Guidelines for diagnosis and treatment of advanced breast cancer in China(2022 edition)

Breast cancer is the most common cancer among women worldwide.It has been estimated that about 416000 new cases and over 117000 deaths of breast cancer occurred in China in 2020.Among the new cases of breast cancer diagnosed each year,3-10%have distant metastasis at the time of initial diagnosis.In addition,approxi-mately 30%of patients with early-stage breast cancer may eventually experience recurrence or metastases.The 5-year survival rate of patients with advanced breast cancer is only 20%with a median overall survival of 2-3 years.Although advanced breast cancer remains incurable at present,new therapeutic options and multidisci-plinary treatment could be utilized to alleviate symptoms,improve quality of life,and prolong patients’survival.The choice of treatment regimens for patients with advanced breast cancer is very important,and the optimal treatment strategy beyond the first-and second-line therapy is often lacking.Herein,the China Advanced Breast Cancer Guideline Panel discussed and summarized recent clinical evidence,updated the guidelines for the diag-nosis and treatment of advanced breast cancer based on the 2020 edition,and formulated the“Guidelines for diagnosis and treatment of advanced breast cancer in China(2022 edition)”for clinicians’reference.

Synchronous multiple primary malignant neoplasms in breast,kidney,and bilateral thyroid:A case report

BACKGROUND Multiple primary malignant neoplasms(MPMNs)are rare,while synchronous MPMNs(SMPMNs)are even less common.Owing to the progression of medical technology and the extension of life expectancy,its incidence is gradually increasing.CASE SUMMARY Although reports of breast and thyroid dual cancers are common,cases of an additional diagnosis of kidney primary cancer within the same individual are rare.CONCLUSION We present a case of simultaneous MPMN of three endocrine organs,reviewing the relevant literature to enhance our understanding of SMPMNs while emphasizing the increasingly important need for accurate diagnosis and multidisciplinary management whenever this challenging situation arises.

Violence against Women with Breast Neoplasms

The aim of this study is to assess the occurrence and type of violence suffered by women with breast cancer in the High Complexity Care Unit of a municipality in the South of Minas and patients in a support group of the University of the South of Minas Gerais. For that aim, a descriptive-exploratory methodology was applied through the quantitative method. Data were collected through a semi-structured form applied in individual interviews over a period of three months. We interviewed 57 patients and among those, 20 women （35.08%） reported having experienced some form of violence at some stage of their life, and the most frequently mentioned was the psychological violence followed by physical aggression. Although it was possible to identify that violence against affected these women, complaints against the aggressor were not affected.

The accuracy of magnetic resonance imaging and ultrasound in evaluating the size of early-stage breast neoplasms

Objective Breast cancer is the most frequently diagnosed cancer in women. Accurate evaluation of the size and extent of the tumor is crucial in selecting a suitable surgical method for patients with breast cancer. Both overestimation and underestimation have important adverse effects on patient care. This study aimed to evaluate the accuracy of breast magnetic resonance imaging(MRI) and ultrasound(US) examination for measuring the size and extent of early-stage breast neoplasms.Methods The longest diameter of breast tumors in patients with T_(1–2)N_(0–1)M_0 invasive breast cancer preparing for breast-conserving surgery(BCS) was measured preoperatively by using both MRI and US and their accuracy was compared with that of postoperative pathologic examination. If the diameter difference was within 2 mm, it was considered to be consistent with pathologic examination.Results A total of 36 patients were imaged using both MRI and US. The mean longest diameter of the tumors on MRI, US, and postoperative pathologic examination was 20.86 mm ± 4.09 mm(range: 11–27 mm), 16.14 mm ± 4.91 mm(range: 6–26 mm), and 18.36 mm ± 3.88 mm(range: 9–24 mm). US examination underestimated the size of the tumor compared to that determined using pathologic examination(t = 3.49, P < 0.01), while MRI overestimated it(t =-6.35, P < 0.01). The linear correlation coefficients between the image measurements and pathologic tumor size were r = 0.826(P < 0.01) for MRI and r = 0.645(P < 0.01) for US. The rate of consistency of MRI and US compared to that with pathologic examination was 88.89% and 80.65%, respectively, and there was no statistically significant difference between them(χ~2 = 0.80, P > 0.05).Conclusion MRI and US are both effective methods to assess the size of breast tumors, and they maintain good consistency with pathologic examination. MRI has a better correlation with pathology. However, we should be careful about the risk of inaccurate size estimation.

A multicenter hospital-based diagnosis study of automated breast ultrasound system in detecting breast cancer among Chinese women

Objective： The automated breast ultrasound system（ABUS） is a potential method for breast cancer detection;however, its diagnostic performance remains unclear. We conducted a hospital-based multicenter diagnostic study to evaluate the clinical performance of the ABUS for breast cancer detection by comparing it to handheld ultrasound（HHUS） and mammography（MG）.Methods： Eligible participants underwent HHUS and ABUS testing; women aged 40–69 years additionally underwent MG. Images were interpreted using the Breast Imaging Reporting and Data System（BI-RADS）.Women in the BI-RADS categories 1–2 were considered negative. Women classified as BI-RADS 3 underwent magnetic resonance imaging to distinguish true-and false-negative results. Core aspiration or surgical biopsy was performed in women classified as BI-RADS 4–5, followed by a pathological diagnosis. Kappa values and agreement rates were calculated between ABUS, HHUS and MG.Results： A total of 1,973 women were included in the final analysis. Of these, 1,353（68.6%） and 620（31.4%）were classified as BI-RADS categories 1–3 and 4–5, respectively. In the older age group, the agreement rate and Kappa value between the ABUS and HHUS were 94.0% and 0.860（P〈0.001）, respectively; they were 89.2% and0.735（P〈0.001） between the ABUS and MG, respectively. Regarding consistency between imaging and pathology results, 78.6% of women classified as BI-RADS 4–5 based on the ABUS were diagnosed with precancerous lesions or cancer; which was 7.2% higher than that of women based on HHUS. For BI-RADS 1–2, the false-negative rates of the ABUS and HHUS were almost identical and were much lower than those of MG.Conclusions： We observed a good diagnostic reliability for the ABUS. Considering its performance for breast cancer detection in women with high-density breasts and its lower operator dependence, the ABUS is a promising option for breast cancer detection in China.

Combined molybdenum target X-ray and magnetic resonance imaging examinations improve breast cancer diagnostic efficacy

BACKGROUND Early-stage breast cancer patients often lack specific clinical manifestations,making diagnosis difficult.Molybdenum target X-ray and magnetic resonance imaging(MRI)examinations both have their own advantages.Thus,a combined examination methodology may improve early breast cancer diagnoses.AIM To explore the combined diagnostic efficacy of molybdenum target X-ray and MRI examinations in breast cancer.METHODS Patients diagnosed with breast cancer at our hospital from March 2019 to April 2021 were recruited,as were the same number of patients during the same period with benign breast tumors.Both groups underwent molybdenum target X-ray and MRI examinations,and diagnoses were given based on each exam.The single(i.e.,X-ray or MRI)and combined(i.e.,using both methods)diagnoses were counted,and the MRI-related examination parameters(e.g.,T-wave peak,peak and early enhancement rates,and apparent diffusion coefficient)were compared between the groups.RESULTS In total,63 breast cancer patients and 63 benign breast tumor patients were recruited.MRI detected 53 breast cancer cases and 61 benign breast tumor cases.Molybdenum target X-ray detected 50 breast cancer cases and 60 benign breast tumor cases.The combined methodology detected 61 breast cancer cases and 61 benign breast tumor cases.The sensitivity(96.83%)and accuracy(96.83%)of the combined methodology were higher than single-method MRI(84.13%and 90.48%,respectively)and molybdenum target X-ray(79.37%and 87.30%,respectively)(P<0.05).The combined methodology specificity(96.83%)did not differ from singlemethod MRI(96.83%)or molybdenum target X-ray(95.24%)(P>0.05).The Twave peak(169.43±32.05)and apparent diffusion coefficient(1.01±0.23)were lower in the breast cancer group than in the benign tumor group(228.86±46.51 and 1.41±0.35,respectively).However,the peak enhancement rate(1.08±0.24)and early enhancement rate(1.07±0.26)were significantly higher in the breast cancer group than in the benign tumor group(0.83±0.19 and 0.75±0.19,respectively)(P<0.05).CONCLUSION Combined molybdenum target X-ray and MRI examinations for diagnosing breast cancer improved the diagnostic sensitivity and accuracy,minimizing the missedand misdiagnoses risks and promoting timely treatment intervention.

Serological Diagnosis of Liver Metastasis in Patients with Breast Cancer

Objective To diagnose and explore the serological diagnostic factors for liver metastasis in patients with breast cancer before symptoms occur. Methods A total of 430 female in-patients with breast cancer of stages 0 to IIIC who came to Tianjin Medical University Cancer Institute and Hospital from January 2003 to January 2004 were studied and followed up until May 2011. Serum levels of biochemical markers for tumor and liver were measured at the time of diagnosis. Results Liver metastasis was more likely to occur in patients with stage Ill cancer or c-erbB-2-positive expression. Alanine aminotransferase, aspartate aminotransferase, ~/-glutamyltransferase （GGT）, alkaline phosphatase, lactate dehvdrogenase （LDH）, and carbohydrate antigen 1153 （CA153） levels were significantly higher in patients with liver metastasis than those without liver metastasis. Diagnostic indices of LDH, GGT, and CA153 were 174 U/L, 32 U/L, and 26.48 Dg/L, respectively. The areas under the curves of LDH, GGT, and CEA were 0.795, 0.784, and 0.661, respectively, and sensitivities of parallel tests for LDH and CA153 and for GGT and CA153 were 88.6% and 85.7 %, respectively. The specificity of serial tests for both pairs of enzymes was 97.7%. Conclusions Tile sensitivity and specificity of combined tumor and biochemical markers could be used as indicators during screening for breast-liver metastasis.

Clinical study of digital mammography,contrast-enhanced MRI as well as their combination in the diagnosis of breast cancer

Objective： To compare the effectiveness of digital mammography and MRI in the detection and diagnosis of breast cancer and to assess the value of these modalities as well as the combination of the two. Methods： Sixty-seven patients with surgery and pathology proved breast lesion （malignant, n = 32; benign, n = 46） underwent digital mammography and MRI, the pulse sequences included T1WI, T2WI, diffuse weighted imaging （DWI）, and dynamic contrast-enhanced MRI before surgery. Of the results of these two modalities, all lesions were classified into 5 groups according to BI-RADS classification, and the imaging findings were correlated to histopathology. The sensitivity and specificity of each modality as well as the combination of the two were calculated. Results： Of these 78 breasts lesions, The sensitivity was 78.13%% （25/32） for digital mammography and 93.75% （30/32） for MRI （P 〉 0.05）. The specificity was 73.91%% （34/46） and 89.13% （41/46） accordingly （P 〈 0.05）, both of them showed statistical difference. The sensitivity and specificity was 98.63% and 97.16% respectively as these two modalities were used in combination. Conclusion： Digital mammography in combination with MRI is helpful in the diagnosis of breast cancer, the sensitivity and specificity was enhanced when compared to that of single modality.

Expert consensus on diagnosis,treatment and fertility management of young breast cancer patients

Breast cancer in young females is a relatively common disease in China.Young breast cancer has aggressive clinical and pathological features.During the treatment of young females with breast cancer,issues involving the choice of surgical methods,early amenorrhea,and fertility protection may have physical,psychological,and social impacts.Thus,a multidisciplinary model of diagnosis and treatment is indispensable.The breast cancer expert committee of the National Cancer Quality Control Center organized experts in related fields in China to compile this consensus as to provide scientific and feasible solutions for rational diagnosis,treatment,and fertility management for young females with breast cancer.This consensus is based on the literature data,the views of relevant international guidelines,and the clinical practice experience of experts in different fields.

The application of DCE-MRI in diagnosing breast cancer

Objective The aim of the study was to further explore the diagnostic value of breast dynamic contrast enhancement (DCE), and improve specificity of breast cancer diagnosis.

更多〉〉相关学者姜玉新严昆华扬张青萍陈敏华段云友刘东戴晴吴瑛蔡胜相关检索词乳腺癌 新辅助化疗 ultrasonography 免疫组化 导管 breast cancer 造影剂 胎儿 乳腺肿块 ultrasound 检出率 改良根治术 多普勒 保乳手术 免疫组织化学 磁共振成像 彩色 肿块 病理检查 准确率 自动乳腺全容积成像在乳腺癌术前测量评估中的应用

目的评价运用自动乳腺全容积成像（ABVS）对乳腺癌术前大小测量的准确率.方法选取经手术病理证实的乳腺癌患者105例（118个病灶,其中导管原位癌病灶36个,非导管原位癌病灶82个）,术前均行常规超声、ABVS 检查,测量病灶最大径并与手术病理测量结果进行对比,比较常规超声与 ABVS 对两类病灶的检测情况.结果病理检查：病灶大小0.2~5.5（2.45±1.18）cm;ABVS 检查：病灶大小0.3~5.8（2.50±1.21）cm;常规超声检查：病灶大小0.8~5.2（2.16±1.12）cm.乳腺癌患者 ABVS 及常规超声检查结果与病理检查结果均呈显著正相关（r=0.906、0.990,均 P〈0.01）.ABVS 对导管原位癌病灶的检出率明显高于常规超声（P〈0.05）,而两种方法对非导管原位癌病灶检出率的差异无统计学意义（P 〉0.05）.结论 ABVS 对乳腺肿块的测量优于常规超声,尤其对于导管原位癌的测量有明显优势.

有氧运动改善化疗期间乳腺癌患者体质及生活质量研究:一项随机对照试验

背景蒽环类药物是乳腺癌基础化疗药物之一,但化疗常伴随着体质改变如体脂增加和心肺功能下降,胃肠道反应和骨髓抑制等毒副作用,影响患者的生活质量。目前关于运动改善以上毒副作用的研究结果不一致,有待进一步研究。临床上,应用运动处方改善乳腺癌患者以上化疗毒副作用的效果和安全性需要进一步探究。目的探究有氧运动改善蒽环类药物化疗期间乳腺癌患者体质和生活质量的效果及有氧运动的安全性。方法本研究是一项随机对照试验,纳入2022年3月—2023年1月在北京市朝阳区三环肿瘤医院接受蒽环类药物化疗方案的44例成年女性乳腺癌患者为研究对象,随机分为运动组(23例)与对照组(21例),对照组患者在化疗结束后提供个性化运动指导。运动组患者在化疗住院期间在康复师监督下进行锻炼,在家时通过患者自我监督和试验人员远程监督进行个性化运动干预。在化疗前后收集主要结局指标,包括体质和生活质量,记录胃肠道反应、骨髓抑制的发生次数、严重程度及运动相关不良事件。以化疗前数据为协变量,采用协方差分析比较两组体质情况和生活质量情况。结果本研究干预、随访过程中共流失4例,最终纳入40例患者(运动组21例,对照组19例)。运动干预期间未观察到严重不良事件。运动干预期间,患者平均依从性为81.8%;每次运动时长的平均依从性为91.9%;运动强度平均依从性为92.5%。化疗后,运动组体脂重、体脂百分比、内脏脂肪面积、腰围、腰臀比低于对照组,惯用手握力、相对峰值摄氧量(VO_(2)peak)高于对照组(P<0.05)。化疗后运动组患者功能性障碍发生率(7/20)低于对照组(12/16)(χ^(2)=5.707,P=0.017)。化疗后运动组生理状况、情感状况、附加得分低于对照组,功能状况得分高于对照组(P<0.05)。化疗后对照组生理状况分数(P<0.001)、运动组功能状况分数(P=0.017)高于化疗前。对照组和运动组患者分别共接受了84例次和94例次蒽环类药物化疗,对照组分别发生了84例次胃肠道反应和71次骨髓抑制,运动组分别发生了54例次胃肠道反应和45例次骨髓抑制,两组患者胃肠道反应和骨髓抑制发生情况比较,差异有统计学意义(P<0.05)。结论在蒽环类药物化疗期间进行有氧运动可以改善乳腺癌患者的体质和生活质量,且有监督的有氧运动是安全的。

Clinical Trial of Letrozole (femara) versus Aminoglutethimide in Postmenopausal Women with Advanced Breast Cancer

Objective： To compare the response and adverse reactions of aminoglutethimide with that of femara, an oral aromatase inhibitor, in postmenopausal women with advanced breast cancer. Methods： Fifty patients were randomly assigned to femara 2.5 mg once daily （n=26） or aminoglutethimide （n=24） 125 mg twice daily in the first week, 250 mg twice daily in the second week, 250 mg three times daily in the third week and 250 mg four times daily in the fourth week, 30 days for one cycle for both groups. Results： Overall objective response rate （complete＋partial） of 26.9% for femara was 12.5% higher than that of aminoglutethimide, but there was no significant difference （P=0.294）. The percentages of stable disease were 53.8% and 50.0% respectively in both treatment groups and that of progressive disease of two groups were 19.2% and 37.5%. There was no significant difference between two arms in the receptor status, disease-free intervals, sites of disease and stages of treatment. Femara-related adverse events were fatigue （15.4%）, anorexia （11.5%）, dizziness （7.7%）, nausea （3.8%） and somnolence （3.8%）. However, incidence of nausea （25.0%） and vomiting （16.7%） in aminoglutethimide group was obviously higher and severer than that in femara group （P=0.045 and P=0.046）. Compared to femara group, frequency in dizziness （25.0%）, fatigue （20.8%）, anorexia （16.7%）, somnolence （12.5%） and cutaneous pruritus （12.5%） was higher in aminoglutethimide group. Allergic rash occurred in aminoglutethimide group. Conclusion： Femara was more effective and well tolerated than aminoglutethimide with respect to side effects in the treatment of postmenopausal women with advanced breast cancer.

Early prediction of pathological outcomes to neoadjuvant chemotherapy in breast cancer patients using automated breast ultrasound

Objective： Early assessment of response to neoadjuvant chemotherapy （NAC） for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy of automated breast ultrasound （ABUS） to predict pathological outcomes after NAC. Methods： A total of 290 breast cancer patients were eligible for this study. Tumor response after 2 cycles of chemotherapy was assessed using the product change of two largest perpendicular diameters （PC） or the longest diameter change （LDC）. PC and LDC were analyzed on the axial and the coronal planes respectively. Receiver operating characteristic （ROC） curves were used to evaluate overall performance of the prediction methods. Youden＇s indexes were calculated to select the optimal cut-off value for each method. Sensitivity, specificity, positive and negative predictive values （PPV and NPV） and the area under the ROC curve （AUC） were calculated accordingly.Results： ypT0/is was achieved in 42 patients （14.5%） while ypT0 was achieved in 30 patients （10.3%） after NAC. All four prediction methods （PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on coronal planes） displayed high AUCs （all〉0.82）, with the highest of 0.89 [95% confidence interval （95% CI）, 0.83-0.95] when mid-treatment ＆BUS was used to predict final pathological complete remission （pCR）. High sensitivities （85.7%-88.1%） were observed across all four prediction methods while high specificities （81.5%-85.1%） were observed in two methods used PC. The optimal cut-off values defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were observed when mid-treatment ABUS was used to predict poor pathological outcomes. Conclusions：ABUS is a useful tool in early evaluation of pCR after NAC while less reliable when predicting poor pathological outcomes.

Trans-arterial chemoperfusion for the treatment of liver metastases of breast cancer and colorectal cancer: Clinical results in palliative care patients

AIM To evaluate the clinical value and efficiency of transarterial chemoperfusion(TACP) in patients with liver metastases from breast cancer(BC) and colorectal cancer(CRC).METHODS We treated 36 patients with liver metastases of BC(n = 19, 19 females) and CRC(n = 17; 8 females, 9 males) with repeated TACP. The treatment interval was 4 wk. TACP was performed with gemcitabine(1000 mg/m2) and mitomycin(10 mg/m2), administered within 1 h after positioning the catheter tip in the hepatic artery. Before treatment, the size, location, tumour volume, vascularization and number of liver tumours were evaluated using magnetic resonance imaging(MRI). Tumour response was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines.RESULTS TACP using gemcitabine and mitomycin for metastases from CRC and BC was performed without any serious side effects. The follow-up MRI showed a therapeutic response in 84.2% of the BC patients-stable disease 47.4% and partial response 36.8%. A progression was seen in 15.8%.CRC patients showed a therapeutic response in 52.9% of cases. A progression of the disease was documented in 47.1% of the patients with CRC. These data show that TACP in patients with liver metastases of BC leads to a significantly better therapeutic response compared with CRC patients(P = 0.042). The median survival time was 13.2 mo for the BC patients, which is significantly longer than for CRC patients at 9.3 mo(P = 0.001).CONCLUSION TACP for liver metastases of BC appears to be a safe and effective palliative treatment with improved outcomes in comparison to patients with CRC.

Current status of ultrasound-guided surgery in the treatment of breast cancer

The primary goal of breast-conserving surgery(BCS) is to obtain tumour-free resection margins. Margins positive or focally positive for tumour cells are associated with a high risk of local recurrence, and in the case of tumour-positive margins, re-excision or even mastectomy are sometimes needed to achieve definite clear margins. Unfortunately, tumour-involved margins and re-excisions after lumpectomy are still reported in up to 40% of patients and additionally, unnecessary large excision volumes are described. A secondary goal of BCS is the cosmetic outcome and one of the main determinants of worse cosmetic outcome is a large excision volume. Up to 30% of unsatisfied cosm-etic outcome is reported. Therefore, the search for better surgical techniques to improve margin status, excision volume and consequently, cosmetic outcome has continued. Nowadays, the most commonly used localization methods for BCS of non-palpable breast cancers are wire-guided localization(WGL) and radioguided localization(RGL). WGL and RGL are invasive procedures that need to be performed pre-operatively with technical and scheduling difficulties. For palpable breast cancer, tumour excision is usually guided by tactile skills of the surgeon performing "blind" surgery. One of the surgical techniques pursuing the aims of radicality and small excision volumes includes intraoperative ultrasound(IOUS). The best evidence available demonstrates benefits of IOUS with a significantly high proportion of negative margins compared with other localization techniques in palpable and non-palpable breast cancer. Additionally, IOUS is non-invasive, easy to learn and can centralize the tumour in the excised specimen with low amount of healthy breast tissuebeing excised. This could lead to better cosmetic results of BCS. Despite the advantages of IOUS, only a small amount of surgeons are performing this technique. This review aims to highlight the position of ultrasoundguided surgery for malignant breast tumours in the search for better oncological and cosmetic outcomes.

Treatment for liver metastases from breast cancer: Results and prognostic factors

AIM: Liver metastases from breast cancer (BCLM) are associated with poor prognosis. Cytotoxic chemotherapy can result in regression of tumor lesions and a decrease in symptoms. Available data, in the literature, also suggest a subgroup of patients may benefit from surgery, but few talked about transcatheter arterial chemoembolization (TACE). We report the results of TACE and systemic chemotherapy for patients with liver metastases from breast cancer and evaluate the prognostic factors. METHODS: Forty-eight patients with liver metastases, from proved breast primary cancer were treated with TACE or systemic chemotherapy between January 1995 and December 2000. Treatment results were assessed according to WHO criteria, along with analysis of prognostic factors for survival using Cox regression model. RESULTS: The median follow-up was 28 mo (1-72 mo). Response rates were calculated for the TACE group and chemotherapy group, being 35.7% and 7.1%, respectively. The difference was significant. The one-, two- and three-year Survival rates for the TACE group were 63.04%, 30.35%, and 13.01%, and those for the systemic chemotherapy group were 33.88%, 11.29%, and 0%. According to univariate analysis, variables significantly associated with survival were the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight. Other factors such as age, the intervals between the primary to the metastases, the maximal diameter of the liver metastases, the number of liver metastases, extrahepatic metastasis showed no prognostic significances. These factors mentioned above such as the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight were also independent factors in multivariate analysis. CONCLUSION: TACE treatment of liver metastases from breast cancer may prolong survival in certain patients. This approach offers new promise for the curative treatment of the patients with metastatic breast cancer.

Evaluation of menopausal status among breast cancer patients with chemotherapy-induced amenorrhea

Objective： In patients with chemotherapy-induced amenorrhea （CIA）, the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausalstatus of breast cancer patients with CIA.Methods： This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution andaccumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potentialconfounding factors including age, serum concentration of estradiol （E2） and follicle-stimulating hormone （FSH）,feeding, pregnancy, parity, abortions, and body mass index （BMI）. The odds ratio （OR） and 95% confidenceinterval （95% CI） of different risk factors were estimated.Results： A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 （65.42%） werepremenopausal patients and 621 （34.58%） were post-menopause patients. Five hundred and fifty patients wereincluded in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age （OR： 1.856, 95% CI：1.732-1.990）, serum concentration of E2 （OR： 0.976, 95% CI： 0.972-0.980） and FSH （OR： 1.060, 95% CI：1.053-i.066）, and menarche age （OR： 1.074, 95% CI： 1.009-1.144） were found to be associated with the patients＇menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status isLogit （P）=-28.396＋0.536Age-0.014E2＋0.031FSH. The sensitivities for this model were higher than 85%, and itsspecificities were higher than 89%.Conclusions： The discriminative model obtained from this study for predicting menstrual state is important forpremenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.

Tim-3 promotes cell aggressiveness and paclitaxel resistance through NF-κB/STAT3 signalling pathway in breast cancer cells

Objective:Although T-cell immunoglobulin and mucin-domain containing molecule-3(Tim-3)has been recognized as a promising target for cancer immunotherapy,its exact role in breast cancer has not been fully elucidated.Methods:Tim-3 gene expression in breast cancer and its prognostic significance were analyzed.Associated mechanisms were then explored in vitro by establishing Tim-3-overexpressing breast cancer cells.Results:In a pooled analysis of The Cancer Genome Atlas(TCGA)database,Tim-3 gene expression levels were significantly higher(P<0.001)in breast cancer tissue,compared with normal tissues.Tim-3 was a prognosis indicator in breast cancer patients[relapse-free survival(RFS),P=0.004;overall survival(OS),P=0.099].Tim-3 overexpression in Tim-3 low breast cancer cells promoted aggressiveness of breast cancer cells,as evidenced by enhanced proliferation,migration,invasion,tight junction deterioration and tumor-associated tubal formation.Tim-3 also enhanced cellular resistance to paclitaxel.Furthermore,Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway and by regulating gene expression[cyclin D1(CCND1),C-Myc,matrix metalloproteinase-1(MMP1),TWIST,vascular endothelial growth factor(VEGF)upregulation,concomitant with Ecadherin downregulation).Lastly,Tim-3 downregulated tight junction-associated molecules zona occludens(ZO)-2,ZO-1 and occludin,which may further facilitate tumor progression.Conclusions:Tim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy.

Identification of the Interaction between P-Glycoprotein and Anxa2 in Multidrug-resistant Human Breast Cancer Cells

Objective To explore the interaction of Anxa2 with P-Glycoprotein （P-gp） in the migration and invasion of the multidrug-resistant （MDR） human breast cancer cell line MCF-7/ADR. Methods A pair of short hairpin RNA （shRNA） targeting P-gp was transfected into MCF-7/ADR cells, and monoclonal cell strains were screened. The expression of P-gp was detected by Western blot. Transwell chambers were used to observe the cell migration capacity and invasion ability. The interaction between P-gp and Anxa2 was examined by immunoprecipitation and immunofluorescence confocal microscopy analyses. Results P-gp expression was significantly knocked down, and there were notable decreasing trends in the migration and invasion capability of MDR breast cancer cells （P〈0.05）. There was a close interaction between Anxa2 and P-gp. Conclusions MCF-7/ADR is an MDR human breast cancer cell line with high migration and invasion abilities. The knockdown of P-gp notably impaired the migration and invasion abilities of the tumor cells. The interaction of Anxa2 with P-pg may play an important role in time enhanced invasiveness of MDR human breast cancer cells.