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对于肿瘤小于5毫米的激素受体阳性且HER2阴性且淋巴结阴性低风险乳腺癌术后患者，由于缺乏有力的前瞻研究证据，如果未常规进行多基因复发风险评分，美国国家综合癌症网络NCCN推荐考虑内分泌辅助治疗。不过，术后内分泌辅助治疗对肿瘤小于5毫米的激素受体阳性且HER2阴性且淋巴结阴性乳腺癌患者死亡风险和生存结局的影响尚不明确。 2020年8月24日，《美国医学会杂志》网络开放版在线发表纽约州立布法罗大学罗斯威尔·帕克综合癌症中心、哈佛大学麻省总医院的研究报告，分析了术后内分泌辅助治疗对肿瘤小于5毫米、激素受体阳性、HER2阴性、淋巴结阴性乳腺癌患者总生存的影响。 该队列研究通过检索美国全国癌症数据库，对2010年1月～2015年12月接受或未接受术后内分泌辅助治疗的4万2708例肿瘤小于5毫米且激素受体阳性且HER2阴性且淋巴结阴性乳腺癌女性（中位年龄63岁，四分位54～71岁，其中白人36985例，占86.6%）进行回顾分析。随访数据截至2016年12月，2020年1月～2020年3月对数据进行分析。主要终点为总生存。通过生存曲线法、多因素比例风险回归模型及其相互影响对生存结局进行分析。为了解决可能存在的混杂因素，通过倾向评分比值比对数，对全部因素按1∶1的比例进行匹配而不进行任何替换。各个因素的标准平均差小于0.1。为了解决难以避免的时间偏倚，剔除生存少于6个月的患者进行重新分析，并对拒绝内分泌辅助治疗的患者亚组进行敏感性分析。 结果，其中内分泌治疗3万1509例（73.8%），其余未内分泌治疗1万1199例（26.2%）。中位随访42.1个月（四分位24.2～62.1）。 通过多因素比例风险回归模型分析，对医疗机构类型、医疗机构患者数量、年龄、种族、收入，保险、合并症评分、诊断年份、手术、放疗、淋巴结检查数量、再次入院等其他影响因素进行校正后，内分泌治疗与未内分泌治疗相比，总死亡风险低31%（风险比：0.69，95%置信区间：0.63～0.76，P<0.001）。 对于7544对倾向评分匹配患者，内分泌治疗与未内分泌治疗相比，总死亡风险低24%（风险比：0.76，95%置信区间：0.66～0.88，P<0.001）。 内分泌治疗与年龄、合并症评分或肿瘤分级等其他基线特征的相互影响无统计学意义。 剔除生存少于6个月的1659例患者（3.9%）之后，内分泌治疗与未内分泌治疗相比，总死亡风险低26%（风险比：0.74，95%置信区间：0.67～0.81，P<0.001）。 对于1万1199例未内分泌治疗患者，其中3492例（31.2%）拒绝临床医师推荐的内分泌治疗。内分泌治疗患者与拒绝内分泌治疗患者相比，总死亡风险低20%（风险比：0.80，95%置信区间：0.69～0.94，P=0.007）。 因此，该大数据分析结果表明，即使对于肿瘤较小、复发风险较低的激素受体阳性HER2阴性淋巴结阴性乳腺癌患者，术后内分泌辅助治疗仍然能够改善总生存结局。不过，应该对术后内分泌辅助治疗的获益和某些患者可能发生的长期毒性反应进行权衡。 JAMA Netw Open. 2020 Aug 24;3(8):e2013973. Association of Endocrine Therapy With Overall Survival in Women With Small, Hormone Receptor-Positive, ERBB2-Negative Breast Cancer. Ma SJ, Oladeru OT, Singh AK. Roswell Park Comprehensive Cancer Center, Buffalo, New York; Massachusetts General Hospital, Boston. This cohort study examines the association of overall survival with endocrine therapy to treat hormone receptor-positive, ERBB2-negative breast cancer. INTRODUCTION: With routine screening mammography, nearly 1 in 5 breast cancer cases are invasive tumors smaller than 1 cm. However, for hormone receptor (HR)-positive, ERBB2 (previously HER2 or HER2/neu)-negative, node-negative breast cancer, pT1a tumors (ie, tumors measuring more than 0.1 cm but not more than 0.5 cm in greatest dimension) were underrepresented in prior prospective trials, ranging from 6% to 13% of participants in prior trials. In the absence of strong prospective evidence, the National Comprehensive Cancer Network recommends consideration of adjuvant endocrine therapy for patients with pT1aN0 breast cancer without the routine use of multigene assay. Thus, we sought to examine the association of overall survival (OS) with endocrine therapy in this cohort of patients. METHODS: In this cohort study, we queried the National Cancer Database query for women diagnosed with HR-positive, ERBB2-negative pT1aN0 breast cancer between January 2010 and December 2015 who were treated with or without adjuvant endocrine therapy. Follow-up occurred until December 2016; analysis was performed from January 2020 to March 2020. Institutional review board approval was obtained from the Roswell Park Comprehensive Cancer Center; informed consent was not needed because data in the National Cancer Database are deidentified and freely available to approved Commission on Cancer-affiliated investigators. Our study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. The primary end point was overall OS. Kaplan-Meier method, Cox multivariable analysis, and interaction analysis were performed for survival outcomes. To address potential confounders, the logit of propensity score matched all variables in a 1:1 ratio without any replacement. The standardized mean difference of variables was less than 0.1. To address immortal time bias, reanalysis was performed after excluding those who survived less than 6 months as a conditional landmark. Sensitivity analysis was also performed on a subgroup of patients who refused endocrine therapy. All analyses were performed with R version 3.6.1 (R Project for Statistical Computing). Statistical significance was set at 2-sided P<0.05. RESULTS: A total of 42708 patients, comprising 36985 (86.6%) White patients and with a median (interquartile range [IQR]) age of 63 (54-71) years, met our criteria, including 31509 patients (73.8%) and 11199 patients (26.2%) with and without endocrine therapy, respectively. The median (IQR) follow up was 42.1 (24.2-62.1) months. On Cox multivariable analysis (adjusted for facility type, facility volume, age, race, income, insurance, Charlson-Deyo comorbidity score, year of diagnosis, surgery, radiation, number of lymph nodes examined, and hospital readmission), the receipt of adjuvant endocrine therapy was associated with improved OS (hazard ratio [HR], 0.69; 95% CI, 0.63-0.76; P<0.001). The Table describes 7544 matched pairs, in whom similarly improved OS was observed (HR, 0.76; 95% CI, 0.66-0.88; P<0.001). There was no statistically significant interaction of endocrine therapy with other baseline characteristics, such as age, comorbidity score, or tumor grade. After excluding 1659 patients (3.9%) with survival of less than 6 months, the addition of adjuvant endocrine therapy remained associated with improved OS (HR, 0.74; 95% CI, 0.67-0.81; P<0.001). Of 11199 patients treated without endocrine therapy, 3492 patients (31.2%) recommended therapy by a clinician refused the treatment. Compared with those who received endocrine therapy, similar findings were observed among those refusing the treatment favoring endocrine therapy (HR, 0.80; 95% CI, 0.69-0.94; P=0.007). DISCUSSION: To our knowledge, this is the largest cohort study to evaluate the OS outcome of endocrine therapy for pT1aN0 breast cancer using a national registry database. The survival benefit identified in our study supports the National Comprehensive Cancer Network's recommendation of adjuvant endocrine therapy in this cohort and is consistent with favorable outcomes previously described. However, the benefit of adjuvant endocrine therapy should be weighed against potential long-term toxic effects in select patients. Limitations of our study include unavailable variables such as performance status, toxicity profiles, and tumor recurrences, which may lead to unmeasured confounding despite matching. Reanalysis using a cohort of patients who declined recommended endocrine therapy revealed consistent findings. The risk of relapse from very small tumors remains significant enough to warrant adjuvant therapy. Our study further affirms clinicians' decisions to recommend adjuvant endocrine therapy in this cohort of patients. PMID: 32833014 DOI: 10.1001/jamanetworkopen.2020.13973 |
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