Gupta Arjun, Mutebi Miriam, Bardia Aditya
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Groote Schuur Hospital, Cape Town, South Africa.
Ann Surg Oncol. 2015 Oct;22(11):3418-32. doi: 10.1245/s10434-015-4703-0. Epub 2015 Jul 28.
An important and often complicated management decision in early stage hormone receptor (HR)-positive breast cancer relates to the use of adjuvant systemic chemotherapy. Although traditional clinicopathologic markers exist, tremendous progress has been achieved in the field of predictive biomarkers and genomics with both prognostic and predictive capabilities to identify patients who will potentially benefit from additional therapy. The use of these genomic tests in the neoadjuvant setting is also being studied and may lead to these tests providing clinical benefit even earlier in the disease course. Landmark articles published in the last few years have expanded our knowledge of breast cancer genomics to an unprecedented level, and mutational analysis via next-generation sequencing methods allows the identification of molecular targets for novel targeted therapeutic agents and clinical trials testing efficacy of targeted therapies, such as PI3K inhibitors, in addition to endocrine therapy for HR-positive breast cancer, are ongoing. We provide an in-depth review on the role of gene expression-based predictors in early stage breast cancer and an overview of future directions, including next-generation sequencing. Over the coming years, we anticipate a significant increase in utilization of genomic-based predictors for individualized selection and duration of endocrine therapy with and without genotype-driven targeted therapy, and a major decrease in the use of chemotherapy, possibly even leading to a chemotherapy-free road for early stage HR-positive breast cancer.
早期激素受体(HR)阳性乳腺癌的一项重要且往往复杂的管理决策涉及辅助性全身化疗的使用。尽管存在传统的临床病理标志物,但在预测生物标志物和基因组学领域已取得巨大进展,这些标志物具有预后和预测能力,可识别可能从额外治疗中获益的患者。这些基因组检测在新辅助治疗中的应用也在研究中,可能会使这些检测在疾病进程中更早地提供临床益处。过去几年发表的具有里程碑意义的文章将我们对乳腺癌基因组学的认识扩展到了前所未有的水平,通过下一代测序方法进行的突变分析能够识别新型靶向治疗药物的分子靶点,并且针对HR阳性乳腺癌除内分泌治疗外的靶向治疗(如PI3K抑制剂)疗效的临床试验正在进行。我们对基于基因表达的预测指标在早期乳腺癌中的作用进行了深入综述,并概述了未来方向,包括下一代测序。在未来几年,我们预计基于基因组的预测指标在个性化选择内分泌治疗以及联合或不联合基因型驱动的靶向治疗的持续时间方面的应用将显著增加,化疗的使用将大幅减少,甚至可能为早期HR阳性乳腺癌开辟一条无化疗之路。