Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Oncology Program, Institute for Research in Biomedicine (IRB Barcelona) and CIBERONC, Spain.
Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Department of Medical Oncology, Hospital Clínic de Barcelona, Spain; SOLTI Breast Cancer Cooperative Group, Barcelona, Spain.
Cancer Treat Rev. 2018 Jun;67:63-70. doi: 10.1016/j.ctrv.2018.04.015. Epub 2018 May 7.
Gene expression profiling has had a considerable impact on our understanding ofbreastcancer biology. Duringthelast decade, 4 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched [HER2-E] and Basal-like) have been identified and intensively studied. In this article, we review and discuss the clinical implications of the 2 non-luminal subtypes (i.e. HER2-E and Basal-like) identified within hormone receptor (HR)-positive disease. After reviewing 32 studies for a total of 13,091 samples, ∼8% and ∼ 15% of early and metastatic HR+/HER2-negative breast cancer, respectively, were found to be non-luminal. Clinically, HR+/HER2-negative/non-luminal subtypes have been associated with estrogen independence, chemo-sensitivity, resistance to CDK4/6 inhibition and poor outcome. Interestingly, EGFR/HER2 tyrosine kinase inhibition might be of value in the HR+/HER2-negative/HER2-E subtype. Finally, the HER2-E subtype within HR+/HER2 + disease represents ∼ 30% and has been associated with anti-HER2 sensitivity, chemo-sensitivity and resistance to CDK4/6 inhibition. In the upcoming years, retrospective and prospective clinical trials evaluating both biomarkers should lead to improvements in patient outcomes.
基因表达谱分析极大地促进了我们对乳腺癌生物学的理解。在过去的十年中，已经确定并深入研究了乳腺癌的 4 种内在分子亚型（Luminal A、Luminal B、HER2 富集型[HER2-E]和基底样）。在本文中，我们回顾和讨论了在激素受体（HR）阳性疾病中鉴定出的 2 种非 Luminal 亚型（即 HER2-E 和基底样）的临床意义。在对 32 项共涉及 13091 个样本的研究进行综述后，约 8%和约 15%的早期和转移性 HR+/HER2-阴性乳腺癌分别被鉴定为非 Luminal 型。临床上，HR+/HER2-阴性/非 Luminal 亚型与雌激素独立性、化疗敏感性、对 CDK4/6 抑制的耐药性和不良预后相关。有趣的是，EGFR/HER2 酪氨酸激酶抑制可能对 HR+/HER2-阴性/HER2-E 亚型有价值。最后，HR+/HER2+疾病中的 HER2-E 亚型占约 30%，与抗 HER2 敏感性、化疗敏感性和对 CDK4/6 抑制的耐药性相关。在未来几年，评估这两种生物标志物的回顾性和前瞻性临床试验应能改善患者的预后。
