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根据NSABP的B-27研究，对于乳腺癌的新辅助化疗，环磷酰胺＋蒽环类→紫杉类，与环磷酰胺＋蒽环类相比，病理学完全缓解率提高一倍（26%比13%，P<0.0001）。不过，由于紫杉醇的水溶性低、过敏性高，注射之前需要使用有机溶剂和抗过敏药。纳米白蛋白结合型紫杉醇（白蛋白结合型纳米紫杉醇）不需要预处理即可安全注射，根据GeparSepto（GBG69）研究，对于乳腺癌的新辅助化疗，白蛋白结合型纳米紫杉醇→环磷酰胺＋蒽环类，与紫杉醇→环磷酰胺＋蒽环类相比，病理学完全缓解率显著提高（38%比29%，P=0.00065）。 2018年1月11日，《美国医学会杂志》肿瘤学分册在线发表意大利、西班牙、俄罗斯、德国、澳大利亚、奥地利、新加坡的研究报告，探讨了白蛋白结合型纳米紫杉醇或紫杉醇相比，能否改善早期或局部晚期人表皮生长因子受体2（ERBB2/HER2）阴性乳腺癌新辅助治疗的结局。 该多中心非盲研究（ETNA）由意大利米开朗基罗肿瘤学研究基金会、西班牙乳腺癌研究协作组（GEICAM）与澳大利亚西部乳腺癌研究中心（BCRC-WA）合作于2013年5月～2015年3月入组刚诊断为单侧浸润性早期乳腺癌（cT2～cT4a-d）尚未接受治疗的814例患者（中位年龄50岁，范围25～79岁），其中695例粗针穿刺活检标本集中进行组织学检查确认为ERBB2/HER2阴性，手术前被随机分配接受紫杉醇90mg/m²（349例）或白蛋白结合型纳米紫杉醇125mg/m²（346例），第1、2、3周给药，第4周停药，如此4个周期后，再由各位研究者自行选择一种蒽环类药物继续化疗4个周期。主要研究终点为病理学完全缓解率，定义为手术时乳腺和腋窝淋巴结无癌细胞浸润（即ypT0/ypN0）。次要终点为两种化疗方案的耐受性和安全性。 根据主要终点病理学完全缓解的意向治疗分析，白蛋白结合型纳米紫杉醇与紫杉醇相比：
根据多变量分析，肿瘤亚型是影响治疗结局最重要的因素，尤其三阴性与管腔B型相比，病理学完全缓解率提高显著（比值比：4.85，95%置信区间：3.28～7.18，P<0.001）。 根据次要终点耐受性和安全性的意向治疗分析，白蛋白结合型纳米紫杉醇与紫杉醇相比：
因此，白蛋白结合型纳米紫杉醇新辅助治疗HER2阴性乳腺癌的病理学完全缓解率提高无统计学意义，除了对于三阴性乳腺癌。 对此，美国纽约爱因斯坦医学院蒙蒂菲奥里医学中心发表同期述评：新辅助全身疗法用于乳腺癌仍需寻找更有效的治愈方案。 相关阅读 JAMA Oncol. 2018 Jan 11. [Epub ahead of print] Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer—the Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial: A Randomized Phase 3 Clinical Trial. Luca Gianni; Mauro Mansutti; Antonio Anton; Lourdes Calvo; Giancarlo Bisagni; Begona Bermejo; Vladimir Semiglazov; Marc Thill; Jose Ignacio Chacon; Arlene Chan; Serafin Morales; Isabel Alvarez; Arrate Plazaola; Milvia Zambetti; Andrew D. Redfern; Christian Dittrich; Rebecca Alexandra Dent; Domenico Magazzù; Raffaella De Fato; Pinuccia Valagussa; Ignacio Tusquets. San Raffaele Scientific Institute, Milano, Italy; Azienda Sanitaria Universitaria Integrata, Udine, Italy; Miguel Servet University Hospital, Aragón Health Research Institute, Zaragoza, Spain; Complejo Hospitalario Universitario de A Coruna, A Coruna, Spain; IRCCS Arcispedale Santa Maria Nuova Azienda Ospedaliera di Reggio Emilia, Reggio Emilia, Italy; Hospital Clinico Universitario Valencia, Valencia, Spain; NN Petrov Research Institute of Oncology, St Petersburg, Russia; Agaplesion Markus Krankenhaus, Klinik für Gynakologie und Geburtshilfe, Frankfurt am Main, Germany; Hospital Virgen de la Salud, Toledo, Spain; Western Australia & Curtin University, Perth, Australia; Hospital Universitario Arnau de Vilanova de Lleida, Lleida, Spain; Hospital Universitario Donostia, San Sebastian, Spain; Onkologikoa, Hospital Donostia, San Sebastián, Spain; Royal Perth Hospital, Perth, Australia; Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna) & Kaiser Franz Josef-Spital, Vienna, Austria; National Cancer Center Singapore, Singapore; Fondazione Michelangelo, Milano, Italy; Hospital del Mar, Barcelona, Spain. This randomized clinical trial determines whether nab-paclitaxel improves the outcomes of early and locally advanced ERBB2/HER2-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting. QUESTION: In the neoadjuvant setting, is nab-paclitaxel significantly more effective than paclitaxel in achieving pathological complete remissions (pCR) in ERBB2/HER2-negative breast cancers? FINDINGS: In this randomized clinical trial that included 695 patients, the rate of pCR was 22.5% with nab-paclitaxel therapy vs 18.6% with paclitaxel, a difference that was not statistically significant. MEANING: At the doses selected for this study, nab-paclitaxel and solvent-based paclitaxel had antitumor activity of the same order of magnitude in all patient subgroups; the extensive biobanking performed in the trial will allow for translational studies and better interpretation of the clinical findings. IMPORTANCE: Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial. OBJECTIVE: To determine whether nab-paclitaxel improves the outcomes of early and locally advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, open-label study, in collaboration with Grupo Espanol de Investigación en Cáncer de Mama (GEICAM) and Breast Cancer Research Center-Western Australia (BCRC-WA), patients with newly diagnosed and centrally confirmed ERBB2/HER2-negative breast cancer were recruited. Participants were randomly allocated to paclitaxel, 90 mg/m² (349 patients), or nab-paclitaxel, 125 mg/m² (346 patients). The 2 drugs were given on weeks 1, 2, and 3 followed by 1 week of rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of pCR, defined as absence of invasive cells in the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A secondary end point was to assess tolerability and safety of the 2 regimens. RESULTS: From May 2013 to March 2015, 814 patients were registered to the study; 695 patients met central confirmation eligibility and were randomly allocated to receive either paclitaxel (349), or nab-paclitaxel (346) (median age, 50 years; range, 25-79 years). The intention-to-treat analysis of the primary end point pCR revealed that the improved pCR rate after nab-paclitaxel (22.5%) was not statistically significant compared with paclitaxel (18.6%; odds ratio [OR], 0.77; 95% CI, 0.52-1.13; P=.19). Overall, 38 of 335 patients (11.3%) 11.3% of patients had at least 1 serious adverse event in the paclitaxel arm and 54 of 337 patient (16.0%) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or higher occurred in 6 of 335 patients (1.8%) and in 15 of 337 (4.5%), respectively. CONCLUSIONS AND RELEVANCE: The improved rate of pCR after nab-paclitaxel was not statistically significant. The multivariate analysis revealed that tumor subtype (triple-negative vs luminal B-like) was the most significant factor (OR, 4.85; 95% CI, 3.28-7.18) influencing treatment outcome. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01822314 DOI: 10.1001/jamaoncol.2017.4612 JAMA Oncol. 2018 Jan 11. [Epub ahead of print] Neoadjuvant Systemic Therapy for Breast Cancer: Searching for More Effectively Curative Therapies. Joseph A. Sparano. Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. DOI: 10.1001/jamaoncol.2017.4651
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