ResearchPad - breast https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![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.

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<![CDATA[Breast cancer diagnosis based on lipid profiling by probe electrospray ionization mass spectrometry]]> https://www.researchpad.co/article/elastic_article_6746 Probe electrospray ionization mass spectrometry (PESI‐MS) is an ambient ionization‐based mass spectrometry method that surpasses the original electrospray ionization technique in features such as the rapidity of analysis, simplicity of the equipment and procedure, and lower cost. This study found that the PESI‐MS system with machine learning has the potential to establish a lipid‐based diagnosis of breast cancer with higher accuracy, using a simpler approach.

Rapid mass spectrometry for breast cancer

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<![CDATA[OR05-04 Steroid Receptor Co-Activators Complexes Cooperate with Progesterone Receptors (PR) to Reprogram Metabolic Pathways that Drive Therapy Resistant Populations in ER+ Breast Cancer]]> https://www.researchpad.co/article/elastic_article_6041 Late recurrence of metastatic disease stemming from acquired therapy resistance remains a significant health burden for women with ER+ breast cancer. Disseminated ER+ tumor cell populations can remain quiescent for years to decades, and contributing factors include breast cancer stem cells (CSCs), which are non-proliferative and frequently exist as a minority population in recurrent therapy-resistant tumors. Progesterone receptors (PR) are known drivers of normal stem and breast CSCs. Our objective was to define novel signaling pathways governing cell fate transitions involved in driving therapy resistance in ER+ breast cancer. We reported that cytoplasmic complexes composed of steroid receptor (SR) co-activators, PELP1 and SRC-3, drive breast CSC outgrowth. SRC-3 knockdown abrogated PELP1-induced CSC expansion and target genes required for cell survival, suggesting an essential role for PELP1/SRC-3 complexes. PELP1 also forms a signaling and transcriptional complex with ER and PR-B. Phospho-PR species are key mediators of stemness in ER+ breast cancer models. Accordingly, PR knockdown and antiprogestins disrupted PELP1/SRC-3 complexes and blocked PELP1-induced breast CSC outgrowth. Mammary stem cell (MaSC) populations were increased in vivo in MMTV-tTA;TRE-cyto-PELP1 transgenic mice as well as in MMTV-tTA;TRE-hPR-B mice. To better understand PELP1-mediated pathways, we performed RNA-seq on MCF-7 PELP1+ models grown in tumorsphere conditions to enrich for CSC populations (ALDH+, CD44+/CD24-). Cytoplasmic PELP1-expressing cells had a different global gene profile relative to WT PELP1 (i.e. nuclear). Gene sets associated with stem cell biology, hypoxic stress, and cancer metabolism were differentially regulated, including members of the glycolytic bi-functional kinase/phosphatase PFKFB family. Seahorse metabolic phenotyping demonstrated cytoplasmic PELP1 influences metabolism by increasing both glycolysis and mitochondrial respiration. Cytoplasmic PELP1 interacted strongly with PFKFB3 and PFKFB4, and inhibition of PFKFB3 or PFKFB4 kinase activity blocked PELP1-induced tumorspheres and protein-protein interactions with SRC-3. Additionally, antiprogestin and PFKFB inhibitors were synergistic when combined with ER+ targeted therapies. These aspects of PELP1/SRC-3 biology were phenocopied in therapy resistant models (tamoxifen resistant [TamR], paclitaxel resistant [TaxR]). Together, our data suggest that PELP1, SRC-3, PR, and PFKFBs form complexes that reprogram cellular metabolism to drive breast CSC expansion. Identifying the mechanisms that regulate recurrent ER+ tumor cell populations will enable specific targeting within heterogeneous breast tumors and may lead to the development of non-ER targets that can be used in combination with endocrine treatments to overcome therapy resistance.

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<![CDATA[OR05-01 Small Heterodimer Partner Modulates Antigen Presenting Myeloid Cells to Impair Regulatory T Cell Expansion, Promoting Anti-Tumor Immunity in Models of Breast Cancer]]> https://www.researchpad.co/article/elastic_article_5967 Immune checkpoint blockade has had underwhelming responses in breast cancer, in part due to the highly immune suppressive microenvironment. As a result, breast cancer continues to be the second most common cancer-related mortality amongst women, providing strong rationale for the development of new therapeutic approaches. Elevated circulating cholesterol is a poor prognostic, while breast cancer patients taking cholesterol-lowering drugs display increased time to recurrence. We and others have previously demonstrated that cholesterol metabolites mediate these effects by promoting breast cancer growth and metastasis, in part by suppressing the immune system. Therefore, given the demonstrated importance of cholesterol and its metabolites in breast cancer pathophysiology and immunology, we hypothesized that proteins involved in the regulation of cholesterol homeostasis would influence cancer progression. Through informatics analysis of breast tumors, we found that elevated expression of Small Heterodimer Partner (SHP; NR0B2) was a favorable prognostic. Antigen presenting cells such as macrophages and dendritic cells were found to express SHP, and manipulation of SHP altered the expression of genes involved in cross-talk with T cells. Intriguingly, when activated T cells were co-cultured with macrophages overexpressing SHP, there was a decrease in the expansion of regulatory T cells (Tregs) and vice versa in the absence of SHP. Adoptive transfer studies confirmed that loss of SHP resulted in immune suppressive Tregs. We hypothesized that myeloid cell-expressed SHP would promote immune surveillance and tumor clearance. In support of this hypothesis, tumors in the MMTV-PyMT model of mammary cancer grew at an accelerated rate in SHP-knockout mice. Tumors from these mice had significantly more Tregs and fewer effector T cells. Furthermore, orthotopic mammary tumor grafts grew at an increased rate in mice lacking SHP expression in myeloid cells (SHPfl/fl;LysMCre), compared to controls. A small molecule agonist of SHP impaired primary and metastatic tumor growth, and significantly enhanced the efficacy of immune checkpoint blockade in murine models of mammary cancer. Therefore, SHP represents a potential target to decrease suppressive Tregs, thereby allowing for immune-clearance of tumors.

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<![CDATA[Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer]]> https://www.researchpad.co/article/N711332f9-c9cf-4b1c-add5-d871710ae8b7

The molecular phenotype of circulating tumor cells is associated with clinical outcome of patients with breast cancer. The aim of this study was to enhance the prognostic accuracy of the circulating tumor cell phenotype in metastatic breast cancer by incorporating miRNA into a combined prediction model.

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<![CDATA[Influence of socioeconomic status on immediate breast reconstruction rate, patient information and involvement in surgical decision‐making]]> https://www.researchpad.co/article/N34444517-5450-47e0-bc7f-880027e6c4bc

Background

Immediate breast reconstruction (IBR) rates in breast cancer differ between healthcare regions in Sweden. This is not explained by regional differences in patient age distribution or tumour characteristics, but by differences in patient‐reported information and patient involvement in the decision‐making process. As socioeconomic status may play a significant role in surgical decision‐making, its potential associations with IBR rates were analysed.

Methods

Women who had undergone therapeutic mastectomy for primary breast cancer in Sweden in 2013 were included in the analysis. Tumour and treatment data were retrieved from the Swedish National Breast Cancer Register, and socioeconomic background data from the Central Bureau of Statistics Sweden. Postal questionnaires regarding information about reconstruction and perceived involvement in the preoperative decision‐making process had been sent out in a previous survey.

Results

In addition to regional differences, lower tumour and nodal category, independent factors increasing the likelihood of having IBR for the 3131 women in the study were living without a registered partner, having current employment and high income per household. Patient‐reported perceived preoperative information (odds ratio (OR) 12·73, 95 per cent c.i. 6·03 to 26·89) and the feeling of being involved in the decision‐making process (OR 2·56, 1·14 to 5·76) remained strong independent predictors of IBR despite adjustment for socioeconomic factors. Importantly, responders to the survey represented a relatively young and wealthy population with a lower tumour burden.

Conclusion

Several socioeconomic factors independently influence IBR rates; however, patient‐reported information and involvement in the surgical decision‐making process remain independent predictors for the likelihood of having IBR.

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<![CDATA[Immediate and delayed autologous abdominal microvascular flap breast reconstruction in patients receiving adjuvant, neoadjuvant or no radiotherapy: a meta‐analysis of clinical and quality‐of‐life outcomes]]> https://www.researchpad.co/article/N36d2d623-b851-47aa-af1e-e9711cecdfa3

Background

Effects of postmastectomy radiotherapy (PMRT) on autologous breast reconstruction (BRR) are controversial regarding surgical complications, cosmetic appearance and quality of life (QOL). This systematic review evaluated these outcomes after abdominal free flap reconstruction in patients undergoing postoperative adjuvant radiotherapy (PMRT), preoperative radiotherapy (neoadjuvant radiotherapy) and no radiotherapy, aiming to establish evidence‐based optimal timings for radiotherapy and BRR to guide contemporary management.

Methods

The study was registered on PROSPERO (CRD42017077945). Embase, MEDLINE, Google Scholar, CENTRAL, Science Citation Index and ClinicalTrials.gov were searched (January 2000 to August 2018). Study quality and risk of bias were assessed using GRADE and Cochrane's ROBINS‐I respectively.

Results

Some 12 studies were identified, involving 1756 patients (350 PMRT, 683 no radiotherapy and 723 neoadjuvant radiotherapy), with a mean follow‐up of 27·1 (range 12·0–54·0) months for those having PMRT, 16·8 (1·0–50·3) months for neoadjuvant radiotherapy, and 18·3 (1·0–48·7) months for no radiotherapy. Three prospective and nine retrospective cohorts were included. There were no randomized studies. Five comparative radiotherapy studies evaluated PMRT and four assessed neoadjuvant radiotherapy. Studies were of low quality, with moderate to serious risk of bias. Severe complications were similar between the groups: PMRT versus no radiotherapy (92 versus 141 patients respectively; odds ratio (OR) 2·35, 95 per cent c.i. 0·63 to 8·81, P = 0·200); neoadjuvant radiotherapy versus no radiotherapy (180 versus 392 patients; OR 1·24, 0·76 to 2·04, P = 0·390); and combined PMRT plus neoadjuvant radiotherapy versus no radiotherapy (272 versus 453 patients; OR 1·38, 0·83 to 2·32, P = 0·220). QOL and cosmetic studies used inconsistent methodologies.

Conclusion

Evidence is conflicting and study quality was poor, limiting recommendations for the timing of autologous BRR and radiotherapy. The impact of PMRT and neoadjuvant radiotherapy appeared to be similar.

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<![CDATA[Immunoexpression of P63 and SOX2 in triple-negative breast cancers, Indonesia]]> https://www.researchpad.co/article/5bf9b277d5eed0c4843d04ab

Background: Using immunohistochemical stains to target specific breast cancer markers has become indispensable for evaluation of small diagnostic tissue specimens, and therefore novel marker cocktails for specific breast cancers are required. This study was conducted to assess the immunoexpression of P63 and SOX2 in triple negative breast cancer (TNBC), and to evaluate the predictive diagnostic value of these markers for specific types of TNBC.

Methods: Histological slides and paraffin blocks of TNBC cases were collected from Dr. Hasan Sadikin Hospital, Bandung, Indonesia from 5-years period (2011-2015). Each histological slide was subjected to immunohistochemical staining for P63 (nucleus and cytoplasm) and SOX2 (nucleus), with specific primer antibodies. Immunoexpression of P63 and SOX2 was evaluated using immunoreactivity scoring. Associations between P63 and SOX2 immunoexpression and TNBC types were assessed using Mann Whitney tests. In addition, the predictive diagnostic values of these markers were assessed.

Results: Forty TNBC histological slides were included, and 23 (57.5%) were Basal-like type TNBC and 17 (42.5%) were Non basal-like type TNBC. Immunoexpression of P63 nucleus and SOX2 was not different between types of TNBC. However, immunoexpression of P63 in the cytoplasm in Basal-like type TNBC was significantly higher than in Non basal-like type TNBC ( p=0.021). Predictor diagnostic value analysis suggested that immunoexpression of P63 in cytoplasm had 56.5% sensitivity and 70.6% specificity for diagnosing Basal-like type TNBC, with area under curve of 0.64.   

Conclusions: Immunoexpression of P63 in the cytoplasm has a relatively weak diagnostic value to discriminate Basal-like and Non basal-like types of TNBC.

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<![CDATA[Ultrafast Dynamic Contrast-Enhanced Breast MRI: Lesion Conspicuity and Size Assessment according to Background Parenchymal Enhancement]]> https://www.researchpad.co/article/N5e4fca26-ce28-42ca-8e76-c2df49622ead

Objective

To evaluate the clinical utility of ultrafast dynamic contrast-enhanced (DCE)-MRI compared to conventional DCE-MRI by studying lesion conspicuity and size according to the level of background parenchymal enhancement (BPE).

Materials and Methods

This study included 360 women (median age, 54 years; range, 26–82 years) with 361 who had undergone breast MRI, including both ultrafast and conventional DCE-MRI before surgery, between January and December 2017. Conspicuity was evaluated using a five-point score. Size was measured as the single maximal diameter. The Wilcoxon signed-rank test was used to compare median conspicuity score. To identify factors associated with conspicuity, multivariable logistic regression was performed. Absolute agreement between size at MRI and histopathologic examination was assessed using the intraclass correlation coefficient (ICC).

Results

The median conspicuity scores were 5 at both scans, but the interquartile ranges were significantly different (5-5 at ultrafast vs. 4-5 at conventional, p < 0.001). Premenopausal status (odds ratio [OR] = 2.2, p = 0.048), non-mass enhancement (OR = 4.1, p = 0.001), moderate to marked BPE (OR = 7.5, p < 0.001), and shorter time to enhancement (OR = 0.9, p = 0.043) were independently associated with better conspicuity at ultrafast scans. Tumor size agreement between MRI and histopathologic examination was similar for both scans (ICC = 0.66 for ultrafast vs. 0.63 for conventional).

Conclusion

Ultrafast DCE-MRI could improve lesion conspicuity compared to conventional DCE-MRI, especially in women with premenopausal status, non-mass enhancement, moderate to marked BPE or short time to enhancement.

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<![CDATA[Automated Breast Ultrasound: Interobserver Agreement, Diagnostic Value, and Associated Clinical Factors of Coronal-Plane Image Features]]> https://www.researchpad.co/article/Nb9b999bc-284b-4b98-be50-d78513bff2f7

Objective

To evaluate the interobserver agreement, diagnostic value, and associated clinical factors of automated breast ultrasound (ABUS) coronal features in differentiating breast lesions.

Materials and Methods

This study enrolled 457 pathologically confirmed lesions in 387 female (age, 46.4 ± 10.3 years), including 377 masses and 80 non-mass lesions (NMLs). The unique coronal features, including retraction phenomenon, hyper- or hypoechoic rim (continuous or discontinuous), skipping sign, and white wall sign, were defined and recorded. The interobserver agreement on image type and coronal features was evaluated. Furthermore, clinical factors, including the lesion size, distance to the nipple or skin, palpability, and the histological grade were analyzed.

Results

Among the 457 lesions, 296 were malignant and 161 were benign. The overall interobserver agreement for image type and all coronal features was moderate to good. For masses, the retraction phenomenon was significantly associated with malignancies (p < 0.001) and more frequently presented in small and superficial invasive carcinomas with a low histological grade (p = 0.027, 0.002, and < 0.001, respectively). Furthermore, continuous hyper- or hypoechoic rims were predictive of benign masses (p < 0.001), whereas discontinuous rims were predictive of malignancies (p < 0.001). A hyperechoic rim was more commonly detected in masses more distant from the nipple (p = 0.027), and a hypoechoic rim was more frequently found in large superficial masses (p < 0.001 for both). For NMLs, the skipping sign was a predictor of malignancies (p = 0.040).

Conclusion

The coronal plane of ABUS may provide useful diagnostic value for breast lesions.

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<![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.

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<![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.

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<![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.

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<![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.

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<![CDATA[Talazoparib in Patients with a Germline BRCA‐Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial]]> https://www.researchpad.co/article/N6ecc4bdf-e429-404f-8dcc-def44777f426

Abstract

Background

In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression‐free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2‐mutated HER2‐negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail.

Materials and Methods

Overall, 412 patients received ≥1 dose of talazoparib (n = 286) or PCT (n = 126). Adverse events (AEs) were evaluated, including timing, duration, and potential overlap of selected AEs. The relationship between talazoparib plasma exposure and grade ≥3 anemia was analyzed. Time‐varying Cox proportional hazard models assessed the impact of dose reductions on PFS. Patient‐reported outcomes (PROs) in patients with common AEs and health resource utilization (HRU) were assessed in both treatment arms.

Results

The most common AEs with talazoparib were hematologic (195 [68.2%] patients) and typically occurred within the first 3–4 months of receiving talazoparib. Grade 3‐4 anemia lasted approximately 7 days for both arms. Overlapping grade 3‐4 hematologic AEs were infrequent with talazoparib. Higher talazoparib exposure was associated with grade ≥3 anemia. Permanent discontinuation of talazoparib due to hematologic AEs was low (<2%). A total of 150 (52.4%) patients receiving talazoparib had AEs associated with dose reduction. Hematologic toxicities were managed by supportive care medication (including transfusion) and dose modifications. Among patients with anemia or nausea and/or vomiting AEs, PROs favored talazoparib. After accounting for the treatment‐emergent period, talazoparib was generally associated with a lower rate of hospitalization and supportive care medication use compared with chemotherapy.

Conclusion

Talazoparib was associated with superior efficacy, favorable PROs, and lower HRU rate versus chemotherapy in gBRCA‐mutated ABC. Toxicities were manageable with talazoparib dose modification and supportive care.

Implications for Practice

Talazoparib was generally well tolerated in patients with germline BRCA‐mutated HER2‐negative advanced breast cancer in the EMBRACA trial. Common toxicities with talazoparib were primarily hematologic and infrequently resulted in permanent drug discontinuation (<2% of patients discontinued talazoparib due to hematologic toxicity). Hematologic toxicities typically occurred during the first 3–4 months of treatment and were managed by dose modifications and supportive care measures. A significant efficacy benefit, improved patient‐reported outcomes, lower rate of health resource utilization and a tolerable safety profile support incorporating talazoparib into routine management of germline BRCA‐mutated locally advanced/metastatic breast cancer.

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<![CDATA[Young Women With Breast Cancer in Mexico: Results of the Pilot Phase of the Joven & Fuerte Prospective Cohort]]> https://www.researchpad.co/article/N78f19ec6-edde-4f4e-8e12-2c2e842ae043

PURPOSE

The pilot-phase report of the Joven & Fuerte prospective cohort broadly characterizes and assesses the needs of Mexican young women with breast cancer (YWBC).

PATIENTS AND METHODS

Women age ≤ 40 years with nonmetastatic primary breast cancer were consecutively accrued from 2 hospitals. Data were collected at the first/baseline oncology visit and 2 years later using a sociodemographic survey, European Organisation for Research and Treatment of Cancer Quality-of-Life (QOL) Questionnaire Core 30 (QLQ-C30) and Breast Cancer–Specific QOL Questionnaire (QLQ-BR23), Hospital Anxiety and Depression Scale (HADS), Female Sexual Functioning Index (FSFI), Sexual Satisfaction Inventory, and patients’ medical records. Pearson χ2 and 2-sided t tests were used for statistical analysis. An unadjusted P value < .05 was considered significant.

RESULTS

Ninety patients were included, all with government health care coverage. Most had low monthly household incomes (98%) and at least a high school education (59%). There was a considerable prevalence of unpartnered patients (36%) and unmet parity (25%). Patients’ most common initial symptom was a palpable mass (84%), and they were most frequently diagnosed with stage III disease (48%), with 51% having had a physician visit ≤ 3 months since detection but 39% receiving diagnosis > 12 months later. At baseline, 66% of patients were overweight/obese, and this proportion had significantly increased by 2 years (P < .001). Compared with baseline, global QLQ-C30 had improved significantly by 2 years (P = .004), as had HADS-Anxiety (P < .001). However, both at baseline and at 2 years, nearly half of patients exhibited FSFI sexual dysfunction.

CONCLUSION

These preliminary findings demonstrate that YWBC in Mexico have particular sociodemographic and clinicopathologic characteristics, reinforcing the necessity to further describe and explore the needs of these young patients, because they may better represent the understudied and economically vulnerable population of YWBC in limited-resource settings.

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<![CDATA[Comparison of One- and Two-Region of Interest Strain Elastography Measurements in the Differential Diagnosis of Breast Masses]]> https://www.researchpad.co/article/N1e1c8635-b787-4160-9b1a-bc0443d2b44f

Objective

To compare the diagnostic performance and interobserver variability of strain ratio obtained from one or two regions of interest (ROI) on breast elastography.

Materials and Methods

From April to May 2016, 140 breast masses in 140 patients who underwent conventional ultrasonography (US) with strain elastography followed by US-guided biopsy were evaluated. Three experienced breast radiologists reviewed recorded US and elastography images, measured strain ratios, and categorized them according to the American College of Radiology breast imaging reporting and data system lexicon. Strain ratio was obtained using the 1-ROI method (one ROI drawn on the target mass), and the 2-ROI method (one ROI in the target mass and another in reference fat tissue). The diagnostic performance of the three radiologists among datasets and optimal cut-off values for strain ratios were evaluated. Interobserver variability of strain ratio for each ROI method was assessed using intraclass correlation coefficient values, Bland–Altman plots, and coefficients of variation.

Results

Compared to US alone, US combined with the strain ratio measured using either ROI method significantly improved specificity, positive predictive value, accuracy, and area under the receiver operating characteristic curve (AUC) (all p values < 0.05). Strain ratio obtained using the 1-ROI method showed higher interobserver agreement between the three radiologists without a significant difference in AUC for differentiating breast cancer when the optimal strain ratio cut-off value was used, compared with the 2-ROI method (AUC: 0.788 vs. 0.783, 0.693 vs. 0.715, and 0.691 vs. 0.686, respectively, all p values > 0.05).

Conclusion

Strain ratios obtained using the 1-ROI method showed higher interobserver agreement without a significant difference in AUC, compared to those obtained using the 2-ROI method. Considering that the 1-ROI method can reduce performers' efforts, it could have an important role in improving the diagnostic performance of breast US by enabling consistent management of breast lesions.

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<![CDATA[Contrast-Enhanced Spectral Mammography Versus Ultrasonography: Diagnostic Performance in Symptomatic Patients with Dense Breasts]]> https://www.researchpad.co/article/N594ac096-54c1-46ac-9cbc-a91632a02e7b

Objective

To compare the diagnostic performance of contrast-enhanced spectral mammography (CESM) versus ultrasonography (US) in symptomatic patients with dense breasts, while using histology as the gold standard.

Materials and Methods

After obtaining approval from the local ethics board, this prospective study collected data from patients with symptomatic breasts who underwent CESM and US examinations from May 1, 2017 to September 30, 2017. We then selected those with dense breasts and pathological results as our sample population. Both CESM and US results were classified by a radiologist through the Breast Imaging Reporting and Data System, and the results were compared with their corresponding histological results. The chi-square test was conducted to compare the diagnostic performance of CESM and US, and the receiver operating characteristic curves for the two imaging modalities were obtained.

Results

A total of 131 lesions from 115 patients with dense breasts were included in this study. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 93.8%, 88.1%, 88.2%, 93.7%, and 90.8% for CESM, and 90.6%, 82.1%, 82.9%, 90.2%, and 86.3% for US, respectively. The p values for sensitivity, specificity, PPV, NPV, and accuracy were 0.687, 0.388, 0.370, 0.702, and 0.238, respectively. The area under the curve of CESM (0.917) was comparable with that of US (0.884); however, the differences between CESM and US were not statistically significant (p = 0.225). Eight false-positive cases and 4 false-negative cases for breast cancer were found in CESM, while 12 false-positive cases and 6 false-negative cases were found in US.

Conclusion

The diagnostic performances of CESM and US are comparable in symptomatic women with dense breasts; however, the routine use of additional US imaging is questionable for lesions that can be detected by CESM.

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<![CDATA[Abstracts]]> https://www.researchpad.co/article/N16e1628c-c3f5-44f1-8bc3-198ec647b8c3 ]]> <![CDATA[Oral Care Evaluation to Prevent Oral Mucositis in Estrogen Receptor‐Positive Metastatic Breast Cancer Patients Treated with Everolimus (Oral Care‐BC): A Randomized Controlled Phase III Trial]]> https://www.researchpad.co/article/N55d95938-a9e1-4de7-b0f8-3e004139eb3c

Abstract

Background

The incidence of oral mucositis (any grade) after everolimus treatment is 58% in the general population and 81% in Asian patients. This study hypothesized that professional oral care (POC) before everolimus treatment could reduce the incidence of everolimus‐induced oral mucositis.

Materials and Methods

This randomized, multicenter, open‐label, phase III study evaluated the efficacy of POC in preventing everolimus‐induced mucositis. Patients were randomized into POC and control groups (1:1 ratio) and received everolimus with exemestane. Patients in the POC group underwent teeth surface cleaning, scaling, and tongue cleaning before everolimus initiation and continued to receive weekly POC throughout the 8‐week treatment period. Patients in the control group brushed their own teeth and gargled with 0.9% sodium chloride solution or water. The primary endpoint was the incidence of all grades of oral mucositis. We targeted acquisition of 200 patients with a 2‐sided type I error rate of 5% and 80% power to detect 25% risk reduction.

Results

Between March 2015 and December 2017, we enrolled 175 women from 31 institutions, of which five did not receive the protocol treatment and were excluded. Over the 8 weeks, the incidence of grade 1 oral mucositis was significantly different between the POC group (76.5%, 62 of 82 patients) and control group (89.7%, 78 of 87 patients; p = .034). The incidence of grade 2 (severe) oral mucositis was also significantly different between the POC group (34.6%, 28 of 82 patients) and control group (54%, 47 of 87 patients; p = .015). As a result of oral mucositis, 18 (22.0%) patients in the POC group and 28 (32.2%) in the control group had to undergo everolimus dose reduction.

Conclusion

POC reduced the incidence and severity of oral mucositis in patients receiving everolimus and exemestane. This might be considered as a treatment option of oral care for patients undergoing this treatment. Clinical trial identification number: NCT 02069093.

Implications for Practice

The Oral Care‐BC trial that prophylactically used professional oral care (POC), available worldwide, did not show a greater than 25% difference in mucositis. The 12% difference in grade 1 or higher mucositis and especially the ∼20% difference in grade 2 mucositis are likely clinically meaningful to patients. POC before treatment should be considered as a treatment option of oral care for postmenopausal patients who are receiving everolimus and exemestane for treatment of hormone receptor‐positive, HER2‐negative advanced breast cancer and metastatic breast cancer. However, POC was not adequate for prophylactic oral mucositis in these patients, and dexamethasone mouthwash prophylaxis is standard treatment before everolimus.

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