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

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. A non-randomized phase II trial of neoadjuvant OvX was conducted in 56 premenopausal women with ER+ breast cancer in Vietnam in order to identify the most important genes and pathways associated with the response to OvX as well as determinants of that response. In addition, the degree to which the relationships differed from those observed after an AI in postmenopausal women (i.e. comparing withdrawal of oestrogen and progesterone vs. withdrawal of oestrogen alone) was assessed. Global gene expression profiles from ERα-positive breast carcinomas before and after OvX treatment were compared. Transcripts responding differently to OvX and estrogen deprivation were identified and integrated using Gene Ontology and pathway analyses. This represents the data for OvX only. Please note that 88 paired frozen samples from 32 patients (out of 56 in the trial; 24 with A, B & C samples; 5 with A & C and 3 with B & C) were used for Illumina whole genome expression BeadChips analysis.