放射治疗和全身治疗在老年乳腺癌患者中的作用。

The role of radiation therapy and systemic therapies in elderly with breast cancer.

作者信息

Nardone Valerio, Falivene Sara, Giugliano Francesca Maria, Gaetano Marcella, Giordano Pasqualina, Muto Matteo, Daniele Bruno, Guida Cesare

机构信息

Unit of Radiation Oncology, Ospedale del Mare, Naples, Italy.

Unit of Medical Oncology, Ospedale del Mare, Naples, Italy.

出版信息

Transl Cancer Res. 2020 Jan;9(Suppl 1):S97-S109. doi: 10.21037/tcr.2019.07.04.

Abstract

The focus of this review deals with the management of elderly patients with early stage breast cancer, discussing the role of systemic therapies [endocrine therapy (ET), chemotherapy, novel agents] and radiation therapy (RT). Several studies have evaluated in elderly low risk patients the possibility of omitting the RT but, at the same time, higher locoregional relapse (LR) rates without significant impact on overall survival (OS) were observed in all studies when RT was excluded. Technological improvements [intensity-modulated RT (IMRT), volumetric modulated arc therapy (VMAT), high dose brachy therapy (HDBT)] are very useful in order to reduce cosmetic outcome and improve quality of life of frail patients. The optimal sequence of ET, concomitant or sequential to RT, is currently under investigation, and specifically in the elderly it is questioned the possible choice of prolonged therapy after standard 5 years. Data regarding chemotherapy suggesting no benefit of OS in endocrine responsive diseases, whereas endocrine non-responsive breast cancer still showed a better outcome. Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen is recognized as the standard protocol, although age-dependent increase in therapy related mortality was reported. Neoadjuvant chemotherapy in elderly showed a lower ratio of pathological complete response in comparison to younger patients, but triple negative breast cancer patients showed a good prognosis regarding OS, comparable to younger patients. The risk of cardiotoxicity seems to increase with age, so the use trastuzumab in this setting is much debated. Currently, other anti-HER2 agents (pertuzumab, lapatinib) are used in neoadjuvant setting, but the data on elderly are still premature. Novel molecules are rapidly changing the clinical management of breast cancer patients but are tested especially in locally advanced and metastatic setting. Among these, particularly interesting are inhibitors of CDK4 and 6, alpelisib (PI3K enzymes mutations), immune checkpoint (PD1, PDL1, CTLA4) inhibitors, atezolizumab. Elderly patients are under-represented in clinical trials, although ageing can be frequently correlated with a decrease in the effectiveness of the immune system. For elderly women, treatment decisions should be individually decided, taking into account the geriatric assessment and limited life expectancy and tumor characteristics.

摘要

本综述的重点是老年早期乳腺癌患者的管理,讨论全身治疗[内分泌治疗(ET)、化疗、新型药物]和放射治疗(RT)的作用。多项研究评估了老年低风险患者省略RT的可能性,但与此同时,所有研究均观察到,排除RT后局部区域复发(LR)率较高,但对总生存期(OS)无显著影响。技术改进[调强放疗(IMRT)、容积调强弧形放疗(VMAT)、高剂量近距离放疗(HDBT)]对于减少美容效果和改善体弱患者的生活质量非常有用。ET与RT同步或序贯的最佳顺序目前正在研究中,特别是在老年人中,标准5年后延长治疗的可能选择受到质疑。关于化疗的数据表明,在内分泌反应性疾病中OS无益处,而内分泌无反应性乳腺癌仍显示出较好的结果。环磷酰胺、甲氨蝶呤和5-氟尿嘧啶(CMF)方案被认为是标准方案,尽管有报道称治疗相关死亡率随年龄增加。与年轻患者相比,老年患者新辅助化疗的病理完全缓解率较低,但三阴性乳腺癌患者的OS预后良好,与年轻患者相当。心脏毒性风险似乎随年龄增加,因此在这种情况下使用曲妥珠单抗存在很大争议。目前,其他抗HER2药物(帕妥珠单抗、拉帕替尼)用于新辅助治疗,但老年患者的数据仍不成熟。新型分子正在迅速改变乳腺癌患者的临床管理,但主要在局部晚期和转移性疾病中进行测试。其中,特别有趣的是细胞周期蛋白依赖性激酶4和6抑制剂、阿培利司(PI3K酶突变)、免疫检查点(PD1、PDL1、CTLA4)抑制剂、阿特珠单抗。尽管衰老常常与免疫系统有效性下降相关,但老年患者在临床试验中的代表性不足。对于老年女性,治疗决策应个体化,考虑老年评估、有限的预期寿命和肿瘤特征。

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