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WJCR

World Journal of Cancer Research

2164-9049

Scientific Research Publishing

10.12677/WJCR.2024.141002

WJCR-78976

WJCR20240100000_38364432.pdf

医药卫生

扶正祛邪滋阴汤结合放化疗治疗三阴性乳腺癌的临床评价 Clinical Evaluation of Fuzhengquxieziyin Decoction Combined with Radiotherapy and Chemotherapy in the Treatment of Triple Negative Breast Cancer

赵

东

² ¹ 斯

晓芳

² ¹ 苟

小琳

² ¹ 齐

萌

² ¹

新疆生产建设兵团奎屯中医院肿瘤科，新疆奎屯

null

09 01 2024

14 01 7 12

2014

This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/

目的：探索扶正祛邪滋阴汤结合放化疗治疗三阴性乳腺癌的临床疗效。方法：自2020年1月至2023年10月选取48例经手术、放疗及化疗后的II至III期三阴性乳腺癌患者，采取随机、双盲、自愿的原则分成两组。治疗组采取扶正祛邪滋阴汤内服8周，对照组采取安慰剂(维生素C)内服8周。入组前均给与CT、彩超及肿瘤标记物检查，治疗结束后再给予彩超及肿瘤标记物检查，之后每3个月随访1次，1年后定期给与CT、彩超及肿瘤标记物检查，随访期共3年。结果：治疗组24例三阴性乳腺癌患者采取扶正祛邪滋阴汤内服治疗后，第1年，23例无复发及转移，1例复发，0例转移。总有效率为95.8%。第2年，22例无复发及转移，1例复发，1例转移。总有效率为91.6%。第3年，20例无复发及转移，1例复发，3例转移。总有效率为83.3%。对照组24例三阴性乳腺癌患者采取安慰剂(维生素C)内服，第1年，22例无复发及转移，1例复发，1例转移。总有效率为91.6%。第2年，19例无复发及转移，1例复发，4例转移。总有效率为79.2%。第3年，16例无复发及转移，2例复发，6例转移。总有效率为66.7%。结论：扶正祛邪滋阴汤结合放化疗治疗三阴性乳腺癌的临床疗效肯定，患者复发及转移率低，值得推广。 Objective: To explore the clinical effect of Fuzhengquxieziyin Decoction combined with radiotherapy and chemotherapy in the treatment of triple-negative breast cancer. Methods: From January 2020 to October 2023, 48 patients with stage II to III triple negative breast cancer after surgery, radio-therapy and chemotherapy were randomly, double-blind and voluntarily divided into two groups. The treatment group took Fuzhengquxieziyin decoction for 8 weeks, and the control group took placebo (vitamin C) for 8 weeks. CT, color Doppler ultrasound and tumor markers were examined before enrollment, and then color Doppler ultrasound and tumor markers were examined after treatment. After that, CT, color Doppler ultrasound and tumor markers were followed up every 3 months, and CT, color Doppler ultrasound and tumor markers were examined regularly 1 year later. The follow-up period was 3 years. Results: In the treatment group, 24 patients with triple- negative breast cancer were treated with Fuzhengquyeziyin Decoction, 23 cases had no recurrence or metastasis, 1 case had relapse and 0 cases had metastasis in the first year. The total effective rate was 95.8%. In the second year, 22 cases had no recurrence or metastasis, 1 case had relapse and 1 case had metastasis. The total effective rate was 91.6%. At the 3rd year, 20 cases had no recurrence or metastasis, 1 case had relapse and 3 cases had metastasis. The total effective rate was 83.3%. In the control group, 24 patients with triple-negative breast cancer took placebo (vitamin C) orally. In the first year, 22 cases had no recurrence or metastasis, 1 case had recurrence and 1 case had metastasis. The total effective rate was 91.6%. In the second year, 19 patients had no recurrence or metastasis, 1 had relapse and 4 had metastasis. The total effective rate was 79.2%. At the 3rd year, 16 cases had no recurrence or metastasis, 2 cases had relapse and 6 cases had metastasis. The total effective rate was 66.7%. Conclusion: Fuzhengquyeziyin Decoction combined with chemoradiotherapy has definite clinical efficacy in the treatment of triple-negative breast cancer, and the recurrence and metastasis rate of patients are low, which is worth promoting.

扶正祛邪滋阴汤，三阴性乳腺癌，有效率, Fuzhengquxieziyin Decoction Triple Negative Breast Cancer Effective Rate

摘要

关键词

扶正祛邪滋阴汤，三阴性乳腺癌，有效率

Clinical Evaluation of Fuzhengquxieziyin Decoction Combined with Radiotherapy and Chemotherapy in the Treatment of Triple Negative Breast Cancer<sup> </sup>

Dong Zhao, Xiaofang Si, Xiaolin Gou, Meng Qi

Oncology Department, Xinjiang Production and Construction Corps Kuitun Traditional Chinese Medicine Hospital, Kuitun Xinjiang

Received: Dec. 2^nd, 2023; accepted: Jan. 2^nd, 2024; published: Jan. 11^th, 2024

ABSTRACT

Objective: To explore the clinical effect of Fuzhengquxieziyin Decoction combined with radiotherapy and chemotherapy in the treatment of triple-negative breast cancer. Methods: From January 2020 to October 2023, 48 patients with stage II to III triple negative breast cancer after surgery, radiotherapy and chemotherapy were randomly, double-blind and voluntarily divided into two groups. The treatment group took Fuzhengquxieziyin decoction for 8 weeks, and the control group took placebo (vitamin C) for 8 weeks. CT, color Doppler ultrasound and tumor markers were examined before enrollment, and then color Doppler ultrasound and tumor markers were examined after treatment. After that, CT, color Doppler ultrasound and tumor markers were followed up every 3 months, and CT, color Doppler ultrasound and tumor markers were examined regularly 1 year later. The follow-up period was 3 years. Results: In the treatment group, 24 patients with triple- negative breast cancer were treated with Fuzhengquyeziyin Decoction, 23 cases had no recurrence or metastasis, 1 case had relapse and 0 cases had metastasis in the first year. The total effective rate was 95.8%. In the second year, 22 cases had no recurrence or metastasis, 1 case had relapse and 1 case had metastasis. The total effective rate was 91.6%. At the 3^rdyear, 20 cases had no recurrence or metastasis, 1 case had relapse and 3 cases had metastasis. The total effective rate was 83.3%. In the control group, 24 patients with triple-negative breast cancer took placebo (vitamin C) orally. In the first year, 22 cases had no recurrence or metastasis, 1 case had recurrence and 1 case had metastasis. The total effective rate was 91.6%. In the second year, 19 patients had no recurrence or metastasis, 1 had relapse and 4 had metastasis. The total effective rate was 79.2%. At the 3^rdyear, 16 cases had no recurrence or metastasis, 2 cases had relapse and 6 cases had metastasis. The total effective rate was 66.7%. Conclusion: Fuzhengquyeziyin Decoction combined with chemoradiotherapy has definite clinical efficacy in the treatment of triple-negative breast cancer, and the recurrence and metastasis rate of patients are low, which is worth promoting.

Keywords:Fuzhengquxieziyin Decoction, Triple Negative Breast Cancer, Effective Rate

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

http://creativecommons.org/licenses/by/4.0/

1. 引言

三阴性乳腺癌(Triple negative breast cancer，简称TNBC)是指癌组织免疫组化检查结果为雌激素受体(ER)、孕激素受体(PR)、原癌基因Her-2均为阴性的乳腺癌。这类乳腺癌占所有乳腺癌病理类型的10%~20.8%，具有特殊的生物学行为和临床病理特征。多项研究表明，三阴性乳腺癌多发于绝经前年轻妇女。三阴性乳腺癌临床表现为一种侵袭性病程，其远处转移风险较高。内脏转移机会较骨转移高，脑转移几率也较高。文献报道其3年复发率达19%，复发后中位生存期仅12个月 [ 1 ] 。三阴性乳腺癌远处转移在三年时达到高峰，之后可能下降。三阴性乳腺癌的中位肿瘤大小为2 cm，50%有淋巴结转移，此类乳腺癌的组织学分级多为3级，细胞增殖比例较高。

三阴性乳腺癌目前还没有针对性的治疗指南，其治疗按一般乳腺癌常规治疗，没有任何靶向药物治疗。本病预后较差，死亡风险较高。目前临床上以手术 + 放化学治疗为主要药物治疗手段，但放化疗虽能诱导癌细胞凋亡，同时难以避免对正常细胞的损伤，进而对机体的免疫、消化、循环及神经系统等功能产生不良影响，给患者带来了极大的身心负担。此外，放化疗后缺乏其他维持性治疗措施。有文献报道，全乳切除术后放疗可提高pT3N0M0期TNBC患者5年生存率(74.3%, P < 0.001) [ 2 ] 。上海交通大学医学院附属瑞金医院发起的一项前瞻性临床研究表明，在接受保乳手术和系统治疗的T1-2N1期乳腺癌患者中，全乳放射治疗附加锁骨上或内乳照射无法降低5年局部区域复发(P锁骨上 = 0.28，P内乳 = 0.19) [ 3 ] 。此外，一项采用术中放疗代替TNBC III期等效性临床试验取得阴性结果。虽不影响长期OS，但术中放疗较TNBC I期会增加早期乳腺癌患者的同侧复发风险 [ 4 ] 。中医认为正虚毒瘀成瘤是TNBC重要病机，临床发现扶正消瘤中药能够增强化疗疗效、减轻化疗不良反应、改善预后 [ 5 ] 。为证实扶正驱邪滋阴汤在TNBC治疗中的作用，本研究通过对扶正驱邪滋阴汤为核心治法治疗TNBC的临床随机对照试验(RCT)进行系统评价，探讨扶正驱邪滋阴汤治疗TNBC的有效性及安全性。

2. 资料与方法 2.1. 病例来源

选取我科自2020年1月至2023年10月48例经手术、放疗及化疗后的II至III期三阴性乳腺癌患者，采取随机、双盲、自愿的原则分成两组。治疗组24例，对照组24例。

2.2. 纳入标准

① 纳入的患者均经病理诊断证实为TNBC；② 均为经手术、放疗及化疗后的II至III期TNBC。

2.3. 排除标准

① 未经病理诊断证实为TNBC；② 未经过手术、放疗及化疗后的TNBC；③ TNM分期不在II至III期TNBC。

2.4. 治疗方法

治疗组采取扶正祛邪滋阴汤内服8周，对照组采取安慰剂(维生素C)内服8周。入组前均给与CT、彩超及肿瘤标记物检查，治疗结束后再给与彩超及肿瘤标记物检查，之后每3个月随访1次，1年后定期给与CT、彩超及肿瘤标记物检查，随访期共3年。

2.5. 评价指标

① 疗效性指标：临床有效率(overall response rate, ORR)、临床控制率(disease control rate, DCR)、疾病稳定(stable disease, SD)、疾病进展(progressive disease, PD)；② 生存质量指标：卡氏评分(Karnofsky KPS)以及KPS改善、稳定、下降率；③ 肿瘤标志物：CEA、CA153、CA125；④ 免疫功能：CD⁴⁺/CD⁸⁺；⑤ 预后指标：复发转移、无进展生存期(progression free survival, PFS)、中位PFS。

2.6. 统计学分析

采用SPSS26.0版软件进行统计学处理。计数资料的比较采用卡方检验，生存分析采用Kaplan-Meier法并行Leg-rank检验，以P < 0.05为差异有统计学意义。

3. 结果 3.1. 两组一般资料的比较，见表1

Table 1 Two sets of general informatio

项目	治疗组(n = 24)	对照组(n = 24)
年龄50岁以上	61.19 ± 5.9 (n = 16)	59.79 ± 5.55 (n = 14)
年龄50岁以下	45.25 ± 4.77 (n = 8)	45.1 ± 3.38 (n = 10)
KPS评分5分以上(n = 19)	7.16 ± 0.9 (n = 19)	7.1 ± 0.91 (n = 20)
KPS评分5分以下(n = 5)	3 ± 0.71 (n = 5)	3 ± 0.82 (n = 4)

表1. 两组一般资料

3.2. 两组疗效对比

治疗组24例三阴性乳腺癌患者采取扶正祛邪滋阴汤内服治疗后，第1年，23例无复发及转移，1例复发，0例转移。总有效率为95.8%。第2年，22例无复发及转移，1例复发，1例转移。总有效率为91.6%。第3年，20例无复发及转移，1例复发，3例转移。总有效率为83.3%。见图1。对照组24例三阴性乳腺癌患者采取安慰剂(维生素C)内服，第1年，22例无复发及转移，1例复发，1例转移。总有效率为91.6%。第2年，19例无复发及转移，1例复发，4例转移。总有效率为79.2%。第3年，16例无复发及转移，2例复发，6例转移。总有效率为66.7%。见图2。

图1. 治疗组疗效对比

图2. 对照组疗效对比

3.3. 两组无进展生存期(PFS)

共纳入2项RCT，异质性检验P < 0.01，I 2 = 95%，应用随机效应模型。结果提示，治疗组可延长患者无进展生存期 PFS，差异有统计学意义[MD = 1.29, 95% CI (0.37, 2.21), Z = 2.74, P < 0.05]，见图3。

图3. 无疾病生存时间PFS

4. 讨论

三阴性乳腺癌(TNBC)比其他BC亚型对全身治疗的反应率更高，且TNBC的肿瘤分化较差，转移倾向较早，复发率较高 [ 6 ] 。复发和转移性TNBC通常进展得更快，对化疗和放疗表现出很强的抵抗力。由于缺乏组合靶向药物，现有治疗往往未能改善TNBC患者的预后和生活质量 [ 7 ] 。TNBC中医可归属于“乳岩”“石痈”等范畴，病因分为外感和内伤，正气不足，外邪乘虚入内，结聚于乳络，脉络不畅，气血运行障碍，痰凝气滞，瘀血内停，蕴结成毒，日久气血更亏，加重毒瘀，终致邪毒痰浊瘀血相搏于乳房而成癌。治法应以扶助正气、祛除毒瘀以消瘤为主，该法重在调节机体阴阳、气血、脏腑、经络功能，从而调节人体微环境、内环境，使机体达到阴阳平衡、正气存内、邪不可干的最佳状态 [ 8 ] 。已有研究表明在TNBC化疗过程中及化疗后辨证使用扶正消瘤中药，一方面可增加化疗直接杀灭肿瘤细胞的作用，另外一方面还能降低化疗引起的不良反应，延缓化疗药物的耐药，有效改善患者的预后以及生活质量 [ 9 ] 。为了更好的指导临床应用扶正消瘤中药，增加选择性的治疗措施和方案，改善TNBC患者生存质量、降低转移率复发率、减少不良反应发生率，因此我们进行了此项Meta分析研究。

现代医学研究证实中医药治疗TNBC具有靶点多、副作用小的独特优势，可作为长期的补充和替代疗法 [ 10 ] 。一项为期2年的多中心观察性队列试验首次评估接受中药治疗的TNBC患者的PFS和总生存期，不仅能证明中医治疗TNBC的效果，而且还有助于为TNBC患者提出一个更加规范化、人性化、标准化的中医治疗方案 [ 7 ] 。扶正消瘤中药在临床应用广泛，对扶正消瘤中药治疗TNBC的作用机制进行初步探索，有研究通过大数据分析显示扶正消瘤中药可以通过干扰细胞周期及PI3K/AKT/mTOR、MAPK和Wnt/β-catenin等途径调控相关靶点基因和蛋白的表达，抑制TNBC细胞的生长、增殖、迁移、侵袭和转移 [ 11 ] 。基础研究进一步证实益气方(扶正消瘤中药组方)可以调节TNBC异种移植小鼠体内中PI3K/AKT通路的主要基因表达，当与厄洛替尼联合使用时，益气方可以增强厄洛替尼对TNBC异种移植小鼠的抗肿瘤作用 [ 12 ] 。这些研究为扶正消瘤中药治疗TNBC提供了科学理论依据，也为进一步深入研究扶正消瘤中药的机制靶点提供方向。

本研究Meta分析后结果显示：① 治疗组在改善临床疗效指标的临床有效率、临床控制率、疾病进展方面明显优于对照组；② 治疗组在改善生活质量上的KPS评分及KPS改善、下降率方面优于对照组；而在稳定KPS方面两组无明显差异；③ 治疗组在降低肿瘤标志物指标CEA、CA153、CA125方面存在优势；④ 治疗组在改善预后如延长患者PFS、中位PFS等指标方面有优势，降低复发转移率有明显优势；综上所述，扶正驱邪滋阴汤联合放化疗在提高TNBC患者的临床有效率、改善患者生存质量、降低肿瘤标志物、改善预后，提高免疫功能、控制复发转移率等方面作用明显。研究表明长期服用扶正驱邪滋阴汤中药治疗可以改善TNBC患者免疫功能、延缓复发转移。

本研究尚存在一定的局限性，所纳入的RCT总体质量偏低，研究样本量较小，缺乏高质量多中心大样本的RCT。此外，研究临床异质性较大，其主要原因可能为：部分研究对治疗前的中医证型未详细描述，所用扶正驱邪滋阴汤的中药配伍、用法、用量也不尽相同；今后的研究可在统一的中医辨证的基础上，针对TNBC肿瘤不同的分期、用药的疗程、具体的方剂和化疗方案制定研究方案，从而开展更多深入的、高质量、多中心、大样本RCTs，为中药治疗TNBC提供更可靠的循证医学。

基金项目

项目编号：2021A02。

文章引用

赵东,斯晓芳,苟小琳,齐萌. 扶正祛邪滋阴汤结合放化疗治疗三阴性乳腺癌的临床评价Clinical Evaluation of Fuzhengquxieziyin Decoction Combined with Radiotherapy and Chemotherapy in the Treatment of Triple Negative Breast Cancer[J]. 世界肿瘤研究, 2024, 14(01): 7-12. https://doi.org/10.12677/WJCR.2024.141002

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