基于患者的预后确定指南
原发性乳腺癌个体患者的预后正在进行缜密的研究。辅助研究!在线程序包括有关患者年龄、共存疾病、肿瘤大小、肿瘤级别、雌激素受体状态以及阳性腋窝淋巴结个数的信息。[252]Ravdin PM, Siminoff LA, Davis GJ, et al. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol. 2001;19:980-991.http://www.ncbi.nlm.nih.gov/pubmed/11181660?tool=bestpractice.com用这些数据进行辅助研究!在线程序计算患者的 10 年复发和死亡可能性。Adjuvant! Online program该程序也能计算辅助内分泌治疗和化疗的绝对收益。
基于肿瘤的预后确定指南
临床医生可能会使用基因表达分析(例如 Oncotype DX®)来指导关于辅助化疗的决策。[75]Goncalves R, Bose R. Using multigene tests to select treatment for early-stage breast cancer. J Natl Compr Canc Netw. 2013;11:174-182.http://www.jnccn.org/content/11/2/174.longhttp://www.ncbi.nlm.nih.gov/pubmed/23411384?tool=bestpractice.com[76]Harbeck N, Sotlar K, Wuerstlein R, et al. Molecular and protein markers for clinical decision making in breast cancer: today and tomorrow. Cancer Treat Rev. 2014;40:434-444.http://www.ncbi.nlm.nih.gov/pubmed/24138841?tool=bestpractice.com[77]National Institute for Health and Care Excellence. Gene expression profiling and expanded immunohistochemistry tests for guiding adjuvant chemotherapy decisions in early breast cancer management: MammaPrint, Oncotype DX, IHC4 and Mammostrat. September 2013. http://www.nice.org.uk/ (last accessed 27 October 2016).http://www.nice.org.uk/guidance/dg10[78]Harris LN, Ismailia N, McShane LM, et al; American Society of Clinical Oncology. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;34:1134-1150.http://ascopubs.org/doi/full/10.1200/JCO.2015.65.2289http://www.ncbi.nlm.nih.gov/pubmed/26858339?tool=bestpractice.comOncotype DX® 分析是一种基于逆转录-聚合酶链反应 (PCR) 的多基因分析,评估患者石蜡包埋肿瘤切片内 21 种前瞻性选择基因的表达。[79]Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817-2826.http://www.nejm.org/doi/full/10.1056/NEJMoa041588#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/15591335?tool=bestpractice.com该化验用于确定患有淋巴结阴性、激素受体阳性乳腺癌的患者是否能从辅助化疗与单独的内分泌治疗中受益。根据该表达确定低、中、高复发分数,然后该分数可用于帮助临床医生和患者确定仅使用内分泌治疗(对比序贯化疗联合内分泌治疗)是否足以治疗淋巴结阴性的乳腺癌患者。
提供个体化治疗选择试验 (TAILORx) 表明,对于 5 年生存率高达 99%、无远处转移且可通过单纯辅助内分泌疗法进行治疗的患者,可选择 21 基因复发评分。[80]Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015;373:2005-2014.http://www.nejm.org/doi/full/10.1056/NEJMoa1510764#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/26412349?tool=bestpractice.com随机分配到标准化疗组与无化疗组的中等风险患者(通过 21 基因复发分析确定)的结果尚未出来。
70 基因分析 MammaPrint® 无法用于确定无需进行化疗或化疗对其无效的早期乳腺癌患者。[78]Harris LN, Ismailia N, McShane LM, et al; American Society of Clinical Oncology. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;34:1134-1150.http://ascopubs.org/doi/full/10.1200/JCO.2015.65.2289http://www.ncbi.nlm.nih.gov/pubmed/26858339?tool=bestpractice.com
还研究了其他生物标志物(包括癌胚抗原、尿激酶型纤维蛋白溶酶原激活剂 (uPA) 和纤溶酶原激活物抑制剂 1 (PAI-1))的预后/预测意义。Chemo-N0 研究随访 10 年数据表明 uPA 和 PAI-1 升高提示复发率增加,还表明用辅助化疗治疗的 uPA 和 PAI-1 升高的患者其复发率比未接受化疗患者低。[78]Harris LN, Ismailia N, McShane LM, et al; American Society of Clinical Oncology. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;34:1134-1150.http://ascopubs.org/doi/full/10.1200/JCO.2015.65.2289http://www.ncbi.nlm.nih.gov/pubmed/26858339?tool=bestpractice.com[253]Harbeck N, Schmitt M, Meisner C, et al; Chemo-N 0 Study Group. Ten-year analysis of the prospective multicentre Chemo-N0 trial validates American Society of Clinical Oncology (ASCO)-recommended biomarkers uPA and PAI-1 for therapy decision making in node-negative breast cancer patients. Eur J Cancer. 2013;49:1825-1835.http://www.ncbi.nlm.nih.gov/pubmed/23490655?tool=bestpractice.com
合并症考量因素
合并症对患者结果有显著的不利影响。一项涉及 936 名年龄为 40~84 的女性(从底特律大都会癌症监测系统获取这些女性的肿瘤和治疗史)的回顾性分析显示了该影响。[254]Satariano WA, Ragland DR. The effect of comorbidity on 3-year survival of women with primary breast cancer. Ann Intern Med. 1994;120:104-110.http://www.ncbi.nlm.nih.gov/pubmed/8256968?tool=bestpractice.com有 3 种及以上合并症的患者其全死因死亡率比无合并症患者高 4 倍。该影响不受年龄、疾病分期、肿瘤大小、组织学分型、治疗类型、种族以及社会和行为因素影响。
此外,埃因霍温癌症登记处的数据表明,虽然存在严重合并症患者有可行的治疗方案,但其总生存期更差。[255]Louwman WJ, Janssen-Heijnen ML, Houterman S, et al. Less extensive treatment and inferior prognosis for breast cancer patient with comorbidity: a population-based study. Eur J Cancer. 2005;41:779-785.http://www.ncbi.nlm.nih.gov/pubmed/15763655?tool=bestpractice.com