Effect of GnRH analogs in advanced male breast cancer:10-year experience from the Henan Breast Cancer Center and literature review

To the Editor:Male breast cancer is relatively rare,accounting for just 1%of all breast cancer cases.[1]The management strategies for male breast cancer are mainly based on a limited number of retrospective studies and speculation based on female breast cancer.This study presents a comprehensive account of a decade-long observation of male metastatic breast cancer(mMBC)in our institution.The Affiliated Cancer Hospital of Zhengzhou University database had records of 2853 advanced breast cancer cases that were treated from January 1,2010 to December 31,2019.Out of the total number,18 cases were identified as mMBC.The analysis encompassed data about the treatment administered,the treatment’s effectiveness,and the patient’s survival outcomes.The present investigation entails a retrospective examination of our institution’s 10-year experience with patients diagnosed with mMBC and a comprehensive evaluation of relevant literature.

Advances in regional nodal management of early-stage breast cancer

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node(SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment(systemic/radiotherapy) that may result from deescalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging nodepositive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy(SLNB), the regional nodal management of breast cancer should adhere to the concept of “updating ideas, making bold assumptions, and carefully seeking proof”, make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the “net benefit” of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

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.

Maintenance treatment of trastuzumab for patients with advanced breast cancer to achieve long term survival: two case reports and literature review

Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. The epidermal growth factor receptor （HER2） overexpressing breast cancers are designated as HER2-postive （HER2＋） breast cancer and carry a particularly unfavorable prognosis. We present two cases of HER2-postive metastatic breast cancer （MBC） who are found to be a challenge to treat, especially due to the occurrence of brain metastasis. Trastuzumab-based therapy improves clinical outcomes, even if the patient has undergone multi-line treatment. These case reports also emphasize the importance of retesting HER2 status because it can be discordance in receptor status between primary and recurrent breast cancer.

Current Status of Diagnosis And Treatment of Primary Breast Cancerin Beijing,2008

Objective：To investigate the status of diagnosis and treatment of primary breast cancer in Beijing,2008.Methods：All the patients who were diagnosed as primary breast cancer in Beijing in 2008 were enrolled in this study.Information of these patients,including the features of tumors,clinical diagnosis and treatment was collected,and filled in the well-designed questionnaire forms by trained surveyors.The missing data were partly complemented through telephone interviews.Results：A total of 3473 Beijing citizens were diagnosed as primary breast cancer（25 patients with synchronal bilateral breast cancer） in Beijing,2008.Of them 82.09% were symptomatic.19.02% and 34.11% were diagnosed using fine needle aspiration biopsy（FNAB） and core needle biopsy（CNB）,respectively.15.92% received sentinel lymph node biopsy（SLNB） and 24.27% received breast conserving surgery（BCS）.Among 476 cases with Her-2 positive,only 96 received anti-Her-2 therapy.We found that the standardization level varied in hospitals of different grades,with higher level in Grade-III hospitals.Of note,some breast cancer patients received non-standard primary tumor therapy：65.63% of the patients with ductal carcinoma in situ（DCIS） received axillary lymph node dissection and 36.88% received chemotherapy;25.89% of the patients underwent breast conserving surgery without margin status;12.10% of the patients received chemotherapy less than 4 cycles.Conclusion：Although most breast cancer patients received basic medical care,the mode of diagnosis and treatment should be improved and should be standardized in the future in Beijing.

Sentinel lymph node metastasis after neoadjuvant treatment in breast cancer:Any size matters?

One of the advantages of neoadjuvant chemotherapy(NAC) treatments is its ability to convert patients who need a mastectomy in breast conservative surgery. NAC has also increased the conversion of node positive patients into node negative in around 40% allowing the use of sentinel node biopsy(SLN) in this setting. Timing of SLN biopsy after NAC has been a subject of debate. In patients with clinically node negative before NAC,rates of success and false negative rates of SLN after NAC are similar to those in the adjuvant setting,so SLN after NAC in previous negative axilla has been incorporated in the staging of the axilla. More controversial is its use in patients with positive axillary nodes before NAC who convert to node negative after NAC. Several randomized studies have reported the identification rates and the false negative rates of the SLN after NAC,concordant in the importance of surgical technique. As there is an agreement in the abandon of the immunohistochemistry(IHC) for SLN in the adjuvant setting as SLN IHC detected metastasis appear to have no impact on overall survival,in patients with SLN after NAC the inclusion of isolated tumor cell(ITC) as positive nodes lowers the false negative rates of the technique,suggesting the importance of assessing the SLN by IHC after NAC and considering it as residual disease. Longer follow up is needed to determine the prognostic implications of ITC in the SLN after NAC.

Value of pre-treatment biomarkers in prediction of response to neoadjuvant endocrine therapy for hormone receptor-positive postmenopausal breast cancer

Objective： To determine the predictive ability of biomarkers for responses to neoadjuvant endocrine therapy （NET） in postmenopausal breast cancer. Methods： Consecutive 160 postmenopausal women with T 1-3 N 0-1 M 0 hormone receptor （HR）-positive invasive breast cancer were treated with anastrozole for 16 weeks before surgery. New slides of tumor specimens taken before and after treatment were conducted centrally for biomarker analysis and classified using the Applied Imaging Ariol MB-8 system. The pathological response was evaluated using the Miller ＆ Payne classification. The cell cycle response was classified according to the change in the Ki67 index after treatment. Multivariable logistic regression analysis was used to calculate the combined index of the biomarkers. Receiver operating characteristic （ROC） curves were used to determine whether parameters may predict response. Results： The correlation between the pathological and cell cycle responses was low （Spearman correlation coefficient =0.241, P〈0.001; Kappa value =0.119, P=0.032）. The cell cycle response was significantly associated with pre-treatment estrogen receptor （ER） status （P=0.001）, progesterone receptor （PgR） status （P〈0.001）, human epidermal growth factor receptor 2 （Her-2） status （P=0.050） and the Ki67 index （P〈0.001）, but the pathological response was not correlated with these factors. Pre-treatment ER levels [area under the curve （AUC） =0.634, 95% confidence interval （95% CI）, 0.534-0.735, P=0.008] and combined index of pre-treatment ER and PgR levels （AUC =0.684, 95% CI, 0.591-0.776, P〈0.001） could not predict the cell cycle response, but combined index including per-treatment ER/PR/Her-2/Ki67 expression levels could （AUC =0.830, 95% CI, 0.759-0.902, P〈0.001）. Conclusions： The combined use of pre-treatment ER/PgR/Her-2/Ki67 expression levels, instead of HR expression levels, may predict the cell cycle response to NET.

Integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of EZR in breast cancer

Distant metastasis is a major cause of increased mortality in breast cancer patients,but the mechanisms underlying breast cancer metastasis remain poorly understood.In this study,we aimed to identify a metastasis-related gene(MRG)signature for predicting progression in breast cancer.By screening using three regression analysis methods,a 9-gene signature(NOTCH1,PTP4A3,MMP13,MACC1,EZR,NEDD9,PIK3CA,F2RL1 and CCR7)was constructed based on an MRG set in the BRCA cohort from TCGA.This signature exhibited strong robustness,and its generalizability was verified in the Metabric and GEO cohorts.Of the nine MRGs,EZR is an oncogenic gene with a well-documented role in cell adhesion and cell migration,but it has rarely been investigated in breast cancer.Based on a search of different databases,EZR was found to be significantly more highly expressed in both breast cancer cells and breast cancer tissue.EZR knockdown significantly inhibited cell proliferation,invasion,chemoresistance and EMT in breast cancer.Mechanistically,RhoA activation assays confirmed that EZR knockdown inhibited the activity of RhoA,Rac1 and Cdc42.In summary,we identified a nine-MRG signature that can be used as an efficient prognostic indicator for breast cancer patients,and owing to its involvement in regulating breast cancer metastasis,EZR might serve as a therapeutic target.

A machine learning model to predict efficacy of neoadjuvant therapy in breast cancer based on dynamic changes in systemic immunity

Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly for human epidermal growth receptor 2-positive and triple-negative breast cancer.The role of peripheral immune components in predicting therapeutic responses has received limited attention.Herein we determined the relationship between dynamic changes in peripheral immune indices and therapeutic responses during NAT administration.Methods:Peripheral immune index data were collected from 134 patients before and after NAT.Logistic regression and machine learning algorithms were applied to the feature selection and model construction processes,respectively.Results:Peripheral immune status with a greater number of CD3^(+)T cells before and after NAT,and a greater number of CD8^(+)T cells,fewer CD4^(+)T cells,and fewer NK cells after NAT was significantly related to a pathological complete response(P<0.05).The post-NAT NK cell-to-pre-NAT NK cell ratio was negatively correlated with the response to NAT(HR=0.13,P=0.008).Based on the results of logistic regression,14 reliable features(P<0.05)were selected to construct the machine learning model.The random forest model exhibited the best power to predict efficacy of NAT among 10 machine learning model approaches(AUC=0.733).Conclusions:Statistically significant relationships between several specific immune indices and the efficacy of NAT were revealed.A random forest model based on dynamic changes in peripheral immune indices showed robust performance in predicting NAT efficacy.

Breast-conserving therapy and modified radical mastectomy for primary breast carcinoma:a matched comparative study

Background- To compare two types of therapy for primary breast carcinoma, breast-conserving therapy （BCT） and modified radical mastectomy （MRM）, in a matched cohort study. Methods： A series of 1,746 patients with primary breast cancer treated with BCT or MRM in a single Chinese institute between January 2000 and February 2009 were analyzed retrospectively to compare their outcomes with respect to the incidence of local recurrence （LR）, distant metastasis, and survival. The patients were matched with regard to age at diagnosis, spreading to axillary lymph nodes, hormone receptor status, the use of neoadjuvant chemotherapy and maximal tumor diameter. The match ratio was 1：1, and each arm included 873 patients. Results： The median follow-up period was 71 months. The 6-year disease-free survival （DFS） and 6-year distant disease-free survival （DDFS） rates differed significantly between two groups. The 6-year local recurrence-free survival （LRFS） rates were 98.2% [95% confidence interval （CI）： 0.973-0.989] in the BCT group and 98.7% （95% CI： 0.980-0.994） in the MRM group （P=0.182）, respectively. DFS rates in BCT and MRM groups were 91.3% （95% CI： 0.894-0.932） and 86.3% （95% CI： 0.840-0.886） （P〈0.001）, respectively, whereas the DDFS rates in BCT and MRM groups were 93.6% （95% CI： 0.922-0.950） and 87.7% （95% CI： 0.854-0.900） （P〈0.001）, respectively. Conclusions： BCT in eligible patients is as effective as MRM with respect to local tumor control, DFS and DDFS, and may result in a better outcome than MRM in Chinese primary breast cancer patients.

Tanshinone IIA Could Inhibit Pancreatic Cancer BxPC-3 Cells through Increasing PERK, ATF6, Caspase-12 and CHOP Expression to Induce Apoptosis

Tanshinone IIA (Tan-IIA) is extracted from Dan-Shen. Tan-IIA could inhibit human pancreatic cancer BxPC-3 cells through decreasing TCTP, Mcl-1 and Bcl-xl expression in vitro. Our previous study showed that Tan-IIA can inhibit hepatocellular carcinoma hep-J5 cells and human breast cancer BT-20 cells through inducing endoplasmic reticulum (ER) stress. In the present study, we investigated the ER stress related protein expressions in human pancreatic cancer BxPC3 cells were treated with Tan-IIA. The ER stress related protein expressions in human pancreatic cancer BxPC-3 cells were evaluated by western blotting. The results showed that Tan-IIA can increase the protein expressions of PERK, ATF6, Caspase-12 and CHOP, but decrease Bip, PDI, Calnexin, Calreticulin and Bcl-2 expression. These findings indicated that Tan-IIA can inhibit human pancreatic cancer BxPC-3 cells by inducing ER stress to induce apoptosis.

激素受体阳性/HER-2阴性乳腺癌新辅助内分泌治疗研究进展

激素受体阳性/HER-2阴性(hormone receptor positive/HER-2 negative,HR+/HER2-)乳腺癌化疗敏感性差,新辅助化疗并未带来明显获益。新辅助内分泌治疗(neoadjuvant endocrine therapy,NET)可以取得与新辅助化疗相似的客观缓解率和更低的毒性,成为一种有效的替代手段。同时,CDK4/6抑制剂改变了HR+/HER2-乳腺癌的治疗格局,对NET的优化选择提出了新的临床问题。在临床实践中应依据肿瘤生物学、疗效与肿瘤负荷,采用适应性研究设计,优化患者治疗策略,进行个体化、精准化治疗。本文就NET的应用价值、疗效评估及联合治疗等方面进行综述。

抗体偶联药物在晚期乳腺癌中的研究进展

抗体偶联药物(antibody-drug conjugate,ADC)在晚期乳腺癌(advanced breast cancer,ABC)的治疗中取得了突破性的进展,为这一难治性疾病带来了新的希望。通过特异性抗体与高效细胞毒性药物的偶联,ADC能够精准地杀伤肿瘤细胞,同时减少对正常组织的损伤。在HER2阳性ABC中,恩美曲妥珠单抗(trastuzumab-emtansine,T-DM1)和德曲妥珠单抗(trastuzumab deruxtecan,T-DXd)等ADC已显示出优异的疗效,显著延长了患者的生存期。此外,针对三阴性乳腺癌(triple negative breast cancer,TNBC)的ADC如戈沙妥珠单抗(sacituzumab govitecan,SG)也在临床试验中取得了积极成果。随着ADC的不断研发和优化,以及联合治疗方案的探索,ADC在ABC的治疗中有望发挥更为重要的作用。本文将对ADC在ABC中的研究进展进行综述,探讨其疗效及安全性,旨在为ABC患者提供更多的治疗选择和希望。

乳腺癌患者新辅助化疗期间认知水平与负性情绪的纵向研究

目的探讨乳腺癌患者新辅助化疗(NAC)期间认知水平与负性情绪变化轨迹并分析二者相关性。方法选取2022年8月至2023年1月重庆大学附属肿瘤医院入院的99例乳腺癌患者,采用FACT-Cog(Version 3)量表、词语流畅性测验、连线测验A型、数字广度测试、焦虑自评量表、抑郁自评量表进行纵向调查,在NAC前(TP0)、行NAC第1周期后(TP1),手术前(TP2)动态评估患者的认知水平、情绪的变化,使用Pearson相关性分析二者之间的相关性。结果乳腺癌患者在NAC期间从TP0~TP2认知水平呈下降趋势(P<0.05);TP0~TP2焦虑、抑郁水平呈先下降后上升趋势(P<0.05);Pearson相关性分析结果显示,新辅助乳腺癌患者认知水平与焦虑、抑郁在TP0时期均呈负相关(r=-0.443、-0.446);认知水平与焦虑、抑郁在TP1时期均呈负相关(r=-0.488、-0.522),认知水平与焦虑、抑郁在TP2时期均呈负相关(r=-0.580、-0.539)。结论乳腺癌患者NAC期间认知水平呈下降趋势,认知能力受负性情绪的影响。

磁控胶囊内镜在老年恶性肿瘤患者消化道检查中的可行性和安全性分析

目的探讨磁控胶囊内镜(MCCE)在老年恶性肿瘤患者消化道检查中的可行性和安全性。方法回顾性分析2019年4月-2022年9月该院消化内镜中心127例行MCCE检查患者的临床资料。根据年龄,将患者分为老年组(≥65岁,n=88)和中年组(≥40岁且<65岁,n=39),再从两组中筛选出合并恶性肿瘤的患者的临床资料,进行分析和比较。结果131例患者均接受MCCE检查,有4例老年患者因吞咽失败被排除出研究,故老年组实际纳入88例。老年组中,45.4%合并严重的心血管系统疾病(40/88),27.3%有恶性肿瘤(24/88),8.0%合并严重的呼吸系统疾病(7/88),6.8%有麻醉问题(6/88),9.1%合并神经系统疾病(8/88)。在24例老年恶性肿瘤患者中,25.0%合并严重的心血管疾病,25.0%一般状况差,20.8%合并脑转移,12.5%合并严重的呼吸功能障碍。老年组胃部P2病变的阳性诊断率(52/88,59.1%)与中年组(13/39,33.3%)比较,差异有统计学意义(P=0.013);两组溃疡阳性诊断率比较(29.5%和10.2%),差异有统计学意义(P=0.032)。在合并恶性肿瘤的患者中,两组溃疡阳性诊断率比较(45.8%和11.1%),差异有统计学意义(P=0.038)。中年组患者近端胃的清洁度和显示度评分高于老年组,差异有统计学意义(P<0.05)。结论MCCE检查在老年患者的诊疗中,尤其是合并恶性肿瘤时,未遗漏任何胃部的明显病变,总体是有效和安全的。

Entinostat,a classⅠselective histone deacetylase inhibitor,plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer:A multicenter,randomized,double-blind,placebo-controlled,phase 3 trial

Entinostat plus exemestane in hormone receptor-positive(HR+)advanced breast cancer(ABC)previously showed encouraging outcomes.This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR+ABC that relapsed/progressed after≥1 endocrine therapy.Patients were randomized(2:1)to oral exemestane 25 mg/day plus entinostat(n=235)or placebo(n=119)5 mg/week in 28-day cycles.The primary endpoint was the independent radiographic committee(IRC)-assessed progression-free survival(PFS).The median age was 52(range,28—75)years and 222(62.7%)patients were postmenopausal.CDK4/6 inhibitors and fulvestrant were previously used in 23(6.5%)and 92(26.0%)patients,respectively.The baseline characteristics were comparable between the entinostat and placebo groups.The median PFS was 6.32(95%CI,5.30—9.11)and 3.72(95%CI,1.91—5.49)months in the entinostat and placebo groups(HR,0.76;95%CI,0.58—0.98;P=0.046),respectively.Grade≥3 adverse events(AEs)occurred in 154(65.5%)patients in the entinostat group versus 23(19.3%)in the placebo group,and the most common grade≥3 treatment-related AEs were neutropenia[103(43.8%)],thrombocytopenia[20(8.5%)],and leucopenia[15(6.4%)].Entinostat plus exemestane significantly improved PFS compared with exemestane,with generally manageable toxicities in HR+ABC(ClinicalTrials.gov#NCT03538171).

Supposition of graphene stacks to estimate the contact resistance and conductivity of nanocomposites

In this study,the effects of stacked nanosheets and the surrounding interphase zone on the resistance of the contact region between nanosheets and the tunneling conductivity of samples are evaluated with developed equations superior to those previously reported.The contact resistance and nanocomposite conductivity are modeled by several influencing factors,including stack properties,interphase depth,tunneling size,and contact diameter.The developed model's accuracy is verified through numerous experimental measurements.To further validate the models and establish correlations between parameters,the effects of all the variables on contact resistance and nanocomposite conductivity are analyzed.Notably,the contact resistance is primarily dependent on the polymer tunnel resistivity,contact area,and tunneling size.The dimensions of the graphene nanosheets significantly influence the conductivity,which ranges from 0 S/m to90 S/m.An increased number of nanosheets in stacks and a larger gap between them enhance the nanocomposite's conductivity.Furthermore,the thicker interphase and smaller tunneling size can lead to higher sample conductivity due to their optimistic effects on the percolation threshold and network efficacy.

Introduction of a multicenter online database for non-metastatic breast cancer in China

Dear Editor,Breast cancer is now the most frequently diagnosed cancer and is the fifth leading cause of cancer-related death in Chinese women. Therefore, the burden of breast cancer in China is gradually increasing. According to figures released by the Chinese Cancer Center in 2018, the number of newly diagnostic breast cancer is about 278,900 cases, accounting for 16.51%of all women who were diagnosed with the first primary malignant tumors;and 66,000 cases of breast cancer died in 2014 (Chen et al., 2016).

Association of a complete breast cancer pathologic response with axillary lymph node metastasis via neoadjuvant chemotherapy:Results from the CSBrS-012 study

To the Editor:In the last decade,neoadjuvant chemotherapy(NAC)has become a well-accepted treatment option for breast cancer,although few detailed description of NAC in China has yet been reported.[1]A previous study found that among patients with clinically node-negative(cN0)breast cancer,97.7%(432/442)with breast pathologic complete response(bpCR)had ypN0(absence of metastases in the axillary lymph nodes);and 71.6%(882/1232)without bpCR achieved ypN0(P<0.001).As for human epidermal growth factor receptor 2(HER2)positive or triple-negative breast cancer(TNBC)that achieved bpCR.

Long-term outcomes of intraoperative radiotherapy for early-stage breast cancer in China: amulticenter real-world study

Dear Editor,Intraoperative radiotherapy(IORT)is an accelerated par-tial breast irradiation(APBI)treatment that is accom-plished intraoperatively.Numerous clinical trials indicate that IORT is safe and effective,non-inferior to standard whole-breast external beam radiotherapy(EBRT)for low-risk patients who receive breast-conserving surgery[1-3].Nevertheless,these studies mainly included non-Asians and thus lack adequate evidence to support the value of IORT in Asian patients with breast cancer.