Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina.
Endocr Relat Cancer. 2012 May 3;19(3):R35-50. doi: 10.1530/ERC-11-0378. Print 2012 Jun.
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. It is accepted that breast cancer is not a single disease, but instead constitutes a spectrum of tumor subtypes with distinct cellular origins, somatic changes, and etiologies. Molecular gene expression studies have divided breast cancer into several categories, i.e. basal-like, ErbB2 enriched, normal breast-like (adipose tissue gene signature), luminal subtype A, luminal subtype B, and claudin-low. Chances are that as our knowledge increases, each of these types will also be subclassified. More than 66% of breast carcinomas express estrogen receptor alpha (ERα) and respond to antiestrogen therapies. Most of these ER+ tumors also express progesterone receptors (PRs), the expression of which has been considered as a reliable marker of a functional ER. In this paper we will review the evidence suggesting that PRs are valid targets for breast cancer therapy. Experimental data suggest that both PR isoforms (A and B) have different roles in breast cancer cell growth, and antiprogestins have already been clinically used in patients who have failed to other therapies. We hypothesize that antiprogestin therapy may be suitable for patients with high levels of PR-A. This paper will go over the experimental evidence of our laboratory and others supporting the use of antiprogestins in selected breast cancer patients.
乳腺癌是全球女性最常见的癌症，也是癌症死亡的主要原因。人们普遍认为乳腺癌不是一种单一的疾病，而是由具有不同细胞起源、体细胞变化和病因的肿瘤亚型组成的谱系。分子基因表达研究已经将乳腺癌分为几类，即基底样、ErbB2 富集型、正常乳腺样（脂肪组织基因特征）、腔 A 型、腔 B 型和 Claudin-low 型。随着我们知识的增加，这些类型中的每一种也有可能被细分。超过 66%的乳腺癌表达雌激素受体 alpha（ERα），并对抗雌激素治疗有反应。这些 ER+肿瘤中的大多数也表达孕激素受体（PRs），其表达被认为是 ER 功能的可靠标志物。本文将回顾表明 PRs 是乳腺癌治疗有效靶点的证据。实验数据表明，两种 PR 异构体（A 和 B）在乳腺癌细胞生长中具有不同的作用，抗孕激素药物已经在对其他治疗方法无效的患者中临床应用。我们假设抗孕激素治疗可能适合 PR-A 水平高的患者。本文将综述我们实验室和其他实验室的实验证据，支持在特定乳腺癌患者中使用抗孕激素药物。
