Treatment Of Breast Cancer Patients Research Articles

A Bayesian group sequential design for randomized biosimilar clinical trials with adaptive information borrowing from historical data

ABSTRACT At the time of developing a biosimilar, the reference product has been on market for years and thus ample data are available on its efficacy and characteristics. We develop a Bayesian adaptive design for randomized biosimilar clinical trials to leverage the rich historical data on the reference product. This design takes a group sequential approach. At each interim, we employ the elastic meta-analytic-predictive (EMAP) prior methodology to adaptively borrow information from the historical data of the reference product to make go/no-go decision based on Bayesian posterior probabilities. In addition, the randomization ratio between the test and reference arms is adaptively adjusted at the interim with the goal to balance the sample size of the two arms at the end of trials. Simulation study shows that the proposed Bayesian adaptive design can substantially reduce the sample size of the reference arm, while achieving comparable power as the traditional randomized clinical trials that ignore the historical data. We apply our design to a biosimilar trial for treating breast cancer patients.

230P A digital therapeutic intervention for breast cancer patients during active treatment: A feasibility study

230P A digital therapeutic intervention for breast cancer patients during active treatment: A feasibility study

Comprehensive Characterization of the Function of Metabolic Genes and Establishment of a Prediction Model in Breast Cancer.

Background Breast cancer (BC) is a highly heterogeneous disease with high morbidity and mortality. Its subtypes may have distinctly different biological behaviors, clinical outcomes, and therapeutic responses. The metabolic status of BC tissue is closely related to its progress. Therefore, we comprehensively characterized the function of metabolic genes in BC and identified new biomarkers to predict BC patients' prognoses. Methods Metabolic genes were identified by intersecting genes obtained from two published pieces of literature. The function of metabolic genes in BC was determined by extracting differentially expressed genes (DEGs), performing functional enrichment analyses, analyzing the infiltrating proportion of immune cells, and conducting metabolic subgroup analyses. A risk score model was constructed to assess the prognoses of BC patients by performing the univariate Cox regression, LASSO algorithm, multivariate Cox regression, Kaplan-Meier survival analyses, and ROC curve analyses in the training set. The prognostic model was then validated on the testing dataset, external dataset, the whole TCGA-BC database, and our clinical specimens. Finally, a nomogram was constructed for clinical prognostic prediction based on the risk score model and other clinicopathological parameters. Results 955 metabolic genes were obtained. Among these, 157 metabolic DEGs were identified between BC and normal tissues for subsequent GO and KEGG pathway enrichment analyses. 5 metabolic genes were negatively correlated with CD8+ T cells, while 49 genes were positively correlated with CD8+ T cells. Furthermore, 5 metabolic subgroups with varying proportions of PAM50 subtypes, TNM classification, and immune cell infiltration were obtained. Finally, a risk score model was constructed to predict the prognoses of BC patients, and a nomogram incorporating the risk score model was established for clinical application. Conclusion In this study, we elucidated tumor heterogeneity from metabolite profiling of BC. The roles of metabolic genes in the occurrence of BC were comprehensively characterized, clarifying the relationship between the tumor microenvironment (TME) and metabolic genes. Meanwhile, a concise prediction model was also constructed based on metabolic genes, providing a convenient and precise method for the individualized diagnosis and treatment of BC patients.

Harnessing the Immunogenic Potential of Gold Nanoparticle-Based Platforms as a Therapeutic Strategy in Breast Cancer Immunotherapy: A Mini Review.

Breast cancer remains the most common malignancy among women worldwide. Although the implementation of mammography has dramatically increased the early detection rate, conventional treatments like chemotherapy, radiation therapy, and surgery, have significantly improved the prognosis for breast cancer patients. However, about a third of treated breast cancer patients are known to suffer from disease recurrences and progression to metastasis. Immunotherapy has recently gained traction due to its ability to establish long-term immune surveillance, and response for the prevention of disease recurrence and extension of patient survival. Current research findings have revealed that gold nanoparticles can enhance the safety and efficacy of cancer immunotherapy, through their unique intrinsic properties of good biocompatibility, durability, convenient surface modification, as well as enhanced permeability and retention effect. Gold nanoparticles are also able to induce innate immune responses through the process of immunogenic cell death, which can lead to the establishment of lasting adaptive immunity. As such gold nanoparticles are considered as good candidates for next generation immunotherapeutic strategies. This mini review gives an overview of gold nanoparticles and their potential applications in breast cancer immunotherapeutic strategies.

MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice

Simple SummaryEntry in the metastatic phase is often devastating for cancer patients. Metastases originate from metastatic progenitor cells that are selected in the primary tumor and which simultaneously possess several phenotypic capabilities, including migration, invasion, and clonogenicity. We previously provided in vitro evidence that these features are collectively enforced by mitochondrial superoxide in a paradigm where mitochondria act as metabolic sensors of the tumor microenvironment and produce subcytotoxic levels of superoxide to prime metastatic progenitor cells. We also showed that these metastatic traits can be collectively countered by MitoQ, a mitochondria-targeted antioxidant that selectively deactivates mitochondrial superoxide. Here, we further establish that MitoQ prevents primary tumor recurrence after surgery, tumor take and metastasis as a whole, notably in a model of human breast cancer in mice. Since MitoQ already successfully passed Phase I clinical trials, our findings support the development of this drug as a preventive treatment against breast cancer metastasis.In oncology, the occurrence of distant metastases often marks the transition from curative to palliative care. Such outcome is highly predictable for breast cancer patients, even if tumors are detected early, and there is no specific treatment to prevent metastasis. Previous observations indicated that cancer cell mitochondria are bioenergetic sensors of the tumor microenvironment that produce superoxide to promote evasion. Here, we tested whether mitochondria-targeted antioxidant MitoQ is capable to prevent metastasis in the MDA-MB-231 model of triple-negative human breast cancer in mice and in the MMTV-PyMT model of spontaneously metastatic mouse breast cancer. At clinically relevant doses, we report that MitoQ not only prevented metastatic take and dissemination, but also local recurrence after surgery. We further provide in vitro evidence that MitoQ does not interfere with conventional chemotherapies used to treat breast cancer patients. Since MitoQ already successfully passed Phase I safety clinical trials, our preclinical data collectively provide a strong incentive to test this drug for the prevention of cancer dissemination and relapse in clinical trials with breast cancer patients.

Clinical study on Yanghe decoction in improving neo-adjuvant chemotherapy efficacy and immune function of breast cancer patients.

Introduction:Neoadjuvant chemotherapy (NAC) plays an important role in downgrading preoperative tumor size, providing information on regimen activity, and increases treatment efficacy in breast cancer patients. An increasing number of patients have sought Traditional Chinese Medicine (TCM) during NAC to relieve discomfort, regulate immune function, and improve survival. However, limited evidence is available on how concurrent TCM treatment combined with NAC affects tumor response. This study aims to assess the efficacy of Yanghe decoction, a classical warming Yang formula, on pathological complete response (pCR) and explore its mechanism via the phosphatidylinositol-3-kinase/ protein kinase B/nuclear factor kappa-B (PI3K/Akt/NF-κB) pathway-mediated immune-inflammation microenvironment.Methods:A single-center, randomized, placebo-controlled, double-blinded randomized control trial (RCT) was designed. This trial aims to recruit 128 participants with breast cancer scheduled to receive NAC in China. All participants will be randomly assigned (1:1) to the Neo-Yanghe group (Yanghe decoction plus NAC) or the control group (placebo plus NAC). The primary outcome will be evaluated by the proportion of participants achieving pCR. The secondary outcomes include the expression level of PI3K/Akt/NF-κB pathway-related proteins, the objective response rate, the time to response, serum level of immune-inflammatory indicators, quality of life, disease-free survival, and overall survival.Discussion:This study will be the first RCT to evaluate the efficacy of Yanghe decoction combined with NAC in treating breast cancer patients, and elucidate the antitumor mechanism via the PI3K/Akt/NF-κB pathway-mediated immune-inflammation microenvironment. If possible, Neo-Yanghe treatment pattern will be a better pharmacological intervention to manage breast cancer than chemotherapy alone. The results of the trial will provide research-based evidence for the development of integrated Chinese and Western medicine guidelines and expert consensus.Trial registration: Chinese Clinical Trial Registry ChiCTR-INR-2000036943. Registered on September 28, 2020 (https://www.chictr.org.cn/hvshowproject.aspx?id=57141).

Abstract P5-13-29: Analytical and clinical validation of a ctDNA assay for detecting copy number loss and structural rearrangement variants contributing to homologous recombination and repair (HRR) deficiency

Abstract Background: Inactivating HRR gene mutations can lead to HRR deficiency (HRD) and predict response to PARPi therapy in patients with breast cancer. Copy number loss and large genomic rearrangements (LGR) can result in HRD but are challenging to detect in ctDNA. Here, we present the analytical validation of homozygous deletions, loss of heterozygosity (LoH) and LGR detection on the Guardant360 (G360) liquid biopsy panel, previously validated for detection of small variants, copy number amplifications, and fusions. We present real-world outcomes of BRCA1/2-mutant PARPi-treated patients to demonstrate the clinical validity of the detected variants. Methods: Analytical validation was performed using the G360 83-gene ctDNA panel. Cell line DNA and clinical patient cfDNA were titrated into matched normal cell line DNA or healthy donor cfDNA to establish the limit of detection (LoD) and precision for copy number loss and LGRs, respectively. Accuracy results were compared to those from an orthogonal, externally validated tissue and ctDNA panel. De-identified, longitudinal, claims data were linked to the cancer genomic profiles in Guardant INFORM, a clinical-genomics database. Advanced PARPi treated breast cancer patients with an inactivating or reversion BRCA1/2 mutation detected by G360 were assessed. Results: The analytical sensitivity (95% LoD) for detecting homozygous and LoH deletions for deletion sizes >10MB was established at tumor fractions (TF) of 12.5% and 25%, respectively. The 95% LoD for LGRs was 0.2% variant allele fraction (VAF). The per-sample false positive rate for copy number loss and LGRs was <0.5%. Prevalence of BRCA1/2 homozygous deletions, LoH and LGRs in >1000 advanced breast cancer patients was 1.8%, 16.6% and 0.25% respectively, compared to 2.4%, 56.7% and 0.3% in TCGA. To verify the clinical impact of cfDNA-detected HRR alterations, overall survival was determined for PARPi-treated patients with >1 BRCA1/2 germline or somatic SNV, indel or LGR reversion mutation to be 23.2 months [16.4, 30, CI, n=75] compared to 54.4 [28, NA, CI, n=14] months for BRCA1/2-mutant patients without a reversion (p-value=0.049). Conclusion:. This analytical validation demonstrates that G360 detection of inactivating mutations, including copy number loss and LGRs, is highly sensitive, reliable and robust. Real-world evidence analysis confirmed worse survival outcomes in PARPi treated patients harboring a BRCA1/2 reversion compared to BRCA1/2-mutant patients with no reversion. This data further supports ctDNA as a compelling non-invasive means to identify potential PARPi sensitizing and resistance mutations in patients with advanced breast cancer. Citation Format: Jennifer Yen, Leylah Drusbosky, Caroline Weipert, Nicole Zhang, David Hanna, Catalin Barbacioru, Hao Wang, Alex Artyomenko, Arielle Yablonovitch, Yu Fu, Aaron Hardin, Nagesh Alla, Robert Foley, Max Maligska, Bhargavi Panchangam, Phil Yen, Jane Meisel, Neelima Vidula, Massimo Cristofanilli, Jeremy Force, Michael Dorschner, Martina Lefterova, Elena Helman, Becky Nagy, Darya Chudova, AmirAli Talasaz. Analytical and clinical validation of a ctDNA assay for detecting copy number loss and structural rearrangement variants contributing to homologous recombination and repair (HRR) deficiency [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-29.

Did the COVID-19 Pandemic Truly Adversely Affect Disease Progress and Therapeutic Options in Breast Cancer Patients? A Single-Centre Analysis.

Purpose: The uncontrolled spread and transmission of SARS-CoV-2 infections has disrupted most areas of social and economic life all over the world. The most important changes concern problems related to the functioning of healthcare systems. The aim of this study was to evaluate clinical consequences associated with the COVID-19 pandemic for patients with newly diagnosed breast cancer, treated at our centre. Methods: The study participants were patients first time diagnosed with breast cancer, treated between January 2019 and March 2021, who were provided any type of cancer treatment at our centre. The study determined the grade of clinical and pathological progress of the disease and types of cancer treatment applied in patients. Results: In total, 2863 patients were included in the analysis. The number of hospitalized patients was 1228 (1123 treated surgically, 105 receiving conservative treatment) in 2019, 1318 (1206 and 112 patients, respectively) in 2020, and 317 (288 and 29 patients, respectively) in 2021. Conclusions: Despite many hazards associated with the new epidemiological situation, we were able to maintain the continuous operation of our centre. We have achieved a measurable success, and even managed to increase the number of treated breast cancer patients.

Abstract PD4-03: Characterization of HER2 amplification in the cerebrospinal fluid of patients with Leptomeningeal Disease in stage IV patients with breast cancer

Abstract Introduction. Breast cancers that metastasize to the central nervous system (BrM) and progress to leptomeningeal disease (LMD) are commonly HER2 amplified. Triple negative breast cancer (TNBC) also may also acquire HER2 amplification and/or copy number changes (HER2+) in BrM and LMD due to genetic heterogeneity. LMD has a dismal prognosis if untreated, but advances in anti-HER2 therapy have been highly effective for improving outcomes in patients with HER2+ LMD. Current methods for evaluating HER2 status in LMD are extremely limited. Cerebrospinal fluid (CSF) cytology is of limited sensitivity with poor cellular yield and preservation due to technical artifacts of preparation that severely limit evaluation of HER2 by FISH or IHC. We evaluated the ability of CNSide™ to selectively enrich CSF tumor cells (CSF-TCs) and assess HER2 gene amplification or copy number gain in breast cancer patients with LMD. Methods. CSF specimens from 77 unique breast cancer patients with suspected LMD were collected using CEE-Sure™ CSF collection tubes and analyzed using the CNSide assay, both produced by Biocept, Inc (San Diego CA). CSF tumor cells (CSF-TCs) stabilized at ambient temperature in CEE-Sure for shipping. In the CLIA laboratory CSF-TCs are labeled using a proprietary mouse anti-human antibody cocktail with secondary biotinylated anti-mouse Ig. All CSF cells are then captured in a streptavidin-coated micro-fluidic channel and fluorescently labeled with DAPI, streptavidin, keratin and CD45 to discriminate nucleated CSF-TCs that are SA+ and cytokeratin+, but CD45 negative. CSF-TCs are digitally imaged, localized and counted with specific X-Y coordinates in the channel that allow further characterization of the HER2 status of each cell using FISH probes for centromere 17 and HER2. Results. Of 77 unique patient CSF specimens, 74.0% (57/77) demonstrated the presence of metastatic tumor cells (defined as cells which were DAPI positive, streptavidin positive, and CD45 negative). HER2 cells ranged from fewer than 10 cells to tens of thousands of cells recovered from a single collection tube of CSF. Of the 57 specimens in which malignant cells were identified, 56.1% (32/57) demonstrated HER2 amplification by FISH (defined as HER2:CEP17 ≥ 2.0 or ≥ 6 HER2 signals) and 43.9% (25/57) did not demonstrate HER2 amplification by FISH. Ten (10) patients also had polysomy of chromosome 17 as well as other gene alterations. Conclusion: HER2 amplification is frequently found in breast cancer patients with LMD and can be reliably detected in tumor cells isolated from CSF. Evaluation of HER2 status in CSF-TCs allows treating physicians the opportunity to rapidly confirm the presence of this biomarker and select a more effective targeted therapy against HER2 in patients who present with life-threatening complications of breast cancer. Additional studies are needed to fully establish the clinical utility of CNSide when using various anti-HER2 therapies or therapy combinations to treat breast cancer patients with LMD. Citation Format: Michael Dugan, Deanna Fisher, Nathan Sweed, Barbara Blouw, Julie Mayer. Characterization of HER2 amplification in the cerebrospinal fluid of patients with Leptomeningeal Disease in stage IV patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD4-03.

Effect of Early-Stage Human Breast Carcinoma on Monocyte Programming.

Circulating monocytes are a major source of tumor-associated macrophages (TAMs). TAMs in human breast cancer (BC) support primary tumor growth and metastasis. Neoadjuvant chemotherapy (NAC) is a commonly used treatment for BC patients. The absence of the response to NAC has major negative consequences for the patient: increase of tumor mass, delayed surgery, and unnecessary toxicity. We aimed to identify the effect of BC on the subpopulation content and transcriptome of circulating monocytes. We examined how monocyte phenotypes correlate with the response to NAC. The percentage of CD14-, CD16-, CD163-, and HLA-DR-expressing monocytes was quantified by flow cytometry for patients with T1-4N0-3M0 before NAC. The clinical efficacy of NAC was assessed by RECIST criteria of RECIST 1.1 and by the pathological complete response (pCR). The percentage of CD14+ and СD16+ monocytes did not differ between healthy women and BC patients and did not differ between NAC responders and non-responders. The percentage of CD163-expressing CD14lowCD16+ and CD14+CD16+ monocytes was increased in BC patients compared to healthy women (99.08% vs. 60.00%, p = 0.039, and 98.08% vs. 86.96%, p = 0.046, respectively). Quantitative immunohistology and confocal microscopy demonstrated that increased levels of CD163+ monocytes are recruited in the tumor after NAC. The percentage of CD14lowCD16+ in the total monocyte population positively correlated with the response to NAC assessed by pCR: 8.3% patients with pCR versus 2.5% without pCR (p = 0.018). Search for the specific monocyte surface markers correlating with NAC response evaluated by RECIST 1.1 revealed that patients with no response to NAC had a significantly lower amount of CD14lowCD16+HLA-DR+ cells compared to the patients with clinical response to NAC (55.12% vs. 84.62%, p = 0.005). NGS identified significant changes in the whole transcriptome of monocytes of BC patients. Regulators of inflammation and monocyte migration were upregulated, and genes responsible for the chromatin remodeling were suppressed in monocyte BC patients. In summary, our study demonstrated that presence of BC before distant metastasis is detectable, significantly effects on both monocyte phenotype and transcriptome. The most striking surface markers were CD163 for the presence of BC, and HLA-DR (CD14lowCD16+HLA-DR+) for the response to NAC.

Pharmacological Basis of Breast Cancer Resistance to Therapies - An Overview.

Breast Cancer (BC) is a molecular heterogeneous disease and patients with similar clinico-pathological characteristics often display different response to treatment. Cellular processes, including uncontrolled cell-cycle, constitutive activation of signalling pathways and alterations in DNA-repair mechanisms are the main altered features in breast cancer. These cellular processes play significant roles in the emergence of resistance to therapies. The introduction of target therapies and immunotherapy significantly improved the survival of breast cancer patients. The incorporation of novel biomarkers together with the introduction of new therapeutic options may help to overcome treatment resistance. Molecular profiling promises to help in refine personalized treatment decisions and catalyse the development of further strategies when resistances inevitably occurs. This review provides a summary of genetic and molecular aspects of resistance mechanisms to available treatments for BC patients, and its clinical implications.

Influence of physician’s lifestyle on the prescription of healthy habits to breast cancer patients (LACOG 1218)

Healthy lifestyle is capable of positively modifying the survival of breast cancer (BC) patients. We aimed to evaluate how physician's lifestyle influences on the prescription of healthy habits to BC patients. An online questionnaire to evaluate physician lifestyle and prescription of healthy habits to BC patients was developed and circulated by e-mail to physicians dedicated to treat BC patients. A multivariate Poisson regression analysis assessed which factors of physician lifestyle could influence on prescription of healthy habits. A total of 267 physicians answered the questionnaire from October to November 2018. In terms of physician lifestyle, 228 (85.4%) had healthy eating habits and 236 (88.4%) practiced physical activity. Overall, 84.3% of the physicians advised their BC patients on the importance of lifestyle modification. Physicians who did not exercise regularly have a higher probability of not advising for health lifestyle (RR 2.48; p = 0.0265) as opposite to physicians ≥ 50years-old (RR 0.37; p = 0.0118). Obesity treatment and management was performed by 45.3% of physicians. Being a breast surgeon (RR 1.29; p = 0.0025) or radiation oncologists (RR 1.82; p = 0.0025) were associated with not performing obesity treatment and management. About 53.4% of physicians referred overweight or obese patients to a dietitian and/or endocrinologist. Male gender (RR 1.35; p = 0.0296), breast surgeons (RR 1.99; p = 0.0001), and clinical practice in public health system (RR 1.53; p = 0.0012) were associated with not referring as opposed to physicians ≥ 50years-old (RR 0.46; p = 0.0005). Our survey showed some influence of physician's lifestyle on the prescription of healthy habits to BC patients. Physicians who practice physical activity regularly had a higher probability of advising lifestyle modification and about half of physicians did some type of overweight and obese management.

Mammographic density to predict response to neoadjuvant systemic breast cancer therapy.

Mammographic density (MD) is a risk factor for breast cancer (BC) development, and recurrence. However, its predictive value has been less studied. Herein, we challenged MD as a biomarker associated with response in patients treated with neoadjuvant therapy (NAT). Data on all NAT treated BC patients prospectively collected in the registry of Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy (2009-2019) were identified. Diagnostic mammograms were used to evaluate and score MD as categorized by the Breast Imaging-Reporting and Data System (BI-RADS), which identifies 4 levels of MD in keeping with relative increase of fibro-glandular over fat tissue. Each case was classified according to the following categories a (MD < 25%), b (26-50%), c (51-75%), and d (> 75%). The association between MD and pathological complete response (pCR), i.e., absence of BC cells in surgical specimens, was analyzed in multivariable setting used logistic regression models with adjustment for clinical and pathological variables. A total of 442 patients were analyzed, 120 of which (27.1%) attained a pCR. BI-RADS categories a, b, c, and d accounted for 10.0%, 37.8%, 37.1% and 15.2% of cases. Corresponding pCR were 20.5%, 26.9%, 30.5%, 23.9%, respectively. At multivariable analysis, when compared to cases classified as BI-RADS a, those with denser breast showed an increased likelihood of pCR with odds ratio (OR) of 1.70, 2.79, and 1.47 for b, c and d categories, respectively (p = 0.0996), independently of age, BMI [OR underweight versus (vs) normal = 3.76], clinical nodal and tumor status (OR T1/Tx vs T4 = 3.87), molecular subtype (HER2-positive vs luminal = 10.74; triple-negative vs luminal = 8.19). In subgroup analyses, the association of MD with pCR was remarkable in triple-negative (ORs of b, c and d versus a: 1.85, 2.49 and 1.55, respectively) and HER2-positive BC cases (ORs 2.70, 3.23, and 1.16). Patients with dense breast are more likely to attain a pCR at net of other predictive factors. The potential of MD to assist decisions on BC management and as a stratification factor in neoadjuvant clinical trials should be considered.

Explainable machine learning of the breast cancer staging for designing smart biomarker sensors

In medical diagnostics, smart biomarker sensors are used to detect and monitor biomarker thresholds. Recent bariatric research has shown a connection between obesity and an elevated risk of breast cancer in women, with the growth of adipose tissues and malignancy as a disease caused by the secretion of proinflammatory cytokines and adipocytokines. The current article focuses on HOMA, leptin, adiponectin, and resistin, the adipocytokines that have been identified as the primary causes of breast cancer in obese women during the last two decades. In this manuscript, the XAI tool is implemented on the breast cancer data and presents graphical interpretation. The clinical significance and molecular processes behind circulating HOMA, leptin, adiponectin, and breast cancer resistance have been explored, and XAI methods have been used to construct models for the identification of novel breast cancer biomarkers. The premise of this study is based on classifying each adipokine into two groups: low- and high-level concentrations. We examine the correlation between each group and the likelihood of developing breast cancer. The results provided useful evidence to develop accurate treatment interventions for breast cancer patients based on their biomarker levels and body mass index.

Feasibility and Possible Effects of Mindful Walking and Moderate Walking in Breast Cancer Survivors: A Randomized Controlled Pilot Study With a Nested Qualitative Study Part.

Introduction:Breast cancer (BC) survivors often suffer from disease- and therapy-related long-term side-effects. The study aim was to explore the feasibility, adherence, and individual experiences as well as possible effects of 2 different walking interventions in BC patients.Methods:This randomized controlled, pragmatic pilot trial included a qualitative study component. BC patients were randomized to either mindful walking (MFW) with mindfulness exercises and walking or moderate walking (MW) alone in weekly group sessions over 8 weeks. After 8 and 16 weeks, satisfaction, and self-perceived effectiveness as well as different health-related outcomes including health-related (WHOQOL-BREF) and disease-specific quality of life (FACT-G), perceived stress (PSQ) and cancer-related fatigue (CFS-D) were assessed. ANCOVA was used to evaluate differences in study outcomes. Qualitative data included 4 focus group interviews including 20 patients and were analyzed using a directed qualitative content analysis approach.Results:Altogether, 51 women (mean age 55.8 years (SD 10.9)) were randomized (n = 24 MFW; n = 27 MW). Both groups would recommend the course to other BC patients (MFW 88.9%; MW 95.2%) and showed possible improvements from baseline to week 8, without statistically significant difference between groups: WHOQOL-BREF (MFW: adjusted mean 65.4 (95% confidence interval (CI), 57.1-73.7); MW: 61.6 (53.6-69.6)); FACT-G (MFW: 76.0 (71.5-80.5); MW: 73.0 (68.5-77.4)); PSQ (MFW: 45.3 (40.5-50.1); MW: 45.4 (40.8-50.0)); CFS-D (MFW: 24.3 (20.8-27.8); MW: 25.5 (22.1-28.8)). Improvements lasted until the 16-weeks follow-up. The qualitative analysis suggested that MFW primarily promoted mindfulness, self-care, and acceptability in BC patients, whereas MW activated and empowered the patients as a result of the physical exercise.Conclusion:Both study interventions were positively evaluated by patients and showed possible pre-post effects in disease-specific health-related outcomes without differences between groups. The qualitative analysis results indicate that different resources and coping strategies were addressed by the 2 study interventions.Trial registration:DKRS00011521; prospectively registered 21.12.2016; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011521.

Screening of oral tamoxifen ocular toxicity in patients with breast cancer

Background Carcinoma of the breast is considered as one of the main cancer types among women. Its prevalence is reported to be the second most common type. Several treatment lines have been used in breast cancer besides surgical and radiological interventions. Tamoxifen is one of the medical treatments used in postsurgical prophylaxis of breast cancer. Various visual problems were reported with tamoxifen therapy. These include posterior subcapsular cataracts, color vision affection, intraretinal crystals, and optic neuritis.Aim The aim of this work was to screen for ocular toxicity of tamoxifen used for breast cancer treatment in patients having no ophthalmic complaints and treated with tamoxifen for at least 2 years with a dose of 20 mg per day.Patients and methods We included 50 women with breast carcinoma on tamoxifen therapy for at least 2 years, and then we divided them into two groups regarding duration of tamoxifen intake from 2 to 4 years (group 1) and from 5 to 8 years (group 2). All participants underwent complete careful history taking and full ophthalmological examination. Best-corrected visual acuity was measured using Snellen chart with conversion to logMAR notation for statistical analysis. We assessed the retinal structural changes by optical coherence tomography (OCT) and correlated these changes with the function affection (color vision testing and electrophysiological studies).Results There was a statistically significant correlation between duration of tamoxifen intake and Retinal Pigment Epithelium (RPE) mottling. No other significant correlations were detected. There was no significant difference between the two groups in mean best-corrected visual acuity; intraocular pressure; cup values; disc parameters; ganglion cell complex thickness; retinal nerve fiber layer zones, except for in the inferior quadrant; and macular thickness, except for in the superior quadrant. OCT layer thinning shows retinal nerve fiber layer affection in 34% of cases, ganglion cell complex affection in 48% of cases, and macula affection in 64% of cases. Color vision defects were found in 12%, and electrophysiological test changes were found in a few cases.Conclusion Tamoxifen therapy causes minimal affection on the ocular structure and function. OCT layer thinning (34–64% of cases) precedes the clinical changes. This highlights the importance of OCT examination in those patients to evaluate tamoxifen toxicity, and further studies will be needed to evaluate the reversibility of these changes after stoppage of therapy. The main ocular complications associated with tamoxifen therapy were correlated with duration of treatment.

Bridging Health Care and the Workplace: Formulation of a Return-to-Work Intervention for Breast Cancer Patients Using an Intervention Mapping Approach

Background: Women of working age who are diagnosed with breast cancer often experience a decline in their ability to work during and after treatment. A hospital-based tailored intervention is needed to restore their labour participation by bridging the gap between the healthcare setting and the workplace. The aim of this intervention is to restore the labour participation and, guided by an occupational therapist, to enhance the quality of life of BC patients during their return-to-work process. This paper mainly focusses on describing that intervention, including the research protocol to evaluate its feasibility and participant’s perceptions. Materials and Methods: The development of the BRIDGE intervention has yielded a roadmap that describes the individual patient’s path to return to work and includes tools for professionals. The Template for Intervention Description and Replication (TIDieR) guidelines were used to systematically describe the intervention. A feasibility study – designed as mimic RCT - was used as protocol for this study. Results: prepared by a phase 0 (indication phase), the five phases of the intervention are as follows: exploration; comparison; preparation; goal-setting and action planning; realisation and evaluation. An overview of the procedures involved, including the stakeholders in each phase and the materials to be used, is also presented. Results of the mimic RCT are currently analysed and prepared for publication. Conclusions: This five-phase BRIDGE intervention is performed by an OT and targets patients in paid work who have been diagnosed with BC. It aims to bridge the gap between the healthcare setting and the workplace.

Early warning model of recurrence site for breast cancer rehabilitation patients based on adaptive mesh optimization XGBoost

Objective: Breast cancer is a malignant disease with a high mortality rate. Using postoperative rehabilitation data of breast cancer patients, this study explored the effects of immune, tumor, microenvironmental, psychological, nutritional, aerobic exercise and advanced work indexes on the rehabilitation of breast cancer patients. To determine the weight of the impact of different indications on cancer recovery. By combining the adaptive grid optimization algorithm with the XGBoost (Extreme Gradient Boosting) algorithm, an intelligent prediction model for breast cancer rehabilitation was constructed using patients indexes as input and the recurrence location as the output. Our results showed that the model constructed in this study could effectively predict cancer cell metastasis during breast cancer recurrence in recovered patients. Compared with artificial intelligence algorithm models such as neural network algorithm, support vector machine algorithm, gradient boosting tree algorithm and Adaboost, the model demonstrated a forecast accuracy rate of &gt;93%. The model established in this study could effectively predict the recurrence position of breast cancer and provide an auxiliary reference for doctors to treat breast cancer patients more effectively.

Endometrial Surveillance in Tamoxifen and Letrozole Treated Breast Cancer Patients.

Background: Our study aimed to assess the risk of endometrial pathologies after tamoxifen and aromatase inhibitors (AIs) adjuvant treatment for female breast cancer patients treated at Sultan Qaboos University Hospital in Oman.Materials and Methods: A total of 457 patients diagnosed with estrogen positive breast cancer between January 2011 and December 2018 were screened. Two hundred and four patients met the inclusion criteria, and their detailed clinicopathological and endometrial surveillance data were collected from their electronic health records.Results: All patients underwent endometrial assessment during tamoxifen or letrozole therapy. The mean diagnostic age of breast cancer patients is 43.6 years, ranging from 27-84 years. Eighty-three percent of those patients are premenopausal, and 17% are postmenopausal. The mean tamoxifen use duration was 33 months. The majority of patients, 123 (60.3%), have had tamoxifen for three years or less, 47 (23.1%) for 3-5 years, and only 22 (10.8%) were on tamoxifen for more than five years. Increased endometrial thickness was reported in 8% of the premenopausal and 14% of the postmenopausal group. Other endometrial pathologies that were detected are inactive endometrium three (1.47%), atrophic endometrium three (1.47%), serous carcinoma one (0.50%), endometrial cancer two (0.98%), and chronic endometritis one (0.50%), which were not significantly associated with tamoxifen or letrozole therapy duration. Two patients have developed endometrial cancer, and both are postmenopausal and > 60 years old.Conclusions: Tamoxifen and letrozole did not increase the risk of endometrial cancer in premenopausal patients. Breast Cancer (BC) patients on tamoxifen or letrozole might need a pre-treatment endometrial evaluation and explanation of alarming symptoms to guide further endometrial surveillance.

Dance/Movement Therapy as an Intervention in Breast Cancer Patients: A Systematic Review.

Aim In this paper, we systematically review the evidence looking at the effect of dance/movement therapy (DMT) and mental health outcomes and quality of life in breast cancer patients. Method The literature search was done with the databases PubMed (MEDLINE), EBSCO, and Cochrane Central by using the following search words: “dancing/dance/movement therapy,” “breast cancer/neoplasms/carcinoma/tumour” or “mammary cancer,” “mental health,” and “quality of life.” Ninety-four articles were found. Only empirical interventional studies (N = 6) were selected for the review: randomised controlled trials (RCT) (n = 5) and non-RCT (n = 1). PRISMA guidelines were used. Results Data from 6 studies including 385 participants who had been diagnosed with breast cancer, were of an average age of 55.7 years, and had participated in DMT programmes for 3–24 weeks were analysed. In each study, the main outcomes that were measured were quality of life, physical activity, stress, and emotional and social well-being. Different questionnaires were used for the evaluation of outcomes. The mental health of the participants who received DMT intervention improved: they reported a better quality of life and decreased stress, symptoms, and fatigue. Conclusion We found only six studies for review, and some had a small number of participants. However, our findings indicate that DMT could be successfully used as a complimentary therapy in addition to standard cancer treatment for improving the quality of life and mental health of women who have been diagnosed with breast cancer. More research is needed to evaluate the complexity of the impact of complimentary therapies. It is possible that DMT could be more effective if used with other therapies.