Systemic oncological therapy in breast cancer patients on dialysis

The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.

Primary Screening for Breast Diseases among 17618 Women in Wufeng Area, a Region with High Incidence of Cervical Cancer in China

In this study, the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated. From March to August, 2009, 17618 women, from Wufeng area of Hubei province, China, were recruited to screen breast diseases by using breast infrared diagnostic apparatus. Other diagnostic methods, such as B-mode ultrasound, X-ray mammography, needle biopsy and pathological examination were, if necessary, used to further confirm the diagnosis. The screening showed that 5990 of 17618 cases (34.00%) had breast diseases, 5843 (33.16%) had mammary gland hyperplasia, 48 (0.27%) had breast fibroadenoma, 11 (0.06%) had breast carcinoma, and 88 (0.50%) had other breast diseases. The peak morbidity of breast cancer was found in the women aged 50–60 ages. The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8, 0.157%) in comparison with that in the subjects younger than 50 years old (n=3, 0.024%) (u=2.327, P<0.05). It was shown that the occurrence of breast diseases was concentrated in women aged 20–40 years, while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40. Compared with the patients elder than or equal to 40 years old (n=3289, 27.46%), the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases, 47.18%; P<0.001). However, there was no significant difference in the morbidity of breast diseases between the age group of 20–29 years and that of 30–39 years (P=0.453), and both of them were high. There was no significant association between the morbidity of breast diseases and cervical cancer. Since the morbidity of breast diseases was higher among young women, more attention should be paid to the screening of breast diseases among young women for early diagnosis.

Role of FDG PET-CT in evaluation of locoregional nodal disease for initial staging of breast cancer

Fluorodeoxyglucose positron emission tomography/computed tomography(FDG PET/CT) is not indicated or recommended in the initial staging of early breast cancer. Although it is valuable for detecting distant metastasis, providing prognostic information, identifying recurrence and evaluating response to chemotherapy, the role of FDG PET/CT in evaluating locoregional nodal status for initial staging of breast cancer has not yet been well-defined in clinical practice. FDG PET/CT has high specificity but compromised sensitivity for identifying axillary nodal disease in breast cancer. Positive axillary FDG PET/CT is a good predictor of axillary disease and correlates well with sentinel lymph node biopsy(SLNB). FDG PET/CT may help to identify patients with high axillary lymph node burden who could then move directly to axillary lymph node dissection(ALND) and would not require the additional step of SLNB. However, FDG PET/CT cannot replace SLNB or ALND due to unsatisfactory sensitivity. The spatial resolution of PET instruments precludes the detection of small nodal metastases. Although there is still disagreement regarding the management of internal mammary node(IMN) disease in breast cancer, it is known that IMN involvement is of prognostic significance, and IMN metastasis has been associated with higher rates of distant metastasis and lower overall survival rates. Limited clinical observationssuggested that FDG PET/CT has advantages over conventional modalities in detecting and uncovering occult extra-axillary especially IMN lesions with upstaging the disease and an impact on the adjuvant management.

Can trastuzumab emtansine be replaced by additional chemotherapy plus targeted therapy for HER2-overexpressing breast cancer patients with residual disease after neoadjuvant chemotherapy?

Human epidermal growth factor receptor 2(HER2)-overexpressing breast cancer is an aggressive phenotype with a poor prognosis,and can easily metastasize and recur.Currently,chemotherapy plus HER2-targeted therapy is the standard systemic treatment for most of these patients.Given that neoadjuvant chemotherapy(NAC)has an efficacy equivalent to that of adjuvant chemotherapy and some additional benefits,many patients,especially those with more advanced tumors,prefer NAC and generally will not receive additional chemotherapy after surgery,irrespective of the pathological response.However,achieving pathological complete response to NAC is strongly correlated with prognosis,especially in triple-negative and HER2-overexpressing breast cancer.Therefore,postoperative treatment of these patients with residual diseases should be optimized to achieve favorable outcomes.The CREATE-X study has confirmed that additional chemotherapy can improve the outcomes of patients with HER2-negative residual disease after NAC.In addition,chemotherapy plays an indispensable role in the treatment of patients who receive surgery directly or who have recurrent lesions.Therefore,can additional chemotherapy improve prognosis of patients with HER2-overexpressing residual breast cancer?At present,no studies have compared the efficacy of additional chemotherapy plus trastuzumab with that of anti-HER2 therapy alone in residual cancer.The KATHERINE study revealed that trastuzumab emtansine(T-DM1)can reduce the risk of recurrence or death by 50%compared with trastuzumab in patients with HER2-positive residual invasive breast cancer after neoadjuvant therapy.T-DM1 is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine,and thus,to an extent,T-DM1 is equivalent to simultaneous application of chemotherapy and targeted therapy.However,high cost and low accessibility limit its use especially in low-and middle-income countries and regions.Hence,we proposed this perspective that additional chemotherapy plus trastuzumab should be given to HER2-overexpressing breast cancer patients with residual disease after NAC to improve their prognosis by discussing that the efficacy of additional chemotherapy plus trastuzumab is superior to that of anti-HER2 therapy alone and not inferior to T-DM1.Additional chemotherapy plus trastuzumab-based HER2-targeted therapy can be used as an alternative regimen to T-DM1 when T-DM1 is unavailable.However,further clinical research on the selection of chemotherapeutic agents is warranted.

Adjuvant treatment for triple-negative breast cancer: a retrospective study of immunotherapy with autologous cytokine-induced killer cells in 294 patients

Objective: To examine the efficacy and safety of a sequential combination of chemotherapy and autologous cytokine-induced killer(CIK) cell treatment in triple-negative breast cancer(TNBC) patients.Methods: A total of 294 post-surgery TNBC patients participated in the research from January 1, 2009 to January 1, 2015. After adjuvant chemotherapy, autologous CIK cells were introduced in 147 cases(CIK group), while adjuvant chemotherapy alone was used to treat the remaining 147 cases(control group). The major endpoints of the investigation were the disease-free survival(DFS) and overall survival(OS). Additionally, the side effects of the treatment were evaluated.Results: In the CIK group, the DFS and OS intervals of the patients were significantly longer than those of the control group(DFS:P = 0.047;OS: P = 0.007). The multivariate analysis demonstrated that the TNM(tumor-node-metastasis) stage and adjuvant CIK treatment were independent prognostic factors for both DFS [hazard ratio(HR)= 0.520, 95% confidence interval(CI):0.271-0.998, P = 0.049;HR = 1.449, 95% CI:1.118-1.877, P = 0.005, respectively] and OS(HR=0.414, 95% CI:0.190-0.903, P = 0.027;HR= 1.581, 95% CI:1.204-2.077, P = 0.001, respectively) in patients with TNBC. Additionally, longer DFS and OS intervals were associated with increased number of CIK treatment cycles(DFS: P = 0.020;OS: P = 0.040). The majority of the patients who benefitted from CIK cell therapy were relatively early-stage TNBC patients.Conclusion: Chemotherapy in combination with adjuvant CIK could be used to lower the relapse and metastasis rate, thus effectively extending the survival time of TNBC patients, especially those at early stages.

A Novel Combined Approach for Metastatic Breast Cancer with Dural and Leptomeningeal Disease with an Impressive Clinical Outcome: A Case Study

Concurrent dural and leptomeningeal metastatic carcinomatosis are very rare and have a poor prognosis. Here we present a woman with advanced estrogen receptor (ER) positive and progesterone receptor (PR) positive breast cancer who presented with leptomeningeal disease. Patient underwent multi targeted epigenetic therapies applied in a protocol called MTET. She continued to respond to the interval treatment, which consisted only of the nutraceutical agents. Here we discuss her case in detail and we believe that such an example might be applied to other patients in this situation resulting clinical improvement and less toxicity.

Reirradiation of recurrent breast cancer with proton beam therapy:A case report and literature review

BACKGROUND Locoregional recurrence of breast cancer is challenging for clinicians,due to the various former treatments patients have undergone.However,treatment of the recurrence with systemic therapy and subsequent reirradiation of chest wall is accompanied by increased toxicities,particularly radiation-induced cardiovascular disease.Reirradiation by proton beam therapy(PBT)enables superior preservation of adjacent organs at risk as well as concurrent dose escalation for delivery to the gross tumor.This technology is expected to improve the overall outcome of recurrent breast cancer.CASE SUMMARY A 47-year-old female presented with an extensive locoregional recurrence at 10 yr after primary treatment of a luminal A breast cancer.Because of tumor progression despite having undergone bilateral ovarectomy and systemic therapy,the patient was treated with PBT BE total dose of 64.40 Gy to each gross tumor and 56.00 Gy to the upper mediastinal and retrosternal lymphatics including the entire sternum in 28 fractions.Follow-up computed tomography showed a partial remission,without evidence of newly emerging metastasis.At 19 mo after the PBT,the patient developed a radiation-induced pericardial disease and pleural effusions with clinical burden of dyspnea,which were successfully treated by drainage and corticosteroid.Cytological analysis of the puncture fluid showed no malignancy,and the subsequent computed tomography scan indicated stable disease as well as significantly decreased pericardial and pleural effusions.The patient remains free of progression to date.CONCLUSION PBT was a safe and effective method of reirradiation for locoregionally recurrent breast cancer in our patient.

A case report of breast Paget’s disease and related literature

Paget’s disease is a relatively rare disease that occurs in the nipple and areola areas,and the early symptoms are not typical.In this study,we notified a case of a patient with Paget’s disease complicated with breast cancer.The tumor found in the postoperative pathological specimen has no blood flow signal,and its tissue density is similar to that of the surrounding glandular tissue,and there is no calcification point.This situation is rare through an extensive literature review.Our research can provide experience for clinical diagnosis and treatment of Paget’s disease with breast cancer.

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis

Background:Programmed cell death 1(PD-1)and programmed cell death ligand 1(PD-L1)inhibitors have become integral elements within the current landscape of breast cancer treatment modalities;however,they are associ-ated with interstitial lung disease(ILD),which is rare but potentially fatal.Notably,only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors.Therefore,this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors.We also reported three cases of ILD after PD-1 inhibitor treatment.Methods:We comprehensively searched PubMed,EMBASE,and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer.Pooled overall estimates of incidence and risk ratio(RR)were calculated with a 95%confidence interval(CI),and a mirror group analysis was per-formed using eligible studies.Results:This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment.A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors(0.05 vs.0.02).The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors(RR=2.34,95%CI,1.13-4.82,P=0.02).Conclusion:Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors.These findings are instrumental for clinicians in treatment deliberations,and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Decrease in the Ki67 index during neoadjuvant chemotherapy predicts favorable relapse-free survival in patients with locally advanced breast cancer

Objective: The purpose of this study was to explore the optimal cutoffs of the three parameters of Ki67 during NAC for predicting patient prognosis and investigate whether the optimal cutoffs of the Ki67 values were associated with relapse-free survival(RFS) or breast cancer-specific survival(BCSS).Methods: A total of 92 patients with locally advanced breast cancer(LABC), who had residual disease after NAC were retrospectively investigated.The optimal cutoff values of the Ki67 parameters were assessed by the online algorithm Cutoff Finder.Kaplan-Meier analysis, the log-rank test and Cox regression analysis were carried out to analyze survival.Results: The optimal cutoff values for the postsurgical Ki67 level and the decrease in the Ki67 level during NAC were defined as 25% and 12.5%, respectively.According to the univariate survival analysis, a higher Ki67 level in residual disease was associated with poor RFS(P = 0.004) and BCSS(P = 0.014).In addition, a Ki67 expression decrease > 12.5% during NAC was related to favorable RFS(P = 0.007), but was not related to BCSS(P = 0.452).Cox regression analysis showed that the Ki67 expression decrease(> 12.5% vs.≤ 12.5%) and histological grade(grade 3 vs.grade 1-2) were the independent factors associated with RFS(P =0.020 and P = 0.023, respectively), with HR values of 0.353(95% CI: 0.147-0.850) and 3.422(95% CI: 1.188-9.858), respectively.Conclusions: The Ki67 decrease was one of the independent factors associated with RFS in LABC patients with residual disease after receiving NAC.

Automated Deep Learning Empowered Breast Cancer Diagnosis UsingBiomedical Mammogram Images

Biomedical image processing is a hot research topic which helps to majorly assist the disease diagnostic process.At the same time,breast cancer becomes the deadliest disease among women and can be detected by the use of different imaging techniques.Digital mammograms can be used for the earlier identification and diagnostic of breast cancer to minimize the death rate.But the proper identification of breast cancer has mainly relied on the mammography findings and results to increased false positives.For resolving the issues of false positives of breast cancer diagnosis,this paper presents an automated deep learning based breast cancer diagnosis(ADL-BCD)model using digital mammograms.The goal of the ADL-BCD technique is to properly detect the existence of breast lesions using digital mammograms.The proposed model involves Gaussian filter based pre-processing and Tsallis entropy based image segmentation.In addition,Deep Convolutional Neural Network based Residual Network(ResNet 34)is applied for feature extraction purposes.Specifically,a hyper parameter tuning process using chimp optimization algorithm(COA)is applied to tune the parameters involved in ResNet 34 model.The wavelet neural network(WNN)is used for the classification of digital mammograms for the detection of breast cancer.The ADL-BCD method is evaluated using a benchmark dataset and the results are analyzed under several performance measures.The simulation outcome indicated that the ADL-BCD model outperforms the state of art methods in terms of different measures.

TNF inhibitors to treat ulcerative colitis in a metastatic breast cancer patient:A case report and literature review

Adalimumab (ADA) is a tumor necrosis factor (TNF) inhibitor, used for the treatment of inflammatory bowel disease. Previous studies have reported an increased risk of cancer following exposure to TNF inhibitors, but little has been reported for patients with cancer receiving TNF-inhibitor treatment. We present a female patient with metastatic breast cancer and ulcerative colitis (UC) who was treated with ADA. A 54-year-old African American female with a past history of left-sided breast cancer (BC) diagnosed at age 30 was initially treated with left-breast lumpectomy, axillary dissection, followed by chemotherapy and radiation therapy. Years after initial diagnosis, she developed recurrent, bilateral BC and had bilateral mastectomy. Subsequent restaging computed tomography (CT) scan demonstrated distant metastases to the bone and lymph nodes. Three years into her treatment of metastatic breast cancer, she was diagnosed with UC by colonoscopy. Her UC was not controlled for 5 mo with 5-aminosalicylates. Subcutaneous ADA was started and resulted in dramatic improvement of UC. Four months after starting ADA, along with ongoing chemotherapy, restaging CT scan showed resolution of the previously seen metastatic lymph nodes. Bone scan and follow-up positron emission tomography/CT scans performed every 6 mo indicated the stability of healed metastatic bone lesions for the past 3 years on ADA. While TNF-&#x003b1; inhibitors could theoretically promote further metastases in patients with prior cancer, this is the first report of a patient with metastatic breast cancer in whom the cancer has remained stable for 3 years after ADA initiation for UC.

Breast Cancer Subtypes and Survival in Chinese Women with Operable Primary Breast Cancer

Objective： To investigate the associations between the different breast cancer subtypes and survival in Chinese women with operable primary breast cancer. Methods： A total of 1538 Chinese women with operable primary breast cancer were analyzed in this study, the median follow-up was 77 months. Estrogen receptor （ER）, progesterone receptor （PR）, and HER2 status were available for these patients. Results： Luminal A （ER＋ and/or PR＋, HER2-） had a favorable disease-free survival （DFS） and overall survival （OS） compared with other subtypes in the entire cohort. Using the luminal A as a reference, among the patients with lymph node positive disease, HER2＋ （ER-, PR-, HER2＋） had the worst DFS （hazard ratio, HR=1.80, 95% CI 1.11 to 2.91, P=0.017） and luminal B （ER＋ and/or PR＋, HER2＋） had the worst OS （HR=2.27, 95% CI 1.50 to 3.45, P0.001）; among the patients with lymph node negative disease, triple-negative （ER-, PR-, HER2-） had the worst DFS （HR=2.21, 95% CI 1.43 to 3.41, P0.001）, whereas no significant difference in DFS between HER2＋ and luminal B or luminal A was observed. Conclusion： As compared with luminal A, luminal B and HER2＋ have the worst survival in patients with lymph node positive disease, but this is not the case in patients with lymph node negative disease; triple-negative subtype has a worse survival in both lymph node positive and lymph node negative patients.

TGF-β1 Precursor and CD8 Are Potential Prognostic and Predictive Markers in Operated Breast Cancer

The transforming growth factor β1（TGF-β1） and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130（stageⅠ–Ⅲ） invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival（DDFS）（HR=8.416, 95% CI=1.636–43.292, P=0.011） in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival（OS） than their counterparts with CD8-positive cell infiltration into tumor nests（Log-Rank, P=0.003）. But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy（Log-Rank, P=0.013） and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor（t-TGF-β1-pre）-positive patients than in the negative patients in patients without recieiving chemotherapy（P=0.053）, OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy（P=0.035） and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS（HR=0.392 95% CI=0.157–0.978, P=0.045） in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.

Immunotherapy in triple-negative breast cancer:A literature review and new advances

Triple-negative breast cancer(TNBC)is a highly complex,heterogeneous disease and historically has limited treatment options.It has a high probability of disease recurrence and rapid disease progression despite adequate systemic treatment.Immunotherapy has emerged as an important alternative in the management of this malignancy,showing an impact on progression-free survival and overall survival in selected populations.In this review we focused on immunotherapy and its current relevance in the management of TNBC,including various scenarios(metastatic and early-neoadjuvant,adjuvant-),new advances in this subtype and the research of potential predictive biomarkers of response to treatment.

Perceived health-related stigma among patients with breast cancer

Breast cancer survivors face many challenges(particularly changes in body image) on their road to restoring physical and psychosocial health following diagnosis. Perceived health-related stigma(PHS)refers to the attachment of negative connotations to some types of disease diagnoses. PHS is common among patients with breast cancer and is associated with adverse emotions, attitudes and behaviors. This article summarizes the latest advances and new perspectives on PHS of breast cancer patients and approaches to block this deleterious process. Effects of PHS on patients with breast cancer, in this paper,and measures, predictors and interventions of PHS have been discussed in depth. Future studies should continue to develop more effective instruments that are specialized for measuring PHS of breast cancer patients, explore the predictors of PHS, and discuss effective interventions on the basis of the predictors.

Metastatic Lobular Carcinoma of the Breast Presenting with Small Bowel Metastases:Case Report and Literature Review

Introduction: Invasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, representing 5% to 15% of invasive tumors. ILC tends to spread to bones, lungs, central nervous system, reproductive organs, and the gastrointestinal tract (GI tract). The most commonly affected organs in the GI tract are the stomach, small intestine, followed by colon and rectum. Case presentation: A 78-year-old woman who was referred to our institution after having a bowel obstruction that required a diagnostic laparoscopy where they identified an obstructing ulcerative lesion in the distal ileum that was managed with a segmental bowel resection. Pathology report showed an invasive lobular breast carcinoma that occluded 90% of the bowel lumen. A PET/CT scan revealed a left breast tumor with increased metabolism. The patient was staged as a clinical cT4b, cN0, cM1 left breast invasive lobular carcinoma (ER/PgR positive, HER-2 negative). She was managed with endocrine therapy with Letrozole (an eight-week course). A follow-up PET/CT showed a peritoneal hypermetabolic nodule adjacent to the previous ileal anastomosis. The lesion decreased in size and metabolic activity. In a multidisciplinary fashion, the endocrine therapy was extended for another three months. Another follow-up PET/CT scan was performed three months after the identification of the peritoneal implant that showed that the nodule increased in size and in metabolism. The lesion continued to decrease significantly in size and became metabolically inactivity. Due to the good breast response and the possibility that the ileal nodule could be a granuloma, she underwent an exploratory laparoscopy with excision of the peritoneal nodule, and a modified left radical mastectomy with immediate breast reconstruction (complex wound closure). The final pathology report of the nodule was negative for malignancy. She continued on endocrine therapy and underwent whole breast irradiation four weeks after the operation. Currently, she is free of disease with no evidence of local, regional, or distant recurrence, and she is still on endocrine therapy. Discussion: The time interval between primary breast cancer and gastrointestinal involvement may range from synchronous presentation to as long as 30 years. The clinical manifestations in GI lobular breast cancer metastasis may range from non-specific complaints to acute GI symptoms, such as a bowel obstruction. There are multiple controversies in the management of ILC. Systemic treatment should be initiated as soon as possible. Indications for postmastectomy radiotherapy are also controversial, given the propensity for multifocal/multicentric tumors and late recurrences, sometimes in atypical locations. Five years of postoperative adjuvant hormonal therapy is an option for women with poor prognosis. Remissions are observed in 32% to 53% of patients. Conclusion: Metastatic lobular carcinoma of the breast has a wide range of clinical presentations. Patients with a history of breast cancer who present with new GI tumors should have these lesions evaluated for evidence of metastasis through histopathologic and immunohistochemical analysis, this will allow for appropriate management. Currently, breast cancer management involves a multidisciplinary approach including surgery, radiotherapy, and systemic medical therapy, and the treatment must be tailored to the patient’s needs.

P─GLYCOPROTEIN EXPRESSION IN PRIMARY BREAST CANCER

In a retrospective study. liquid nitrogen preserved specimens from 50 women with primary breast cancer, who underwent surgery at the Beijing Institute for Cancer Research between June. 1986 and September, 1988, were investigated. All patients under this study were staged in TNM II or later, involved with axillary lymph node metastasis. and treated with systemic postoperative adjuvant chemotherapy. The median length of follow-up was 69 months. The expression of P-glycoprotein was investigated by means of immunohistochemistry, using a monoclonal antibody C219 specifically against P-glycoprotein and avidin -biotin peroxidase method. Posrtive staining for P-glycoprotein was found in 23(16%) of the 50 patients. The P-glycoprotein expression negative group fared better than the group that was P-glycoprotein posrtive in overall survival curves (p= 0. 0008 , by the generalized Wilcoxon test). The prognostic effect of P-glycoprotein expression remained statistically significant (p=0. 0007) after adjustment by multivariate analysis(Cox’s model)for other prognostic factors. It is demonstrated that P-glycoprotein expression is a significant and independent Predictor of postoperative survival in breast cancer patients. The results of the present study suggest that P-glycoprotein expression might also influence the bioiogical behavior of breast cancers.

Breast cancer immunotherapy:Realities and advances

Breast cancer(BC)is the most common malignant tumor and the main cause of death in women worldwide.With increased knowledge regarding tumor escape mechanisms and advances in immunology,many new antitumor strategies such as nonspecific immunotherapies,monoclonal antibodies,anticancer vaccines,and oncolytic viruses,among others,make immunotherapy a promising approach for the treatment of BC.However,these approaches still require meticulous assessment and readjustment as resistance and modest response rates remain important barriers.In this article,we aim to summarize the most recent data available in BC immunotherapy to include the results of ongoing clinical trials and approved therapies used as monotherapies or in combination with conventional treatments.

Blood cellular mutant LXR-α protein stability governs initiation of coronary heart disease

AIM: To investigate the role of [breast and ovarian cancer susceptibility 1（BRCA1）-associated RING domain 1（BARD1）]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-（LXR-α） protein in coronary heart disease（CHD） subjects.METHODS: The expression analysis of various genes was carried out by quantitative real time polymerase chain reaction and western blotting within blood mononuclear cells of human CHD subjects at various stages of coronary occlusion and their corresponding normal healthy counterparts.Immunoprecipitation experiments were performed to establish protein interactions between LXR-αand BARD1.Peripheral blood mononuclear cells were cultured and exposed to Vitamin D3 and Cisplatin to validate the degradation of mutant LXR-αprotein in CHD subjects by BARD1/BRCA1 complex.RESULTS: The expression of mutant LXR-αprotein in CHD subjects was found to decrease gradually with the severity of coronary occlusion exhibiting a strong negative correlation,r =-0.975 at P 【 0.001.Further,the expression of BARD1 and BRCA1 also increased with the disease severity,r = 0.895 and 0.873 respectively（P 【 0.001）.Immunoprecipitation studies established that BARD1/BRCA1 complex degrades mutant LXR-αvia ubiquitination.The absence of functional LXR-αprotein resulted in increased expression of inflammatory cytokines such as interleukin（IL）-6,IL-8 and interferon-and decreased expression of ABCA1（ATP-binding cassette A1）（r = 0.932,0.949,0.918 and-0.902 with respect to Gensini score;P 【 0.001）.Additionally,cell culture experiments proved that Vitamin D3 could prevent the degradation of mutant LXR-αand restore its functional activity to some extent.CONCLUSION: Mutant LXR-αprotein in CHD subjects is degraded by BARD1/BRCA1 complex and Vitamin D3 can rescue and restore its function.