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基于 PET 的雌二醇挑战试验预测乳腺癌孕激素受体与内分泌治疗反应的相关性。

Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy.

机构信息

Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.

Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.

出版信息

Nat Commun. 2021 Feb 2;12(1):733. doi: 10.1038/s41467-020-20814-9.

DOI:10.1038/s41467-020-20814-9
PMID:33531464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7854611/
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-[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.

摘要

雌激素受体 (ER) 检测对乳腺癌内分泌治疗 (ET) 的反应预测并不完美。我们假设，短暂的雌二醇刺激只会增加功能性 ER 肿瘤中的孕激素受体 (PgR) 水平。在这项前瞻性、2 期、单中心、单臂试验 (NCT02455453) 中，我们报告了 ET 反应与肿瘤摄取孕激素类似物 21-[F]氟代呋喃诺孕酮 (FFNP) 的变化之间的关联，该变化发生在雌二醇刺激前后一天。在 43 名绝经后患有晚期 ER+乳腺癌的女性中，我们发现仅在 28 名从 ET 中获得临床获益的受试者（应答者）中，肿瘤 FFNP 摄取在刺激后增加，而在 15 名没有临床获益的受试者（无应答者）中没有增加 (p<0.0001)，表明 100%的敏感性和特异性。我们进一步表明，应答者的生存时间显著延长 (p<0.0001)。我们的结果表明，雌二醇刺激后肿瘤 FFNP 摄取的变化高度预测了 ER+乳腺癌女性对 ET 的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/e242da473223/41467_2020_20814_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/bbb6c2b3f900/41467_2020_20814_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/90bb89d8e1d0/41467_2020_20814_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/02fdc8b5ff50/41467_2020_20814_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/c0e86c39bde1/41467_2020_20814_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/e242da473223/41467_2020_20814_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/bbb6c2b3f900/41467_2020_20814_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/90bb89d8e1d0/41467_2020_20814_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/02fdc8b5ff50/41467_2020_20814_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/c0e86c39bde1/41467_2020_20814_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebf/7854611/e242da473223/41467_2020_20814_Fig5_HTML.jpg

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