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Molecular changes in premenopausal estrogen receptor-positive primary breast cancer after oophorectomy

ABSTRACT: For premenopausal women with primary ER+ breast cancer, oophorectomy (OvX) is an evidence-based cost-effective option and is standard treatment in many countries. However, there is virtually no data describing the effects of OvX on breast tumour biology. We therefore characterized the endocrine and genome-wide transcriptional impact of OvX in 56 premenopausal women with ER+ breast cancer for two weeks prior to mastectomy. Plasma estradiol concentrations decreased from 421±305 to 24.1±24.5 pmol/l (mean±sd) 24 hours after OvX and to 8.8±7.3pmol/l two weeks later at mastectomy. Ki67 decreased in 33/36 (91.7%) tumours. The expression of 655 genes changed significantly (FDR<1%) with an absolute mean fold-change (FC) ≥1.25 (257 up, 398 down). Archetypal oestrogen-regulated genes, proliferation-associated genes and putative progesterone-regulated genes were strongly down-regulated. The gene expression changes did not differ according to HER2 status and correlated strongly with those after aromatase inhibitor (AI) treatment in 81 postmenopausal women. However, after OvX the mean FC was significantly higher compared to AI. In conclusion, changes in tumoural gene expression after OvX were largely similar but of a greater magnitude to those observed after AI in postmenopausal patients but OvX appeared to have a greater effect on progesterone-regulated genes than AI.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97221 | GEO | 2018/02/14

REPOSITORIES: GEO

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