Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer:A Single-Institution Study

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC.Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups.Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszelχ^(2)test,P<0.001,Pearson’s R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%.Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer

Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.

Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity

Genetic information is transcribed from genomic DNA to mRNA,which is then translated into threedimensional proteins.mRNAs can undergo various post-transcriptional modifications,including RNA editing that alters mRNA sequences,ultimately affecting protein function.In this study,RNA editing was identified at the 499th base(c.499)of human vaccinia-related kinase 2(VRK2).This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine(with adenine base)to valine(with guanine base).Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2,which leads to an increase in tumor cell proliferation.Earlier we reported that VRK2 directly interacts with dystrobrevin-binding protein(dysbindin)and results in reducing its stability.Herein,we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valinecontaining VRK2.Dysbindin interacts with cyclin D and thereby regulates its expression and function.The reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression,resulting in increased tumor growth and reduction in survival rates.It has also been observed that in patient samples,VRK2 level was elevated in breast cancer tissue compared to normal breast tissue.Additionally,the isoleucine form of VRK2 exhibited a greater increase in breast cancer tissue.Therefore,it is concluded that VRK2,especially dependent on the 167th variant amino acid,can be one of the indexes of tumor progression and proliferation.

Dysregulated microRNAs in type 2 diabetes and breast cancer:Potential associated molecular mechanisms

Type 2 diabetes(T2D)is a multifaceted and heterogeneous syndrome associated with complications such as hypertension,coronary artery disease,and notably,breast cancer(BC).The connection between T2D and BC is established through processes that involve insulin resistance,inflammation and other factors.Despite this comprehension the specific cellular and molecular mechanisms linking T2D to BC,especially through microRNAs(miRNAs),remain elusive.miRNAs are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological processes.However,the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been elucidated.This review aims to identify dysregulated miRNAs in both T2D and BC,exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.

Downregulation of the circadian clock gene period 2 aggravates prognosis in breast cancer patients with obesity

Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.

Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer

BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.

Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer

The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.

双靶向新辅助药物联合不同化疗治疗HER-2阳性乳腺癌临床疗效比较

目的探讨双靶向新辅助药物联合不同化学药物治疗(简称化疗)的方案治疗人类表皮生长因子受体-2(HER-2)阳性乳腺癌的临床疗效。方法选取凉山彝族自治州第一人民医院2019年1月至2022年12月收治的HER-2阳性乳腺癌患者110例,按治疗方案的不同分为TcbHP组和AC-THP组,各55例。TcbHP组患者予曲妥珠单抗和帕妥珠单抗联合紫杉类(多西他赛或紫杉醇)和卡铂治疗,以21 d为1个周期,共治疗6个周期;AC-THP组患者予曲妥珠单抗和帕妥珠单抗联合蒽环类药物(吡柔比星或表柔比星)和环磷酰胺治疗,以21 d为1个周期,曲妥珠单抗和帕妥珠单抗及其他药物分别治疗4个周期,共8个周期。结果TcbHP组患者病理完全缓解率为61.80%,稍高于AC-THP组的50.90%(P>0.05)。治疗后,TcbHP组恶心,呕吐,腹泻,心脏毒性及手足综合征程度均显著低于AC-THP组(P<0.05);各肿瘤标志物[糖类抗原(CA19-9,CA125,CA153),癌胚抗原(CEA)]水平均显著低于AC-THP组(P<0.05);左心室射血分数(LVEF)及血清心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶MB(CK-MB)、氨基末端脑钠肽前体(NT-proBNP)水平均无明显变化(P>0.05),且均显著优于AC-THP组(P<0.05)。结论TcbHP方案治疗HER-2阳性乳腺癌的疗效与AC-THP方案相当,但前者降低肿瘤标志物生成的作用更明显,且心脏毒性风险相对更低。

伊尼妥单抗治疗人表皮生长因子受体2阳性转移性乳腺癌伴胃肠功能紊乱1例

乳腺癌是女性常见的肿瘤,如今乳腺癌实体肿瘤通过相应的治疗可取得较好的疗效,但人表皮生长因子受体2(HER2)阳性乳腺癌侵袭性较强、恶性程度高,需引起患者及医务人员的重视。本文回顾性分析1例激素受体阴性、HER2阳性伴胃肠功能紊乱的乳腺癌患者诊治经过。患者初诊为局部晚期炎症乳腺癌伴腋窝淋巴结转移,给予新辅助化疗及手术治疗。术后3年后病情进展,予以伊尼妥单抗联合白蛋白紫杉醇,后续伊尼妥单抗单独靶向治疗,病情持续缓解。提示对于HER2阳性晚期乳腺癌,伊尼妥单抗是个很好的单抗类药物选择。

3D-STI参数评价抗HER-2药物对乳腺癌患者心室功能变化的价值

目的 探讨三维斑点追踪成像(Three Dimensional Speckle Tracking Imaging,3D-STI)参数评价抗人表皮生长因子受体-2(Human Epidermal Growth Factor Receptor-2,HER-2)药物对乳腺癌患者心室功能变化的价值。方法 选取我院2021年6月至2022年6月收治的50例需行辅助化疗乳腺癌患者作为观察组,选择同期30名健康志愿者作为对照组。比较对照组与观察组化疗前,化疗第2、4、6周期常规超声心动图指标与3D-STI参数,以临床病理诊断为“金标准”,并绘制3D-STI参数受试者工作特征(Receiver Operating Characteristic,ROC)曲线。结果 观察组化疗第6周期E/A值低于对照组和化疗前(P<0.05),观察组化疗第2、4、6周期左心室扭转、心肌综合指数值低于对照组和化疗前(P<0.05),观察组化疗第4、6周期整体纵向应变(GlobalLongitudinalStrain,GLS)低于对照组和化疗前(P<0.05);ROC曲线显示GLS敏感度最高,为96.00%,整体圆周应变特异性最高,为96.67%。结论 3D-STI参数可评估乳腺癌患者抗HER-2药物化疗后心室功能变化,为临床早期干预提供诊断依据。

MRI影像组学模型预测乳腺癌组织中HER-2低表达状态的价值

目的:探讨使用基于动态增强磁共振成像(dynamic contrast-enhanced magnetic resonance imaging,DCE-MRI)影像组学模型早期预测乳腺癌患者人表皮生长因子受体2(human epithelial growth factor receptor 2,HER-2)低表达的可能性及其价值。方法:收集294例经穿刺或手术病理证实的乳腺浸润性导管癌女性乳腺癌患者的临床及病理资料,对MRI图像原始数据进行瘤内感兴趣区(regions of interest,ROI)勾画及特征提取,经Mann-Whitney U筛选出相关性的特征,LASSO回归进行特征选择,使用10折交叉验证建模,受试者工作特征曲线(receiver operator curve,ROC)分析模型对模型的性能进行评价。结果:经10折交叉验证Linear SVC建模后,所得验证集的平均准确性为79.6%,敏感性为73.7%,特异性为85.6%,ROC分析平均AUC为0.87;经过1000次置换检验后的置换数据集的诊断效能与原数据集相比较,平均准确性、敏感性和特异性的P值均小于0.05,差异有统计学意义,经交叉验证后建立的模型可以对乳腺癌患者HER-2阳性和HER-2低表达进行分类,并且其模型的分类效能高于机会水平。结论:DCE-MRI影像组学模型可以帮助预测乳腺癌组织中HER-2受体低表达状态,具有较好的预测效能,这将为临床进行无创HER-2状态的诊断提供新的思路。

THP方案新辅助治疗HER-2阳性乳腺癌的真实世界研究

目的 了解THP方案在真实世界临床实践的应用状况,同时评价该方案的疗效、安全性和耐受性。方法 选择在保定市第一中心医院等河北省11家三级甲等医院接受THP方案新辅助治疗并完成序贯手术的HER-2阳性乳腺癌患者70例为研究对象,制订专用的患者资料信息收集表,专人负责收集符合纳入标准患者的临床病理资料。评估THP方案的有效性、安全性和耐受性。主要研究终点为病理完全缓解(pCR)率、≥3级不良反应的发生率、既定治疗方案完成率。结果 总人群pCR率为54.3%。亚组分析显示,cTNMⅠ-Ⅱ期、激素受体阴性、HER-2 IHC3+患者的pCR率分别显示出高于c TNMⅢ期、激素受体阳性、HER-2 IHC2+/FISH+患者的趋势,但差异无统计学意义(P>0.05)。4周期患者的pCR率显著高于4周期以上患者(P<0.05)。≥3级不良反应发生率为4.3%。既定方案完成率为98.6%。结论THP方案在河北省得到广泛应用,是HER-2阳性乳腺癌患者新辅助治疗的有效方案,安全性及耐受性良好,可以考虑作为激素受体阴性、肿瘤负荷较小、对联合化疗耐受性差患者的新辅助备选方案。

乳腺癌组织lncRNA CASC2、miR-532-3p表达水平与患者术后5年内生存的相关性

目的探究乳腺癌(BC)组织长链非编码RNA癌易感性候选基因2(lncRNA CASC2)、微小RNA-532-3p(miR-532-3p)表达与患者术后5年内生存的相关性。方法选择2015年1月—2018年6月大同市第五人民医院普通外科收治BC患者127例,术中收集BC组织及癌旁正常组织,荧光定量PCR法检测BC组织和癌旁正常组织中lncRNA CASC2、miR-532-3p表达;对BC患者术后进行为期5年的随访,记录患者5年内生存和死亡情况。比较癌旁正常组织和BC组织lncRNA CASC2及miR-532-3p表达,BC组织中lncRNA CASC2和miR-532-3p表达在不同临床病理特征中的差异,生存组和死亡组临床病理特征和BC组织中lncRNA CASC2及miR-532-3p表达的差异。分析BC组织lncRNA CASC2、miR-532-3p表达的相关性;BC组织中lncRNA CASC2和miR-532-3p表达与术后5年内生存的关系;影响BC患者术后5年内生存的因素;lncRNA CASC2、miR-532-3p对BC患者术后5年内生存的预测价值。结果BC组织中lncRNA CASC2表达水平低于癌旁正常组织,miR-532-3p表达水平高于癌旁正常组织(t/P=38.239/<0.001,49.406/<0.001);肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、淋巴结转移者比例lncRNA CASC2低表达组高于高表达组,而miR-532-3p低表达组低于高表达组(lncRNA CASC2:χ^(2)/P=17.361/<0.001、17.052/<0.001、14.694/<0.001、13.173/<0.001;miR-532-3p:χ^(2)/P=10.733/0.001、9.813/0.002、10.134/0.001、7.444/0.006);127例BC患者术后随访5年,生存99例(生存组),死亡28例(死亡组),肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、淋巴结转移者比例及miR-532-3p表达水平死亡组高于生存组,而lncRNA CASC2表达水平死亡组低于生存组[χ^(2)(t)/P=5.211/0.022、27.149/<0.001、27.990/<0.001、4.590/0.032、19.155/<0.001、10.818/<0.001];BC组织中lncRNA CASC2与miR-532-3p表达呈负相关(r/P=-0.561/<0.001);lncRNA CASC2高表达组BC患者术后5年内总生存率为89.23%(58/65),高于lncRNA CASC2低表达组66.13%(41/62)(χ^(2)/P=9.854/0.002);miR-532-3p高表达组BC患者术后5年内总生存率为65.57%(40/61),低于miR-532-3p低表达组89.39%(59/66)(χ^(2)/P=10.466/0.001);肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、有淋巴结转移、lncRNA CASC2低表达、miR-532-3p高表达均是影响BC患者术后5年内生存的独立危险因素[HR(95%CI)=2.255(1.192~4.263)、2.143(1.252~3.666)、3.089(1.386~6.887)、2.219(1.223~4.026)、2.606(1.174~5.788)、2.855(1.592~5.120)];lncRNA CASC2、miR-532-3p及二者联合预测BC患者术后5年内生存的AUC分别为0.840、0.852、0.908,二者联合预测的AUC大于lncRNA CASC2、miR-532-3p各自单独预测的AUC(Z/P=2.246/0.025、2.033/0.042)。结论BC组织中lncRNA CASC2表达下调,miR-532-3p表达上调,且术后5年内死亡的BC患者较存活患者变化更显著,二者表达与临床病理特征相关,对预测BC患者术后5年内生存情况价值较高。

曲妥珠单抗联合化疗致人表皮生长因子受体2阳性乳腺癌患者心脏毒性的影响因素分析

目的:探讨曲妥珠单抗联合化疗致人表皮生长因子受体2(Human Epidermal Growth Factor Receptor-2,HER-2)阳性乳腺癌患者心脏毒性的影响因素。方法:选取2020年12月-2022年12月徐州市中心医院诊治的152例HER-2阳性乳腺癌患者为研究对象。所有患者均采用曲妥珠单抗联合化疗(AC→PH)方案治疗,治疗期间每3个月使用超声监测心功能,统计心脏毒性发生情况。收集患者的临床资料,包括年龄、体质量指数、肿瘤分期、合并症(高血压病、糖尿病、高脂血症)、雌激素受体(Estrogen Receptor,ER)/孕激素受体(Progesterone Receptor,PR)的表达情况、吸烟史、饮酒史、同期行放疗及右丙亚胺使用情况,采用单因素分析、多因素Logistic回归分析患者发生心脏毒性的危险因素。结果:152例患者中心脏毒性发生率为26.31%,发生心脏毒性的患者常见的心电图改变有:T波改变、窦性心率过缓/过速、ST段异常等。单因素分析显示,年龄≥60岁、合并高血压病、合并高脂血症、同期行放疗、联合使用右丙亚胺是发生心脏毒性的影响因素(P <0.05)。多因素Logistic回归分析显示,年龄[95%置信区间(CI):2.429~5.135]、合并高血压病(95%CI:1.625~3.962)、合并高脂血症(95%CI:2.054~5.362)、同期行放疗(95%CI:1.759~4.637)是曲妥珠单抗联合化疗致HER-2阳性乳腺癌患者心脏毒性的危险因素(P<0.05),而联合使用右丙亚胺(95%CI:3.772~6.015)可显著减少心脏毒性的发生(P <0.05)。结论:年龄≥60岁、合并高血压病/高脂血症、同期行放疗是曲妥珠单抗联合化疗致HER-2阳性乳腺癌患者心脏毒性发生的危险因素,使用右丙亚胺是HER-2阳性乳腺癌患者发生心脏毒性的保护因素;化疗期间应将年龄≥60岁、合并高血压病和高脂血症、同期行放疗的患者列为心脏毒性的重点防治人群,联合应用右丙亚胺有助于减少心脏毒性发生。

乳腺癌患者HER2、CA153表达与声触诊组织成像定量技术参数的相关性分析

目的:分析乳腺癌患者人表皮生长因子受体2(HER2)、糖类抗原153(CA153)表达与声触诊组织成像定量(VTIQ)技术参数的相关性。方法:选取2018年5月至2020年5月合肥市第三人民医院收治的80例女性乳腺癌患者,其中世界卫生组织(WHO)分期Ⅰ期14例、Ⅱ期22例、Ⅲ期31例、Ⅳ期13例;另选取同时间段收治的53例女性乳腺良性疾病患者为对照。所有患者先行常规超声检查,随后进入超声VTIQ成像模式获得剪切波速度(SWV)均值参数;采用免疫组织化学法检测乳腺组织中HER2表达,采用罗氏E411电化学发光免疫分析仪检测血清CA153水平;采用Pearson法分析乳腺癌患者血清CA153水平与SWV均值的相关性。结果:与良性患者比较,乳腺癌患者VTIQ技术参数SWV均值、血清CA153水平及HRR2阳性表达率均显著升高,差异有统计学意义(F=39.107,78.353,P<0.05);与乳腺癌Ⅰ+Ⅱ期患者比较,乳腺癌Ⅲ、Ⅳ期患者VTIQ技术参数SWV均值、血清CA153水平、HRR2阳性表达率均显著升高,差异有统计学意义(t=2.685、3.556、8.326、10.455,P<0.05);与乳腺癌Ⅲ期比较,乳腺癌Ⅳ期患者VTIQ技术参数SWV均值、血清CA153水平、HRR2阳性表达率均显著升高,差异有统计学意义(t=4.632、8.659,P<0.05)。与HER2阴性表达乳腺癌患者SWV均值比较,HER2阳性表达乳腺癌患者SWV均值升高,差异有统计学意义(χ^(2)=59.751,P<0.05)。乳腺癌患者血清CA153水平与SWV均值呈正相关(r=0.501,P<0.05)。结论:乳腺癌患者VTIQ参数SWV均值与乳腺癌患者生物标志物HER2、CA153表达水平密切相关。