Therapy In Breast Cancer Patients Research Articles

The efficacy and safety of paclitaxel plus bevacizumab therapy in breast cancer patients with visceral crisis

BackgroundVisceral crisis in metastatic breast cancer (MBC) is defined as severe organ dysfunction requiring rapidly efficacious therapy. Although weekly paclitaxel plus bevacizumab (wPTX + BV) achieves a high response rate in human epidermal growth factor receptor 2 (HER2)-negative MBC, the efficacy and safety of wPTX + BV for visceral crisis is unclear. MethodsWe retrospectively investigated patients with MBC with visceral crisis who received wPTX + BV. Visceral crisis was defined as follows: liver dysfunction (aspartate or alanine aminotransferase >200 U/L or total bilirubin >1.5 mg/dl), respiratory dysfunction (carcinomatous lymphangiomatosis, SpO2 <93% in ambient air or required thoracentesis), superior vena cava (SVC) syndrome, or bone marrow carcinomatosis. The primary outcome was the proportion of patients on-treatment with wPTX + BV after 12 weeks. We also investigated time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and adverse events. ResultsA total of 44 patients with respiratory dysfunction (n = 29), liver dysfunction (n = 10), bone marrow carcinomatosis (n = 7), and SVC syndrome (n = 2) were eligible for this investigation. The proportion of patients on-treatment with wPTX + BV after 12 weeks was 63% (30/44), and the other patients discontinued wPTX + BV because of adverse events (n = 5) and disease progression (n = 9). Median TTF and OS, and the ORR were 131 days and 323 days, and 41%, respectively. No treatment-related death occurred.Conclusion: wPTX + BV achieved favorable efficacy and safety for treating patients with visceral crisis and may therefore be considered an option for the treatment of this acutely severe clinical condition.

Therapy of breast cancer patients with disorders of the anxiety-depressive spectrum

IntroductionBreast cancer (BC) is one of the leading causes of cancer death worldwide. The problem of mental health and quality of life of patients is currently particularly relevant. Most patients with breast cancer in the process of adapting to the disease experience certain mental disorders: depressive, anxiety-phobic and psychosomatic disorders.ObjectivesTo study the severity of anxiety-depressive disorders in the clinical picture in patients with breast cancer and evaluate the effectiveness of specialized pharmacotherapy using antidepressants in combination with antitumor therapy.MethodsThe study included 30 patients with a first established diagnosis of breast cancer and 52 patients with a follow-up history of 3-17 years. The main method of work was the clinical, psychopathological, and statistical research methods (a method using contingency tables and the Fechner coefficient, a method - Chi-square test).ResultsTo assess the severity in the clinical picture of anxiety-depressive tendencies and the effectiveness of treatment, special scales were used: hospital scale of anxiety and depression (HADS); general clinical impression scale (CGI) for assessing disease severity (CGI-S “severity”) and improvement (CGI-I “improvement”). High antidepressant therapy efficacy indicators were obtained in combination with benzodiazepine drugs and hypnotics in a group of patients with anxiety-depressive nosogenia (15 patients, 88% of respondents with reduction in starting anxiety and depression scores HADS more than 50%, CGI 85%), in the group with chronic hypochondriac dysthymia and cyclotymic endoform depression.ConclusionsThe data obtained in the study confirm the effectiveness of psychopharmacotherapy with antidepressants in breast cancer patients with identified disorders of the anxiety-depressive spectrum.DisclosureNo significant relationships.

Clinical Implications of Geometric and Dosimetric Uncertainties of Inter- and Intra-Fractional Movement during Volumetric Modulated Arc Therapy for Breast Cancer Patients.

Simple SummaryRadiotherapy is an essential treatment modality for breast cancer. Compared to conventional radiotherapy techniques, modern radiotherapy with fewer fractions and smaller target volumes requires higher accuracy. Image-guidance using cone-beam computed tomography (CBCT) is one of the most common methods used for positional verification before treatment. This study reports geometric and dosimetric outcomes evaluated by analyzing CBCT images acquired before and during treatments. The positional change and internal movement of the patient were less than 1 cm in most cases without significant deviation in the dosimetric parameters of interest. However, there were cases involving extreme variation, which resulted in insufficient radiation delivered to the target areas and increased radiation exposure to adjacent normal organs. The results of the current study suggest that unexpected intra-fractional motion may occur, prompting for marginal adaptation in selected patients who are deemed to suffer from this kind of event.With the introduction of modern sophisticated radiotherapy (RT) techniques, the significance of accuracy has increased considerably. This study evaluated the necessity of pre-treatment and intra-fractional cone-beam computed tomography (CBCT) by analyzing inter- and intra-fractional CBCT images of breast cancer patients receiving RT. From 57 patients, 1206 pre-treatment CBCT and 1067 intra-fractional CBCT images were collected. Geometric movements of patients were measured quantitively in both inter- and intra-fractional CBCT, and changes in dosimetric parameters were evaluated in selected patients with extreme intra-fractional movement. For right-sided breast cancer patients, left-sided breast cancer patients treated using deep-inspiration breath hold (DIBH), and left-sided breast cancer patients treated using continuous positive airway pressure (CPAP), median inter-fractional deviations were 0.53 (range 0.06–2.98) cm, 0.66 (range 0.08–4.41) cm, and 0.69 (range 0.04–3.80) cm, and median intra-fractional deviations were 0.14 (range 0.00–0.62) cm, 0.23 (range 0.02–0.96) cm, and 0.24 (0.00–1.15) cm, respectively. Modified plans reflecting large changes in intra-fractional position in 10 selected cases revealed insufficient target coverage in seven cases and more than 20-fold increase in the volume of heart receiving at least 25 Gy in two cases. Intra-fractional verification, as well as pre-treatment verification, might be considered in patients using DIBH or CPAP.

First clinical experience with CDK4/6 inhibitors in breast cancer therapy

For hormone receptor-positive, HER2-negative breast cancer patients with metastatic or advanced disease, therapy with CDK4/6 inhibitors in addition to aromatase inhibitors (AIs) or to the estrogen receptor (ER) downregulator fulvestrant has resulted in an additional therapy option and a longer progression-free survival. In the Gynecologic-Oncology Clinic, Diakonie-Klinikum Schwäbisch Hall, we followed and registered our initial clinical experience with CDK4/6 inhibitors, following the side effects and tumor response over two years since they were officially approved for general use in Germany. Differences were observed when palbociclib or ribociclib was used in combination with letrozole or anastrozole or fulvestrant. The dynamic side effects and tumor response under therapy with palbociclib or ribociclib were found to be comparable with the main reported data in the official drug information. The CDK4/6 inhibitors have an important and promising role in the therapy of breast cancer patients. Patient age and therapy duration do not influence the use of palbociclib or ribociclib, although it may be important which AI is used in combination with palbociclib.

P092 - Analysis of primary endocrine therapy in breast cancer patients over 70 years from a single unit in South Africa: analysis of those that choose no surgery first. Highlighting COVID-19 sensitive issues

P092 - Analysis of primary endocrine therapy in breast cancer patients over 70 years from a single unit in South Africa: analysis of those that choose no surgery first. Highlighting COVID-19 sensitive issues

Development of a Novel Weighted Ranking Method for Immunohistochemical Quantification of a Heterogeneously Expressed Protein in Gastro-Esophageal Cancers.

Simple SummaryHigh levels of the protein Junctional Adhesion Molecule-A (JAM-A) have been linked with aggressive disease in patients with several different cancers. However, its distribution is often non-uniform (heterogeneous) across tumors, and can be difficult to quantify. JAM-A has also been linked with high levels of HER2 (an important oncogene) in breast tumors, and the development of resistance to HER2-targeted drugs in those patients. Since gastro-esophageal (GE) cancers are often high in HER2 and have also been approved for HER2-targeted drugs, the aim of this study was to investigate if levels of JAM-A and HER2 are linked in GE cancer. JAM-A was expressed very heterogeneously across miniaturized tissue sections called tissue microarrays (TMAs) of GE cancer patients. In this model, therefore, there was no correlation between JAM-A and HER2 expression. However, when we used larger tissue sections and developed a scoring system to account for heterogeneity, a significant correlation between JAM-A and HER2 levels emerged. This work illustrates the importance of taking intra-tumor heterogeneity into account, particularly in an era when analysis of protein levels by this method is increasingly used to select patients for targeted cancer drugs.High expression of Junctional Adhesion Molecule-A (JAM-A) has been linked with poor prognosis in several cancers, including breast cancers overexpressing the human epidermal growth factor receptor-2 (HER2). Furthermore, JAM-A expression has been linked with regulating that of HER2, and associated with the development of resistance to HER2-targeted therapies in breast cancer patients. The purpose of this study was to establish a potential relationship between JAM-A and HER2 in HER2-overexpressing gastro-esophageal (GE) cancers. Interrogation of gene expression datasets revealed that high JAM-A mRNA expression was associated with poorer survival in HER2-positive gastric cancer patients. However, high intra-tumoral heterogeneity of JAM-A protein expression was noted upon immunohistochemical scoring of a GE cancer tissue microarray (TMA), precluding a simple confirmation of any relationship between JAM-A and HER2 at protein level. However, in a test-set of 25 full-face GE cancer tissue sections, a novel weighted ranking system proved effective in capturing JAM-A intra-tumoral heterogeneity and confirming statistically significant correlations between JAM-A/HER2 expression. Given the growing importance of immunohistochemistry in stratifying cancer patients for the receipt of new targeted therapies, this may sound a cautionary note against over-relying on cancer TMAs in biomarker discovery studies of heterogeneously expressed proteins. It also highlights a timely need to develop validated mechanisms of capturing intra-tumoral heterogeneity to aid in future biomarker/therapeutic target development for the benefit of cancer patients.

Role of a metastatic suppressor gene KAI1/CD82 in the diagnosis and prognosis of breast cancer.

Globally, breast cancer is the most common type of cancer in females and is one of the leading causes of cancer death in women. The advancement in the targeted therapies and the slight understanding of the molecular cascades of the disease have led to small improvement in the rate of survival of breast cancer patients. However, metastasis and resistance to the current drugs still remain as challenges in the management of breast cancer patients. Metastasis, potentially, leads to failure of the available treatment, and thereby, makes the research on metastatic suppressors a high priority. Tumor metastasis suppressors are several genes and their protein products that have the capability of arresting the metastatic process without affecting the tumor formation. The metastasis suppressors KAI1 (also known as CD82) has been found to inhibit tumor metastasis in various types of solid cancers, including breast cancer. KAI1 was identified as a metastasis suppressor that inhibits the process of metastasis by regulating several mechanisms, including cell motility and invasion, induction of cell senescence, cell–cell adhesion and apoptosis. KAI1 is a member of tetraspanin membrane protein family. It interacts with other tetraspanins, chemokines and integrins to control diverse signaling pathways, which are crucial for protein trafficking and intracellular communication. It follows that better understanding of the molecular events of such genes is needed to develop prognostic biomarkers, and to identify specific therapies for breast cancer patients. This review aims to discuss the role of KAI1/CD82 as a prognosticator in breast cancer.

Sentinel lymph node BIOPSY after neoadjuvant therapy in breast cancer patients with lymph node involvement at diagnosis. Could wire localization of clipped node improve our results?

IntroductionSentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) in node-positive (N+) breast cancer patients at diagnosis remains a controversial issue, with no consensus on implementation or safety. ObjectivesWe sought to assess the accuracy of SLNB after NAT in biopsy-proven N+ cases at diagnosis and the efficacy and accuracy of wire localization of the clipped node to improve results. Material and methodsA cross-sectional diagnostic technique validation study in N+ patients following NAT was performed. The biopsy-proven affected lymph node was clipped at diagnosis. SLNB and axillary lymph node dissection (ALND) were performed in cases of clinical-radiological lymph node response after NAT. For the purposes of our study we added wire localization of the clipped node. Results103 patients were included (mean age, 54.4 years [± 12.7]). Wire marking was performed in 28 cases. The overall identification rate (IR) of SLN was 81.6%. The median number of nodes removed was 2 (range 2). The overall false negative rate (FNR) was 6.1%. Sensitivity and overall accuracy were 93.9% and 95.2%, respectively (area under curve 0.97). In the double-marked (clip and wire) group the FNR decreased to 0% and accuracy was 100%. Axillary pathologic complete response was observed in 24.3% of cases. ConclusionsSLNB is useful in node-positive patients at diagnosis who respond to NAT. Combining this with preoperative wire localization of the biopsied lymph node reduces the FNR without increasing the number of complications.

Abstract PS6-48: Clinicopathologic features and follow-up outcomes of breast cancers with HER2 FISH group 3 Results: A single institution experience

Abstract INTRODUCTION: There is dearth information on the long-term outcome and role of HER2 targeted therapy in breast cancer patients in the HER2 FISH group 3 category, which is defined as breast cancer with a HER2/CEP17 ratio &amp;lt; 2 and HER2 copy number ≥ 6 signals/cell. In this study, we report the clinicopathologic features and outcomes of breast cancer patients in the HER2 FISH group 3 category at our institution. METHODS: We identified 52/2,874 (1.8%) breast cancer patients with HER2 FISH group 3 results between 1/2007 and 3/2020. 28 of these 52 patients had available detailed clinicopathologic and follow-up data, with an average follow-up of 38.5 months. RESULTS: Most of the cases with group 3 FISH results were high grade ductal carcinomas with positive hormonal receptor expressions and equivocal HER2 expression by immunohistochemistry. Among all the clinicopathologic variables, only tumor size (p=0.048) significantly contributed to the poor clinical outcomes. HER2 copy number failed to show any significant association with histologic grade, tumor size, clinical stage, hormonal receptor status or disease outcomes. There was no statistically significant difference in disease outcome between patients who were treated with HER2 targeted therapy and patients who did not receive HER2 targeted therapy, regardless of the HER2 copy number or clinical stage (Table 1). CONCLUSION: Our preliminary findings suggest that certain patients with HER2 FISH group 3 category breast cancer may not need HER-2 targeted therapy. Larger-scale studies are needed to further evaluate which HER2 FISH group 3 results are more likely to benefit from the HER-2 targeted therapy. Table 1. Response to HER2 targeted therapy in HER2 FISH group 3 breast cancer patients based on HER2 copy numbers and clinical stageHER 2 targeted therapyp-valueGivenNot givenTotal populationGood outcome (n=21)1380.371Bad outcome (n=7)61HER2 copy number &amp;lt; 10Good outcome (n=16)1060.366Bad outcome (n=7)61HER2 copy number ≥ 10Good outcome (n=5)321.000Bad outcome (n=0)00Stage I-IIGood outcome (n=16)970.737Bad outcome (n=3)21Stage III-IVGood outcome (n=5)410.343Bad outcome (n=4)40*Good outcome = No evidence of disease**Bad outcome = Local recurrence, distant metastasis, and/or died of disease Citation Format: Huina Zhang, Rana Ajabnoor, David Hicks, Bradley Turner. Clinicopathologic features and follow-up outcomes of breast cancers with HER2 FISH group 3 Results: A single institution experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-48.

Interleukin-10 Levels are Associated with Doxorubicin-Related Cardiotoxicity in Breast Cancer Patients in a One-Year Follow-Up Study

ABSTRACT Background Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data. Methods Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2). Results Higher IL-10 levels were observed in the case group compared to controls at T1 (p = .006) and T2 (p = .046). The IL-1β, IL-6 and TNF levels did not change during treatment in each group (p > .05), nor between the case and control groups. The IL-10 levels were higher at T1 than at T0 and T2 (p < .05 for both) in the cardiotoxicity group. A correlation between IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at T0 and T2 in the cardiotoxicity group was observed (p = .048 and p = .004, respectively). Conclusion Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.

Association between clinical risk factors and left ventricular function in patients with breast cancer following chemotherapy

Abstract Funding Acknowledgements Type of funding sources: None. Background The sequential or concurrent use of two different types of agents such as anthracyclines and trastuzumab may increase myocardial injury and cancer therapeutics-related cardiac dysfunction (CTRCD), which is often the result of the combined detrimental effect of the two therapies for breast cancer patients. For risk stratification to detect the development of CTRCD, the current position paper from the European Society of Cardiology (ESC) lists several factors associated with risk of cardiotoxicity. Purpose Our purpose was to investigate the impact of baseline risk factors on left ventricular (LV) function in patients with preserved LV ejection fraction (LVEF) who have undergone chemotherapy for breast cancer. Methods We studied 86 breast cancer patients treated with anthracyclines, trastuzumab, or both. Mean age was 59 ± 13 years and LVEF was 67 ± 5%. In accordance with the current definition, CTRCD was defined as a decline in LVEF of &amp;gt;10% to an absolute value of &amp;lt;53% after chemotherapy. Based on the 2016 ESC position paper, clinical risk factors for CTRCD were defined as: (1) a cumulative total doxorubicin dose of ≥ 240mg/m², (2) age ≥ 65-year-old, (3) body mass index ≥ 30kg/m², (4) a previous history of radiation therapy to chest or mediastinum, (5) B-type natriuretic peptide ≥ 100pg/mL, (6) a previous history of cardiovascular disease, (7) atrial fibrillation, (8) hypertension, (9) diabetes mellitus, (10) current or ex-smoker. Results The relative decrease in LVEF after chemotherapy for patients with more than four risk factors was significantly greater than that for patients without (-9.3 ± 10.8% vs. -2.2 ± 10.2%; p = 0.02). However, this finding did not apply to patients with more than one, two or three risk factors. Patients with more than four risk factors also tended to show a higher prevalence of CTRCD than those without (14.3% vs. 2.8%, p = 0.12). Moreover, patients with more than four risk factors were more likely to have higher LV mass index (109.3 ± 29.0g/m² vs. 83.2 ± 21.0g/m², p &amp;lt; 0.001), lower global longitudinal strain (18.4 ± 2.8% vs. 20.0 ± 2.6%, p = 0.06) and higher E/e’ (10.4 (8.9-13.0) vs. 9.0 (7.4-10.9), p = 0.06) compared to those without. Furthermore, receiver-operator characteristics curve analysis showed that an optimal cut off value of a cumulative total doxorubicin dose for developing LV dysfunction in patients with more than any of four risk factors was lower than that in those without (180 mg/m² vs. 280 mg/m²). Conclusions Association between clinical risk factors and LV dysfunction following chemotherapy became stronger with an increase in the number of risk factors in breast cancer patients, and was especially strong for patients treated with chemotherapy who had more than four risk factors. Our findings can thus be expected to have clinical implications for better management of patients with breast cancer referred for chemotherapy. Abstract Figure.

How Canadian Oncologists Use Oncotype DX for Treatment of Breast Cancer Patients.

Background: The literature suggests that medical oncologists differ on how they use the Oncotype DX (ODX) genomic assay for making decisions about systemic therapy in breast cancer patients. Given the emergence of data supporting the use of genomic profiling for the prognosis and predicting benefit of chemotherapy, we surveyed medical oncologists in Canada to assess their usage and perception of the ODX assay. Methods: A 34-item survey was distributed to Canadian medical oncologists via the Canadian Association of Medical Oncologists. Data was collected on physician demographics, ODX usage patterns, and physicians’ perception of the impact clinical and pathologic characteristics make on ODX utilization. Results: Response rate was 20.6% with 47 responses received from 228 survey sent. Forty-five responses were eligible for analysis. Sixty-two percent (28/45) of respondents treated predominantly breast cancer, and 60% (27/45) have been in practice for at least 10 years. The most cited reason for using ODX was to avoid giving patients unnecessary chemotherapy (64%; 29/45). Sixty-seven percent (30/45) deferred making treatment decisions until ODX testing was completed. Factors most strongly impacting ODX utilization included: patient request, medical comorbidities and tumor grade. In clinical scenarios, ODX was more frequently selected for patients aged 40–65 (vs. <40 or >65), grade 2 tumors (vs. grade 1 or 3), and Ki-67 index of 10–20% (vs. <10% or >20%). Conclusions: This survey demonstrated that Canadian medical oncologists are preferentially using ODX to avoid giving patients unnecessary chemotherapy. The utilization of ODX is mainly in patients with intermediate clinical and pathologic features.

Adherence to Newly Implemented Tamoxifen Therapy for Breast Cancer Patients in Rural Western Ethiopia

Introduction: Endocrine therapy for breast cancer (BC) patients is highly underutilized in rural Ethiopia and other African countries. Objective: This study aims to assess the feasibility of and adherence to tamoxifen therapy in rural Ethiopia. Methods: We ascertained the hormone receptor (HR) status in 101 women diagnosed with BC from January 2010 to December 2015 and who had surgery in Aira Hospital, in rural Ethiopia. From 2013, tamoxifen was offered to patients with HR-positive (HR+) tumors. Prescription refill records and a structured questionnaire were used to assess receipt of and adherence to tamoxifen. Results: Of the 101 BC patients tested for HR status during the study period, 66 (65%) patients were HR+ and were eligible for tamoxifen treatment. However, 15 of the HR+ patients died before tamoxifen became available in 2013. Of the remaining 51 HR+ patients, 26 (51%) initiated tamoxifen but only 9 of them (35%) adhered to therapy (medication possession rate ≥80%, median observation 16.2 months). After 1 year, 52% of the patients were still adherent, and 9 patients had discontinued therapy. The reasons for non-initiation of tamoxifen included patient factors (n = 5), including financial hardship or lack of transportation, and health care provider factors (n = 12). Conclusions: Endocrine therapy for BC patients seems feasible in rural Western Ethiopia, although non-adherence due to financial hardship and a less developed health care infrastructure remains a major challenge. We postulate that the implementation of breast nurses could reduce patient and health system barriers and improve initiation of and adherence to endocrine treatment.

Identification of significantly mutated subnetworks in the breast cancer genome

Recent studies showed that somatic cancer mutations target genes that are in specific signaling and cellular pathways. However, in each patient only a few of the pathway genes are mutated. Current approaches consider only existing pathways and ignore the topology of the pathways. For this reason, new efforts have been focused on identifying significantly mutated subnetworks and associating them with cancer characteristics. We applied two well-established network analysis approaches to identify significantly mutated subnetworks in the breast cancer genome. We took network topology into account for measuring the mutation similarity of a gene-pair to allow us to infer the significantly mutated subnetworks. Our goals are to evaluate whether the identified subnetworks can be used as biomarkers for predicting breast cancer patient survival and provide the potential mechanisms of the pathways enriched in the subnetworks, with the aim of improving breast cancer treatment. Using the copy number alteration (CNA) datasets from the METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) study, we identified a significantly mutated yet clinically and functionally relevant subnetwork using two graph-based clustering algorithms. The mutational pattern of the subnetwork is significantly associated with breast cancer survival. The genes in the subnetwork are significantly enriched in retinol metabolism KEGG pathway. Our results show that breast cancer treatment with retinoids may be a potential personalized therapy for breast cancer patients since the CNA patterns of the breast cancer patients can imply whether the retinoids pathway is altered. We also showed that applying multiple bioinformatics algorithms at the same time has the potential to identify new network-based biomarkers, which may be useful for stratifying cancer patients for choosing optimal treatments.

The Determinant of Coping Mechanisms among Breast Cancer Patients in Sidoarjo Regency, Indonesia

Breast cancer patients need coping mechanisms to adapt to changes due to breast cancer. The constructivecoping mechanism is very influential on the attitude, response, decision making towards breast cancermanagement, and quality of life. The study aimed to determine the determinants of coping mechanisms ofbreast cancer patients in Sidoarjo Regency, Indonesia. The sample size was 98 breast cancer patients. Thevariables analyzed included coping mechanism, age, educational, marital, work, time diagnosed, genetic,stage of cancer, therapy, social support, and spiritual need. The results found that breast cancer patients withhigher education had a 51.200 times chance compared to breast cancer patients with no education to haveadaptive coping mechanisms. Therapy for breast cancer patients has a positive effect on adaptive copingmechanisms. Social support has a positive influence on breast cancer patients to have an adaptive copingmechanism. The higher the social support provided, the more adaptive coping mechanism is for breastcancer patients. Tree variables have proven to be significant as determinants of coping mechanisms amongbreast cancer patients in the Sidoarjo Regency, namely education, therapy, and social support.

Challenges of oral antithrombotic therapy in breast cancer patients treated with cyclin-dependent kinase inhibitors: A case report

Challenges of oral antithrombotic therapy in breast cancer patients treated with cyclin-dependent kinase inhibitors: A case report

The effect of combined Pilates and yoga training on insulin and leptin level in breast cancer survivors: A randomized clinical trial

Context: Elevated levels of insulin and leptin can be associated with poor prognosis in breast cancer patients. A safe and effective exercise protocol seems necessary as an adjuvant therapy in breast cancer patients. Aims: This study aimed to assess the effect of concurrent yoga and Pilates training on insulin and leptin in breast cancer survivors. Setting and Design: This study was a randomized clinical trial research with control group in a selected oncology and radiotherapy center in Rasht, Iran, in 2019. Materials and Methods: This clinical trial was performed on thirty breast cancer survivors. The participants were allocated in exercise group (n = 15) and control group (n = 15) by simple randomly. Exercise group underwent 12 weeks of concurrent yoga and Pilates training, 3 sessions/week and 75 min of workout in each session. Every participant completed the demographic questionnaire. Weight, insulin, leptin, carcinoembryonic antigen (CEA), and cancer antigen 15-3 (CA 15-3) levels were measured before and after 12 weeks of exercise in both groups. Statistical Analysis Used: Data were analyzed using descriptive statistics, one-way ANCOVA, and paired t-test and Wilcoxon. Results: Mean score of weight in the exercise group decreased from 73.03 ± 16.75 to 69.92 ± 15.46 (P = 0.01), but in control group, there was no significant improvement (from 85.54 ± 11.7 to 85.27 ± 9.71). There was a significant decrease in leptin levels (from 33.70 ± 15.93 to 21.21 ± 15.37) in exercise group (P = 0.02). However, there was no significant effect on insulin (from 7.66 ± 2.96 to 10.67 ± 4.51), CEA, and CA 15-3 (P > 0.05). Conclusion: Twelve weeks of concurrent yoga and Pilates training have positive effects on leptin levels in breast cancer survivors.

Phase I Trial of 131I-GMIB-Anti-HER2-VHH1, a New Promising Candidate for HER2-Targeted Radionuclide Therapy in Breast Cancer Patients.

131I-GMIB-anti-human epidermal growth factor receptor type 2 (HER2)-VHH1 is a targeted radionuclide theranostic agent directed at HER2-expressing cancers. VHH1 is a single-domain antibody covalently linked to therapeutic 131I via the linker N-succinimidyl 4-guanidino-methyl-3-iodobenzoate (SGMIB). The phase I study was aimed at evaluating the safety, biodistribution, radiation dosimetry, and tumor-imaging potential of 131I-GMIB-anti-HER2-VHH1 in healthy volunteers and breast cancer patients. Methods: In a first cohort, 6 healthy volunteers were included. The biodistribution of 131I-GMIB-anti-HER2-VHH1 was assessed using whole-body (anterior and posterior) planar images obtained at 40 min and at 2, 4, 24, and 72 h after intravenously administered (38 ± 9 MBq) 131I-GMIB-anti-HER2-VHH1. Imaging data were analyzed using OLINDA/EXM software to determine the dosimetry. Blood and urine samples were obtained over 72 h. In the second cohort, 3 patients with metastatic HER2-positive breast cancer were included. Planar whole-body imaging was performed at 2 and 24 h after injection. Additional SPECT/CT images were obtained after the whole-body images at 2 and 24 h if there was relevant uptake in known cancer lesions. Results: No drug-related adverse events were observed throughout the study. The biologic half-life of 131I-GMIB-anti-HER2-VHH1 in healthy subjects was about 8 h. After intravenous administration, the compound was eliminated from the blood with a 2.5-h half-life. The drug was eliminated primarily via the kidneys. The drug was stable in circulation, and there was no increased accumulation in the thyroid or stomach. The absorbed dose to the kidneys was 1.54 ± 0.25 mGy/MBq, and to bone marrow it was 0.03 ± 0.01 mGy/MBq. SPECT/CT imaging in patients with advanced breast cancer showed focal uptake of 131I-GMIB-anti-HER2-VHH1 in metastatic lesions. Conclusion: Because of its favorable toxicity profile and its uptake in HER2-positive lesions, this radiopharmaceutical can offer new therapeutic options to patients who have progressed on trastuzumab, pertuzumab, or trastuzmab emtansine, given its difference in mode-of-action. A dose escalation is planned in a subsequent phase I/II study to assess the therapeutic window of this compound (NCT04467515).

Assessing the effect of hyperbaric oxygen therapy in breast cancer patients with late radiation toxicity (HONEY trial): a trial protocol using a trial within a cohort design

BackgroundBreast cancer treatment with radiotherapy can induce late radiation toxicity, characterized by pain, fibrosis, edema, impaired arm mobility, and poor cosmetic outcome. Hyperbaric oxygen therapy (HBOT) has been proposed as treatment for late radiation toxicity; however, high-level evidence of effectiveness is lacking. As HBOT is standard treatment and reimbursed by insurers, performing classic randomized controlled trials is difficult. The “Hyperbaric OxygeN therapy on brEast cancer patients with late radiation toxicity” (HONEY) trial aims to evaluate the effectiveness of HBOT on late radiation toxicity in breast cancer patients using the trial within cohorts (TwiCs) design.MethodsThe HONEY trial will be conducted within the Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation (UMBRELLA). Within UMBRELLA, breast cancer patients referred for radiotherapy to the University Medical Centre Utrecht are eligible for inclusion. Patients consent to collection of clinical data and patient-reported outcomes and provide broad consent for randomization into future intervention studies. Patients who meet the HONEY in- and exclusion criteria (participation ≥ 12 months in UMBRELLA, moderate/severe breast or chest wall pain, completed primary breast cancer treatment except hormonal treatment, no prior treatment with HBOT, no contraindications for HBOT, no clinical signs of metastatic or recurrent disease) will be randomized to HBOT or control group on a 2:1 ratio (n = 120). Patients in the control group will not be informed about participation in the trial. Patients in the intervention arm will undergo 30–40 HBOT treatment sessions in a high pressure chamber (2.4 atmospheres absolute) where they inhale 100% oxygen through a mask. Cohort outcome measures (i.e., physical outcomes, quality of life, fatigue, and cosmetic satisfaction) of the HBOT group will be compared to the control group at 3 months follow-up.DiscussionThis pragmatic trial within the UMBELLA cohort was designed to evaluate the effectiveness of HBOT on late radiation toxicity in breast cancer patients using the TwiCs design. Use of the TwiCs design is expected to address issues encountered in classic randomized controlled trials, such as contamination (i.e., HBOT in the control group) and disappointment bias, and generate information about acceptability of HBOT.Trial registrationClinicalTrials.gov. NCT04193722. Registered on 10 December 2019.

Combined the SMAC mimetic and BCL2 inhibitor sensitizes neoadjuvant chemotherapy by targeting necrosome complexes in tyrosine aminoacyl-tRNA synthase-positive breast cancer

BackgroundChemotherapy is the standard treatment for breast cancer; however, the response to chemotherapy is disappointingly low. Here, we investigated the alternative therapeutic efficacy of novel combination treatment with necroptosis-inducing small molecules to overcome chemotherapeutic resistance in tyrosine aminoacyl-tRNA synthetase (YARS)-positive breast cancer.MethodsPre-chemotherapeutic needle biopsy of 143 invasive ductal carcinomas undergoing the same chemotherapeutic regimen was subjected to proteomic analysis. Four different machine learning algorithms were employed to determine signature protein combinations. Immunoreactive markers were selected using three common candidate proteins from the machine-learning algorithms and verified by immunohistochemistry using 123 cases of independent needle biopsy FFPE samples. The regulation of chemotherapeutic response and necroptotic cell death was assessed using lentiviral YARS overexpression and depletion 3D spheroid formation assay, viability assays, LDH release assay, flow cytometry analysis, and transmission electron microscopy. The ROS-induced metabolic dysregulation and phosphorylation of necrosome complex by YARS were assessed using oxygen consumption rate analysis, flow cytometry analysis, and 3D cell viability assay. The therapeutic roles of SMAC mimetics (LCL161) and a pan-BCL2 inhibitor (ABT-263) were determined by 3D cell viability assay and flow cytometry analysis. Additional biologic process and protein-protein interaction pathway analysis were performed using Gene Ontology annotation and Cytoscape databases.ResultsYARS was selected as a potential biomarker by proteomics-based machine-learning algorithms and was exclusively associated with good response to chemotherapy by subsequent immunohistochemical validation. In 3D spheroid models of breast cancer cell lines, YARS overexpression significantly improved chemotherapy response via phosphorylation of the necrosome complex. YARS-induced necroptosis sequentially mediated mitochondrial dysfunction through the overproduction of ROS in breast cancer cell lines. Combination treatment with necroptosis-inducing small molecules, including a SMAC mimetic (LCL161) and a pan-BCL2 inhibitor (ABT-263), showed therapeutic efficacy in YARS-overexpressing breast cancer cells.ConclusionsOur results indicate that, before chemotherapy, an initial screening of YARS protein expression should be performed, and YARS-positive breast cancer patients might consider the combined treatment with LCL161 and ABT-263; this could be a novel stepwise clinical approach to apply new targeted therapy in breast cancer patients in the future.