Molecular changes in premenopausal oestrogen receptor-positive primary breast cancer in Vietnamese women 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 tumourbiology. We therefore, characterised the endocrine and genome-wide transcriptional impact of OvX in 56 premenopausal women with ER + breast cancer for 2 weeks prior to mastectomy. Plasma estradiol concentrations decreased from 406 ± 41 to 20.7 ± 2.6 pmol/l (mean ± sem) 24 h after OvX, and to 8.1 ± 0.8 pmol/l 2 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(TFF1, GREB1, PGR and PDZK1) showed large decreases in expression (FC = 0.20–0.69; p < 1e-6-1e-7). Proliferation-associated genes (e.g. TOP2A, AURKA and UBE2C) were also strongly downregulated (FC = 0.38–0.56; p < 1e-7) along with putative progesterone- regulated genes(e.g. FKBP4, MYB; FC = 0.64–0.68; p < 1e-4-1e-7). The gene expression changes did not differ according to HER2 status and correlated strongly with the changes reported previously after aromatase inhibitor(AI) treatment in postmenopausal women (rho = 0.55, p < 1e-04). However, after OvX the mean FC was significantly higher compared to AI (p < 1e-04). 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; however, OvX appeared to have a greater effect on progesterone- regulated genesthan AI.