Improving breast cancer outcomes: FDG PET peers in on adrenoceptor blockers

Adrenoceptor blockers have been found to stave off metastasis and recurrence of breast cancer. This may be due to their interruption of key genes involved in glucose metabolism as visualized by FDG-PET, according to a study published Feb. 6 in the Journal of Nuclear Medicine.

There are more diagnoses of breast cancer than any other cancers and more women die of breast cancer than any other type. In 2011, breast cancer was attributed to 23 percent of all cases of cancer and 14 percent of cancer deaths. The current five-year survival rate has increased in recent years to somewhere between 77.5 percent and 90.3 percent, but metastasis and recurrence threaten remission within the 10-year mark following treatment.

Recent studies have hailed adrenoceptor blockers as a protective measure in addition to conventional breast cancer therapy. Propranolol (PROP) alone has been shown to reduce risk of metastasis by 57 percent and breast cancer death by 71 percent after 10 years following breast cancer therapy. Until now researchers did not fully understand why, but their suspicions were rightly focused on mechanisms of glucose metabolism.

Fei Kang, a researcher from the department of nuclear medicine at Xijing Hospital and Fourth Military Medical University in Xi’an, China, and colleagues evaluated beta 1 and 2 adrenoceptors (ADRB1/2), adrenoceptor blockers including PROP and their impact on glucose transporter 1 (GLUT-1) and hexokinase 2 (HK-2) genetic expression in order to pinpoint the pathway of their protective effect in breast cancer cell lines. Preclinical F-18 FDG PET was also utilized to determine effects on glucose metabolism in vivo. Results of the study showed that while PROP had little effect on GLUT-1 expression, the ADRB blocker did downregulate expression of HK-2, which could be impeding the glucose metabolism cancerous breast tissues depend on.

“The expression of HK-2 can be influenced by the activation of ADRB2 through posttranscriptional regulation in 4T1 breast cancer cells,” wrote Kang et al. “Moreover, glucose metabolism and F-18 FDG uptake of 4T1 breast cancer tumors can be inhibited by PROP.”

Researchers determined ADRB1/2 expression in four different types of breast cancer cell lines, 4T1, MDA-MB-231, and MCF-7 by Western blotting and immunofluorescence. Regulation of GLUT-1 and HK-2 by was determined via RNA interference and pharmacologic administration of phosphate-buffered saline, isoproterenol (ISO) or PROP. In vivo, GLUT-1 and HK-2 expression was determined by immunohistochemical analysis and Western blotting, and glucose uptake was observed in mouse models using FDG and preclinical PET scanner.

“Overall, the influence of PROP or ISO on the F-18 FDG uptake of 4T1 tumors in vivo was not always distinguishable, which was consistent with the observations of a previous clinical study; however, some individuals in each group still exhibited obvious differences,” added the authors.

The findings of this study further knowledge of adrenoceptor blockers and could potentially improve management of patients with breast cancer in an effort to improve relapse-free survival.