PET shows early response to hormone therapy in breast cancer

Molecular imaging of progesterone receptor status in breast tumors using positron emission tomography (PET) may be an effective and noninvasive means of identifying early in the course of endocrine, or hormone-based, therapy which patients will respond well to treatment. 

In a recent study, mice with mammary cell lines derived from breast tumors that were positive for estrogen receptor-alpha (ERα) and for progesterone receptor (PR) underwent small-animal (PET)/computed tomography (CT). ¹⁸F-fluoroestradiol (¹⁸F-FES)-PET was used to image ER status, ¹⁸F-fluoro furanyl norprogesterone (¹⁸F-FFNP)-PET was used to image PR status, and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-PET was used to image glucose uptake.

“PET has typically been used to identify the target for endocrine therapy in breast cancer by demonstrating that ER is present in tumors using [¹⁸F-FES-PET] or by monitoring for hormone-induced changes in tumor metabolism—“metabolic flare”—with [¹⁸F-FDG-PET] once therapy has begun,” explained the study’s lead author, Amy M. Fowler, MD, PhD, of the Mallinckrodt Institute of Radiology at the Washington University School of Medicine in St. Louis, Missouri, in a statement issued by the Society of Nuclear Medicine. (Fowler’s group’s results were published in The Journal of Nuclear Medicine [2012;53(7):1119-1126], a publication of the Society of Nuclear Medicine.) “What is novel about our study is that we chose to image progesterone receptor levels to see how the estrogen signaling pathway is functioning in response to endocrine therapy.”

Primary mammary tumors and implanted tumors from the SSM2 and SSM3 mammary cell lines showed high uptake of ¹⁸F-FES and ¹⁸F-FFNP, and were confirmed to be ERα-positive and PR-positive. Classic estrogen-induced regulation of the PR gene was demonstrated by increased ¹⁸F-FFNP uptake of estradiol-treated SSM3 tumors.

Treatment with fulvestrant decreased ¹⁸F-FFNP, ¹⁸F-FES, and ¹⁸F-FDG uptake and inhibited growth of SSM3 tumors, but decreased only ¹⁸F-FES uptake in SSM2 tumors, with no effect on growth despite the fact that like the SSM3 tumors, the SSM2 tumors were also ERα-positive and PR-positive. Decreased ¹⁸F-FFNP uptake by SSM3 tumors occurred early after the start of therapy, before measurable tumor growth inhibition.

The results served to identify a profile that distinguished fulvestrant-sensitive from fulvestrant-resistant ERα-positive/PR-positive tumors before changes in tumor size, summarized the researchers. They added that based on this work, noninvasive imaging of baseline tumoral ¹⁸F-FES uptake and initial changes in ¹⁸F-FFNP uptake is a potentially useful strategy for identifying responders and nonresponders to endocrine therapy at an early stage.