Seiffert Katharina, Schmalfeldt Barbara, Müller Volkmar
Dtsch Med Wochenschr. 2017 Nov;142(22):1669-1675. doi: 10.1055/s-0043-108468. Epub 2017 Oct 27.
Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival. For patients with HER2-positive disease the addition of Pertuzumab to Trastuzumab in combination with chemotherapy has been a significant improvement in anti-HER2 therapy in early as well as metastatic breast cancer. Evidence-based further line therapy options in the metastatic setting include T-DM1 and in later lines Lapatinib. For triple negative disease the angiogenesis inhibitor Bevacizumab is approved, which increases progression free survival. Immune checkpoint inhibitors, PARP-inhibitors or anti-androgens represent promising strategies, all of which are currently being evaluated in clinical trials. The development of predictive biomarkers to guide targeted therapies is still the subject of research.
在过去几年中,乳腺癌治疗取得了显著进展,尤其是随着靶向治疗的发展。在确定雌激素受体阳性乳腺癌的恶性生长驱动因素和内分泌治疗耐药机制方面取得了重大进展。这一进展已转化为多种增强内分泌治疗疗效的靶向治疗方法;细胞周期蛋白依赖性激酶CDK4和CDK6抑制剂(如帕博西尼)以及mTOR抑制剂可显著改善无进展生存期。对于HER2阳性疾病的患者,在曲妥珠单抗联合化疗中加入帕妥珠单抗,在早期和转移性乳腺癌的抗HER2治疗中是一项重大进展。转移性情况下基于证据的进一步治疗选择包括T-DM1以及后续治疗中的拉帕替尼。对于三阴性疾病,血管生成抑制剂贝伐单抗已获批准,可提高无进展生存期。免疫检查点抑制剂、PARP抑制剂或抗雄激素代表了有前景的策略,所有这些目前都在临床试验中进行评估。开发预测性生物标志物以指导靶向治疗仍是研究的主题。