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Impact of Nuclear Oestrogen Receptor Beta Expression in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

ABSTRACT: Introduction Oestrogen receptor beta (ER-?) is abundantly expressed in breast cancer (BC), but its impact on neoadjuvant chemotherapy outcome is unknown. Patients and Methods Patients treated in the neoadjuvant GeparTrio trial with available tissue for immunohistochemical analyses were included. Nuclear ER-? expression was correlated with clinico-pathologic characteristics. The impact of its expression on pathological complete response (pCR [ypT0/ypN0]) and survival was determined. Results Samples of 570 patients were available. Low nuclear ER-? expression (IRS

SUBMITTER: Heitz F

PROVIDER: S-EPMC6805199 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Impact of Nuclear Oestrogen Receptor Beta Expression in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

Heitz Florian F Kümmel Sherko S Lederer Bianca B Solbach Christine C Engels Knut K Ataseven Beyhan B Sinn Bruno B Blohmer Jens Uwe JU Denkert Carsten C Barinoff Jana J Fisseler-Eckhoff Annette A Loibl Sibylle S

Geburtshilfe und Frauenheilkunde 20191022 10

<b>Introduction</b> Oestrogen receptor beta (ER-β) is abundantly expressed in breast cancer (BC), but its impact on neoadjuvant chemotherapy outcome is unknown. <b>Patients and Methods</b> Patients treated in the neoadjuvant GeparTrio trial with available tissue for immunohistochemical analyses were included. Nuclear ER-β expression was correlated with clinico-pathologic characteristics. The impact of its expression on pathological complete response (pCR [ypT0/ypN0]) and survival was determined. ...[more]

PMID: 31656321

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Project description:BackgroundChemotherapy efficacy in early-stage hormone receptor-positive (HR+) breast cancer (BC) according to menopausal status needs a biological explanation.MethodsWe compared early-stage HR+ BC biological features before and after (neo)adjuvant chemotherapy or endocrine therapy (ET), and assessed oestrogen receptor (ER) pathway activity in both pre- and post-menopausal patients. The nCounter platform was used to detect gene expression levels.FindingsIn 106 post-menopausal patients with HR+/HER2-negative BC randomized to neoadjuvant chemotherapy or ET (letrozole+ribociclib), a total of 19 oestrogen-regulated genes, including progesterone receptor (PGR), were found downregulated in the ET-based arm-only. We confirmed this finding in an independent dataset of 20 letrozole-treated post-menopausal patients and found, conversely, an up-regulation of the same signature in HR+/HER2-negative MCF7 cell line treated with estradiol. PGR was found down-regulated by 2 weeks of ET+anti-HER2 therapy in pre-/post-menopausal patients with HR+/HER2-positive (HER2+) BC, while anti-HER2 therapy alone increased PGR expression in HR-negative/HER2+ BC. In 88 pre- and post-menopausal patients with newly diagnosed HR+/HER2-negative BC treated with chemotherapy, the 19 oestrogen-regulated genes were found significantly downregulated only in pre-menopausal patients. In progesterone receptor (PR)+/HER2-negative BC treated with neoadjuvant chemotherapy (n=40), tumours became PR-negative in 69.2% of pre-menopausal patients and 14.8% of post-menopausal patients (p=0.001). Finally, a mean decrease in PGR levels was only observed in pre-menopausal patients undergoing anti-HER2-based multi-agent chemotherapy.InterpretationChemotherapy reduces the expression of ER-regulated genes in pre-menopausal women suffering from hormone-dependent BC by supressing ovarian function. Further studies should test the value of chemotherapy in this patient population when ovarian function is suppressed by other methods.FundingInstituto de Salud Carlos III, Breast Cancer Now, the Breast Cancer Research Foundation, the American Association for Cancer Research, Fundació La Marató TV3, the European Union's Horizon 2020 Research and Innovation Programme, Pas a Pas, Save the Mama, Fundación Científica Asociación Española Contra el Cáncer, PhD4MDgrant of "Departament de Salut", exp SLT008/18/00122, Fundación SEOM and ESMO. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the author(s).

Dataset Information

Impact of Nuclear Oestrogen Receptor Beta Expression in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

Publications

Impact of Nuclear Oestrogen Receptor Beta Expression in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

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