【原】HER2阳性乳腺癌治疗标准进步与挑战

　　近20年来，人类表皮生长因子受体HER2阳性乳腺癌的治疗不断进步，这些重大进步已经促使美国食品药物监督管理局批准了7种HER2靶向药物，用于治疗HER2阳性早期和（或）晚期乳腺癌。

　　不过，虽然肿瘤结局不断改善，但是大多数HER2阳性晚期乳腺癌患者最终由于对治疗的原发性或获得性耐药而死亡。此外，术前全身治疗残留浸润病变的HER2阳性早期乳腺癌患者远处复发和死亡风险仍然较高。

　　2020年8月19日，影响因子高达292.278的全球第一神刊、美国癌症学会《临床医师癌症杂志》在线发表梅奥医学中心的长篇综述：HER2阳性乳腺癌治疗标准进步与挑战。

　　简化与强化、降级与升级、减法与加法的理念，对于优化HER2阳性乳腺癌患者个体化治疗越来越重要，也是该综述的主要重点。该综述讨论了这方面的研究工作，以及不断进步的早期乳腺癌术前和术后、晚期乳腺癌转移后治疗标准更新内容，包括新的联合治疗。

　　此外，该综述还简要讨论了HER2阳性乳腺癌治疗面临的挑战（例如原发性与获得性耐药、生物学预测标志、整合影像技术指导临床实践）以及HER2阳性乳腺癌脑转移的治疗。不断开展研究解决这些挑战，对于确保HER2阳性乳腺癌治疗不断进步至关重要。

1. 曲妥珠单抗
   

2. 帕妥珠单抗

3. 恩美曲妥珠单抗（T-DM1）

4. 德卢曲妥珠单抗（DS-8201a）

5. 拉帕替尼

6. 奈拉替尼、吡咯替尼

7. 妥卡替尼

8. 马吉妥昔单抗

9. 多卡曲妥珠单抗（SYD985）

10. 阿尔卑利昔

11. CDK4和CDK6抑制剂（哌柏西利、瑞博西利、阿贝西利）

CA Cancer J Clin. 2020 Aug 19. Online ahead of print.

Evolving standards of care and new challenges in the management of HER2-positive breast cancer.

Choong GM, Cullen GD, O'Sullivan CC.

Mayo Clinic, Rochester, Minnesota.

The management of human epidermal growth factor receptor (HER2)-positive breast cancer (BC) has rapidly evolved over the last 20 years. Major advances have led to US Food and Drug Administration approval of 7 HER2-targeted therapies for the treatment of early-stage and/or advanced-stage disease. Although oncologic outcomes continue to improve, most patients with advanced HER2-positive BC ultimately die of their disease because of primary or acquired resistance to therapy, and patients with HER2-positive early BC who have residual invasive disease after preoperative systemic therapy are at a higher risk of distant recurrence and death. The concept of treatment de-escalation and escalation is increasingly important to optimally tailor therapy for patients with HER2-positive BC and is a major focus of the current review. Research efforts in this regard are discussed as well as updates regarding the evolving standard of care in the (neo)adjuvant and metastatic settings, including the use of novel combination therapies. The authors also briefly discuss ongoing challenges in the management of HER2-positive BC (eg, intrinsic vs acquired drug resistance, the identification of predictive biomarkers, the integration of imaging techniques to guide clinical practice), and the treatment of HER2-positive brain metastases. Research aimed at superseding these challenges will be imperative to ensure continued progress in the management of HER2-positive BC going forward.

KEYWORDS: (neo)adjuvant therapy; breast cancer brain metastases; de-escalation; human epidermal growth factor receptor 2 (HER2)-positive breast cancer; mechanisms of resistance

PMID: 32813307

DOI: 10.3322/caac.21634