Spring Laura M, Gupta Arjun, Reynolds Kerry L, Gadd Michele A, Ellisen Leif W, Isakoff Steven J, Moy Beverly, Bardia Aditya
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
Department of Medicine, University of Texas Southwestern Medical Center, Dallas.
JAMA Oncol. 2016 Nov 1;2(11):1477-1486. doi: 10.1001/jamaoncol.2016.1897.
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.
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.
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.
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.
Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model.
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%).
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.
乳腺雌激素受体阳性（ER+）肿瘤通常对内分泌治疗高度敏感。尽管内分泌治疗是ER+乳腺癌辅助治疗的主要手段，但内分泌治疗在新辅助治疗中的作用尚不清楚。
评估新辅助内分泌治疗（NET）对ER+乳腺癌的缓解率和保乳手术（BCS）率的影响。
根据PRISMA指南，由图书馆员主导检索PubMed和Ovid MEDLINE，以识别从创刊至2015年5月15日发表的符合条件的试验。检索于2015年5月进行。
纳入标准为前瞻性、随机、新辅助临床试验，这些试验报告了至少1个包含NET的治疗组的缓解率（n = 20）。两位作者独立分析纳入的研究。
使用固定效应和随机效应统计模型估计终点的合并比值比（OR）、95%置信区间（CI）和P值。
分析纳入了20项研究，共3490例独特患者。与联合化疗相比，NET作为芳香化酶抑制剂单药治疗的临床缓解率相似（OR，1.08；95%CI，0.50 - 2.35；P = 0.85；n = 378），放射学缓解率相似（OR，1.38；95%CI，0.92 - 2.07；P = 0.12；n = 378），BCS率相似（OR，0.65；95%CI，0.41 - 1.03；P = 0.07；n = 334），但毒性较低。与他莫昔芬相比，芳香化酶抑制剂的临床缓解率显著更高（OR，1.69；95%CI，1.36 - 2.10；P < 0.001；n = 1352），放射学缓解率显著更高（OR，1.49；95%CI，1.18 - 1.89；P < 0.001；n = 1418），BCS率显著更高（OR，1.62；95%CI，1.24 - 2.12；P < 0.001；n = 918）。与内分泌单药治疗相比，生长因子通路抑制剂的双重联合治疗的放射学缓解率更高（OR，1.59；95%CI，1.04 - 2.43；P = 0.03；n = 355），但临床缓解率无差异（OR，0.76；95%CI，0.54 - 1.07；P = 0.11；n = 537）。病理完全缓解的发生率较低（<10%）。
新辅助内分泌治疗，即使作为单药治疗，与新辅助联合化疗的缓解率相似，但毒性显著更低，这表明在合适的情况下，需要重新考虑将NET作为一种潜在选择。需要进一步研究以开发合理的NET联合方案和预测性生物标志物，从而为ER+乳腺癌制定个性化的最佳新辅助治疗策略。
