Purpose: Premenopausal physiologic steroid levels change cyclically, in contrast to steady state low levels seen in postmenopausal patients. The purpose of this study was to evaluate whether 18F-fluorodeoxyglucose (18F-FDG) uptake in breast cancer is influenced by physiological hormonal fluctuations.
Methods: A total of 160 primary invasive breast cancers from 155 females (54 premenopausal, 101 postmenopausal) who underwent 18F-FDG positron emission tomography/computed tomography before therapy were retrospectively analyzed. The maximal standardized uptake values (SUVmax) of tumors were compared with menstrual phases and menopausal status according to the following subgroups: 'luminal A-like,' 'luminal B-like,' and 'non-luminal.' Additionally, the effect of estradiol (E2) on 18F-FDG uptake in breast cancer cells was evaluated in vitro.
Results: Among premenopausal patients, SUVmax during the periovulatory-luteal phase was significantly higher than that during the follicular phase in luminal A-like tumors (n = 25, p = 0.004), while it did not differ between the follicular phase and the periovulatory-luteal phase in luminal B-like (n = 24) and non-luminal tumors (n = 7). Multiple regression analysis showed menstrual phase, tumor size, and Ki-67 index are independent predictors for SUVmax in premenopausal luminal A-like tumors. There were no significant differences in SUVmax between pre- and postmenopausal patients in any of the subgroups. In in vitro studies, uptake in estrogen receptor-positive cells was significantly augmented when E2 concentration was increased from 0.01 to ≥ 1 nM.
Conclusions: Our data suggest that 18F-FDG uptake may be impacted by physiological hormonal fluctuations during menstrual cycle in luminal A-like cancers, and that E2 could be partly responsible for these events.
Keywords: 18F-FDG PET; Breast cancer; Hormonal dependency; Menstrual cycle; Metabolic flare.