Effects In Breast Cancer Patients Research Articles

Fabrication and characterization of transdermal delivery of ribociclib nanoemulgel in breast cancer treatment.

The objective of this study is to create a nanoemulgel formulation of Ribociclib (RIBO), a highly selective inhibitor of CDK4/6 through the utilization of spontaneous emulsification method. An experimental investigation was conducted to construct pseudo-ternary phase diagram for the most favourable formulation utilizing rice bran oil, which is known for its diverse anticancer properties. The formulation consisted of varying combination of the surfactant and as the co-surfactant (Tween 80 and Transcutol, respectively) referred to as Smix and the trials were optimized to get the desired outcome. The nanoemulsion (NE) formulations that were developed exhibited a droplet size of 179.39 nm, accompanied with a PDI of 0.211. According to the data released by Opt-RIBO-NE, it can be inferred that the Higuchi model had the most favourable fit among many kinetics models considered. The results indicate that the use of nanogel preparations for the topical delivery of RIBO in breast cancer therapy, specifically RIBO-NE-G, is viable. This is supported by the extended release of the RIBO, and the appropriate level of drug permeation observed in Opt-RIBO-NE-G. Due to RIBO and Rice Bran oil, RIBO-NE-G had greater antioxidant activity, indicating its effectiveness as antioxidants. The stability of the RIBO-NE-G was observed over a period of three months, indicating a favourable shelf life. Therefore, this study proposes the utilization of an optimized formulation of RIBO-NE-G may enhance the efficacy of anticancer treatment and mitigate the occurrence of systemic side effects in breast cancer patients, as compared to the use of suspension preparation of RIBO.

Chemotherapy-induced cardiotoxic effect in breast cancer patients treated with trastuzumab (Herceptin) by MRI

BackgroundChemotherapy-associated cardiomyopathy is a well-known cardiotoxicity of contemporary cancer treatment. As cancer outcomes improve, cardiovascular disease has become a leading cause of morbidity and mortality among cancer survivors. The objective of this study was to evaluate the role of CMR in the detection of early cardiotoxic changes and in the identification of patients at risk of developing CTRCD.Patients and methodsFifty patients diagnosed breast cancer examined by echocardiography and cardiac MRI before the start of chemotherapeutic regimen followed by 2 and 4 months post-chemotherapy.ResultsBy echocardiography, all measures were within normal range at the start and at the first follow-up. Twenty (40%) patients show decreased LVEF at second follow-up reaching up to 50% with milder affection of the other parameters. CMR examination shows decreased LVF at second and third follow-up (p = 0.005). There was significant elevation of T2 value for 10 patients at first follow-up (p value 0.04) and for 22 patients at second follow-up (p value 0.01) in correlation with baseline. The T1 mapping and ECV showed elevation at first and second follow-up as compared to baseline (p = < 0.05).ConclusionT1 and T2 mapping is superior to echocardiography in early detection of the cardiotoxic effects of chemotherapy applied for breast cancer patients and can guide the management and patient lifestyle.

Antiproliferative effect of Solanum nigrum L. water extract on breast can-cer cells: potential roles of apoptosis and oxidative stress.

Breast cancer is the most progressive cancer among women worldwide. The currently available chemotherapeutic agents induce severe unacceptable adverse effects in breast cancer patients. In this context, natural medicinal herbs are gaining importance to find non-toxic effective anticancer drugs. Solanum nigrum is one of the major traditional medicinal plants widely used in Ayurveda for the treatment of various diseases. This study investigated the anticancer effect of Solanum nigrum water extract (SNWE) against MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines. SNWE significantly induced oxidative stress-mediated apoptotic cell death in a concentration-dependent manner. Real-time PCR results illustrated the upregulation of proapoptotic genes and downregulation of antiapoptotic genes after SNWE treatment in MCF-7 and MDA-MB-231 cell lines. Immunofluorescence analysis showed increased expressions of apoptotic markers like p53, Caspase3 and BAX by SNWE treatment. In conclusion, the findings of this study indicate the antiproliferative effect and apoptosis-inducing property of SNWE in both cell lines. Further studies are warranted on testing the anticancer activity of S. nigrum L. using animal models of cancer.

A prognostic mathematical model based on tumor microenvironment-related genes expression for breast cancer patients.

Tumor microenvironment (TME) status is closely related to breast cancer (BC) prognosis and systemic therapeutic effects. However, to date studies have not considered the interactions of immune and stromal cells at the gene expression level in BC as a whole. Herein, we constructed a predictive model, for adjuvant decision-making, by mining TME molecular expression information related to BC patient prognosis and drug treatment sensitivity. Clinical information and gene expression profiles were extracted from The Cancer Genome Atlas (TCGA), with patients divided into high- and low-score groups according to immune/stromal scores. TME-related prognostic genes were identified using Kaplan-Meier analysis, functional enrichment analysis, and protein-protein interaction (PPI) networks, and validated in the Gene Expression Omnibus (GEO) database. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to construct and verify a prognostic model based on TME-related genes. In addition, the patients' response to chemotherapy and immunotherapy was assessed by survival outcome and immunohistochemistry (IPS). Immunohistochemistry (IHC) staining laid a solid foundation for exploring the value of novel therapeutic target genes. By dividing patients into low- and high-risk groups, a significant distinction in overall survival was found (p < 0.05). The risk model was independent of multiple clinicopathological parameters and accurately predicted prognosis in BC patients (p < 0.05). The nomogram-integrated risk score had high prediction accuracy and applicability, when compared with simple clinicopathological features. As predicted by the risk model, regardless of the chemotherapy regimen, the survival advantage of the low-risk group was evident in those patients receiving chemotherapy (p < 0.05). However, in patients receiving anthracycline (A) therapy, outcomes were not significantly different when compared with those receiving no-A therapy (p = 0.24), suggesting these patients may omit from A-containing adjuvant chemotherapy. Our risk model also effectively predicted tumor mutation burden (TMB) and immunotherapy efficacy in BC patients (p < 0.05). The prognostic score model based on TME-related genes effectively predicted prognosis and chemotherapy effects in BC patients. The model provides a theoretical basis for novel driver-gene discover in BC and guides the decision-making for the adjuvant treatment of early breast cancer (eBC).

The Predictors of Taxane Induce Peripheral Neuropathy as a Side Effect in Breast Cancer Patients among Iraqi Women

The Predictors of Taxane Induce Peripheral Neuropathy as a Side Effect in Breast Cancer Patients among Iraqi Women

Effect of Electrocardiogram Observation on Chemotherapy and Radiotherapy Combined with Trastuzumab in Breast Cancer Postoperative Patients

In order to improve the therapeutic effect of breast cancer patients, trastuzumab combined with chemotherapy followed by radiotherapy was applied to breast cancer patients in this study and to observe the effect of this treatment on the abnormal rate of electrocardiogram and serum indexes of breast cancer patients. 60 patients received targeted therapy and chemotherapy during perioperative period. All patients received local radiotherapy after surgery. At the same time, for patients with poor peripheral blood vessels, jugular vein or subclavian vein catheterization should be performed before chemotherapy to avoid vein inflammation. The abnormal rate of electrocardiogram and serum indexes and rate of adverse reactions of 60 patients were examined. The results show that the abnormal electrocardiogram rate at T1, T2 and T3 was gradually increasing. The serum indexes after chemotherapy and radiotherapy are lower than those before chemotherapy and radiotherapy respectively. After chemotherapy and radiotherapy, there were 3 cases of radiation pneumonitis, 2 cases of pain and 2 cases of abnormal liver function. Postoperative chemotherapy and radiotherapy combined with trastuzumab can decrease serum levels in breast cancer patients. Meanwhile, the abnormal rate of electrocardiogram and cardiotoxicity were higher. Therefore, before trastuzumab therapy, cardiac function safety tests should be conducted in breast cancer patients and cardiac function should be closely monitored.

Oxidative stress in breast cancer after chemotherapy.

It is of interest to evaluate the influence of breast cancer on oxidative stress, liver function tests, renal biomarkers, action of doxorubicin, cyclophosphamide and paclitaxel (AC-T) in the treatment and mechanism over altering the measured markers in breast cancer. Sixty histopathological confirmed cases of female patients suffering with breast carcinoma from the Department of Oncology at Omega Cancer Hospital, Visakhapatnam were included in the study. The investigation was performed in 3 groups: a control group containing 30 healthy females of similar age, 30 breast cancer patients without treatment and 30 patients receiving treatment with anticancer combination drugs AC-T. The venous blood samples from both controls and patients were measured for total antioxidant status (TAS), nitric oxide (NO), malondialdehyde, alanine aminotransferase, aspartate aminotransferase, and blood urea, serum creatinine. One-way ANOVA and Tukey-Kramer multiple comparisons post-test were applied as statistical analysis tools through SPPS software version 20.0. P<0.05 was regarded as significant. According to the findings, higher stages of breast cancer were linked to considerable increase in oxidative stress markers during AC-T treatment. The findings of the study revealed that oxidative stress is linked to breast cancer, and that chemotherapy exacerbates this oxidative stress, causing damage to a variety of cellular targets. Monitoring serum oxidative stress markers may aid in the evaluation of chemotherapy effects in breast cancer patients. According to our findings, AC-T chemotherapy will elevate malondialdehyde, a lipid peroxidation marker, and lowers the total antioxidant status.

Supplementation in suppressing Troponin I and NT-proBNP level in breast cancer patients with 5- fluorouracil, adriamycin, and cyclophosphamide chemotherapy

Background: Breast cancer is a malignancy originating from breast tissue, where chemotherapy is one of the choice therapy. Doxorubicin, 5-fluorouracil, and cyclophosphamide (FAC) are the most commonly used combination of chemotherapy. One of the side effects of chemotherapy is cardiotoxicity. Multiflora honey prevents cardiotoxic effects through its flavonoids and polyphenols compounds. The aim of this research is to analyze the effectiveness of adding honey in preventing cardiotoxic effects in breast cancer patients receiving FAC chemotherapy. Methods: An experimental study with double-blind randomized pre and post-test with control group design. Ductal invasive breast cancer patients were divided into 2 groups, the control group, who received FAC chemotherapy (n=18) and the treatment group, who received chemotherapy and 90 ml/day honey consumption for 14 days (n=18). The patient's Troponin I and NT-proBNP enzyme levels before and after 14 days of the study were assessed. Results: Post-treatment, there was an increase in Troponin I levels from the treatment group (0.22 ± 0.07 vs. 0.24 ± 0.07) vs. control (0.25 ± 0.11 vs. 0.34 ± 0.20) with a significant difference. (p = 0.031). There was a decrease in NT-proBNP levels in the treatment group (461.0 ± 610.4 vs. 215.6 ± 260.3) and an increase in NT-proBNP levels (275.9 ± 392.4 vs. 315.4 ± 293.9) with a significant difference (p = 0.006). Conclusion: Multiflora honey can prevent cardiotoxic effects in breast cancer patients receiving FAC chemotherapy.

Remifentanil combined with dexmedetomidine on the analgesic effect of breast cancer patients undergoing modified radical mastectomy and the influence of perioperative T lymphocyte subsets.

To study the analgesic effect of breast cancer patients undergoing modified radical mastectomy (MRM) and the influence of perioperative T lymphocyte subsets by remifentanil combined with dexmedetomidine. 80 breast patients were divided into control group and research group based on the anesthesia protocol. Patients in control group was given remifentanil for anesthesia induction and maintenance, and patients in research group was given remifentanil and dexmedetomidine for anesthesia induction and maintenance. We compared the anesthesia time, operation time, surgical blood loss, postoperative wake-up time, extubation time, incidence of adverse reactions, VAS score and T lymphocyte subsets in peripheral blood in the two groups of patients. The baseline data including age, height, weight and BMI, ASA classification, stage of breast cancer, frequency of neoadjuvant therapy, and surgical characteristics including anesthesia time, operation time and bleeding volume all have no significant difference between two groups (P > 0.05). Compared to control group, the time of wake up and extubation in patients of research group were all significantly decreased (P < 0.05), and significantly decreased MBP and HR after loading dose of dexmedetomidine in research group (P < 0.05). The VAS scores of patients at 4, 8, 12, 16, 20 and 24 h after surgery in the research group are all significantly lower than those in the control group (P < 0.05). Before induction of anesthesia, there was no significant difference in the ratio of CD4+, CD8+ and CD4+/CD8+ T lymphocytes in peripheral blood between the two groups (P > 0.05). At 1 h during operation and 24 h after operation, the ratio of CD4+ and CD4+/CD8+ cells in the research group was significantly higher than these of the control group (P < 0.05), while the ratio of CD8+ cells was lower than that of the control group (P < 0.05). For breast cancer patients undergoing MRM, the use of remifentanil combined with dexmedetomidine can enhance postoperative analgesia and reduce postoperative immunosuppression.

FN1 overexpression is correlated with unfavorable prognosis and immune infiltrates in breast cancer.

Objective: To investigate the correlation of fibronectin 1 (FN1) expression with prognosis and tumor-infiltrating immune cells in breast cancer (BRCA). Methods: FN1 mRNA and protein expressions were analyzed through Tumor Immune Estimation Resource (TIMER), Gene Set Cancer Analysis (GSCA), Human Protein Atlas (HPA) databases, and immunohistochemical analysis. The clinicopathological characteristics and genetic factors affecting the FN1 mRNA expression were assessed by various public databases. Then, we analyzed the prognostic value of FN1 in BRCA by Kaplan-Meier plotter, receiver operating characteristic, and Cox regression analyses. Further, the UCSC Xena database was used to retrieve TCGA-BRCA expression profiles for functional enrichment analysis and immune cell infiltration analysis. The potential drugs for the BRCA patients with high- FN1 expression were identified using the connectivity map analysis. Results: FN1 was upregulated in BRCA tissues compared with normal tissues. High FN1 mRNA expression was correlated with poor clinical outcomes and had good performance in predicting the survival status of BRCA patients. Further, Cox regression analysis showed that FN1 was an independent prognostic factor for predicting the overall survival of patients with BRCA. Moreover, hypermethylation of FN1 contributed to a better prognosis for BRCA patients. Functional enrichment analyses revealed the ECM-receptor interaction pathway and focal adhesion as the common pathways. Moreover, FN1 showed a significant association with tumor-infiltrating immune cells and immune checkpoint inhibitors. Several drugs such as telmisartan, malotilate, and seocalcitol may have therapeutic effects in BRCA patients with high FN1 expression. Conclusion: FN1 might serve as a novel prognostic biomarker and a novel therapeutic target for BRCA. Besides, the association of FN1 with immune cells and immune checkpoint inhibitors may provide assistance for BRCA treatment.

Chemotherapy-associated oral microbiome changes in breast cancer patients.

Cytotoxic chemotherapy with or without a combination of humanized monoclonal antibodies is regarded as the gold standard of personalized medicine for the treatment of breast cancer patients. Significant medication-related side effects are common accompanying phenomena for these patients, such as oral discomfort, mucositis, or even osteonecrosis of the jaw. In this study, we analyze the saliva samples of 20 breast cancer patients at three time points throughout their chemotherapy: at the baseline prior to treatment initiation (T1), after four-to-six cycles of chemotherapy (T2), and 1 year after the start of the treatment (T3) to investigate and characterize the long-term effects of chemotherapy on the oral microbiome. We aimed to characterize changes in the oral bacterial microbiome based on 16S rRNA gene amplicon analysis during chemotherapeutic treatment, as a potential target to treat common oral side effects occurring during therapy. The chemotherapeutic drugs used in our study for patient treatment were trastuzumab, docetaxel, pertuzumab, epirubicin, and cyclophosphamide. We find a significant increase in the relative abundance of potentially pathogenic taxa like Escherichia/Shigella and non-significant trends in the relative abundance of, for example, Actinomyces ssp. In conclusion, the role of microbiota in the oral side effects of chemotherapeutic treatment needs to be considered and should be analyzed in more detail using larger patient cohorts. Oral side effects in breast cancer patients undergoing chemotherapy are a common burden and should be treated for a better tolerability of the therapy.

Obesity Impact on Managing Aromatase Inhibitors Side Effects in Breast Cancer Patients

ObjectivesBecause the main aromatase inhibitors side effects are osteoporosis and dyslipidemia, vitamin D, calcium dietary supplements and statins are frequently co-administered alongside the antiestrogenic treatment. Does this common clinical practice have scientific arguments behind it? MethodsThe scientific literature available since 2000 addressing the efficacy of vitamin D, calcium dietary supplements and statins in preventing osteoporosis and dyslipidemia was searched and efficacy randomized controlled trials, meta-analysis and systematic reviews results are further reported. ResultsThe current scientific data on cardiovascular disease shows that successfully achieved lowered LDL-cholesterol does not associate lowered mortality, the difference in survival between people with high cardiovascular risk who take statins compared to those who do not take statins being only 4 days. Furthermore, taking vitamin D supplements for cardiovascular protection or for cancer prevention for that matter is a recommendation unsupported by the current scientific literature. Also, the current scientific data on osteoporosis prevention shows that the prophylactic prescription of vitamin D and calcium dietary supplements in patients without objectively proven deficiencies does not prevent osteoporosis, increasing fractures risk. Aromatase inhibitors side effects are highly influenced by patient’s adiposity. Current data shows that obesity increases cardiovascular risk, and that obese patients have lower vitamin D blood levels because of its deposition inside the fat tissue, vitamin D levels going back up to normal without supplements when adiposity decreases. ConclusionsObesity decreases statins, vitamin D and calcium dietary supplements efficacy in counteracting AI side effects. But, because of the potential negative metabolic impact of improper diets, weight loss in breast cancer patients under antiestrogenic treatment should be carefully designed and monitored by dietitians with expertise in oncology nutrition. Funding SourcesNone.

Aromatase Inhibitors and Risk of Metabolic and Cardiovascular Adverse Effects in Breast Cancer Patients-A Systematic Review and Meta-Analysis.

Aromatase inhibitors (AIs) have been considered first-line therapy for patients with hormone-dependent breast cancer due to their high efficacy and good tolerability. However, AIs are not free of adverse events, and studies show that therapy with AIs is associated with an increased risk of cardiovascular events and the development of insulin resistance and diabetes. We searched the Cochrane Central Register of Controlled Trials, PubMed and EMBASE up to 27 October 2020 for the prevalence of cardiovascular and/or metabolic adverse effects during treatment with AIs in postmenopausal women with breast cancer. A meta-analysis was performed using a random effects model. Odds ratios and 95% confidence intervals were calculated and illustrated using forest plot charts. We performed separate analyses depending on trial design. Twenty two studies met the inclusion criteria. AIs were associated with a higher risk of cardiovascular events, especially when we compared study arms in which AIs were used (alone or in sequence with TAM) with the arms in which TAM was used alone (OR = 1.16; 95%CI 1.04–1.30) or when comparing patients taking AIs alone to patients taking TAM alone or in sequence with AIs (OR = 1.24; 95%CI 1.11–1.38). A pooled analysis of five trials comparing adjuvant AIs to TAM showed the odds for arterial hypertension being 1.31 times higher for patients taking AIs; however, this did not reach statistical significance (OR = 1.31; 95%CI 0.47–3.65). We have not shown an increased risk of dyslipidemia or weight gain with the use of AIs. Our results suggest that postmenopausal women with breast cancer treated with AIs have an increased risk of cardiovascular events in comparison with TAM, potentially due more to a cardioprotective effect of the latter than the cardiotoxicity of AIs. We were unable to prove a similar association for hypertension, dyslipidemia, hyperglycemia or weight gain. Further high-quality RCTs and post-marketing safety observational studies are needed to definitively evaluate the impact of AIs on metabolic disorders in breast cancer patients.

Nanomedicine-Based Delivery Strategies for Breast Cancer Treatment and Management.

Breast cancer is one of the most common types of cancer among women globally. It is caused by mutations in the estrogen/progesterone receptors and conventional treatment methods are commonly utilized. About 70–80 percent of individuals with the early-stage non-metastatic disease may be cured. Conventional treatment is far less than the optimal ratio, as demonstrated through the high mortality rate of women with this cancer. However, conventional treatment methods like surgery, radiotherapy, and chemotherapy are not as effective as expected and lead to concerns about low bioavailability, low cellular uptake, emerging resistance, and adverse toxicities. A nanomedicine-based approach is a promising alternative for breast cancer treatment. The present era is witnessing rapid advancements in nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. This paper focuses on nanomedicine-based therapeutic interventions that are becoming more widely accepted for improving treatment effectiveness and reducing undesired side effects in breast cancer patients. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review.

Analysis of Clinical Characteristics, Treatment, and Prognostic Factors of 106 Breast Cancer Patients With Solitary Pulmonary Nodules.

ObjectiveThe clinical features of solitary pulmonary nodules (SPN) in breast cancer patients were retrospectively analyzed, and the clinical features of primary lung cancer (PLC) and metastatic pulmonary breast cancer (MBC) in breast cancer patients were compared, and the treatment plan, curative effect and influencing factors were analyzed.MethodsThe clinical data of 106 patients of SPN combined with breast cancer surgery in our hospital from January 2015 to June 2020 were analyzed. There were 65 patients of PLC and 41 patients of MBC. Record the characteristics of the primary breast cancer lesion in our patient, the interval between the initial diagnosis of breast cancer and the appearance of SPN, the previous treatment history of our patient, and the characteristics and surgical method of SPN. The survival status of all patients during the follow-up period was recorded.ResultsThe onset age, interval, maximum nodule diameter, ER expression positive rate and radiotherapy history ratio of PLC patients were higher than those of MBC patients, and the lymph node positive rate and triple negative rate were lower than those of MBC patients (P < 0.05). Median survival was 51 months in patients with PLC and 37 months in patients with MBC. The 1, 3, and 5 year overall survival rates in patients with PLC were higher than those in patients with MBC (P < 0.05). Vascular tumor thrombus, SPN type and chemotherapy were all independent factors affecting the prognosis of patients with breast cancer combined with SPN (P < 0.05).ConclusionPLC patients and MBC patients have significant differences in pathological characteristics, like the onset age, interval, maximum nodule diameter, ER expression positive rate, radiotherapy history ratio, the lymph node positive rate, and triple negative rate. Septum, vascular tumor thrombus, SPN type, and chemotherapy are all independent factors that affect the curative effect of breast cancer patients with SPN. Based on the nature of SPN, it can provide reference for clinicians to decide the treatment plan, improve patients' quality of life and prolong their survival time.

Unraveling the Effect of Breast Cancer Patients’ Plasma on the Targeting Ability of Folic Acid-Modified Chitosan Nanoparticles

The formation of protein corona (PC) around nanoparticles (NPs) has been reported inside biological conditions. This effect can alter delivery capacity toward the targeted tissues. Here, we synthesized folic acid-modified chitosan NPs (FA-CS NPs) using different concentrations of folic acid (5, 10, and 20%). FA-CS NPs were exposed to plasmas of breast cancer patients and healthy donors to evaluate the possibility of PC formation. We also monitored uptake efficiency in in vitro conditions after incubation with human breast cancer cell line MDA-MB-231 and monocyte/macrophage-like Raw264.7 cells. Data showed that the formation of PC around FA-CS NPs can change physicochemical properties coincided with the rise in NP size and negative surface charge. SDS-PAGE electrophoresis revealed differences in the type and content rate of plasma proteins attached to NP surface in a personalized manner. Based on MTT data, the formation of PC around NPs did not exert cytotoxic effects on MDA-MB-231 cells while this phenomenon reduced uptake rate. Fluorescence imaging and flow cytometry analyses revealed reduced cellular internalization rate in NPs exposed to patients' plasma compared to the control group. In contrast to breast MDA-MB-231 cells, Raw264.7 cells efficiently adsorbed the bare and PC-coated NPs from both sources, indicating the involvement of ligand-receptor-dependent and independent cellular engulfment. These data showed that the PC formed on the FA-CS NPs is entirely different in breast cancer patients and healthy counterparts. PC derived from patients' plasma almost abolishes the targeting efficiency of FA-CS NPs even in different mechanisms, while this behavior was not shown in the control group. Surprisingly, Raw264.7 cells strongly adsorbed the PC-coated NPs, especially when these particles were in the presence of patients' sera. It is strongly suggested that the formation of PC around can affect delivering capacity of FA-CS NPs to cancer cells. It seems that the PC-coated FA-CS NPs can be used as an efficient delivery strategy for the transfer of specific biomolecules in immune system disorders.

Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy

BackgroundTumour-infiltrating lymphocyte (TIL)-high breast tumours have a high rate of pathological complete response (pCR) with neoadjuvant chemotherapy. In our routine pathological diagnoses of biopsy specimens from pCR cases, we have observed a high infiltration of plasma cells (PCs). A positive correlation of PCs with favourable patient outcome has recently been reported, but little is known about how PCs contribute to local tumour immunity.MethodsWe retrospectively examined biopsy specimens from 146 patients with invasive breast cancer who received neoadjuvant chemotherapy. CD138+ PC infiltration was assessed by immunohistochemistry. Multiplexed fluorescent immunohistochemistry (mfIHC) with T and B cell markers was also conducted to elucidate the profile of immune cells.ResultsGreater PC infiltration was observed in the pCR group (p = 0.028) and this trend was confirmed in another patient cohort. With mfIHC, we observed significantly more CD8+, T-bet+CD4+, and CD8+FOXP3+ T cells, total B cells and PCs in pCR cases. Such cases were also characterised by high expression of both PD-1 and PD-L1 on B cells and PCs. In patients with hormone receptor-negative tumours, high PC infiltration was correlated with significantly longer disease-free survival (p = 0.034).ConclusionsWe found that higher PC infiltration in biopsy specimens before neoadjuvant chemotherapy was associated with pCR. With mfIHC, we also revealed that the local cytotoxic immune response was clearly enhanced in pCR cases, as was the infiltration of B cells including PCs. Moreover, higher PC levels were correlated with favourable outcomes in hormone receptor-negative breast cancer patients.

Cardiac late effects after modern 3D-conformal radiotherapy in breast cancer patients: a retrospective cohort study in Germany (ESCaRa)

PurposeRadiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany.MethodsA total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account.ResultsAfter a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85–1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88–1.25).ConclusionsEven though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.

Interventions for Preventing Cardiotoxicity in Breast Cancer Patients Receiving Trastuzumab: A Systemic Review and Bayesian Network Meta-Analysis.

Background: Trastuzumab is associated with the risk of cardiotoxicity. Here, we aim to explore interventions for preventing trastuzumab-related cardiotoxic effects in breast cancer patients.Methods: A systematic review was performed including trials of breast cancer patients with intervention to prevent cardiotoxicity of trastuzumab. Trials were searched through databases including PubMed, Embase, and Cochrane Library.Results: Eight RCTs were included. Five trials reported the outcomes of short-duration interventions, including 6-month and 9-week durations, and only 9-week treatment has a significant difference from the 12-month group (OR 0.38; 95% CI 0.18–0.83) using cardiotoxicity as the outcome. However, 6-month treatment turned out to yield less occurrence of trastuzumab discontinuation (OR 0.32; 95% CI 0.24–0.42). Three trials reported interventions of cardioprotective drugs, and there is no significant difference shown in any cardioprotective group compared with placebo (cardiotoxicity outcome: angiotensin-converting enzyme inhibitor: OR 0.48; 95% CI 0.057–2.3; angiotensin receptor blocker: OR 1.3; 95% CI 0.12–14; β-blocker: OR 0.48; 95% CI 0.057–2.3; trastuzumab interruption outcome: angiotensin-converting enzyme inhibitor: OR 0.45; 95% CI 0.12–1.3; angiotensin receptor blocker: OR 0.87; 95% CI 0.15–4.8; β-blocker: OR 0.41; 95% CI 0.11–1.2).Conclusion: Only the 9-week group has a significant difference from the 12-month group using cardiotoxicity as the outcome. And 6-month treatment turned out to yield less occurrence of trastuzumab discontinuation. The use of cardioprotective drugs failed to prevent trastuzumab-related cardiotoxic effects in breast cancer patients.

Cardiovascular toxicity of breast cancer treatment: an update.

Novel chemotherapeutic agents have marked a new era in oncology during the past decade, prolonging significantly the overall survival of breast cancer patients. Nevertheless, contemporary antineoplastic treatments can frequently cause adverse cardiovascular side effects. Common manifestations of chemotherapy-induced cardiotoxicity include cardiomyopathy, ischemia, conduction disturbances, hypertension and thromboembolic events, while the type of the treatment regimen administered crucially determines clinical outcome. The aim of this literature review is to analyze the incidence and the underlying mechanisms of cardiovascular toxicity caused by agents approved for breast cancer, as well as to describe ways of monitoring and treating the cardiotoxic effects in breast cancer patients. Moreover, our work intends to provide an easy-to-grasp synopsis of recent and clinically meaningful advances in the field.