Breast Cancer Coverage from Every Angle

Can PET-Based Estradiol Challenge Test Monitor Response to Endocrine Therapy?

By: Noelle Cutter, PhD
Posted: Tuesday, June 1, 2021

To reliably identify patients most likely to benefit from endocrine therapy, better methods are needed to determine the quantity and functional status of breast cancer tumor estrogen receptor (ER) and progesterone receptor (PgR). Researchers from the Alvin J. Siteman Cancer Center at the Washington University School of Medicine, St. Louis, reported a change in tumor uptake of the progestin analog 21-[18F] fluorofuranylnorprogesterone (FFNP) in subjects after a brief estradiol challenge. Their results were published in Nature Communications and suggest that tumor ER functional status may prove to be a strong predictor of benefit from endocrine therapy.

“FFNP-PET before and after administration of estradiol over 24 hours can be accomplished in as little as 2 days before endocrine therapy is started and discriminates likely responders from nonresponders with high accuracy, thus allowing for risk stratification equivalent to that obtained by much longer clinical observations alone,” noted Barry A. Siegel, MD, of Washington University, and colleagues.

A total of 47 postmenopausal women with ER-positive; HER2-negative; and locally advanced, locally recurrent, or metastatic breast cancer enrolled in the single-center, single-arm phase II clinical trial. FFNP-PET imaging was used to evaluate tumor PgR response to estradiol challenge (6 mg, administered orally as one 2-mg tablet every 8 hours).

A clinical benefit to endocrine therapy was seen in 28 patients (65%), whereas 15 patients (35%) were nonresponders and experienced disease progression within 6 months. Tumor FFNP significantly increased compared with baseline in responding patients versus nonresponding patients (25.4% vs. –0.7%; P < .0001). All 28 responders had a standardized uptake value (SUV) change of at least 7%, and all 15 nonresponders had an SUV change of less than 7%. Significantly longer survival was seen in clinical responders versus nonresponders, and median survival was not reached among responding patients.

“While the results of this study are extremely promising, our findings need to be confirmed in a multicenter trial before this method can be used to guide ET in clinical practice,” the authors cautioned.

Disclosure: For full disclosures of the study authors, visit

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