Gao Zhichao, Xu Junnan, Wang Yan, Wu Jie, Sun Tao
Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
Department of Breast Medicine, Key Laboratory of Liaoning Breast Cancer Research, Shenyang, China.
Front Oncol. 2021 Oct 14;11:715554. doi: 10.3389/fonc.2021.715554. eCollection 2021.
The prognosis for female patients with locally advanced breast cancer (LABC) has improved with the emergence of novel drugs, especially for those who have HER2 overexpression or ERBB-2 amplification. Trastuzumab-based regimen has been the paradigm in guidelines as first-line therapy, whereas many patients got progressive disease after several cycles of treatment or rapidly progress because of primary resistance. Point mutations of ERBB2 gene occur in both HER2-amplication and non-amplification patients, with a 2% ratio in HER2 non-amplification cohort and 1.48% in HER2 amplication population. The acquired mutation ratio of ERBB2 substantially raised to 16.7%-17.7% in patients prior to trastuzumab treatment. ERBB2 mutation may be a critical reason of resistance and disease progression among the patients treated with anti-HER2 monoclonal trastuzumab or dual anti-HER2 antibodies with trastuzumab and pertuzumab, or tyrosine-kinase inhibitor. ERBB-2 mutation with L755S and V842I indicates resistance to trastuzumab, while that with L755S and K753I indicates resistance to lapatinib; these mutations maybe sensitive to pan-HER tyrosine-kinase inhibitors. A 48-year woman diagnosed with HER2-positive LABC developed trastuzumab resistance after three lines of trastuzumab cross-line treatment with partial response (PR) as the best response. The tissue was performed by next-generation sequencing (NGS), and the results discovered L755S in ERBB2 gene. Then, she received effective treatment with pyrotinib plus capecitabine and underwent mastectomy after six cycles of combined treatment with PR. Subsequently, breast mastectomy was performed, and she took pyrotinib plus capecitabine for 1 year and pyrotinib monotherapy for another 1 year as adjuvant therapy and achieved a long-term clinical benefit. In conclusion, pyrotinib is a potential neoadjuvant agent for patients who are heavily pretreated and harbor both ERBB2 amplification and ERBB2 mutant in locally advanced breast cancer.
随着新型药物的出现，局部晚期乳腺癌（LABC）女性患者的预后有所改善，尤其是对于那些HER2过表达或ERBB-2扩增的患者。基于曲妥珠单抗的方案一直是指南中一线治疗的范例，然而许多患者在几个周期的治疗后病情进展，或因原发性耐药而迅速进展。ERBB2基因的点突变在HER2扩增和非扩增患者中均有发生，在HER2非扩增队列中的比例为2%，在HER2扩增人群中的比例为1.48%。在接受曲妥珠单抗治疗前，患者中ERBB2的获得性突变率大幅提高至16.7%-17.7%。ERBB2突变可能是接受抗HER2单克隆曲妥珠单抗或曲妥珠单抗与帕妥珠单抗联合的双抗HER2抗体或酪氨酸激酶抑制剂治疗的患者耐药和疾病进展的关键原因。具有L755S和V842I的ERBB-2突变表明对曲妥珠单抗耐药，而具有L755S和K753I的突变表明对拉帕替尼耐药；这些突变可能对泛HER酪氨酸激酶抑制剂敏感。一名48岁诊断为HER2阳性LABC的女性在接受三线曲妥珠单抗跨线治疗后出现曲妥珠单抗耐药，最佳反应为部分缓解（PR）。对组织进行了二代测序（NGS），结果在ERBB2基因中发现了L755S。然后，她接受了吡咯替尼联合卡培他滨的有效治疗，并在联合治疗6个周期达到PR后接受了乳房切除术。随后，进行了乳房切除，她接受了1年的吡咯替尼联合卡培他滨治疗和另外1年的吡咯替尼单药辅助治疗，并获得了长期临床获益。总之，对于局部晚期乳腺癌中接受过大量预处理且同时存在ERBB2扩增和ERBB2突变的患者，吡咯替尼是一种潜在的新辅助药物。
