Tolaney Sara M, Barry William T, Dang Chau T, Yardley Denise A, Moy Beverly, Marcom P Kelly, Albain Kathy S, Rugo Hope S, Ellis Matthew, Shapira Iuliana, Wolff Antonio C, Carey Lisa A, Overmoyer Beth A, Partridge Ann H, Guo Hao, Hudis Clifford A, Krop Ian E, Burstein Harold J, Winer Eric P
From the Departments of Medical Oncology (S.M.T., B.A.O., A.H.P., I.E.K., H.J.B., E.P.W.) and Biostatistics and Computation Biology (W.T.B., H.G.), Dana-Farber Cancer Institute, and Department of Hematology-Oncology, Massachusetts General Hospital (B.M.) - both in Boston; Breast Cancer Medicine Service, Department of Medicine, Solid Tumor Division, Memorial Sloan Kettering Cancer Center, and Department of Medicine, Weill Cornell Medical Center, New York (C.T.D., C.A.H.), and Department of Medical Oncology, Hofstra North Shore-LIJ School of Medicine, New Hyde Park (I.S.) - all in New York; Sarah Cannon Cancer Center, Department of Medical Oncology, Nashville (D.A.Y.); Department of Medicine, Division of Medical Oncology, Duke Cancer Institute, Durham (P.K.M.), and Department of Medical Oncology, University of North Carolina, Chapel Hill (L.A.C.) - both in North Carolina; Cardinal Bernardin Cancer Center, Department of Medicine, Division of Hematology-Oncology, Loyola University Chicago Stritch School of Medicine, Maywood, IL (K.S.A.); Comprehensive Cancer Center, Department of Medicine, Division of Oncology, University of California, San Francisco, San Francisco (H.S.R.); Department of Medical Oncology, Washington University in St. Louis, St. Louis (M.E.); and Johns Hopkins Kimmel Cancer Center, Department of Oncology, Baltimore (A.C.W.).
N Engl J Med. 2015 Jan 8;372(2):134-41. doi: 10.1056/NEJMoa1406281.
No single standard treatment exists for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)-positive breast cancers, because most of these patients have been ineligible for the pivotal trials of adjuvant trastuzumab.
We performed an uncontrolled, single-group, multicenter, investigator-initiated study of adjuvant paclitaxel and trastuzumab in 406 patients with tumors measuring up to 3 cm in greatest dimension. Patients received weekly treatment with paclitaxel and trastuzumab for 12 weeks, followed by 9 months of trastuzumab monotherapy. The primary end point was survival free from invasive disease.
The median follow-up period was 4.0 years. The 3-year rate of survival free from invasive disease was 98.7% (95% confidence interval [CI], 97.6 to 99.8). Among the 12 relapses seen, 2 were due to distant metastatic breast cancer. Excluding contralateral HER2-negative breast cancers and nonbreast cancers, 7 disease-specific events were noted. A total of 13 patients (3.2%; 95% CI, 1.7 to 5.4) reported at least one episode of grade 3 neuropathy, and 2 had symptomatic congestive heart failure (0.5%; 95% CI, 0.1 to 1.8), both of whom had normalization of the left ventricular ejection fraction after discontinuation of trastuzumab. A total of 13 patients had significant asymptomatic declines in ejection fraction (3.2%; 95% CI, 1.7 to 5.4), as defined by the study, but 11 of these patients were able to resume trastuzumab therapy after a brief interruption.
Among women with predominantly stage I HER2-positive breast cancer, treatment with adjuvant paclitaxel plus trastuzumab was associated with a risk of early recurrence of about 2%; 6% of patients withdrew from the study because of protocol-specified adverse events. (Funded by Genentech; ClinicalTrials.gov number, NCT00542451.).
对于肿瘤较小、无淋巴结转移且人表皮生长因子受体2（HER2）阳性的乳腺癌患者，不存在单一的标准治疗方案，因为这些患者中的大多数不符合曲妥珠单抗辅助治疗的关键试验入组条件。
我们开展了一项非对照、单组、多中心、研究者发起的研究，对406例最大径达3 cm肿瘤的患者采用紫杉醇和曲妥珠单抗进行辅助治疗。患者接受紫杉醇和曲妥珠单抗每周治疗，持续12周，随后接受9个月的曲妥珠单抗单药治疗。主要终点是无侵袭性疾病生存。
中位随访期为4.0年。3年无侵袭性疾病生存率为98.7%（95%置信区间[CI]，97.6至99.8）。在观察到的12例复发中，2例是远处转移性乳腺癌所致。排除对侧HER2阴性乳腺癌和非乳腺癌，记录到7例疾病特异性事件。共有13例患者（3.2%；95%CI，1.7至5.4）报告至少有一次3级神经病变发作，2例有症状性充血性心力衰竭（0.5%；95%CI，0.1至1.8），二者在停用曲妥珠单抗后左心室射血分数均恢复正常。共有13例患者的射血分数出现了符合研究定义的显著无症状下降（3.2%；95%CI，1.7至5.4），但其中11例患者在短暂中断后能够恢复曲妥珠单抗治疗。
在主要为Ⅰ期HER2阳性乳腺癌的女性中，辅助紫杉醇加曲妥珠单抗治疗的早期复发风险约为2%；6%的患者因方案规定的不良事件退出研究。（由基因泰克公司资助；ClinicalTrials.gov编号，NCT00542451。）
