Coudert Bruno P, Largillier Remy, Arnould Laurent, Chollet Philippe, Campone Mario, Coeffic David, Priou Frank, Gligorov Joseph, Martin Xavier, Trillet-Lenoir Véronique, Weber Béatrice, Bleuse Jean Pierre, Vasseur Berangère, Serin Daniel, Namer Moïse
Department of Oncology, CAC G.F. Leclerc and IFR 100, Dijon, France.
J Clin Oncol. 2007 Jul 1;25(19):2678-84. doi: 10.1200/JCO.2006.09.9994. Epub 2007 May 21.
Trastuzumab plus chemotherapy has become the standard of care for human epidermal growth factor receptor-2 (HER-2) -positive breast cancer. Trastuzumab-based preoperative systemic therapy (PST; neoadjuvant therapy) also appears promising, warranting further investigation.
Patients with HER-2-positive, stage II/III, noninflammatory, operable breast cancer requiring a mastectomy (but who wanted to conserve the breast) received trastuzumab 4 mg/kg (day 1), followed by 2 mg/kg weekly, plus docetaxel 75 mg/m2 every 3 weeks, and carboplatin (area under curve, 6) for six cycles before surgery. The primary end point was pathologic complete response (pCR) rate, determined from surgical specimens.
Seventy patients were enrolled. Most patients had clinical T2/T3 tumors (100%) or clinical N1/2 nodes (53%). Sixty-seven patients (96%) completed six cycles of therapy, one patient withdrew due to progressive disease, and two patients withdrew for toxicity. A complete or partial objective clinical response occurred in 95% of patients (85% and 10%, respectively). Surgery was breast conservative in 45 (64%) of 70 patients. In an intent-to-treat analysis, tumor and nodal pCR were seen in 27 (39%) of 70 patients. Centralized retrospective analysis of HER-2 status demonstrated a 43% pCR rate in the 24 of 56 confirmed HER-2-overexpressing (3+) and/or fluorescence in situ hybridization-positive tumors. Treatment was generally well tolerated. Grade 3/4 neutropenia and febrile neutropenia were uncommon (2%). Two patients withdrew prematurely due to a transient, asymptomatic decrease in left ventricular ejection fraction. No symptomatic cardiac dysfunction occurred.
PST with trastuzumab plus docetaxel and carboplatin achieved promising efficacy, with a good pCR rate and favorable tolerability in stage II or III HER-2-positive breast cancer.
曲妥珠单抗联合化疗已成为人表皮生长因子受体2（HER-2）阳性乳腺癌的标准治疗方案。基于曲妥珠单抗的术前全身治疗（PST；新辅助治疗）似乎也很有前景，值得进一步研究。
HER-2阳性、II/III期、非炎性、可手术切除但需要行乳房切除术（但希望保留乳房）的乳腺癌患者，先接受4mg/kg曲妥珠单抗（第1天），随后每周2mg/kg，联合多西他赛75mg/m²每3周1次，以及卡铂（曲线下面积为6），术前进行6个周期治疗。主要终点为病理完全缓解（pCR）率，通过手术标本确定。
共纳入70例患者。大多数患者有临床T2/T3肿瘤（100%）或临床N1/2淋巴结转移（53%）。67例患者（96%）完成了6个周期治疗，1例患者因疾病进展退出，2例患者因毒性反应退出。95%的患者出现了完全或部分客观临床缓解（分别为85%和10%）。70例患者中有45例（64%）接受了保乳手术。在意向性分析中，70例患者中有27例（39%）出现肿瘤和淋巴结pCR。对HER-2状态进行的集中回顾性分析显示，在56例经确认HER-2过表达（3+）和/或荧光原位杂交阳性的肿瘤中，24例的pCR率为43%。治疗总体耐受性良好。3/4级中性粒细胞减少和发热性中性粒细胞减少并不常见（2%）。2例患者因左心室射血分数短暂无症状下降而提前退出。未发生有症状的心脏功能障碍。
曲妥珠单抗联合多西他赛和卡铂的术前全身治疗在II期或III期HER-2阳性乳腺癌中取得了有前景的疗效，pCR率良好且耐受性良好。
