Ashraf Sara, Biglow Layana, Dotson Jennifer, Tirona Maria Tria
Department of Hematology-Oncology, Joan C Edwards School of Medicine at Marshall University, Huntington, WV, USA.
Department of Internal Medicine, Joan C Edwards School of Medicine at Marshall University, Huntington, WV, USA.
Transl Breast Cancer Res. 2022 Jan 31;3:9. doi: 10.21037/tbcr-21-19. eCollection 2022.
Breast cancer is the second most common cancer amongst women in the United States following non-melanoma skin cancer. There were an estimated 276,480 new cases and 42,170 deaths in 2020. The lifetime risk for developing breast cancer in females is about 13%. In the United States this year approximately 284,200 people out of which 281,550 women and 2,650 men, will be diagnosed with invasive breast cancer. In recent years, treatment options with novel mechanisms have emerged. Cyclin dependent kinase (CDK) 4/6 inhibitors, namely palbociclib, ribociclib and abemaciclib, are relatively new targeted therapies for treating breast cancers express estrogen receptors (ER) and/or progesterone receptors (PR). CDKs are important regulatory enzymes in cell cycle transitions and cell division. Selective inhibition of CDK4/6 causes cell cycle to arrest in the G1 phase, resulting in reduced cell viability and tumor response. Abemaciclib is the only one approved as monotherapy. Palbociclib and ribociclib must be used as adjunctive therapy to endocrine therapy such as tamoxifen, aromatase inhibitors or fulvestrant. Common side effects include neutropenia, thrombocytopenia, fatigue, nausea, and vomiting. A black box warning for all CDK inhibitors is a rare but possibly fatal severe inflammation of the lungs, called pneumonitis. We present a fatal case of severe pneumonitis with superimposed fungal respiratory infection in the setting of hypogammaglobulinemia in a 65-year-old female with metastatic ER and PR positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer who received abemaciclib.
乳腺癌是美国女性中第二常见的癌症,仅次于非黑色素瘤皮肤癌。2020年估计有276,480例新发病例和42,170例死亡病例。女性患乳腺癌的终生风险约为13%。今年在美国,约有284,200人将被诊断为浸润性乳腺癌,其中包括281,550名女性和2,650名男性。近年来,出现了具有新作用机制的治疗选择。细胞周期蛋白依赖性激酶(CDK)4/6抑制剂,即哌柏西利、瑞博西利和阿贝西利,是相对较新的靶向疗法,用于治疗表达雌激素受体(ER)和/或孕激素受体(PR)的乳腺癌。CDK是细胞周期转换和细胞分裂中的重要调节酶。选择性抑制CDK4/6会导致细胞周期停滞在G1期,从而降低细胞活力并产生肿瘤反应。阿贝西利是唯一被批准作为单一疗法的药物。哌柏西利和瑞博西利必须作为辅助疗法与内分泌疗法(如他莫昔芬、芳香化酶抑制剂或氟维司群)联合使用。常见副作用包括中性粒细胞减少、血小板减少、疲劳、恶心和呕吐。所有CDK抑制剂的黑框警告是一种罕见但可能致命的严重肺部炎症,称为肺炎。我们报告了一例65岁患有转移性ER和PR阳性、人表皮生长因子受体2(HER-2)阴性乳腺癌且接受阿贝西利治疗的女性患者,在低丙种球蛋白血症背景下发生严重肺炎并叠加真菌呼吸道感染的致命病例。