雌激素受体阳性乳腺癌新辅助内分泌疗法的系统回顾与荟萃分析

　　2016年6月30日，《美国医学会杂志肿瘤学分册》在线发表哈佛医学院、麻省总医院（马萨诸塞州综合医院）癌症中心、德克萨斯大学西南医学中心的研究报告，对雌激素受体阳性乳腺癌新辅助内分泌疗法进行了系统回顾与荟萃分析。

　　雌激素受体阳性乳腺肿瘤对于内分泌治疗通常高度有效。虽然内分泌疗法是（早期）雌激素受体阳性乳腺癌（术后）辅助治疗的中流砥柱，但是尚不清楚内分泌疗法的（术前）新辅助作用。

　　为了评估新辅助内分泌疗法对雌激素受体阳性乳腺癌保乳率和有效率的作用，本研究根据《系统回顾与荟萃分析首选报告项目》（PRISMA）指南，由图书馆员牵头检索了PubMed和Ovid MEDLINE从建库至2015年5月15日符合条件的研究，于2015年5月进行检索。入选标准为报告有效率的前瞻性、随机、新辅助临床研究，至少有1组结合新辅助内分泌疗法（n=20）。两位作者独立分析收录的研究。汇总比值比、95%置信区间和P值使用固定和随机效应统计模型估计终点。

　　结果该系统回顾与荟萃分析共收录了20项研究3490例患者。芳香酶抑制剂单药新辅助内分泌疗法与联合化疗相比，临床有效率（比值比：1.08，95%置信区间：0.50～2.35，P=0.85，n=378）、影像学有效率（比值比：1.38，95%置信区间：0.92～2.07，P=0.12，n=378）、保乳术率（比值比：0.65，95%置信区间：0.41～1.03，P=0.07，n=334）相似，但是毒性较低。芳香酶抑制剂与他莫昔芬相比，临床缓解率（比值比：1.69，95%置信区间：1.36～2.10，P＜0.001，n=1352）、影像学有效率（比值比：1.49，95%置信区间：1.18～1.89，P＜0.001，n=1418）和保乳术率（比值比：1.62，95%置信区间：1.24～2.12，P＜0.001，n=918）显著提高。生长因子通路抑制剂双重联合疗法与内分泌疗法相比，影像学有效率提高（比值比：1.59，95%置信区间：1.04～2.43，P=0.03，n=355），临床有效率（比值比：0.76，95%置信区间：0.54～1.07，P=0.11，n=537）无显著差异。病理学完全有效率低（＜10%）。

　　因此，新辅助内分泌疗法（即使单药）与新辅助联合化疗的有效率相似，但是毒性显著较低，提示新辅助内分泌疗法在适当情况下需要被重新考虑作为一项潜在选择。需要更多研究制定合理的新辅助内分泌疗法联合以及预测性生物标记物，以个性化雌激素受体阳性乳腺癌的最佳新辅助策略。

JAMA Oncol. 2016 Jun 30. [Epub ahead of print]

Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis.

Laura M. Spring, Arjun Gupta, Kerry L. Reynolds, Michele A. Gadd, Leif W. Ellisen, Steven J. Isakoff, Beverly Moy, Aditya Bardia.

Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston; University of Texas Southwestern Medical Center, Dallas.

IMPORTANCE: Estrogen receptor-positive (ER+) tumors of the breast are generally highly responsive to endocrine treatment. Although endocrine therapy is the mainstay of adjuvant treatment for ER+ breast cancer, the role of endocrine therapy in the neoadjuvant setting is unclear.

OBJECTIVE: To evaluate the effect of neoadjuvant endocrine therapy (NET) on the response rate and the rate of breast conservation surgery (BCS) for ER+ breast cancer.

DATA SOURCES: Based on PRISMA guidelines, a librarian-led search of PubMed and Ovid MEDLINE was performed to identify eligible trials published from inception to May 15, 2015. The search was performed in May 2015.

STUDY SELECTION: Inclusion criteria were prospective, randomized, neoadjuvant clinical trials that reported response rates with at least 1 arm incorporating NET (n = 20). Two authors independently analyzed the studies for inclusion.

DATA EXTRACTION AND SYNTHESIS: Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model.

RESULTS: The analysis included 20 studies with 3490 unique patients. Compared with combination chemotherapy, NET as monotherapy with aromatase inhibitors had a similar clinical response rate (OR, 1.08; 95% CI, 0.50-2.35; P = .85; n = 378), radiological response rate (OR, 1.38; 95% CI, 0.92-2.07; P = .12; n = 378), and BCS rate (OR, 0.65; 95% CI, 0.41-1.03; P = .07; n = 334) but with lower toxicity. Aromatase inhibitors were associated with a significantly higher clinical response rate (OR, 1.69; 95% CI, 1.36-2.10; P < .001; n = 1352), radiological response rate (OR, 1.49; 95% CI, 1.18-1.89; P < .001; n = 1418), and BCS rate (OR, 1.62; 95% CI, 1.24-2.12; P < .001; n = 918) compared with tamoxifen. Dual combination therapy with growth factor pathway inhibitors was associated with a higher radiological response rate (OR, 1.59; 95% CI, 1.04-2.43; P = .03; n = 355), but not clinical response rate (OR, 0.76; 95% CI, 0.54-1.07; P = .11; n = 537), compared with endocrine monotherapy. The incidence of pathologic complete response was low (<10%).

CONCLUSIONS AND RELEVANCE: Neoadjuvant endocrine therapy, even as monotherapy, is associated with similar response rates as neoadjuvant combination chemotherapy but with significantly lower toxicity, suggesting that NET needs to be reconsidered as a potential option in the appropriate setting. Additional research is needed to develop rational NET combinations and predictive biomarkers to personalize the optimal neoadjuvant strategy for ER+ breast cancer.

DOI: 10.1001/jamaoncol.2016.1897