TAC新辅助化疗方案治疗三阴性乳腺癌的疗效及预后

【摘要】目的 探讨TAC新辅助化疗方案治疗三阴性乳腺癌（triple-negative breast cancer,TNBC）的临床疗效。方法 对接受4～6个周期TAC新辅助化疗方案治疗的63例TNBC进行回顾性研究,分析近远期化疗疗效。结果 63例患者总有效率(RR)96.83%,其中完全缓解(CR)57.14%（36/63),部分缓解(PR)39.68%(25/63）。主要不良反应中性粒细胞减少36例（57.14%）,中性粒细胞减少性发热25例（39.68%）,恶心呕吐33例（52.38%）,腹泻14例（22.22%）,口腔黏膜炎13例（20.63%）,乏力虚弱10例（15.87%）。术后死亡7例,局部复发8例,远处转移21例,3年生存率88.89%。结论 应用TAC新辅助化疗方案能提高TNBC治疗效果,改善患者生活质量,提高3年生存率。     

三阴性乳腺癌治疗进展

三阴性乳腺癌(TNBC)是乳腺癌中恶性程度最高的分子亚型,具有侵袭性强,易于早期复发转移,高异质性等特点.目前化疗仍然是TNBC的标准系统治疗方案,但随着组学技术的高速发展,研究者对TNBC分子生物学本质认识不断加深,发现可以将其分为多种亚型,根据各种分型的生物学特征进行分类治疗,同时针对肿瘤细胞自身特征与外部微环境特...     

2023年乳腺癌临床研究进展年终盘点

乳腺癌作为全球发病例数第一的恶性肿瘤,多年来一直是研究的热点。2023年,乳腺癌临床研究在局部治疗和系统治疗方面取得显著进展。在局部治疗方面,如何评估腋窝肿瘤负荷及选择合适的治疗手段是研究焦点。SOUND研究发现前哨淋巴结活检（SLNB）与无腋窝手术对于术前腋窝超声淋巴结阴性早期乳腺癌患者的5年无远处转移生存率相似,在术前超声对腋窝淋巴结筛查结果明确的情况下可避免SLNB。SENOMAC研究提供证据支持低负荷前哨淋巴结患者不进行腋窝淋巴结清扫（ALND）的可能性。OPBC05研究指出新辅助治疗后残留孤立肿瘤细胞（ITCs）的患者中ALND不改善长期生存,暗示豁免ALND的可行性。NSABP B-51研究显示,新辅助化疗（NAC）后腋窝淋巴结阴性（ypN0）患者的局部淋巴结放疗（RNI）并未显著改善主要研究终点。这些研究强调了个体化治疗方案的重要性,为乳腺癌的外科治疗和后续治疗提供重要指导。在系统治疗方面,早期激素受体阳性［HR（+）］乳腺癌治疗主要依赖手术、放疗及术后辅助内分泌治疗,但约30%的中高危患者仍面临复发和转移风险。MoHER2narchE和NATALEE研究证实了CDK4/6抑制剂（CDK4/6i）在早期HR（+）/人表皮生长因子受体2阴性［HER-2（-）］乳腺癌患者中的效果。此外,有关免疫治疗的研究,如KEYNOTE-756和CheckMate 7FL试验,探讨了PD-1单抗联合NAC在提高病理完全缓解（pCR）率和降低高危患者复发风险中的潜力。晚期HR（+）乳腺癌的标准治疗已从单一内分泌治疗发展为CDK4/6i联合内分泌治疗,但仍存在耐药问题,新型药物如ADC药物、PI3K/Akt/mTOR抑制剂正在被探索以提供更多治疗选项。TROPiCS-02和TROPION-Breast01研究验证了TROP2靶向ADC药物在治疗耐药HR（+）/HER-2（-）晚期乳腺癌患者中的有效性。同时,INAVO 120和Capitello-291研究突显了PI3K/Akt/mTOR信号通路抑制剂在提高治疗效果方面的潜力,尤其是对PIK3CA突变患者。在早期HER-2（+）乳腺癌治疗方面,PHERGain研究表明,基于¹⁸F-FDG PET/CT和根据pCR调整的降阶梯化疗在早期HER-2（+）乳腺癌新辅助治疗中有效。APTneo研究发现阿替利珠单抗联合化疗对新辅助治疗的pCR率提升有限,需进一步研究以优化疗效和安全性。在晚期HER-2（+）乳腺癌方面,PHILA和HER2CLIMB-02研究展示了TKI药物在一线和二线治疗中的有效性。DESTINY-Breast系列研究证明了德曲妥珠单抗（T-DXd）对HER-2（+）转移性乳腺癌各年龄段患者都有效且展现出良好的安全性。同时其对经治/稳定和未经治/活动性脑转移患者均有显著的疗效。早期三阴性乳腺癌（TNBC）的研究重点在于免疫治疗与化疗的联合应用,KEYNOTE-522研究显示化疗联合帕博利珠单抗的新辅助治疗及其作为后续辅助治疗显著提高了pCR率和无事件生存率,美国食品药品管理局和欧洲药物管理局已批准其用于高危早期TNBC的治疗。然而,IMpassion030研究表明,术后辅助免疫治疗可能并非所有早期TNBC患者的有效选项。对于晚期TNBC,KEYLYNK-009研究结果显示帕博利珠单抗联合PARP抑制剂奥拉帕利与帕博利珠单抗加化疗相比,并未显著改善预后,但在具有tBRCA突变的患者群体中,该联合疗法显著提高了中位无进展生存期（PFS）,表明其可作为这一患者群体的晚期一线维持治疗。BEGONIA研究的结果表明,Dato-DXd和度伐利尤单抗联合治疗显示出高反应率和较长的PFS,可能为晚期TNBC患者提供新的治疗选择。综上,2023年乳腺癌治疗领域的研究不仅在治疗方法上取得了突破,也在治疗理念上进行了革新,为乳腺癌患者带来了新的希望。     

三阴性乳腺癌新辅助治疗现状

目的 三阴性乳腺癌高侵袭、高复发、高转移且预后差,对内分泌治疗、抗Her-2靶向治疗不敏感。本研究总结了近年来三阴性乳腺癌新辅助治疗进展。方法 应用PubMed、CNKI、万方等数据库,以“TNBC、新辅助治疗、病理完全缓解”等作为搜索关键词,检索近年的相关文献。结果 病理完全缓解被认为是新辅助治疗预后评判的重要标准之一。蒽环类联合紫杉类药物仍然是TNBC患者的首选新辅助化疗方案,铂类药物的应用使BRCA基因突变TNBC患者有了更优的新辅助化疗方案,但血液学、消化系统等相关不良反应不可忽视。免疫调定点抑制剂相关药物被证实在TNBC新辅助治疗上能提高pCR,改善长期生存预后,且因药物不良反应停药较铂类药物发生率更低。肿瘤微环境靶向药物、多聚ADP核糖聚合酶抑制剂、PI3K/AKT/mTOR通路抑制剂等相关药物在多药联合方面上的临床研究有积极治疗效果。结论 TNBC新辅助治疗中,化疗是基础,免疫治疗已有相关临床试验成果,肿瘤微环境靶向药物、多聚ADP核糖聚合酶抑制剂、PI3K/AKT/mTOR通路抑制剂具有很大研究前景。     

紫杉醇/白蛋白紫杉醇为基础的化疗联合PD-1/PD-L1抑制剂治疗三阴性乳腺癌的疗效和安全性：荟萃分析

目的探讨以紫杉醇/白蛋白紫杉醇为主体的化疗方案联合程序性死亡受体-1（PD-1）/程序性死亡受体-配体1（PD-L1）抑制剂在治疗三阴性乳腺癌（TNBC）的疗效及安全性。 方法检索国内外数据库，检索时限均从数据库建库起至2021年12月9日。根据纳入及排除标准选择接受治疗的TNBC患者，试验组方案为PD-1/PD-L1抑制剂联合以紫杉醇/白蛋白紫杉醇为基础的化疗，对照组方案为安慰剂联合以紫杉醇/白蛋白紫杉醇为基础的化疗。采用RevMan 5.4.1软件分析相关数据。通过异质性检验后，采用固定效应模型或随机效应模型进行Meta分析，通过漏斗图评价发表偏倚性。 结果PD-1/PD-L1抑制剂联合以紫杉醇/白蛋白紫杉醇为基础的化疗试验组，其总生存率（OS）显著长于安慰剂联合化疗的对照组（P<0.05）；在无进展生存期（PFS）及客观缓解率（ORR）方面，试验组也均优于对照组（P<0.05）；试验组中出现治疗相关不良反应（TRAE）患者人数高于对照组（P<0.05）；PD-L1受体阳性的TNBC患者中，在OS及PFS方面，试验组均优于对照组。 结论接受PD-1/PD-L1抑制剂治疗联合紫杉醇/白蛋白紫杉醇为基础的TNBC化疗患者OS、PFS、ORR方面均有显著改善。     

三阴性乳腺癌治疗的新进展

乳腺癌是目前世界上女性最常见的恶性肿瘤之一。三阴性乳腺癌(TNBC)是乳腺癌的一种特殊类型,其侵袭性高,临床预后较差,且目前还没有系统的治疗方案。笔者就TNBC治疗新的研究进展做一综述。     

表阿霉素联合多西紫杉醇新辅助化疗治疗三阴、非三阴乳腺癌的疗效及预后评价

目的比较表阿霉素联合多西紫杉醇新辅助化疗方案(ET方案)对三阴乳腺癌(TNBC)和非三阴乳腺癌(non-TNBC)的临床疗效及预后差别。方法回顾性分析接受ET新辅助化疗方案治疗的198例乳腺癌患者的临床资料,依据免疫组化结果将乳腺癌分为TNBC及non-TNBC两组,对两类乳腺患者接受ET新辅助化疗方案后的病理疗效及预后的差别进行分析比较。结果 198例乳腺癌患者中,TNBC43例,non-TNBC155例。所有患者的临床总有效率(cOR)为76.8%,其中完全缓解率24.7%,部分缓解率48.5%;TNBC患者的临床有效率84.2%,病理完全缓解率(pCR)27.9%;non-TNBC患者临床有效率70.4%,病理完全缓解率12.9%。TNBC患者与非TNBC患者5年无病生存率(DFS)分别为52.9%和70.9%(P<0.05);TNBC患者与非TNBC患者5年总体生存率分别为59.1%和80.5%(P<0.05)。结论表阿霉素联合多西紫杉醇新辅助化疗方案治疗三阴乳腺癌患者能够获得较好的临床效果。     

三阴性乳腺癌的治疗进展

目的总结近年来三阴性乳腺癌(TNBC)基于基因治疗、免疫治疗、靶向治疗等方面综合治疗的研究进展,以期提高对该病的认识和治疗水平。方法检索国内外近5年来关于TNBC治疗的相关文献并进行分析总结。结果 TNBC因其治疗缺乏靶向受体,较其他分型的乳腺癌侵袭性强、复发转移早,治疗方案目前仍为手术治疗为主,辅以化疗、放疗等的综合治疗。结论虽然近年来TNBC在手术治疗、放化疗、靶向治疗等方面的研究均显示出不错的临床应用前景,但目前仍需要更多大样本的临床试验证据。随着分子机制研究的不断深入,包括雄激素受体阳性的内分泌治疗、靶向药物治疗等为TNBC的治疗提供了一些新的想法。     

三阴性乳腺癌的临床病理特征和预后影响因素分析

目的：探讨三阴性乳腺癌(TNBC)的临床病理特征和预后影响因素。 方法：回顾性分析2008年1月—2013年6月期间收治的并有完整临床病理资料的508例乳腺癌患者，患者分为TNBC组（105例）与非TNBC组（403例），对TNBC的临床病理特征与预后影响因素进行分析。 结果：TNBC组出现局部复发和远处转移患者54例（51.4%），其中死亡11例；非TNBC组出现局部复发和远处转移患者24例（6.0%），TNBC组总体转移率高于非TNBC组（P<0.05）；且TNBC组肝、肺、脑转移率均显著性高于非TNBC组（P<0.05），而骨转移率低于非TNBC组（P<0.05）。Kaplan-Meier 曲线显示，TNBC组前5年DFS及OS均差于非TNBC组，而三阴性亚群5年后DFS及OS较非三阴性亚群好，非TNBC组总生存率高于TNBC组（58.4% vs. 47.4%）（P=0.041）；免疫组化结果显示肿瘤大小（RR=5.5）和淋巴结状态（RR=8.7）均是影响预后的独立危险因素。 结论：TNBC是一种特殊类型的乳腺癌亚型，具有发病年龄小、家族史、有淋巴结转移等特点，其较早发生局部复发和远处转移，肿瘤直径、淋巴结状态是影响预后的独立危险因素。

     

Caspase-1/GSDMD介导的细胞焦亡在三阴性乳腺癌顺铂抗肿瘤效应中的作用

目的:探讨Caspase-1/焦孔素D（gasdermin D,GSDMD）介导的细胞焦亡在三阴性乳腺癌（triple-negative breast cancer,TNBC）顺铂（DDP）抗肿瘤效应中的作用。方法:采用HE染色和免疫组化染色检测以DDP为基础的新辅助化疗（neoadjuvant chemotherap...     

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??Choosing and evaluation of chemotherapy regimens in multimodality therapy of triple negative breast cancer XU Bing-he. Breast Disease Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College??Beijing 100021??China
Abstract Triple negative (estrogen receptor, progesterone receptor and HER-2 are all negative) breast cancer (TNBC), a subgroup of breast cancer, has distinct biological, clinical and pathologic characteristics. TNBC is sensitive to chemotherapy which is main therapeutic method for early and metastatic TNBC. Taxanes or platinum-based chemotherapy may be more effective for TNBC. However, there are still no standard chemoterapeutic regimens. In recent years, target agents have become hotspot of study and direction of future study.     

Current treatment options in triple negative breast cancer

Triple negative breast cancer (TNBC) refers to a subgroup of breast carcinomas that do not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor type 2. This heterogeneous group of tumors has significant overlap with both basal-like tumors (defined through gene expression array) and BRCA1 mutation-associated tumors. Due to a lack of well defined clinical targets, chemotherapy is the standard of care treatment for TNBC. When compared with other breast cancer subtypes, TNBC exhibits at least equivalent, or often superior sensitivity to chemotherapy. However, despite this increased chemosensitivity, TNBC has a worse clinical outcome than other breast cancer subtypes. This has led to the investigation of DNA damaging chemotherapy agents, including platinum drugs, angiogenesis inhibitors, poly(ADP-ribose) polymerase inhibitors, novel microtubule inhibitors, and other targeted therapies in an effort to improve the outcome for patients with these high-risk tumors. Treatment decisions for patients with TNBC should be based on the best currently available evidence, which consists mainly of retrospective and prospective subgroup analyses and phase II prospective data. This review summarizes data from select neoadjuvant, adjuvant, and metastatic chemotherapy clinical trials which included analyses of treatment effects and outcomes in TNBC and/or basal-like breast cancer.     

三阴乳腺癌的特征及治疗现状

目的探讨三阴乳腺癌的特征及治疗现状。方法以"三阴乳腺癌"、"特征"、"治疗"为关键词进行检索并筛选阅读相关文献进行综述。结果三阴乳腺癌是乳腺癌的一种特殊亚型,肿瘤细胞缺乏雌激素受体、孕激素受体及人类上皮细胞生长因子受体2,其临床特点及预后不同于其他类型的乳腺癌,发病年龄小、无病生存率及总生存率较低。目前尚缺乏针对三阴乳腺癌的治疗指南,多参照非三阴乳腺癌的治疗,主要包括外科手术治疗且保乳手术后推荐常规行放射治疗、全身化疗,靶向治疗正处于临床研究阶段。结论三阴乳腺癌是乳腺癌表现异质性特征之一,其间还存在着许多的不同点。为了改善三阴乳腺癌的预后,我们期待在将来的工作中发现更多对于三阴乳腺癌有意义的检测指标,便于制定出三阴乳腺癌个体化治疗方案。     

State of art of advanced triple negative breast cancer

Advanced triple negative breast cancer (TNBC) is an aggressive disease (high probability of visceral metastasis) with poor outcome. Triple negative breast cancer is characterized by lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor‐2 (HER2), high histologic grade, and high mitotic rate. Chemotherapy remains the primary systemic treatment, with international guidelines supporting the use of single‐agent taxanes (with or without bevacizumab) or anthracyclines as first‐line therapy, with a median overall survival of approximately 18 months or less. Given the suboptimal outcomes with chemotherapy, new targeted therapies for advanced TNBC are urgently needed. This review summarizes the current status of treatment, and future challenges of using new treatment options for advanced TNBC, such as poly‐adenosine‐diphosphate‐ribose‐polymerase inhibitors (olaparib and talazoparib) and immune checkpoint inhibitors (eg atezolizumab) as monotherapy or in combination with chemotherapy.     

三阴性乳腺癌新辅助治疗的机遇与挑战

三阴性乳腺癌是一类特殊类型的乳腺癌,由于缺乏治疗靶点,化疗是目前主要的治疗方法。三阴性乳腺癌患者接受新辅助治疗并获得病理完全缓解,则预后明显改善。目前三阴性乳腺癌新辅助治疗方案仍以蒽环类药物和紫杉类药物化疗为主,但随着对三阴性乳腺癌分子本质认识的深入,新辅助治疗方案不断地获得探索和优化,包括铂类药物的优化,免疫检查点抑制剂、多聚二磷酸腺苷核糖聚合酶抑制剂的使用,均获得较好效果。     

微小RNA在三阴性乳腺癌中的研究进展

三阴性乳腺癌(triple-negative breast cancer,TNBC)是指免疫组织指标ER、PR、HER2三者均为阴性的一种乳腺癌分子亚型,也是一种高度异质性的疾病。TNBC与其他乳腺癌分子亚型相比,生物学行为上表现侵袭性强、易复发和内脏转移,易产生耐药性,预后不良。miRNA是一种很有前景的生物标志物和预测工具,可用于乳腺癌诊断与治疗的各个阶段。本文从高侵袭性机制分析、潜在的治疗靶点探索、预后生物标记物筛选、药物耐药性研究、新辅助治疗pCR预测、与BRCA1/2突变的关联性等方面综述miRNA在TNBC中的研究进展,为TNBC的早期筛查、早期诊断、临床治疗和预后判断提供参考与借鉴。     

Triple‐Negative Breast Cancer in Ghanaian Women: The Korle Bu Teaching Hospital Experience

Breast cancers that have negative or extremely low expression of estrogen receptor and progesterone receptor and non‐amplification of human epidermal growth factor receptor‐2 (HER2)/neu are termed triple‐negative breast cancer (TNBC). The majority of TNBC tumors belong to the biologically aggressive basal subtype, and they cannot be managed with targeted endocrine or anti‐HER2/neu agents. In western, high resource environments, risk factors for TNBC include younger age at diagnosis and hereditary susceptibility. Women of African ancestry in the United States and in continental Africa have higher frequencies of TNBC, prompting speculation that this risk may have an inherited basis and may at least partially explain breast cancer survival disparities related to racial/ethnic identity. Efforts to document and confirm the breast cancer burden of continental Africa have been hampered by the limited availability of registry and immunohistochemistry resources. Our goal was to evaluate the breast cancers diagnosed in one of the largest health care facilities in western Africa, and to compare the frequencies as well as risk factors for TNBC versus non‐TNBC in this large referral tertiary hospital. The Korle Bu Teaching Hospital is affiliated with the University of Ghana and is located in Accra, the capital of Ghana. We conducted an institutional, Department of Pathology‐based review of the breast cancer cases seen at this facility for the 2010 calendar year, and for which histopathologic specimens were available. The overall study population of 223 breast cancer cases had a median age of 52.4 years, and most had palpable tumors larger than 5 cm in diameter. More than half were TNBC (130; 58.3%). We observed similar age‐specific frequencies, distribution of stage at diagnosis and tumor grade among cases of TNBC compared to cases of non‐TNBC. Ghanaian breast cancer patients tend to have an advanced stage distribution and relatively younger age at diagnosis compared to Caucasian Americans and African Americans. The triple‐negative molecular marker pattern was the most common subtype of breast cancer seen among this sample of Ghanaian women, regardless of age, tumor grade, or stage of diagnosis. Research into the molecular pathogenesis of TNBC may help elucidate the reasons for its increased prevalence among women with African ancestry.     

Triple‐negative breast cancer—Role of immunology: A systemic review

Recently, the complex role of immune therapy has been the target of increased attention in breast cancer, particularly in triple‐negative breast cancer (TNBC). Although TNBC is sensitive to chemotherapy, the recurrence and mortality rates are worse compared with the other breast cancer types. In addition, TNBC still lacks targeted treatment options. With the improved understanding of the immune system in TNBC, it is expected that new predictive and prognostic markers will be identified, and innovative treatment modalities will be developed. The aim of this review was to provide an overview of the effector cells in the TNBC's microenvironment and to highlight a novel approach to treat this kind of cancer. A computer‐based literature research was carried out using PubMed, American Society of Clinical Oncology Annual Meeting (ASCO) and San Antonio Breast Cancer Symposium (SABCS). To date, studies have shown that tumor‐infiltrating lymphocytes (TILs) and tumor‐associated macrophages ( TAMs) play a very important role in the TNBC's microenvironment. Tumor‐infiltrating lymphocytes can even be considered as biomarkers to predict chemotherapy response in TNBC. Furthermore, TNBC was shown to have immune active subtypes, and therefore, the use of immunotherapy may be an attractive treatment approach. In this respect, several randomized studies have been designed or are currently ongoing to explore the combination of chemotherapy with immunotherapy in TNBC. Combination of chemo‐ and immunotherapy is likely to be beneficial in a subgroup of patients with TNBC.     

三阴性乳腺癌组织中BCL11A的表达及新辅助化疗的影响

目的:探讨BCL11A在三阴性乳腺癌(TNBC)中的表达,以及新辅助化疗对其表达的影响。方法:用免疫组化检测BCL11A在43例TNBC癌组织标本(新辅助化疗前后),以及49例管腔型乳腺癌与50例HER-2阳性型乳腺癌癌组织标本中的表达。比较BCL11A在不同类型乳腺癌中的表达差异,分析BCL11A表达与TNBC临床病理因素的关系,以及新辅助化疗对TNBC组织BCL11A表达的影响。结果:TNBC组织中BCL11A的阳性表达率与表达量均明显高于管腔型乳腺癌与HER-2阳性型乳腺癌组织(均P0.05);BCL11A的阳性表达与TNBC原发肿块大小明显有关(P0.05);新辅助化疗后TNBC组织BCL11A的阳性表达率与表达量较新辅助化疗前均明显降低(均P0.05)。结论:BCL11A在TNBC组织中表达升高,且可能是肿瘤增殖的促进因素,新辅助化疗能降低TNBC组织BCL11A的表达。