Abstract:
PARP inhibitors are progressively becoming a part of our therapeutic arsenal against BRCA-defective tumors, because of their capacity to induce synthetic lethality in cells with a deficiency in the homologous recombination repair system. Olaparib and talazoparib have been approved for metastatic breast cancer in carriers of germline BRCA mutations, which are found in approximately 6% of patients with breast cancer. We report the case of a patient with metastatic breast cancer, carrier of a germline mutation in BRCA2, with a complete response to first-line treatment with talazoparib, maintained after 6 years. To the best of our knowledge, this is the longest response reported with a PARP inhibitor in a BRCA-mutated tumor. We have made a review of literature, regarding the rationale for PARP inhibitors in carriers of BRCA mutations and their clinical relevance in the management of advanced breast cancer, as well as their emerging role in early stage disease, alone and in combination with other systemic therapies.
摘要:
PARP抑制剂正逐渐成为我们治疗BRCA缺陷肿瘤的一部分,因为它们在同源重组修复系统缺陷的细胞中诱导合成致死性的能力。Olaparib和talazoparib已被批准用于种系BRCA突变携带者的转移性乳腺癌,在大约6%的乳腺癌患者中发现。我们报道了一名转移性乳腺癌患者的病例,BRCA2种系突变的携带者,对他拉佐帕尼的一线治疗有完全反应,6年后维持。据我们所知,这是在BRCA突变的肿瘤中使用PARP抑制剂报道的最长应答.我们做了一个文献综述,关于BRCA突变携带者PARP抑制剂的基本原理及其在晚期乳腺癌治疗中的临床意义,以及它们在早期疾病中的新兴作用,单独和与其他全身疗法联合使用。