Kuemmel Sherko, Harrach Hakima, Schmutzler Rita K, Kostara Athina, Ziegler-Löhr Katja, Dyson Mark H, Chiari Ouafaa, Reinisch Mattea
Interdisciplinary Breast Unit, Kliniken Essen-Mitte, Essen, Germany.
Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
NPJ Breast Cancer. 2020 Jul 24;6:31. doi: 10.1038/s41523-020-00174-9. eCollection 2020.
There is a strong biologic rationale that poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors may benefit a broader range of metastatic breast cancer (MBC) patients than covered by current approvals, which require a germline sequence variant affecting function. We report a patient with germline/somatic wild-type MBC, who had a dramatic response to the PARP inhibitor olaparib of at least 8 months' duration. The patient is a 37-year-old woman with recurrent, hormone receptor-positive, HER2-negative MBC that had progressed despite hormonal therapy and palbociclib. Sensitivity to olaparib was likely conferred by a germline sequence variant affecting function in (exon 1, c.18G>T, p.(=)). This case documenting activity of olaparib monotherapy in germline/somatic wild-type MBC illustrates that the clinical potential of PARP inhibition in MBC extends beyond currently approved indications to additional patients whose tumors have (epi)genetic changes affecting homologous recombination repair.
有充分的生物学依据表明，聚（腺苷二磷酸 - 核糖）聚合酶（PARP）抑制剂可能使比目前获批范围更广的转移性乳腺癌（MBC）患者受益，目前的获批要求存在影响功能的种系序列变异。我们报告了一名种系/体细胞野生型MBC患者，其对PARP抑制剂奥拉帕利产生了至少持续8个月的显著反应。该患者为一名37岁女性，患有复发性、激素受体阳性、HER2阴性MBC，尽管接受了激素治疗和哌柏西利，但病情仍进展。对奥拉帕利的敏感性可能由一个影响功能的种系序列变异（外显子1，c.18G>T，p.(=)）所致。该病例记录了奥拉帕利单药治疗种系/体细胞野生型MBC的活性，表明PARP抑制在MBC中的临床潜力超出了目前获批的适应症，还适用于其他肿瘤发生（表观）遗传变化影响同源重组修复的患者。
