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对于绝经前雌激素受体阳性乳腺癌女性，卵巢切除术是一种证实经济有效的选择，在许多国家是标准的治疗方案。然而，几乎没有数据描述卵巢切除术对乳腺肿瘤生物学的影响。 2017年11月27日，美国乳腺癌研究基金会与英国《自然》旗下《乳腺癌》在线发表英国伦敦大学癌症研究院、皇家马斯登医院、加拿大多伦多大学、渥太华大学、渥太华医院、美国纽约大学医学院、朗格尼医学中心、珀尔马特癌症中心、越南河内国立癌症医院的研究报告，分析了卵巢切除术对56例绝经前雌激素受体阳性乳腺癌女性乳房切除术前两周内分泌和全基因组转录的影响。 结果发现，卵巢切除术后血浆雌二醇浓度由406 ± 41降低至20.7 ± 2.6 pmol/l，2周后降低至8.1 ± 0.8 pmol/l。36例其中33例（91.7%）肿瘤Ki67降低。 655个基因表达变化显著（FDR<1%），绝对平均变化倍数≥1.25（257个基因表达增加，398个基因表达减少）。雌激素调节基因（TFF1、GREB1、PGR、PDZK1）、增殖相关基因（TOP2A、AURKA、UBE2C）、孕激素调节基因（FKBP4、MYB）表达大幅减少。 基因表达变化与HER2状态无关，与绝经后女性既往接受芳香酶抑制剂治疗显著相关（ρ=0.55，P<0.0001）。不过，卵巢切除术后与芳香酶抑制剂治疗后相比，基因表达平均变化倍数显著较高（P<0.0001）。 因此，卵巢切除术后的肿瘤基因表达变化大致相似，但是既往接受芳香酶抑制剂治疗的绝经后患者变化较大。不过，卵巢切除术与芳香酶抑制剂相比，似乎对孕激素调节基因的影响更大。 NPJ Breast Cancer. 2017 Nov 27;3:47. Molecular changes in premenopausal oestrogen receptor-positive primary breast cancer in Vietnamese women after oophorectomy. Ben P. Haynes, Ophira Ginsburg, Qiong Gao, Elizabeth Folkerd, Maria Afentakis, Le Hong Quang, Pham Thi Han, Pham Hong Khoa, Nguyen Van Dinh, Ta Van To, Mark Clemons, Ian E. Smith, Mitch Dowsett. Royal Marsden Hospital, London, UK; University of Toronto, Toronto, Canada; NYU School of Medicine, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, USA; The Institute of Cancer Research, London, UK; National Cancer Hospital, Hanoi, Vietnam; The Ottawa Hospital, University of Ottawa, Ottawa, Canada. 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, 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 genes than AI. DOI: 10.1038/s41523-017-0049-z |
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