TY - JOUR
T1 - Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy
AU - Dehdashti, Farrokh
AU - Wu, Ningying
AU - Ma, Cynthia X.
AU - Naughton, Michael J.
AU - Katzenellenbogen, John A.
AU - Siegel, Barry A.
N1 - Funding Information:
F.D. reports grants from the National Cancer Institute, grants from Siteman Cancer Center/Barnes-Jewish Hospital Foundation during the conduct of the study, and grants from the ECOG-ACRIN Medical Research Foundation and the National Cancer Institute, and grants from NIH/NIBIB outside the submitted work. C.M. reports research funding from Pfizer, consulting fees from Pfizer, AstraZeneca, Eli Lilly, and Novartis. M.N. reports being a speaker for Merck and Esai. J.A.K. was a founder and has an equity interest in Radius Health, Inc., which is developing Elacestrant (RAD 1901), an antiestrogen for breast cancer. B.A.S. reports funding by the ECOG-ACRIN Medical Research Foundation and American College of Radiology for his contribution in administrative roles and also is a consultant for Avid Radiopharmaceutical, Inc., Capella Imaging, LLC., Curium Pharma, General Electric Healthcare, Imaginab, Inc., Progenics Pharmaceuticals, American College of Radiology, American Medical Foundation for Peer Review and Education and Siemens Healthineers.
Funding Information:
This work was supported in part by NCI Grant R01 CA195450 and by a grant from the Alvin J. Siteman Cancer Center/Barnes-Jewish Hospital Foundation. We thank the Siteman Cancer Center (supported in part by NCI Grant P30 CA91842) for use of the Imaging and Response Assessment Core. Dr. John Katzenellenbogen has been supported by CA025836 and a Breast Cancer Research Foundation Grant 20-084. We thank our patients for their willingness to participate in this study. We greatly appreciate the efforts of the nuclear medicine research coordinators, Jennifer Frye and Helen Kaemmerer, without whose assistance this study would not have been possible.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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-[18F]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.
AB - 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-[18F]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.
UR - http://www.scopus.com/inward/record.url?scp=85100253368&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-20814-9
DO - 10.1038/s41467-020-20814-9
M3 - Article
C2 - 33531464
AN - SCOPUS:85100253368
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 733
ER -