对于高风险早期乳腺癌，术前新辅助治疗可以提高手术的可行性和成功率、减少术后复发风险。目前，紫杉类化疗方案已被广泛用于乳腺癌术前新辅助治疗。不过，紫杉醇、多西他赛、脂质体紫杉醇等常用紫杉类化疗药物对于乳腺癌术前新辅助治疗的有效性和安全性究竟孰高孰低尚不明确。
2020年8月10日，德国施普林格旗下《乳腺癌研究与治疗》在线发表山东第一医科大学（山东省医学科学院）山东省肿瘤防治研究院（山东省肿瘤医院）毕钊、陈鹏、刘雁冰、赵桐、孙晓、宋现让、王永胜等学者的研究报告，对乳腺癌术前紫杉醇、多西他赛、脂质体紫杉醇新辅助治疗的效果和不良事件进行了比较。
该单中心回顾研究对2014年4月～2020年4月山东省肿瘤医院647例乳腺癌术前新辅助治疗后手术患者进行回顾分析。这些患者手术前接受了蒽环类＋紫杉类完整疗程化疗。紫杉类治疗方案包括紫杉醇、多西他赛、脂质体紫杉醇。对三组患者的治疗效果和不良事件进行分析。同时，还分析了腋窝病理完全缓解。
结果，乳腺病理完全缓解198例（30.6%），三组患者的乳腺病理完全缓解比例相似（P=0.067）
紫杉醇组：28.6%
多西他赛组：28.3%
脂质体紫杉醇组：39.3%
总体病理完全缓解（同时获得乳腺病理完全缓解和腋窝病理完全缓解）140例（21.6%），脂质体紫杉醇组患者的总体病理完全缓解比例显著较高（P=0.026）
紫杉醇组：13.3%
多西他赛组：19.4%
脂质体紫杉醇组：34.4%
多因素逻辑分析结果表明，总体病理完全缓解显著相关因素包括：
肿瘤临床分期（P<0.001）
肿瘤分子亚型（P<0.001）
对于592例临床淋巴结阳性患者，腋窝病理完全缓解231例（39.0%），脂质体紫杉醇组患者的腋窝病理完全缓解比例显著较高（P<0.001）
紫杉醇组：24.6%
多西他赛组：34.8%
脂质体紫杉醇组：63.5%
多因素逻辑分析结果表明，腋窝病理完全缓解独立预测因素包括：
紫杉化疗方案（P<0.001）
肿瘤分子亚型（P<0.001）
不同分子亚型的亚组分析结果表明，对于三阴性乳腺癌或HER2阳性乳腺癌，脂质体紫杉醇组患者的腋窝病理完全缓解比例显著较高（P=0.024、P<0.001）
紫杉醇组：33.3%、27.3%
多西他赛组：44.1%、46.4%
脂质体紫杉醇组：77.8%、80.4%
不过，对于激素受体阳性乳腺癌或HER2阴性乳腺癌，三组患者的腋窝病理完全缓解比例相似（P=0.050）。
安全性分析表明，脂质体紫杉醇组与紫杉醇组和多西他赛组相比，III～IV级中性粒细胞减少、I～II级周围神经毒性、口腔黏膜炎、过敏反应、手足综合征的发生比例显著较低（全部P<0.05），其他不良事件的发生比例相似（全部P>0.05）。
因此，该研究结果表明，对于乳腺癌术前新辅助治疗患者，脂质体紫杉醇与紫杉醇和多西他赛相比，肿瘤抑制作用相似，腋窝淋巴结缓解比例显著较高，避免腋窝淋巴结清扫的机会较大，化疗所致不良事件比例显著较低，故建议脂质体紫杉醇用于术前新辅助治疗患者，尤其对于三阴性乳腺癌和HER2阳性乳腺癌临床淋巴结阳性患者。
相关链接
Breast Cancer Res Treat. 2020 Aug 10. Online ahead of print.
Efficacy and safety analysis of paclitaxel, docetaxel and liposomal paclitaxel after neoadjuvant therapy in breast cancer.
Bi Z, Chen P, Liu YB, Zhao T, Sun X, Song XR, Wang YS.
Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China; Shandong Cancer Hospital and Institute, Shandong University, Jinan, Shandong, China.
BACKGROUND AND PURPOSE: Paclitaxel-based regimens are widely used in the neoadjuvant therapy (NAT) of breast cancer. The purpose is to analysis the efficacy and adverse events (AEs) among common paclitaxel (PTX), docetaxel and liposomal paclitaxel. At the same time, we want to analysis the axillary nodal pathologic complete response (apCR) after NAT among the three groups.
METHODS: From April 2014 to 2020, 647 breast cancer patients underwent operation after NAT were included in this study. Patients received full course of anthracycline- and paclitaxel-based chemotherapy before surgery. The paclitaxel-based regimens included PTX, docetaxel and liposomal paclitaxel. The therapy efficacy and AEs of the three groups were evaluated. At the same time, the apCR was also analyzed.
RESULTS: In general, 30.6% (198/647) of patients achieved breast pathologic complete response (bpCR), which was 28.6%, 28.3% and 39.3% among PTX, docetaxel and liposomal paclitaxel group, respectively (p = 0.067). The total pathologic complete response (tpCR) (achieving both bpCR and apCR) was 21.6% (140/647). The tpCR was 13.3%, 19.4% and 34.4% among PTX, docetaxel and liposomal paclitaxel group, respectively (p = 0.026). The multivariate logistic analysis result showed that clinical tumor stage and molecular subtype were significantly associated with tpCR (all p < 0.05). Among 592 clinical positive patients (cN+), the apCR was 39.0% (231/592). The multivariate logistic analysis showed that paclitaxel- based regimens and molecular subtype were indicated as independent predictors for apCR of NAT. The apCR was significantly higher in liposomal paclitaxel group (63.5%) than in PTX (24.6%) and docetaxel group (34.8%) (p < 0.001). The subgroup analysis among different molecular subtypes found that in triple negative (TN) and HER-2 positive (HER2+) subgroup, the apCR in liposomal paclitaxel group was significantly higher than those in PTX and docetaxel group (all p < 0.05). But no significant result was found in the subgroup analysis in hormone receptor positive/HER-2 negative subgroup (p = 0.050). Safety analysis indicated that the incidence of neutropenia (grade III-IV) and peripheral neurotoxicity (grade I-II) was significantly lower in the liposomal paclitaxel group than in the PTX and docetaxel group. The incidence of oral mucositis, anaphylaxis and palmar-plantar erythrodysesthesia syndrome was also much lower in liposomal paclitaxel than other two groups (all p < 0.05). And there was no significant difference in other AEs among the three groups (all p > 0.05).
CONCLUSION: Liposome paclitaxel had similar tumor suppressor effect compared with PTX and docetaxel in NAT setting. Moreover, it had a better axillary lymph node (ALN) response after NAT than PTX and docetaxel. These patients who received liposome paclitaxel had more chance to avoid ALN dissection after NAT. At the same time, the application of liposome enables liposome paclitaxel could significantly reduce AEs caused by chemotherapy. Therefore, we suggested the application of liposome paclitaxel in the NAT setting, especially for cN+ patients with TN and HER2 + disease.
KEYWORDS: Breast cancer, Neoadjuvant therapy, Liposome, Paclitaxel, Pathologic complete response
PMID: 32776291
DOI: 10.1007/s10549-020-05851-8
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