomy seemed to be correlated with recurrence (Table 1); however, adjustment for the TN stage covariate corrected for the deviation in surgical protocol, which could be attributed to staging (Table 2). The stage and hormone receptor status of breast cancer are considered prognostic factors. Although BMI showed a positive correlation with SUVRmax, it was not an independent prognostic factor in the multivariate analysis.
A retrospective study by Korean researchers demonstrated that higher 18F-FDG uptake (SUVmax) in the psoas muscle was positively correlated with incipient metabolic syndrome (HR = 3.26, P = 0.0174) [10]. The study showed that higher SUVmax of the psoas muscle was an independent risk factor for metabolic syndrome among 157 participants with a balanced sex ratio (60% male and 40% female). This result is contradictory with those of previous studies that showed lower uptake in skeletal muscle in a group of patients with IR. According to previous studies that used the gold standard hyperinsulinemic-euglycemic clamp technique [6,7,8,9], excess insulin in patients with IR might result in the saturation of overexpressed GLUT4 in the plasma membrane, and the decreased intracellular GLUT4 levels could not respond to infused insulin. This might hinder the uptake of 18F-FDG in hyperinsulinemic-euglycemic patients with IR. The 18F-FDG PET-CT approach utilized by these Korean researchers was based on a routine clinical setting; thus, it was performed after 4–6 h of fasting. Moreover, the imaging approach used in the present study was similar to that used by the Korean researchers, but this study involved patients with breast cancer.
Another retrospective study comprising 59 patients with esophageal cancer in the United States reported that a higher psoas SUVmax was a favorable prognostic factor for overall survival (HR = 0.37, P = 0.04) [16]. They stated that less fatty infiltration of the muscle might result in higher 18F-FDG uptake and reflect a more robust muscle tissue in patients. They included 90% of male patients, and 30% of the patients had stage IV esophageal cancer. The small sample size, biased sex ratio, and advanced stage of cancer might have influenced the result. Moreover, they used SUVmax, and we used SUVRmax.
They included 32% of diabetes mellitus (DM) patients while this study has 9% of DM. Although it is not usual that a study regarding IR includes DM, we regard that diagnosed DM patients are well treated. The patients with uncontrolled DM and high level of serum glucose could not take 18F-FDG PET-CT in our institution. There are diabetes medications which reduce IR including biaguanides and thiazolidinediones. We consider the level of IR itself which was measured by 18F-FDG PET-CT at the time of diagnosis of breast cancer. Differences in SUV values between DM or non-DM patients and correlations between SUV values, FBS and BMI are presented as supplemental tables.
In the context of various cancers, IR has been reported using the hyperinsulinemic-euglycemic clamp technique [17,18,19,20]. Several researchers using the same technique have reported that insulin sensitivity had been restored after surgical tumor resection [21, 22]. This suggests that IR in patients with cancer could be caused by the tumor itself. IR accompanied by cancer could be a prognostic factor or surrogate marker for residual disease.
This study has several limitations. This was a retrospective study from a single institution. The study’s small sample size limited subgroup analyses, although breast cancer has various subgroups that have been well established. Additive information such as HOMA-IR data, which could validate high SUVRmax of the psoas muscle as a definite surrogate marker of IR, was not available in this study.