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.

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.

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).

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.

示踪用盐酸米托蒽醌注射液与核素用于乳腺癌前哨淋巴结活检的疗效对比研究

背景与目的:国内外指南均推荐核素用作前哨淋巴结活检术(sentinel lymph node biopsy,SLNB)示踪剂,但多种原因导致该技术在国内未得到普及。示踪用盐酸米托蒽醌注射液(mitoxantrone hydrochloride injection for tracing,MHI)是一种新型乳腺癌前哨淋巴结(sentinel lymph node,SLN)示踪剂,其在乳腺癌SLNB中的效果尚未明确。本研究是一项大样本阳性对照临床试验,旨在评价MHI和核素在SLNB中的示踪差异。方法:试验纳入了2019年12月—2020年7家医院的早期乳腺癌患者。所有入组的早期乳腺癌患者均在手术前注射MHI和核素作为SLN示踪剂。分别统计MHI和核素的SLN检出数量和SLN检出率,分析两种示踪剂示踪效果的差异。结果:MHI的SLN检出率为96.9%(370/382),核素的SLN检出率为97.4%(372/382),两者检出率差异无统计学意义(P>0.05)。两种示踪剂共同检测到362例(94.7%)受试者的SLN;16例(4.1%)发生可能与试验药物相关的不良事件。结论:本研究发现MHI示踪效果不劣于核素。且MHI的使用无需特殊仪器/设备辅助。

Clinical practice guidelines for modified radical mastectomy of breast cancer: Chinese Society of Breast Surgery (CSBrs) practice guidelines 2021

The proportion of patients with early-stage breast cancer undergoing mastectomy exceeds 70%in China/11 among which Auchincloss operation is the major surgical technique for patients with axillary lymph node positive breast cancer.In order to standardize the clinical application of modified radical mastectomy of breast cancer,Chinese Society of Breast Surgery(CSBrS)organized domestic experts to conduct literature retrieval and expert discussion on the theoretical basis and technical details of modified radical mastectomy for breast cancer.With reference to the grading of recommendations assessment,development,and evaluation system。

High risk factors of brain metastases in 295 patients with advanced breast cancer

Background The incidence of brain metastases in patients with breast cancer is approximately 10%-16%, and survival after diagnosis of brain metastases is usually short. This study was designed to evaluate the risk factors associated with brain metastases in advanced breast cancer patients, with a view to help predict patient groups with high risk of brain metastases. Methods In total, 295 patients with advanced breast cancer were evaluated. All patients were pathologically confirmed and metastatic lesions were confirmed pathologically or by imaging. All patients were examined at least once every 6 months with head CT or MRI. Patients showing symptoms underwent immediate inspection, and brain metastatic lesions were confirmed by head CT and/or MRI. Results At a median follow-up of 12 months from the occurrence of metastases, brain metastases had occurred in 49 patients （16.6%）. In our univariate analysis, variables significantly related to increased risk of brain metastases were hormone receptor-negative tumors, epidermal growth factor receptor 2 （HER2）-positive tumors, and multiple distant metastases. Patients with dominant tumor sites in soft tissue, or defined as Luminal A subtype, tended to have a lower risk of brain metastases than patients with visceral metastases, Luminal B subtype, triple-negative subtype or HER2-enriched subtype tumors. Conclusions Our results strongly suggest that factors such as Luminal B, triple-negative, and HER2-enriched subtypes are high risk factors for brain metastases. These data, therefore, provide pivotal clinical evidence towards a comprehensive understanding of the risk factors of brain metastases in advanced breast cancer patients.

Diagnostic diversity and heterogeneity of tumors: a real-world study of metastasis re-biopsy in advanced breast cancer

Background::Re-biopsy of metastasis in advanced breast cancer(ABC)has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity.This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER2)expression levels between primary and metastatic lesions.Methods::We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018.The pathological diagnosis of biopsies,distribution of biopsy sites,and severe puncture complications at each site were collected.In addition,the inconsistency rates and related factors of ER,PR,and HER2 expression between primary and metastatic lesions were analyzed fully considering patients’demographic profiles and disease characteristics.Results::In total,1670 cases of breast cancer(BC)patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment,producing 2019 histopathological specimens which were analyzed in the study.Pathological diagnosis showed that eight patients had benign pathological diagnoses,11 patients had second primary malignant tumors but without recurrences of breast cancer,and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer.In 1173 patients who presented ER,PR,and HER2 expressions in primary and metastatic lesions,the inconsistency rates of ER,PR,and HER2 were 17.5%(205/1173),31.3%(367/1173),and 13.9%(163/1173),respectively.The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level.Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax,no other severe puncture complications occurred in 1950 non-surgical rebiopsies.Conclusions::The pathological diagnosis of metastasis re-biopsy of ABC was diverse,and the ER,PR,and HER2 expression levels were inconsistent between primary and metastatic lesions.Therefore,more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.

Clinical practice guidelines for multigene assays in patients with early-stage breast cancer: Chinese Society of Breast Surgery (CSBrS) practice guidelines 2021

The role of multigene assays in chemotherapy decision-making in patients with early invasive breast cancer has been widely recognized.In 2017,the American Society of Clinical Oncology(ASCO)clinical guidelines for multigene profiling assays focused on increasing the intensity of recommendations for the clinical use of MammaPrint®.[1]The 8th edition of the American Joint Committee on Cancer(AJCC)staging system,officially launched in 2018,established the concept of prognostic staging for the first time,adding the use of non-anatomical information to evaluate the prognosis.Initially,Oncotype Dx®was recommended for suitable patients based on Level I evidence.Subsequently,five testing techniques,Oncotype Dx®,MammaPrint®,EndoPredict®,PAM50®,and BCI,were formally incorporated into the system.[2]To assist breast disease specialists in China in their selection of appropriate multigene profiling assays and detection methods for patients,and also to instill caution on decision-making with reference to multigene assays,the Chinese Society of Breast Surgery(CSBrS)has,through literature investigation and expert discussion,provided information on the key clinical problems and guidelines for the use of multigene assays,evaluating the evidence with reference to the Grades of Recommendations Assessment Development and Evaluation(GRADE)system.Combined with the availability of these assays in China,the clinical practice guidelines for multigene assays were formulated and published.The purpose of this guideline is to provide a reference for clinicians specializing in breast diseases in China.

Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer

Background:Endocrine therapy(ET)and ET-based regimens are the preferred first-line treatment options for hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative metastatic breast cancer(HR+/HER2-MBC),while chemotherapy(CT)is commonly used in clinical practice.The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2-MBC.Methods:Patients diagnosed with HR+/HER2-MBC between January 1st,1996 and September 30th,2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database.The initial and maintenance first-line treatment,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Among the 1877 included patients,1215(64.7%)received CT and 662(35.3%)received ET as initial first-line treatment.There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population(PFS:12.0 vs.11.0 months,P=0.22;OS:54.0 vs.49.0 months,P=0.09)and propensity score matched population.For patients without disease progression after at least 3 months of initial therapy,maintenance ET following initial CT(CT-ET cohort,n=449)and continuous schedule of ET(ET cohort,n=527)had longer PFS than continuous schedule of CT(CT cohort,n=406)in the total population(CT-ET cohort vs.CT cohort:17.0 vs.8.5 months;P<0.01;ET cohort vs.CT cohort:14.0 vs.8.5 months;P<0.01)and propensity score matched population.OS in the three cohorts yielded the same results as PFS.Conclusions:ET was associated with similar clinical outcome to CT as initial first-line treatment.For patients without disease progression after initial CT,switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.

CACA Guidelines for Holistic Integrative Management of Breast Cancer

Purpose:Breast cancer is now the most common malignant tumor worldwide.About one-fourth of female cancer patients all over the world sufer from breast cancer.And about one in six female cancer deaths worldwide is caused by breast cancer.In terms of absolute numbers of cases and deaths,China ranks frst in the world.The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China.Methods:The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to classify evidence and consensus.Results:The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer,breast cancer screening,breast cancer diagnosis,early breast cancer treatment,advanced breast cancer treatment,follow-up,rehabilitation,and traditional Chinese medicine treatment of breast cancer patients.Conclusion:We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

腹壁下动脉穿支皮瓣乳房重建术后并发症对患者报告结局的影响

目的探讨腹壁下动脉穿支皮瓣乳房重建术后并发症的影响因素,以及术后并发症是否会影响患者的生活质量。方法回顾性分析郑州大学附属肿瘤医院乳腺科2019年12月至2023年3月行腹壁下动脉穿支皮瓣乳房重建手术患者的临床及随访资料。结果85例行腹壁下动脉穿支皮瓣乳房重建的患者入组。其中Ⅰ期重建71例,Ⅱ期重建14例。22例(25.9%)出现了术后并发症,11例(12.9%)出现了皮瓣并发症,11例(12.9%)出现了腹部供区并发症。单因素及多因素分析显示,总体并发症发生与高的BMI、早期开展的手术相关(P<0.05),皮瓣并发症与高的BMI、早期开展的手术、术中采用内乳血管的分支作为受区血管有关(P<0.05),而腹部并发症与既往腹部手术瘢痕相关(P<0.05)。BREAST-Q评分显示,与无手术并发症组相比,手术并发症组在乳房满意度、心理健康、躯体健康-胸部、躯体健康-腹部、对腹部的满意度、性健康等维度差异均无统计学意义(P>0.05)。结论腹壁下动脉穿支皮瓣乳房重建存在明显的学习曲线,患者的临床特征(BMI、腹部切口瘢痕)以及术中受区血管的选择可能对患者术后的并发症产生影响,而术后并发症的出现并未对患者报告结局产生影响。

哌柏西利联合内分泌治疗对HR+/HER2-晚期乳腺癌患者的疗效观察

目的回顾性分析在真实世界中,哌柏西利联合内分泌治疗在激素受体阳性(HR+)/人表皮生长因子受体2阴性(HER2-)晚期乳腺癌的临床应用、疗效及不良反应。方法收集2018年9月至2020年9月在河南省肿瘤医院接受哌柏西利治疗的晚期乳腺癌患者(HR+/HER2-)信息,共55例,均为女性,中位年龄57(34~79)岁。汇总一般病史资料、疾病特征。分析客观缓解率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)、至治疗失败时间(TTF)、安全性及相关预后因素分析。结果收集接受含哌柏西利治疗方案的HR+/HER2-患者共55例,ORR为48.8%,DCR为88.4%;中位PFS和TTF分别为12.0个月(95%CI,11.1~13.0个月)和8.50个月(95%CI,2.5~14.5个月);其中哌柏西利在一线中优于多线治疗(P=0.0001);非肝转移患者预后较佳(P=0.01)。血液学毒性为重点观察不良事件,包括白细胞减少、中性粒细胞减少及血小板减少,其发生率为分别为78.2%、85.5%和34.5%;未发现其他3~4级非血液学毒性。结论哌柏西利联合内分泌治疗在HR+/HER2-晚期乳腺癌患者的疗效可,且不良反应可控,可以作为HR+/HER2-晚期乳腺癌一线或多线治疗选择。

Targeting HECTD3-IKKα axis inhibits inflammation-related metastasis

Metastasis is the leading cause of cancer-related death.The interactions between circulating tumor cells and endothelial adhesion molecules in distant organs is a key step during extravasation in hematogenous metastasis.Surgery is a common intervention for most primary solid tumors.However,surgical trauma-related systemic inflammation facilitates distant tumor metastasis by increasing the spread and adhesion of tumor cells to vascular endothelial cells(ECs).Currently,there are no effective interventions to prevent distant metastasis.Here,we show that HECTD3 deficiency in ECs significantly reduces tumor metastasis in multiple mouse models.HECTD3 depletion downregulates expression of adhesion molecules,such as VCAM-1,ICAM-1 and E-selectin,in mouse primary ECs and HUVECs stimulated by inflammatory factors and inhibits adhesion of tumor cells to ECs both in vitro and in vivo.We demonstrate that HECTD3 promotes stabilization,nuclear localization and kinase activity of IKKa by ubiquitinating IKKa with K27-and K63-linked polyubiquitin chains at K296,increasing phosphorylation of histone H3 to promote NF-kB target gene transcription.Knockout of HECTD3 in endothelium significantly inhibits tumor cells lung colonization,while conditional knockin promotes that.IKKa kinase inhibitors prevented LPS-induced pulmonary metastasis.These findings reveal the promotional role of the HECTD3-IKKa axis in tumor hematogenous metastasis and providea potential strategy for tumormetastasis prevention.