Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy
Farrokh Dehdashti, Ningying Wu, X. Cynthia, Michael Naughton, John A. Katzenellenbogen, Barry A. Siegel
Abstract
Abstract Estrogen receptor (ER) testing of breast cancer imperfectly predicts response to endocrine therapy (ET). We hypothesize that a brief estradiol challenge will increase tumor progesterone receptor (PgR) levels only in tumors with functional ER. In this prospective, phase 2, single-center, single-arm trial (NCT02455453), we report the association of response to ET with change in tumor uptake of the progestin analog, 21-[ 18 F]fluorofuranylnorprogesterone (FFNP), before and after a one-day estradiol challenge. In 43 postmenopausal women with advanced ER+ breast cancer, we show a post-challenge increase in tumor FFNP uptake only in 28 subjects with clinical benefit from ET (responders), but not in 15 without clinical benefit (nonresponders) ( p < 0.0001), indicating 100% sensitivity and specificity. We further show significantly longer survival ( p < 0.0001) in the responding subjects. Our results demonstrate that change in tumor FFNP uptake after estradiol challenge is highly predictive of response to ET in women with ER+ breast cancer.