ResearchPad - breast-tumors https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Changes and prognostic values of tumor-infiltrating lymphocyte subsets after primary systemic therapy in breast cancer]]> https://www.researchpad.co/article/elastic_article_14496 Tumor-infiltrating lymphocyte (TIL) levels have prognostic and predictive values in treatment-naïve breast cancers. However, there have been controversies regarding TIL subset changes and their clinical implications in post-treatment breast cancers. This study aimed to explore change and prognostic significance of TIL subset infiltration after primary systemic therapy (PST) in breast cancer. One-hundred-fifty-five patients who had residual disease after anthracycline- or anthracycline plus taxane-based PST were included. The quantities of intratumoral and stromal TIL subsets (CD8+, CD4+, and FOXP3+ TILs) in pre- and post-PST breast cancer samples, as well as changes between them, were analyzed along with their correlations with clinicopathologic features and outcome of patients. As a whole, intratumoral CD8+ and CD4+ TILs increased after PST while stromal TILs decreased. Both intratumoral and stromal FOXP3+ TILs decreased after PST. The chemo-sensitive group [residual cancer burden (RCB) class I and II] showed the same pattern of change in intratumoral CD8+ TILs as the whole group, whereas the chemo-resistant group (RCB class III) showed no significant change in intratumoral CD8+ TIL infiltration after PST. Survival analyses for each TIL subset as well as their ratios revealed that high levels of intratumoral, stromal, and total CD8+ TIL infiltration after PST were independent predictors of longer patient survival. In subgroup analyses, CD8+ TIL infiltration after PST revealed prognostic significance in the chemo-resistant group but not in the chemo-sensitive group. In conclusion, infiltration of CD8+, CD4+, and FOXP3+ TIL changed after PST in the intratumoral and stromal compartments. Especially, increase of intratumoral CD8+ TILs was associated with chemo-responsiveness. Moreover, CD8+ TIL status in residual tumors after PST may be used as a potential prognostic marker in breast cancer patients who receive PST and provide additional prognostic information to chemo-resistant group.

]]>
<![CDATA[<i>In silico</i> analyses identify lncRNAs: WDFY3-AS2, BDNF-AS and AFAP1-AS1 as potential prognostic factors for patients with triple-negative breast tumors]]> https://www.researchpad.co/article/elastic_article_13870 Long non-coding RNAs (lncRNAs) are characterized as having 200 nucleotides or more and not coding any protein, and several been identified as differentially expressed in several human malignancies, including breast cancer.MethodsHere, we evaluated lncRNAs differentially expressed in triple-negative breast cancer (TNBC) from a cDNA microarray data set obtained in a previous study from our group. Using in silico analyses in combination with a review of the current literature, we identify three lncRNAs as potential prognostic factors for TNBC patients.ResultsWe found that the expression of WDFY3-AS2, BDNF-AS, and AFAP1-AS1 was associated with poor survival in patients with TNBCs. WDFY3-AS2 and BDNF-AS are lncRNAs known to play an important role in tumor suppression of different types of cancer, while AFAP1-AS1 exerts oncogenic activity.ConclusionOur findings provided evidence that WDFY3-AS2, BDNF-AS, and AFAP1-AS1 may be potential prognostic factors in TNBC development. ]]> <![CDATA[Early budget impact analysis on magnetic seed localization for non-palpable breast cancer surgery]]> https://www.researchpad.co/article/elastic_article_13866 Current localization techniques used in breast conserving surgery for non-palpable tumors show several disadvantages. Magnetic Seed Localization (MSL) is an innovative localization technique aiming to overcome these disadvantages. This study evaluated the expected budget impact of adopting MSL compared to standard of care.MethodsStandard of care with Wire-Guided Localization (WGL) and Radioactive Seed Localization (RSL) use was compared with a future situation gradually adopting MSL next to RSL or WGL from a Dutch national perspective over 5 years (2017–2022). The intervention costs for WGL, RSL and MSL and the implementation costs for RSL and MSL were evaluated using activity-based costing in eight Dutch hospitals. Based on available list prices the price of the magnetic seed was ranged €100-€500.ResultsThe intervention costs for WGL, RSL and MSL were respectively: €2,617, €2,834 and €2,662 per patient and implementation costs were €2,974 and €26,826 for MSL and RSL respectively. For standard of care the budget impact increased from €14.7m to €16.9m. Inclusion of MSL with a seed price of €100 showed a budget impact of €16.7m. Above a price of €178 the budget impact increased for adoption of MSL, rising to €17.6m when priced at €500.ConclusionMSL could be a cost-efficient localization technique in resecting non-palpable tumors in the Netherlands. The online calculation model can inform adoption decisions internationally. When determining retail price of the magnetic seed, cost-effectiveness should be considered. ]]> <![CDATA[Regulation of cell growth and migration by miR-96 and miR-183 in a breast cancer model of epithelial-mesenchymal transition]]> https://www.researchpad.co/article/elastic_article_7836 Breast cancer is the most commonly diagnosed malignancy in women, and has the second highest mortality rate. Over 90% of all cancer-related deaths are due to metastasis, which is the spread of malignant cells from the primary tumor to a secondary site in the body. It is hypothesized that one cause of metastasis involves epithelial-mesenchymal transition (EMT). When epithelial cells undergo EMT and transition into mesenchymal cells, they display increased levels of cell proliferation and invasion, resulting in a more aggressive phenotype. While many factors regulate EMT, microRNAs have been implicated in driving this process. MicroRNAs are short noncoding RNAs that suppress protein production, therefore loss of microRNAs may promote the overexpression of specific target proteins important for EMT. The goal of this study was to investigate the role of miR-96 and miR-183 in EMT in breast cancer. Both miR-96 and miR-183 were found to be downregulated in post-EMT breast cancer cells. When microRNA mimics were transfected into these cells, there was a significant decrease in cell viability and migration, and a shift from a mesenchymal to an epithelial morphology (mesenchymal-epithelial transition or MET). These MET-related changes may be facilitated in part by the regulation of ZEB1 and vimentin, as both of these proteins were downregulated when miR-96 and miR-183 were overexpressed in post-EMT cells. These findings indicate that the loss of miR-96 and miR-183 may help facilitate EMT and contribute to the maintenance of a mesenchymal phenotype. Understanding the role of microRNAs in regulating EMT is significant in order to not only further elucidate the pathways that facilitate metastasis, but also identify potential therapeutic options for preventing or reversing this process.

]]>
<![CDATA["Clicks, likes, shares and comments" a systematic review of breast cancer screening discourse in social media]]> https://www.researchpad.co/article/N8d8d3073-6769-4a60-aed8-e2beb958c228

Background

Unsatisfactory participation rate at population based organised breast cancer screening is a long standing problem. Social media, with 3.2 billion users in 2019, is potentially an important site of breast cancer related discourse. Determining whether these platforms might be used as channels by screening providers to reach under-screened women may have considerable public health significance.

Objectives

By systematically reviewing original research studies on breast cancer related social media discourse, we had two aims: first, to assess the volume, participants and content of breast screening social media communication and second, to find out whether social media can be used by screening organisers as a channel of patient education.

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After searching PubMed, ScienceDirect, Web of Science, Springer and Ebsco, 17 studies were found that met our criteria. A systematic narrative framework was used for data synthesis. Owing to the high degree of heterogeneity in social media channels, outcomes and measurement included in this study, a meta-analytic approach was not appropriate.

Results

The volume of breast cancer related social media discourse is considerable. The majority of participants are lay individuals as opposed to healthcare professionals or advocacy groups. The lay misunderstandings surrounding the harms and benefits of mammography is well mirrored in the content of social media discourse. Although there is criticism, breast cancer screening sentiment on the social media ranges from the neutral to the positive. Social media is suitable for offering peer emotional support for potential participants.

Conclusion

Dedicated breast screening websites operated by screening organisers would ensure much needed quality controlled information and also provide space for reliable question and answer forums, the sharing of personal experience and the provision of peer and professional support.

]]>
<![CDATA[Deep learning assessment of breast terminal duct lobular unit involution: Towards automated prediction of breast cancer risk]]> https://www.researchpad.co/article/N8ae86a5e-90c1-41b1-ba31-58a5a939e3bc

Terminal duct lobular unit (TDLU) involution is the regression of milk-producing structures in the breast. Women with less TDLU involution are more likely to develop breast cancer. A major bottleneck in studying TDLU involution in large cohort studies is the need for labor-intensive manual assessment of TDLUs. We developed a computational pathology solution to automatically capture TDLU involution measures. Whole slide images (WSIs) of benign breast biopsies were obtained from the Nurses’ Health Study. A set of 92 WSIs was annotated for acini, TDLUs and adipose tissue to train deep convolutional neural network (CNN) models for detection of acini, and segmentation of TDLUs and adipose tissue. These networks were integrated into a single computational method to capture TDLU involution measures including number of TDLUs per tissue area, median TDLU span and median number of acini per TDLU. We validated our method on 40 additional WSIs by comparing with manually acquired measures. Our CNN models detected acini with an F1 score of 0.73±0.07, and segmented TDLUs and adipose tissue with Dice scores of 0.84±0.13 and 0.87±0.04, respectively. The inter-observer ICC scores for manual assessments on 40 WSIs of number of TDLUs per tissue area, median TDLU span, and median acini count per TDLU were 0.71, 0.81 and 0.73, respectively. Intra-observer reliability was evaluated on 10/40 WSIs with ICC scores of >0.8. Inter-observer ICC scores between automated results and the mean of the two observers were: 0.80 for number of TDLUs per tissue area, 0.57 for median TDLU span, and 0.80 for median acini count per TDLU. TDLU involution measures evaluated by manual and automated assessment were inversely associated with age and menopausal status. We developed a computational pathology method to measure TDLU involution. This technology eliminates the labor-intensiveness and subjectivity of manual TDLU assessment, and can be applied to future breast cancer risk studies.

]]>
<![CDATA[Plasma membrane expression of G protein-coupled estrogen receptor (GPER)/G protein-coupled receptor 30 (GPR30) is associated with worse outcome in metachronous contralateral breast cancer]]> https://www.researchpad.co/article/Naf611639-dea0-4cb3-8951-2157f0424339

Background

G protein-coupled estrogen receptor (GPER), or G protein-coupled receptor 30 (GPR30), is reported to mediate non-genomic estrogen signaling. GPR30 associates with breast cancer (BC) outcome and may contribute to tamoxifen resistance. We investigated the expression and prognostic significance of GPR30 in metachronous contralateral breast cancer (CBC) as a model of tamoxifen resistance.

Methods

Total GPR30 expression (GPR30TOT) and plasma membrane-localized GPR30 expression (GPR30PM) were analyzed by immunohistochemistry in primary (BC1; nBC1 = 559) and contralateral BC (BC2; nBC2 = 595), and in lymph node metastases (LGL; nLGL1 = 213; nLGL2 = 196). Death from BC (BCD), including BC death or death after documented distant metastasis, was used as primary end-point.

Results

GPR30PM in BC2 and LGL2 were associated with increased risk of BCD (HRBC2 = 1.7, p = 0.03; HRLGL2 = 2.0; p = 0.02). In BC1 and BC2, GPR30PM associated with estrogen receptor (ER)-negativity (pBC1<0.0001; pBC2<0.0001) and progesterone receptor (PR)-negativity (pBC1 = 0.0007; pBC2<0.0001). The highest GPR30TOT and GPR30PM were observed in triple-negative BC. GPR30PM associated with high Ki67 staining in BC1 (p<0.0001) and BC2 (p<0.0001). GPR30TOT in BC2 did not associate with tamoxifen treatment for BC1. However, BC2 that were diagnosed during tamoxifen treatment were more likely to express GPR30PM than BC2 diagnosed after treatment completion (p = 0.01). Furthermore, a trend was observed that patients with GPR30PM in an ER-positive BC2 had greater benefit from tamoxifen treatment.

Conclusion

PM-localized GPR30 staining is associated with increased risk of BC death when expressed in BC2 and LGL2. Additionally, PM-localized GPR30 correlates with prognostic markers of worse outcome, such as high Ki67 and a triple-negative subtype. Therefore, PM-localized GPR30 may be an interesting new target for therapeutic exploitation. We found no clear evidence that total GPR30 expression is affected by tamoxifen exposure during development of metachronous CBC, or that GPR30 contributes to tamoxifen resistance.

]]>
<![CDATA[Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: A randomized, double-blind, placebo-controlled trial]]> https://www.researchpad.co/article/Nf52b3d22-02a5-4e7e-bb1d-9e73ca6c7e6b

This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment. We evaluated the effects of melatonin on cognition, depressive symptoms and sleep quality, and whether these effects were related to serum levels of Brain Derived Neurotrophic Factor (BDNF) and its receptor, tropomyosin kinase B (TrkB). Thirty-six women were randomly assigned to receive melatonin or placebo for 10 days. To evaluate cognitive performance, we used the Trail-Making-Test Parts A and B (A-B), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and an inhibitory task type Go / No-Go. Our results revealed that melatonin improved executive function on TMT scores, enhanced episodic memory (immediate and delayed) and recognition on RAVLT, and increased verbal fluency in the orthographic COWAT. The TMT-A-B(A-B) were negatively correlated with baseline levels of TrkB and BDNF, respectively. At the end of treatment, changes in TrkB and BDNF were inversely associated with depressive symptoms and sleep quality, but not with the TMT scores. These results suggest a neuroprotective effect of melatonin to counteract the adverse effects of ACBC on cognitive function, sleep quality and depressive symptoms.

]]>
<![CDATA[Integrated structural variation and point mutation signatures in cancer genomes using correlated topic models]]> https://www.researchpad.co/article/5c99020ad5eed0c484b97533

Mutation signatures in cancer genomes reflect endogenous and exogenous mutational processes, offering insights into tumour etiology, features for prognostic and biologic stratification and vulnerabilities to be exploited therapeutically. We present a novel machine learning formalism for improved signature inference, based on multi-modal correlated topic models (MMCTM) which can at once infer signatures from both single nucleotide and structural variation counts derived from cancer genome sequencing data. We exemplify the utility of our approach on two hormone driven, DNA repair deficient cancers: breast and ovary (n = 755 samples total). We show how introducing correlated structure both within and between modes of mutation can increase accuracy of signature discovery, particularly in the context of sparse data. Our study emphasizes the importance of integrating multiple mutation modes for signature discovery and patient stratification, and provides a statistical modeling framework to incorporate additional features of interest for future studies.

]]>
<![CDATA[Tailored NEOadjuvant epirubicin, cyclophosphamide and Nanoparticle Albumin-Bound paclitaxel for breast cancer: The phase II NEONAB trial—Clinical outcomes and molecular determinants of response]]> https://www.researchpad.co/article/5c6f152dd5eed0c48467ae8b

Background

This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored.

Patients and outcome measures

Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25. Patients were treated with epirubicin and cyclophosphamide, followed by nab-paclitaxel, with the addition of trastuzumab if HER2-amplified. The primary endpoint was pathological complete response (pCR) in the breast. Pre- and post-treatment tumour samples underwent variant burden, gene and gene pathway, mutational signature profile and clonal evolution analyses.

Results

The pCR rates were: overall 55% (n = 22), HER2-amplified 80% (n = 12), triple-negative 46% (n = 7) and HR-positive, HER2-non-amplified 30% (n = 3). Grade 3 or 4 adverse events included febrile neutropenia (8%), neutropenia (18%), sensory neuropathy (5%), deranged transaminases (5%), fatigue (2%), diarrhoea (2%), and pneumothorax (2%). Molecular analyses demonstrated strong similarities between residual disease and matched primary tumour. ATM signalling pathway alterations and the presence of a COSMIC Signature 3 implied the majority of tumours contained some form of homologous repair deficiency. ATM pathway alterations were identified in the subset of TNBC patients who did not achieve pCR; Signature 3 was present in both pCR and non-pCR subgroups. Clonal evolution analyses demonstrated both persistence and emergence of chemoresistant clones.

Conclusions

This treatment regime resulted in a high rate of pCR, demonstrating that tailored neoadjuvant therapy using a genomic recurrence score is feasible and warrants further investigation. Molecular analysis revealed few commonalities between patients. For TNBC future clinical gains will require precision medicine, potentially using DNA sequencing to identify specific targets for individuals with resistant disease.

Trial registration

Clinicaltrials.gov NCT01830244

]]>
<![CDATA[Alcohol and breast cancer risk: Middle-aged women’s logic and recommendations for reducing consumption in Australia]]> https://www.researchpad.co/article/5c6dca15d5eed0c48452a756

Background

We aimed to understand the factors shaping alcohol consumption patterns in middle-aged women (45–64), and to identify participant-driven population- and policy-level strategies that may be used to addresses alcohol consumption and reduce breast cancer risk.

Methods

Semi-structured interviews (n = 35) were conducted with ‘middle-aged’ women conversant in English and living in South Australia with no history of breast cancer diagnosis. Data were deductively coded using a co-developed framework including variables relevant to our study objectives. Women were asked about their current level of awareness of the association between alcohol and breast cancer risk, and their personal recommendations for how to decrease consumption in middle-aged Australian women.

Results

Women discussed their previous efforts to decrease consumption, which we drew on to identify preliminary recommendations for consumption reduction. We identified a low level of awareness of alcohol and breast cancer risk, and confusion related to alcohol as a risk for breast cancer, but not always causing breast cancer. Participants suggested that education and awareness, through various means, may help to reduce consumption.

Conclusions

Participants’ description of strategies used to reduce their own consumption lead us to suggest that campaigns might focus on the more salient and immediate effects of alcohol (e.g. on physical appearance and mental health) rather than longer-term consequences. Critical considerations for messaging include addressing the personal, physical and social pleasures that alcohol provides, and how these may differ across socio-demographics.

]]>
<![CDATA[Complex harmonic regularization with differential evolution in a memetic framework for biomarker selection]]> https://www.researchpad.co/article/5c6f1534d5eed0c48467aebf

For studying cancer and genetic diseases, the issue of identifying high correlation genes from high-dimensional data is an important problem. It is a great challenge to select relevant biomarkers from gene expression data that contains some important correlation structures, and some of the genes can be divided into different groups with a common biological function, chromosomal location or regulation. In this paper, we propose a penalized accelerated failure time model CHR-DE using a non-convex regularization (local search) with differential evolution (global search) in a wrapper-embedded memetic framework. The complex harmonic regularization (CHR) can approximate to the combination p(12p<1) and q (1 ≤ q < 2) for selecting biomarkers in group. And differential evolution (DE) is utilized to globally optimize the CHR’s hyperparameters, which make CHR-DE achieve strong capability of selecting groups of genes in high-dimensional biological data. We also developed an efficient path seeking algorithm to optimize this penalized model. The proposed method is evaluated on synthetic and three gene expression datasets: breast cancer, hepatocellular carcinoma and colorectal cancer. The experimental results demonstrate that CHR-DE is a more effective tool for feature selection and learning prediction.

]]>
<![CDATA[A data-driven interactome of synergistic genes improves network-based cancer outcome prediction]]> https://www.researchpad.co/article/5c648d3fd5eed0c484c82364

Robustly predicting outcome for cancer patients from gene expression is an important challenge on the road to better personalized treatment. Network-based outcome predictors (NOPs), which considers the cellular wiring diagram in the classification, hold much promise to improve performance, stability and interpretability of identified marker genes. Problematically, reports on the efficacy of NOPs are conflicting and for instance suggest that utilizing random networks performs on par to networks that describe biologically relevant interactions. In this paper we turn the prediction problem around: instead of using a given biological network in the NOP, we aim to identify the network of genes that truly improves outcome prediction. To this end, we propose SyNet, a gene network constructed ab initio from synergistic gene pairs derived from survival-labelled gene expression data. To obtain SyNet, we evaluate synergy for all 69 million pairwise combinations of genes resulting in a network that is specific to the dataset and phenotype under study and can be used to in a NOP model. We evaluated SyNet and 11 other networks on a compendium dataset of >4000 survival-labelled breast cancer samples. For this purpose, we used cross-study validation which more closely emulates real world application of these outcome predictors. We find that SyNet is the only network that truly improves performance, stability and interpretability in several existing NOPs. We show that SyNet overlaps significantly with existing gene networks, and can be confidently predicted (~85% AUC) from graph-topological descriptions of these networks, in particular the breast tissue-specific network. Due to its data-driven nature, SyNet is not biased to well-studied genes and thus facilitates post-hoc interpretation. We find that SyNet is highly enriched for known breast cancer genes and genes related to e.g. histological grade and tamoxifen resistance, suggestive of a role in determining breast cancer outcome.

]]>
<![CDATA[Ectopic Otoconin 90 expression in triple negative breast cancer cell lines is associated with metastasis functions]]> https://www.researchpad.co/article/5c6f1491d5eed0c48467a304

Triple negative breast cancer (TNBC) is an aggressive tumor with propensity to metastasize and poor treatment options. Improving treatment options would be impactful; thus, finding a tumor-specific cell surface protein with metastasis promoting functions that could be knocked out was the goal of this study. The Otoconin 90 gene (OC90), frequently amplified in tumors on chromosome 8q24.22, was identified as a potential therapeutic candidate. Normally OC90 is expressed in the cochlea with no known function in other normal tissues. In silico analysis of The Cancer Genome Atlas (TCGA) multi-tumor RNAseq cohorts revealed that OC90 is expressed in many tumor types at high prevalence and genomic amplification is associated with the elevated mRNA expression. In vitro assays in TNBC cell lines revealed OC90 expression with control over cell viability, apoptosis and invasion. RNA-seq analysis of OC90-siRNA knockdown and OC90-overexpression in BT20, BT549, HCC38 cell lines identified co-expressed transcripts, HMGA2, POLE2 and TRIB3. Altered expression of HMGA2, POLE2 and TRIB3 was predictive of survival among members of the Metabric breast cancer cohort. Thus, OC90 represents a potential therapeutic target whose knockdown could improve the treatment of TNBC.

]]>
<![CDATA[Reproductive characteristics modify the association between global DNA methylation and breast cancer risk in a population-based sample of women]]> https://www.researchpad.co/article/5c6f1484d5eed0c48467a21a

DNA methylation has been implicated in breast cancer aetiology, but little is known about whether reproductive history and DNA methylation interact to influence carcinogenesis. This study examined modification of the association between global DNA methylation and breast cancer risk by reproductive characteristics. A population-based case-control study assessed reproductive history in an interviewer-administered questionnaire. Global DNA methylation was measured from white blood cell DNA using luminometric methylation assay (LUMA) and pyrosequencing assay (long interspersed elements-1 (LINE-1). We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) among 1 070 breast cancer cases and 1 110 population-based controls. Effect modification was assessed on additive and multiplicative scales. LUMA methylation was associated with elevated breast cancer risk across all strata (comparing the highest to the lowest quartile), but estimates were higher among women with age at menarche ≤12 years (OR = 2.87, 95%CI = 1.96–4.21) compared to >12 years (OR = 1.66, 95%CI = 1.20–2.29). We observed a 2-fold increase in the LUMA methylation-breast cancer association among women with age at first birth >23 years (OR = 2.62, 95%CI = 1.90–3.62) versus ≤23 years (OR = 1.32, 95% CI = 0.84–2.05). No modification was evident for parity or lactation. Age at menarche and age at first birth may be modifiers of the association between global DNA methylation and breast cancer risk.

]]>
<![CDATA[Assessment of patient information needs: A systematic review of measures]]> https://www.researchpad.co/article/5c5ca313d5eed0c48441f0cf

Background

Providing patient information is a central aspect of patient-centered care. Fulfilling personal information needs has positive effects on several health-related outcomes. Measurement instruments help to identify individual information needs in an effective way. The present study gives an overview of existing information needs measures and further evaluates the quality of their psychometric properties and their psychometric studies.

Methods

We conducted a systematic search on psychometric studies of measures that assess information needs in PubMed and Embase. Furthermore, we carried out a secondary search with reference and citation tracking of the included articles. Title, abstracts and full texts were screened by two independent reviewers for eligibility. We extracted data on content of the measures, validation samples and psychometric properties. In addition we rated the methodological quality with the COSMIN checklist and the quality of psychometric properties with the criteria of Terwee and colleagues.

Results

24 studies on 21 measures were included. Most instruments assessed information needs of patients with cancer or cardiac diseases. The majority of the instruments were in English language and from western countries. Most studies included information on internal consistency and content validity. The ratings showed mixed results with clear deficiencies in the methodological quality of most studies.

Discussion

This is the first systematic review that summarized the existing evidence on measures on patient information needs using two instruments for a systematic quality assessment. The results show a need for more psychometric studies on existing measures. In addition, reporting on psychometric studies needs to be improved to be able to evaluate the reliability of the psychometric properties. Furthermore, we were not able to identify any measures on information needs for some frequent chronic diseases. Other methods to elicit information needs (e.g. open-ended interviews, question prompt sheets) could be considered as alternatives if sound measures are missing.

]]>
<![CDATA[Clinical outcomes and dosimetric study of hypofractionated Helical TomoTherapy in breast cancer patients]]> https://www.researchpad.co/article/5c5ca2a6d5eed0c48441e7f4

We present a single center’s experience of treatment outcomes and dosimetric parameters for breast cancer patients treated with hypofractionated Helical TomoTherapy (HT). This is a retrospective study of one hundred and thirty-six patients with invasive breast cancer treated between March 2012 and October 2016. Dosimetric parameters and 3-year loco-regional failure free survival (LRFFS) were analyzed. Dose to ipsilateral lung, heart and contralateral breast as well as acute and late toxicities were recorded. The median follow-up time is 45 months (range: 5–83). Two patients had loco-regional failure. The 3-year LRFFS was 99%. Acute grade 1 and 2 skin toxicities occurred in 95% and 1%, respectively. Coverage of the target volumes was achieved with the mean ± standard deviation (SD) of homogeneity and conformity index being 0.1 ± 0.04, and 0.8 ± 0.07, respectively. Dose to ipsilateral lung, contralateral breast, and heart was also within the limited constraints regardless of the complexity of target volumes. Only two percent of patients experienced late grade 2 skin toxicity. No late grade 2 subcutaneous tissue toxicity was found. Nine percent of patients developed late grade 1 lung toxicity. Hypofractionated radiotherapy using Helical TomoTherapy in breast irradiation provides excellent 3-year LRFFS and minimal acute and late toxicities. A careful, longer follow-up of healthy tissue effects to lung, heart, and contralateral breast is warranted.

]]>
<![CDATA[A qualitative comparison of how older breast cancer survivors process treatment information regarding endocrine therapy]]> https://www.researchpad.co/article/5c5ca2e5d5eed0c48441ecbb

Background

It remains unclear how information about aromatase inhibitors (AI) impacts women’s decision-making about persistence with endocrine therapy.

Purpose

To describe and compare how women treated for primary early stage breast cancer either persisting or not persisting with an AI received, interpreted, and acted upon AI-related information.

Design

Thematic analysis was used to sort and compare the data into the most salient themes.

Participants

Women (N = 54; 27 persisting, 27 not persisting with an AI) aged 65–93 years took part in qualitative interviews.

Results

Women in both subgroups described information similarly in terms of its value, volume, type, and source. Aspects of AI-related information that either differed between the subgroups or were misunderstood by one or both subgroups included: (1) knowledge of AI or tamoxifen prior to cancer diagnosis, (2) use of online resources, (3) misconceptions about estrogen, hormone replacement therapies and AI-related symptoms, and (4) risk perception and the meaning and use of recurrence statistics such as Oncotype DX.

Conclusions

Persisters and nonpersisters were similar in their desire for more information about potential side effects and symptom management at AI prescription and subsequent appointments. Differences included how information was obtained and interpreted. Interactive discussion questions are shared that can incorporate these findings into clinical settings.

]]>
<![CDATA[Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein]]> https://www.researchpad.co/article/5c5b524ad5eed0c4842bc5fc

It is generally accepted that radiotherapy must target clonogenic cells, i.e., those cells in a tumour that have self-renewing potential. Focussing on isolated clonogenic cells, however, may lead to an underestimate or even to an outright neglect of the importance of biological mechanisms that regulate tumour cell sensitivity to radiation. We develop a new statistical and experimental approach to quantify the effects of radiation on cell populations as a whole. In our experiments, we change the proximity relationships of the cells by culturing them in wells with different shapes, and we find that the radiosensitivity of T47D human breast carcinoma cells in tight clusters is different from that of isolated cells. Molecular analyses show that T47D cells express a Syncytin-1 homologous protein (SyHP). We observe that SyHP translocates to the external surface of the plasma membrane of cells killed by radiation treatment. The data support the fundamental role of SyHP in the formation of intercellular cytoplasmic bridges and in the enhanced radioresistance of surviving cells. We conclude that complex and unexpected biological mechanisms of tumour radioresistance take place at the cell population level. These mechanisms may significantly bias our estimates of the radiosensitivity of breast carcinomas in vivo and thereby affect treatment plans, and they call for further investigations.

]]>
<![CDATA[Prediction of local recurrence risk after neoadjuvant chemotherapy in patients with primary breast cancer: Clinical utility of the MD Anderson Prognostic Index]]> https://www.researchpad.co/article/5c5ca2e2d5eed0c48441ec55

Background

Locoregional recurrence after neoadjuvant chemotherapy for primary breast cancer is associated with poor prognosis. It is essential to identify patients at high risk of locoregional recurrence who may benefit from extended local therapy. Here, we examined the prediction accuracy and clinical applicability of the MD Anderson Prognostic Index (MDAPI).

Methods

Prospective clinical data from 456 patients treated between 2003 and 2011 was analyzed. The Kaplan-Meier method was used to examine the probabilities of locoregional recurrence, local recurrence and distant metastases according to individual prognosis score, stratified by type of surgery (breast conserving therapy or mastectomy). The possible confounding of the relationship between recurrence risk and MDAPI by established risk factors was accounted for in multiple survival regression models. To define the clinical utility of the MDAPI we analyzed its performance to predict locoregional recurrence censoring patients with prior or simultaneous distant metastases.

Results

Mastectomized patients (42% of the patients) presented with more advanced tumor stage, lower tumor grade, hormone-receptor positive disease and consequently lower pathological complete response rates. Only a few patients presented with high-risk scores (2,7% MDAPI≥3). All patients with high-risk MDAPI score (MDAPI ≥3) who developed locoregional recurrence were simultaneously affected by distant metastases.

Conclusion

Our data do not support a clinical utility of the MDAPI to guide local therapy.

]]>