曲妥珠单抗联合新辅助化疗对HER-2阳性乳腺癌患者近远期疗效的影响

目的 探讨曲妥珠单抗联合新辅助化疗对表皮生长因子受体-2(HER-2)阳性乳腺癌患者的疗效.方法 选取HER-2阳性乳腺癌患者58例,随机分为观察组和对照组,各29例.对照组给予表柔比星联合多西他赛的方案进行新辅助化疗,观察组在对照组的基础上给予曲妥珠单抗治疗.比较两组患者的近期、远期疗效.结果 观察组有效率(RR)及病理完全缓解(pCR)率明显优于对照组,5年总生存率(OS)及5年无病生存率(DFS)明显高于对照组.结论 曲妥珠单抗联合新辅助化疗治疗HER-2阳性乳腺癌近期疗效显著,并可有效改善患者预后,值得临床推广应用.     

HER2阳性乳腺癌治疗的研究进展

[摘要] 人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）阳性乳腺癌侵袭性高,预后差。随着抗HER2药物的不断出现及广泛应用,HER2 阳性乳腺癌患者的预后出现了非常显著的改善。10 年随访结果证实1 年曲妥珠单抗辅助治疗可以显著降低疾病复发风险;对于术后的高危人群,曲妥珠单抗联合帕妥珠单抗或者曲妥珠单抗序贯来那替尼可以进一步减少复发。5 年随访结果表明帕妥珠单抗+曲妥珠单抗为基础的新辅助治疗可使病理完全缓解（pathological complete response,pCR）转化为长期生存获益;白蛋白紫杉醇代替普通紫杉醇与抗HER2 药物联用可以进一步提高pCR率;而抗HER2 药物联合内分泌治疗尚不能达到与联合化疗在新辅助治疗中疗效,即使联合CDK4/6 抑制剂,对于pCR的提高依然有限。曲妥珠单抗+帕妥珠单抗联合紫杉类药物是晚期HER2 阳性乳腺癌的标准一线方案;对于老年、体弱的患者,节拍环磷酰胺可以作为紫杉类药物的替代品;拉帕替尼+曲妥珠单抗联合内分泌治疗可以作为HER2 阳性伴激素受体阳性的选择,疗效优于曲妥珠单抗联合内分泌治疗;T-DM1 无论是作为二线治疗还是三线及以后的治疗均提高了患者生存获益,是治疗晚期、耐药HER2阳性乳腺癌的首选。     

HER-2阳性乳腺癌患者新辅助化疗联合曲妥珠单抗治疗的影响因素及预后分析

目的:探讨人类表皮生长因子受体（human epidermal growth factor receptor 2,HER-2）阳性乳腺癌患者应用新辅助化疗联合曲妥珠单抗的疗效及其预后的影响因素。方法:选取2014年01月01日至2018年12月31日郑州市第三人民医院乳腺甲状腺外科收治经穿刺病理证实为乳腺癌的患者151例,免疫组化结果均显示为HER-2阳性,并行新辅助化疗,根据患者经济条件及意愿选择是否接受曲妥珠单抗治疗,将其分为单纯新辅助化疗组（neoadjuvant chemotherapy,NAC）94例,新辅助化疗联合曲妥珠单抗组（NAC+H）57例,对比两组患者无病生存期（disease-free survival,DFS）和总生存期（overall survival,OS）情况,并分析影响预后的相关因素。结果: 151例HER-2阳性乳腺癌患者中,NAC+H组患者DFS（P=0.046）和OS（P=0.026）均明显优于NAC组,两组比较差异具有统计学意义。术前淋巴结状态、术后淋巴结状态、肿瘤大小、MP分级是影响患者DFS和OS的主要影响因素（P值分别为0.032、0.018、0.038、0.010）。结论:接受新辅助化疗联合曲妥珠单抗的HER-2阳性乳腺癌患者预后较好,两组在新辅助治疗后肿瘤大小、淋巴结状态及MP分级结果存在明显差异,该结果对选择合理的治疗方案、判断预后有重要作用。     

曲妥珠单抗联合蒽环类及紫杉类方案在乳腺癌新辅助化疗中安全性的观察和分析

人表皮生长因子受体2(human epidermal growth factorreceptor,HER-2)是乳腺癌明确的预后指标,HER-2阳性的乳腺癌具有恶性度高、预后差等特点,应用曲妥珠单抗能够有效的提高pCR率。NOAH临床研究证实,新辅助化疗中采用曲妥珠单抗联合AT方案对比单纯化疗能显著提高pCR率(P=0.002)[1]。目前相关的研究报道相对较少,由于蒽环类和曲妥珠单抗均存在心脏毒性,尽管最新的Meta分     

帕妥珠单抗在HER-2阳性乳腺癌治疗中的临床转化

帕妥珠单抗(pertuzumab)作为一种新的抗人表皮生长因子受体-2(human epidermal growth factor receptor,HER-2)治疗药物,其作用区域不同于曲妥珠单抗,两者联合可以发挥更全面的HER-2抑制作用,基础和临床转化研究均证实帕妥珠单抗和曲妥珠单抗有协同的抗肿瘤作用.Ⅱ期和Ⅲ期临床转化试验结果显示,抗HER-2两药治疗(帕妥珠单抗+曲妥珠单抗)联合化疗可使HER-2阳性晚期乳腺癌的中位无疾病进展时间(progression-free survival,PFS)延长到18个月以上,中位总生存时间(overall survival,OS)接近5年(56.5个月),显著改善了晚期HER-2阳性乳腺癌患者的预后.两项Ⅱ期新辅助治疗临床转化研究也确认帕妥珠单抗联合曲妥珠单抗的协同作用疗效同样突出,病理完全缓解(pathological complete response,pCR)率最高可达66.2％.安全性分析发现,即使是与蒽环类药物联用,加用帕妥珠单抗治疗也并未增加心脏毒性.本文对帕妥珠单抗在HER-2阳性乳腺癌治疗中的上述相关临床转化研究进行综述.     

曲妥珠单抗在乳腺癌新辅助化疗中的应用

人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)蛋白在20%~25%的乳腺癌患者中呈过度表达状态,其过表达与肿瘤侵袭性强、复发率高和死亡率高密切相关。曲妥珠单克隆抗体(简称曲妥珠单抗)作为人源化抗HER-2单抗,通过多种机制表现出其对乳腺癌具有较好的疗效。目前,曲妥珠单抗已被常规应用于乳腺癌患者的手术后辅助化疗或转移性乳腺癌的治疗。手术前应用新辅助曲妥珠单抗联合化疗也可使HER-2阳性的乳腺癌患者从中受益,本文对此类新辅助化疗的疗效及不良反应进行了总结分析。     

曲妥珠单抗联合内分泌维持治疗HR和HER-2阳性晚期乳腺癌的临床观察

目的 探讨曲妥珠单抗联合内分泌维持治疗激素受体（HR）和人表皮生长因子受体-2（HER-2）阳性复发转移性乳腺癌的疗效与安全性。方法 回顾性分析本院2013年1月至2016年1月收治的HR和HER-2阳性复发转移性乳腺癌患者31例,一线曲妥珠单抗联合化疗达到病情缓解或稳定后继续曲妥珠单抗联合内分泌维持治疗,采用RECIST 1.1版标准评估维持治疗的疗效,采用常见不良反应事件评价标准（CTCAE）4.0版评价毒性反应,根据随访资料分析预后。结果 31例复发转移性乳腺癌维持治疗的中位无进展生存期为12.0个月（95％CI：5.4～18.6个月）。5例患者在一线化疗后获完全缓解,无可评估病灶,其余26例可评估近期疗效,总有效率和临床获益率分别为26.9％和88.5％。内分泌联合曲妥珠单抗的主要不良反应较轻,主要包括乏力（19.4％）、潮热（16.1％）和恶心呕吐（9.7％）。结论 一线曲妥珠单抗联合化疗有效后,曲妥珠单抗联合内分泌维持治疗HR+／HER-2+转移性乳腺癌可进一步改善患者的临床获益,且安全性良好。     

人表皮生长因子受体2过表达乳腺癌耐药后的治疗策略

人表皮生长因子受体2（human epidermal growth factor receptor-2,Her-2）过表达是乳腺癌患者的一个独立预后因子。曲妥珠单抗单药治疗Her-2阳性转移性乳腺癌具有一定疗效。但由于一些生长因子（如EGFR、IGF1-R）转导作用增强,以及曲妥珠单抗与Her-2的亲和力下降,一些患者会对曲妥珠单抗的抗Her-2治疗产生原发性耐药或获得性耐药。研究显示,HER-2阳性乳腺癌患者即使在曲妥珠单抗治疗进展后,继续使用曲妥珠单抗,并与化疗药物联合或更换靶向药物或采用双靶向治疗,仍可以进一步改善预后。     

HER2阳性乳腺癌治疗模式的进展和优化

随着抗人表皮生长因子受体2（human epidermalgrowth factor receptor 2 ,HER2）抗肿瘤药物的不断出现及广泛应用,HER2 阳性乳腺癌患者的治疗以及预后得到了显著的改善。PEONY 研究结果的发布再次奠定了帕妥珠单抗+曲妥珠单抗的双靶治疗模式在新辅助治疗领域中的地位;结合TRYPHAENA 和TRAIN-2 两项研究,紫杉类+铂类应该是抗HER2 双靶治疗的首选化疗方案,疗程宜6 个周期。结合中国乳腺癌新辅助治疗专家共识和辅助APT 研究的最新随访结果,新辅助治疗适用人群为肿瘤直径超过3 cm 和/或淋巴结阳性的患者,新辅助治疗后如果没有获得pCR,T-DM1 应该是辅助治疗的首选模式,帕妥珠单抗+曲妥珠单抗的双靶辅助模式期待PEONY 研究的后续生存随访;对于没有淋巴结转移的小肿瘤（≤3 cm）低危患者可以考虑免除新辅助治疗,采取直接手术+术后给予曲妥珠单抗联合单药紫杉醇的辅助治疗模式。曲妥珠单抗+帕妥珠单抗联合紫杉类药物依然是晚期HER2 阳性患者的标准一线治疗;对于中国患者而言,吡咯替尼联合卡培他滨可以作为二线的优选;T-DM1 可以作为三线及后线选择;曲妥珠单抗、帕妥珠单抗、T-DM1 治疗失败的情况下,DS-8201 成为新的选择模式;伴有脑转移的HER2 阳性晚期乳腺癌患者则可以考虑图卡替尼与曲妥珠单抗和卡培他滨的联合治疗模式。     

靶向HER-2受体二聚化的新药——帕妥珠单抗研究进展

帕妥珠单抗（pertuzumab）系新一代人源化单克隆抗体类药物,通过与HER-2胞外受体结构域Ⅱ区的结合,特异性地抑制HER-2受体二聚化。实验研究表明,帕妥珠单抗联合曲妥珠单抗能够更全面地阻断HER-2的信号转导。2012年6月FDA批准帕妥珠单抗用于联合曲妥珠单抗和多西他赛治疗HER-2阳性的转移性乳腺癌,2013年9月30日FDA进一步加速批准该方案作为新辅助治疗用于高风险HER-2阳性的早期乳腺癌。本文全面回顾了帕妥珠单抗的研究进展,并重点介绍该药的临床试验情况,以期为帕妥珠单抗的临床实践应用提供相关的参考依据。     

Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.     

Randomized phase II study of weekly docetaxel plus trastuzumab versus weekly paclitaxel plus trastuzumab in patients with previously untreated advanced nonsmall cell lung carcinoma

BACKGROUND: Trastuzumab is a monoclonal antibody directed against the human epidermal growth factor receptor-2 (HER-2). Nonsmall cell lung carcinoma (NSCLC) overexpresses HER-2 protein in approximately 20% of cases. In the current study, the authors combined trastuzumab with weekly taxanes in an attempt to improve outcomes over standard chemotherapy in patients with advanced NSCLC. METHODS: The primary objective was to determine whether docetaxel plus trastuzumab or paclitaxel plus trastuzumab was the superior regimen based on response and toxicity, and to determine whether either regimen was appropriate for further testing in a randomized Phase III trial. After stratification based on the results of HER-2 immunohistochemistry, chemotherapy-naive patients were randomized to receive trastuzumab plus docetaxel or trastuzumab plus paclitaxel. The study was designed so patients with or without HER-2 overexpression would be distributed equally between the study arms. RESULTS: Immunohistochemistry for HER-2 protein expression was attempted for 182 pathologic samples from 169 patients. Twenty-eight of the 179 evaluable samples (16%) revealed 2+ or 3+ staining. The objective response rate was 23% (7 of 30 patients) in the patients treated with docetaxel plus trastuzumab and 32% (11 of 34 patients) in the patients treated with paclitaxel plus trastuzumab (P=0.76, Wilcoxon test). No difference was noted in the median survival (16 mos vs. 14 mos) or 1-year survival (57% vs. 55%) (P=0.998). Toxicities were mild in both treatment arms. No difference with regard to response rates or survival was noted between HER-2-positive (2+ or 3+) and HER-2-negative (0-1+) patients. CONCLUSIONS: The expression of HER-2 protein in patients with advanced NSCLC in this study was found to be similar to that reported in previous series. The response rates and toxicities for patients treated with docetaxel and trasuzumab or paclitaxel and trasuzumab were not significantly different, though survival in both arms was better than expected. HER-2 expression status did not appear to affect outcomes for this uniform group of patients who were treated in a comparable fashion. Because of the infrequency of HER-2 overexpression, and the absence of improved outcomes in patients with NSCLC who were treated with trastuzumab plus chemotherapy in other studies, neither regimen tested will be advanced to a Phase III trial.     

Pre-operative systemic (neo-adjuvant) therapy with trastuzumab and docetaxel for HER2-overexpressing stage II or III breast cancer: results of a multicenter phase II trial.

BACKGROUND: Trastuzumab plus chemotherapy has become the standard of care for women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Trastuzumab-based pre-operative systemic (neo-adjuvant) therapy (PST) also appears promising, warranting further investigation. PATIENTS AND METHODS: Patients with HER2-positive, stage II/III non-inflammatory, operable breast cancer requiring a mastectomy (but who wished to conserve the breast) received weekly trastuzumab and 3-weekly docetaxel for six cycles before surgery. The primary end point was pathological complete response (pCR) rate, determined from surgical specimens. RESULTS: Thirty-three patients were enrolled. The majority (79%) had T2 tumors, with 42% being N1/2. Twenty-nine patients completed six cycles of therapy and one patient withdrew prematurely due to progressive disease. A complete or partial objective clinical response was seen in 96% (73% and 23%, respectively) of patients. Surgery was performed in 30 patients, breast conserving in 23 (77%). In an intention-to-treat analysis, tumor and nodal pCR was seen in 14 (47%) patients. Treatment was generally well tolerated. Grade 3/4 neutropenia occurred in 85% of patients while febrile neutropenia was encountered in 18%. Only three patients withdrew prematurely due to toxicity. No symptomatic cardiac dysfunction was reported. CONCLUSIONS: PST with trastuzumab plus docetaxel achieved promising efficacy, with a high pCR rate and good tolerability, in women with stage II or III HER2-positive breast cancer.     

TCH与TAC新辅助化疗在HER-2过表达乳腺癌中的疗效观察

  目的  观察TCH与TAC新辅助化疗方案在HER-2过表达乳腺癌的临床疗效。  方法  收集深圳市第二人民医院甲乳外科自2008年5月至2012年9月收治的64例HER-2过表达的乳腺癌患者,随机分为两组:TCH组39例,采用曲妥珠单抗联合多西他赛及卡铂治疗方案;TAC组25例,采用多西他赛、表阿霉素及环磷酰胺治疗方案。新辅助化疗6个周期后进行疗效对比。  结果  TCH与TAC两组患者总有效率（OR）分别为94.9%（37/39）和72.0%（18/25）,差异有统计学意义（P < 0.05）;病理完全缓解率（pCR）分别为69.2%（27/39）和32.0%（8/25）,差异有统计学意义（P < 0.05）;两组患者在心功能障碍、骨髓抑制及肝功能损害等不良反应方面疗效均无显著性差异。  结论  在HER-2过表达乳腺癌的新辅助化疗中,多西他赛及卡铂联合曲妥珠单抗疗效良好,病理完全缓解率高。      

Advances in first-line treatment for patients with HER-2+ metastatic breast cancer

Background.

The prognosis for breast cancer patients overexpressing human epidermal growth factor receptor (HER)-2 has changed with anti–HER-2–targeted therapy. Although anti–HER-2 therapy with trastuzumab and chemotherapy is the standard first-line treatment, the best therapeutic regimen has yet to be defined, and new strategies are evolving.

Methods.

A literature review of well-established and recently published trials, reviews, and ongoing clinical trials addressing first-line treatment for HER-2⁺ metastatic breast cancer patients was performed.

Results.

Taxanes are the agents most commonly used in combination with trastuzumab, but other chemotherapy drugs, such as anthracyclines, vinorelbine, and gemcitabine and triple-combination therapies including platinum compounds, capecitabine, and taxanes have been studied. The combination of aromatase inhibitors with anti–HER-2 therapies is a new therapeutic option for some patients who coexpress HER-2 and hormone receptors, although its activity observed in randomized clinical trials seems to be inferior to that of chemotherapy plus anti–HER-2 therapies. In addition, new anti–HER-2 therapies have shown activity in HER-2⁺ tumors, both alone and in combination with trastuzumab.

Conclusions.

Trastuzumab plus chemotherapy is the current standard of care for the upfront treatment of HER-2⁺ breast cancer patients, though other anti–HER-2–targeting agents may appear as new standards in the upcoming years.     

HER-2-targeted therapy: lessons learned and future directions.

HER-2 is overexpressed in 20-25% of invasive breast cancers and is associated with an aggressive tumor phenotype and reduced survival rates. The HER-2 status of a tumor is the critical determinant of response to the HER-2-targeted antibody trastuzumab. Thus, accurate assessment of HER-2 expression levels is essential for identifying breast cancer patients who will benefit from HER-2-targeted therapy. Trastuzumab combined with chemotherapy increases response rates, time to progression, and survival. However, the majority of cancers that initially respond to trastuzumab begin to progress again within 1 year. This minireview describes HER-2 targeting strategies currently in use or in stages of development for the treatment of breast cancer.     

Trastuzumab in gastric cancer

Trastuzumab is a fully humanised monoclonal antibody directed at the human epidermal growth factor receptor-2 (HER-2) which has been a component of standard therapy for advanced and resected HER-2-positive breast cancers for almost a decade.HER-2 over-expression, defined as HER-2 protein over-expression using immunohistochemistry scored as 3+ and/or erbB-2 amplification detected by fluorescent in situ hybridisation, was detected in 22.1% of 3807 patients with advanced gastric and oesophagogastric junction (OGJ) adenocarcinoma screened for eligibility for the phase III ToGA study. The validated scoring system for HER-2 positivity in gastric cancers differs from that recommended for breast cancer due to an increased frequency of incomplete membranous immunoreactivity and heterogeneity of HER-2 expression in gastric cancers. The highest rates of HER-2 over-expression are observed in patients with OGJ rather than gastric tumours and intestinal-type rather than diffuse or mixed histology.The international multicentre randomised phase III ToGA study assessed the addition of trastuzumab to a cisplatin plus fluoropyrimidine (FP) chemotherapy doublet for patients with HER-2-positive advanced gastric or OGJ adenocarcinoma. The investigators reported a clinically and statistically significant benefit in terms of response rate (47.3% versus 34.5%, p = 0.0017), median progression-free survival (6.7 versus 5.5 months, p = 0.0002) and median overall survival (13.8 versus 11.1 months, p = 0.0046). Trastuzumab plus FP chemotherapy is now the standard of care for patients with advanced gastric and OGJ cancers which over-express HER-2.Further research to evaluate trastuzumab delivered beyond progression, in combination with alternative first-line chemotherapy regimens, and in the perioperative and adjuvant setting is urgently needed. Additionally, research into mechanisms of resistance and strategies to overcome primary or acquired resistance to trastuzumab must now be expedited, using lessons learnt over the past decade in HER-2-positive breast cancer to maximise the benefit from this agent.     

Response and Long-Term Effect of Patients with Triple-Negative Breast Cancer Receiving Neo-Adjuvant Anthracycline-Based

OBJECTIVE The breast cancer lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) is defined as the Triple-negative breast cancer (TNBC). Our purpose is to compare the response and long-term effect of the TNBC and non-TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy, and to investigate the mechanisms of TNBC affecting the survivals. METHODS Data of long-term follow-up (median, 5.4 years) of 326 patients who received neo-adjuvant chemotherapy with anthracycline-based regimen, during a period from 2000 to 2003, were analyzed. Expressions of ER, PR, HER-2, P53, Ki-67 and E-cadherin were determined using immunohistochemical staining method. A multivariate Cox regression analysis was used to analyze independent prognostic factors affecting the relapse-free survival (RFS) and overall survival (OS) rates. Clinical effects of the neo-adjuvant anthracycline-based chemotherapeutic regimen and the RFS and OS rates were compared between the patients with TNBC and non-TNBC, and the correlations among the triple- negative phenotype (TNP), tumor grading and the expressions of P53, Ki-67 and E-cadherins were analyzed. RESULTS TNP, TNM staging, histological grades, clinical response of the neo-adjuvant chemotherapy and pathological complete remission (pCR) rate were the independent prognostic factors affecting the survival rates. Furthermore, 70 (21.5%) of the 326 patients suffered TNBC. Compared with the subjects in non- TNBC group, the patients with TNBC had a significantly higher pCR rate (P=0.046) and clinical response rate (P＝0.037), but also decreased 5-year RFS (P=0.001) and OS (P=0.004) rates. The RFS and OS rates were not improved in the TNBC patients who achieved a clinical remission after the neo-adjuvant chemotherapy. The triple-negative phenotype was positively correlated with the level of P53, Ki-67 expression (P＝0.007, P＝0.028), but negatively correlated with level of E-cadherin (P＝0.034).CONCLUSION Both clinical remission rate and pCR rate of the TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy are high, however, the long-term effect is poor.The mechanism may relate to a strong potential of proliferation and invasive metastasis, as well as lack of an effective therapeutic target in the TNBC patients.     

What is the current standard of care for anti-HER2 neoadjuvant therapy in breast cancer?

Neoadjuvant treatment with a sequential anthracycline-taxane-based chemotherapy in combination with trastuzumab (Herceptin) is currently a preferred therapy for patients with HER2-positive breast cancer. This approach is based on the higher pathologic complete response (pCR) of 40% seen with the addition of trastuzumab, compared with a 17% pCR with chemotherapy alone. The pCR can be increased to 75% with dual HER2-receptor blockade and chemotherapy. Higher pCR rates are found in hormone-receptor-negative tumors. Patients with a pCR after chemotherapy and trastuzumab showed a significantly better outcome compared with those who did not have a pCR. The need for additional or alternate treatment options is great in patients who do not achieve a pCR. Addition of lapatinib (Tykerb) or pertuzumab (Omnitarg) to trastuzumab is a therapeutic option. Recent findings suggest pCR might not be the appropriate surrogate for long-term outcome in patients with hormone receptor-positive and HER2-positive tumors.     

Efficacy of Neoadjuvant Single or Dual Anti-HER-2 Therapy Combined with Chemotherapy in Patients with HER-2-Positive Breast Cancer: A Single-Center Retrospective Study

Background: Studies have shown that neoadjuvant anti-HER-2 therapy and chemotherapy can increase pathologic complete response (pCR) rate in HER-2-positive breast cancer patients and improve prognosis. However, data from Chinese patients are limited. Therefore, we conducted a single-center retrospective study to evaluate the effects of neoadjuvant single or dual anti-HER-2 therapy and chemotherapy in Chinese HER-2-positive breast cancer patients and to explore the prognostic indicators of pCR and progression-free survival (PFS). Methods: We included patients with HER-2-positive breast cancer treated with neoadjuvant anti-HER-2 therapy and chemotherapy at the First Affiliated Hospital of Chongqing Medical University in China from January 2016 to July 2020. We analyzed the relationship between patient characteristics and the pCR rate or PFS. Results: Forty-seven patients with HER-2-positive breast cancer receiving neoadjuvant anti-HER-2 therapy and chemotherapy were included. Univariate analysis suggested that compared with patients receiving neoadjuvant single anti-HER-2 therapy, patients receiving neoadjuvant dual anti-HER-2 therapy tended to have a higher pCR rate and better PFS. Patients who achieved pCR also tended to have longer PFS. Multivariate analysis indicated that patients with greater systemic inflammation response index (SIRI) reduction (>0.54) during neoadjuvant treatment (NAT) and patients with a lower T stage were more likely to achieve pCR. Patients aged ≤60 years with lower Ki-67 had longer PFS. Conclusion: Greater SIRI reduction during NAT was an independent influencing factor for pCR. Patients receiving neoadjuvant dual anti-HER-2 therapy and chemotherapy tended to have higher pCR rates and longer PFS. Patients who achieved pCR also tended to have longer PFS.