Eur J Radiol. 2022 May 18;153:110363. doi: 10.1016/j.ejrad.2022.110363. Online ahead of print.

ABSTRACT

PURPOSE: To call attention to a highly fatal breast cancer subtype arising from the major lactiferous ducts that is currently underdiagnosed as ductal carcinoma in situ (DCIS) with or without microinvasion.

METHOD: All breast cancers diagnosed at the Department of Mammography, Falun Central Hospital, Sweden, since 1977 have been classified according to their mammographic tumour features (imaging biomarkers) and followed up at regular intervals for the past four decades. The imaging biomarkers characteristic of breast cancers apparently arising from the major lactiferous ducts have been correlated with large format thin and thick section histopathology and long-term patient outcome.

RESULTS: Breast cancers arising within the major lactiferous ducts propagate intraductally and produce continuously branching neoducts through epithelial-mesenchymal transformation (EMT), an invasive process termed neoductgenesis, which eventually forms a massive tumour burden. The high fatality of this breast cancer subtype indicates its truly invasive nature, although it is conventionally termed ductal carcinoma in situ, DCIS, terminology which is at odds with its poor long-term patient outcome. The neoducts are filled with multiple layers of malignant cells, have no attached lobules, and propagate by forming multiple invasive side branches. These newly formed duct-like structures are surrounded by a desmoplastic reaction (cancer associated fibroblasts, CAFs) and periductal lymphocytic infiltration. The neoducts are tightly packed together in irregular formations bearing no resemblance to the paniculate branching structure of normal lactiferous ducts. Cancers originating from the major ducts have six imaging biomarkers which can be easily recognized at breast imaging. These are described in detail in an accompanying article.

CONCLUSIONS: Neoductgenesis in the breast, DAB, is similar in appearance and prognosis to ductal adenocarcinoma of the prostate, DAP. We propose the term ductal adenocarcinoma of the breast, DAB, to facilitate its recognition as a distinct invasive breast cancer subtype. The high fatality rates associated with neoductgenesis reflect the failure of current histopathologic diagnostic criteria to effectively guide therapeutic practice. When the neoducts are associated with small stellate/spiculated or spherical/oval-shaped invasive cancers arising from the terminal ductal lobular units (TDLUs), the prognosis and management are erroneously estimated according to the smaller invasive tumour(s), giving a false sense of security often resulting in undertreatment. Recognition that neoductgenesis is an invasive malignancy is a prerequisite for preventing treatment failure.

PMID:35605334 | DOI:10.1016/j.ejrad.2022.110363

Arch Gynecol Obstet. 2022 May 23. doi: 10.1007/s00404-022-06604-2. Online ahead of print.

ABSTRACT

BACKGROUND: This study examined the relationship between social service counseling (SSC) and financial and role functioning problems in primary breast cancer (BC) patients over a 5-year observation period.

METHODS: In the multicenter prospective study, patients were approached before surgery (t1), before initiation of adjuvant treatment (t2), after therapy completion (t3), and 5 years after surgery (t4). We examined the proportion of BC survivors who had financial and role functioning problems and the proportion who were employed at t4. We examined how frequently patients were informed about, offered, or used SSC, and we used multivariate logistic regression analyses to examine the relationship between this and financial and role functioning problem prevalence.

RESULTS: Of the 456 BC survivors, 33% had financial problems and 22% reported role functioning problems at t4. There was no evidence that women with increased financial problems were informed about SSC more often than those without (OR 1.1, p = 0.84) or that they used SSC more often (OR 1.3, p = 0.25). However, women with role functioning problems were informed about SSC significantly more often (OR 1.7, p = 0.02) and attended counseling significantly more often (OR 1.6, p = 0.03). Among participants aged < 65 years at t4 (n = 255), 70% were employed. Patients who had received SSC were more likely to be employed at t4 than patients who did not (OR 1.9, p = 0.04).

CONCLUSION: These findings underline the importance of SSC for BC patients with role functioning issues. They indicate that individuals who use SSC are more likely to be employed later on than individuals who do not.

PMID:35604446 | DOI:10.1007/s00404-022-06604-2

JNCI Cancer Spectr. 2022 Mar 2;6(2):pkac021. doi: 10.1093/jncics/pkac021.

ABSTRACT

BACKGROUND: Few studies investigated long-term overall survival and causes of death among men and women diagnosed with most commonly occurring cancers.

METHODS: We estimated long-term (≥30-year) overall and cause-specific cumulative mortality for men diagnosed with prostate (n = 6873), lung and bronchus (n = 1290), colon and rectum (n = 1418), bladder (n = 1321), and melanoma (n = 2654) cancer in the Health Professionals Follow-up Study between 1986 and 2012 and women with breast (n = 18 280), lung and bronchus (n = 3963), colon and rectum (n = 3461), uterine corpus (n = 1641), and thyroid (n = 1103) cancer in the Nurses' Health Study between 1976 and 2012 and Nurses' Health Study II between 1989 and 2013.

RESULTS: We reported overall and cause-specific cumulative mortality of 30 years among men and 35 years among women. Among male cancer survivors, the 30-year cumulative cancer-specific mortality was 15.4% (95% confidence interval [CI] = 14.4% to 16.4%) for prostate, 83.5% (95% CI = 81.2% to 85.5%) for lung and bronchus, 37.0% (95% CI = 34.4% to 39.5%) for colon and rectum, 22.5% (95% CI = 20.0% to 25.0%) for urinary bladder, and 8.0% (95% CI = 6.9% to 9.1%) for melanoma. Among female cancer survivors, the 35-year cumulative cancer-specific mortality rate was 20.6% (95% CI = 19.7% to 21.6%) for breast, 83.5% (95% CI = 81.6% to 85.2%) for lung and bronchus, 39.6% (95% CI = 37.5% to 41.6%) for colon and rectum, 16.6% (95% CI = 14.7% to 18.6%) for uterine corpus, and 3.2% (95% CI = 2.1% to 4.3%) for thyroid. Except for lung cancer, most patients with common cancer were more likely to die from causes other than primary cancers. We observed 2 basic trends for cumulative cancer-specific mortality. The first is a sustained but nevertheless excess risk: Prostate or breast cancer-specific cumulative mortality continued to increase after diagnosis from 5 to 30 years or longer. The second is greatly diminished risk of index cancer-specific mortality following diagnosis 10 years or longer previously. For example, colorectal cancer-specific mortality increased by less than 4 percentage points between 10 and 30 or 35 years after diagnosis, and this finding also applied to lung, bladder, melanoma, uterine corpus, and thyroid cancer.

CONCLUSIONS: Except for lung cancer, patients diagnosed with common cancers were more likely to die from causes other than primary cancers. Patients with lung, colorectal, bladder, melanoma, uterine corpus, or thyroid cancer surviving longer than 10 years after diagnosis are unlikely to die from that disease.

PMID:35603853 | DOI:10.1093/jncics/pkac021

JNCI Cancer Spectr. 2022 Mar 2;6(2):pkac018. doi: 10.1093/jncics/pkac018.

NO ABSTRACT

PMID:35603846 | DOI:10.1093/jncics/pkac018

JNCI Cancer Spectr. 2022 Mar 2;6(2):pkac016. doi: 10.1093/jncics/pkac016.

ABSTRACT

BACKGROUND: Scant research has analyzed contemporary US cancer incidence rates in relation to historical redlining (ie, 1930s US federally imposed residential segregation), implemented via the color-coded federal Home Owners' Loan Corporation (HOLC) maps.

METHODS: We analyzed Massachusetts Cancer Registry data for all patients with primary invasive breast cancer (BC) diagnosed in 2005-2015 among women in the 28 Massachusetts municipalities with digitized 1930s HOLC maps. Multilevel Poisson regression estimated BC incidence rate ratios (IRR), overall and by tumor estrogen receptor (ER-positive, ER-negative) and progesterone receptor (PR-positive, PR-negative) status, in relation to HOLC grade and contemporary census tract (CT) social characteristics.

RESULTS: Net of age and racialized group, the extremes of BC incidence were detected by combinations of HOLC grade and contemporary CT racialized economic segregation. Compared with CTs with the best HOLC grade (A + B) and most privileged contemporary characteristics (T1), for all, ER-positive and PR-positive BC, incidence was highest in T1 and mixed HOLC grade CTs (eg, IRRER+; Mixed-T1 = 1.10, 95% confidence interval [CI] = 1.01 to 1.21) and lowest in CTs with most concentrated racialized economic deprivation (T3) and no HOLC grade (eg, IRRER+; No Grade-T3 = 0.85, 95% CI = 0.75 to 0.95). For ER-negative and PR-negative BC, incidence was highest in CTs with the most contemporary deprivation, but the best HOLC grade (eg, IRRER-; A+B-T3 = 1.27, 95% CI = 0.93 to 1.75) and lowest in T1 and worst HOLC-graded CTs (eg, IRRER-; D-T1 = 0.84, 95% CI = 0.56 to 1.25).

CONCLUSION: Breast cancer risk may be shaped by combined histories of redlining and present-day CT characteristics.

PMID:35603845 | DOI:10.1093/jncics/pkac016

Math Biosci Eng. 2022 Apr 6;19(6):5793-5812. doi: 10.3934/mbe.2022271.

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive subtype of mammary carcinoma characterized by low expression levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Along with the rapid development of the single-cell RNA-sequencing (scRNA-seq) technology, the heterogeneity within the tumor microenvironment (TME) could be studied at a higher resolution level, facilitating an exploration of the mechanisms leading to poor prognosis during tumor progression. In previous studies, hypoxia was considered as an intrinsic characteristic of TME in solid tumors, which would activate downstream signaling pathways associated with angiogenesis and metastasis. Moreover, hypoxia-related genes (HRGs) based risk score models demonstrated nice performance in predicting the prognosis of TNBC patients. However, it is essential to further investigate the heterogeneity within hypoxic TME, such as intercellular communications. In the present study, utilizing single-sample Gene Set Enrichment Analysis (ssGSEA) and cell-cell communication analysis on the scRNA-seq data retrieved from Gene Expression Omnibus (GEO) database with accession number GSM4476488, we identified four tumor subpopulations with diverse functions, particularly a hypoxia-related one. Furthermore, results of cell-cell communication analysis revealed the dominant role of the hypoxic tumor subpopulation in angiogenesis- and metastasis-related signaling pathways as a signal sender. Consequently, regard the TNBC cohorts acquired from The Cancer Genome Atlas (TCGA) and GEO as train set and test set respectively, we constructed a risk score model with reliable capacity for the prediction of overall survival (OS), where ARTN and L1CAM were identified as risk factors promoting angiogenesis and metastasis of tumors. The expression of ARTN and L1CAM were further analyzed through tumor immune estimation resource (TIMER) platform. In conclusion, these two marker genes of the hypoxic tumor subpopulation played vital roles in tumor development, indicating poor prognosis in TNBC patients.

PMID:35603379 | DOI:10.3934/mbe.2022271

Front Immunol. 2022 May 4;13:880769. doi: 10.3389/fimmu.2022.880769. eCollection 2022.

ABSTRACT

BACKGROUND: Breast cancer (BC) is one of the most common malignancies in women, and long non-coding RNAs (lncRNAs) are key regulators of its development. T cells can recognize and kill cancer cells, and CD4⁺ T conventional (Tconv) cells are the main orchestrators of cancer immune function. However, research on CD4⁺ Tconv-related lncRNAs (CD4TLAs) prognostic signature in patients with BC is still lacking.

METHOD: A TCGA database and a GEO database were used to collect the BC patients. Through LASSO Cox regression analysis CD4TLAs-related prognostic models were further constructed, and risk scores (RS) were generated and developed a nomogram based on CD4TLAs. The accuracy of this model was validated in randomized cohorts and different clinical subgroups. Gene set enrichment analysis (GSEA) was used to explore potential signature-based functions. The role of RS has been further explored in the tumor microenvironment (TME), immunotherapy, and chemotherapy.

RESULT: A prognostic model based on 16 CD4TLAs was identified. High-RS was significantly associated with a poorer prognosis. RS was shown to be an independent prognostic indicator in BC patients. The low-RS group had a significant expression of immune infiltrating cells and significantly enriched immune-related functional pathways. In addition, the results of immunotherapy prediction indicated that patients with low-RS were more sensitive to immunotherapy.

CONCLUSIONS: Our signature has potential predictive value for BC prognosis and immunotherapy response. The findings of this work have greatly increased our understanding of CD4TLA in BC.

PMID:35603183 | PMC:PMC9114647 | DOI:10.3389/fimmu.2022.880769

Front Immunol. 2022 May 4;13:895110. doi: 10.3389/fimmu.2022.895110. eCollection 2022.

ABSTRACT

PURPOSE: To identify molecular clusters associated with ferroptosis and to develop a ferroptosis-related signature for providing novel potential targets for the recurrence-free survival and treatment of breast cancer.

METHODS: Ferroptosis-related gene (FRG) signature was constructed by univariate and multivariate Cox regression and least absolute shrinkage and selection operator (LASSO). Receiver operating characteristic curves, Kaplan-Meier survival analysis, principal component analysis, and univariate and multivariate Cox regression analyses in the training and test cohorts were used to evaluate the application of this signature. Quantitative reverse transcriptase-PCR (qRT-PCR) was employed to detect the expression of FRGs in the model. Furthermore, the correlations between the signature and immune microenvironment, somatic mutation, and chemotherapeutic drugs sensitivity were explored.

RESULTS: Internal and external validations affirmed that relapse-free survival differed significantly between the high-risk and low-risk groups. Univariate and multivariate Cox regression analyses indicated that the riskScore was an independent prognostic factor for BRCA. The areas under the curve (AUCs) for predicting 1-, 2-, and 3-year survival in the training and test cohorts were satisfactory. Significant differences were also found in the immune microenvironment and IC50 of chemotherapeutic drugs between different risk groups. Furthermore, we divided patients into three clusters based on 18 FRGs to ameliorate the situation of immunotherapy failure in BRCA.

CONCLUSIONS: The FRG signature functions as a robust prognostic predictor of the immune microenvironment and therapeutic response, with great potential to guide individualized treatment strategies in the future.

PMID:35603151 | PMC:PMC9115856 | DOI:10.3389/fimmu.2022.895110

Comput Intell Neurosci. 2022 May 11;2022:5667264. doi: 10.1155/2022/5667264. eCollection 2022.

ABSTRACT

Early diagnosis of breast cancer is an important component of breast cancer therapy. A variety of diagnostic platforms can provide valuable information regarding breast cancer patients, including image-based diagnostic techniques. However, breast abnormalities are not always easy to identify. Mammography, ultrasound, and thermography are some of the technologies developed to detect breast cancer. Using image processing and artificial intelligence techniques, the computer enables radiologists to identify chest problems more accurately. The purpose of this article was to review various approaches to detecting breast cancer using artificial intelligence and image processing. The authors present an innovative approach for identifying breast cancer using machine learning methods. Compared to current approaches, such as CNN, our particle swarm optimized wavelet neural network (PSOWNN) method appears to be relatively superior. The use of machine learning methods is clearly beneficial in terms of improved performance, efficiency, and quality of images, which are crucial to the most innovative medical applications. According to a comparison of the process's 905 images to those of other illnesses, 98.6% of the disorders are correctly identified. In summary, PSOWNNs, therefore, have a specificity of 98.8%. Furthermore, PSOWNNs have a precision of 98.6%, which means that, despite the high number of women diagnosed with breast cancer, only 830 (95.2%) are diagnosed. In other words, 95.2% of images are correctly classified. PSOWNNs are more accurate than other machine learning algorithms, SVM, KNN, and CNN.

PMID:35602611 | PMC:PMC9117073 | DOI:10.1155/2022/5667264

Comput Math Methods Med. 2022 May 11;2022:9166873. doi: 10.1155/2022/9166873. eCollection 2022.

ABSTRACT

In this work, a novel hybrid neuro-fuzzy classifier (HNFC) technique is proposed for producing more accuracy in input data classification. The inputs are fuzzified using a generalized membership function. The fuzzification matrix helps to create connectivity between input pattern and degree of membership to various classes in the dataset. According to that, the classification process is performed for the input data. This novel method is applied for ten number of benchmark datasets. During preprocessing, the missing data is replaced with the mean value. Then, the statistical correlation is applied for selecting the important features from the dataset. After applying a data transformation technique, the values normalized. Initially, fuzzy logic has been applied for the input dataset; then, the neural network is applied to measure the performance. The result of the proposed method is evaluated with supervised classification techniques such as radial basis function neural network (RBFNN) and adaptive neuro-fuzzy inference system (ANFIS). Classifier performance is evaluated by measures like accuracy and error rate. From the investigation, the proposed approach provided 86.2% of classification accuracy for the breast cancer dataset compared to other two approaches.

PMID:35602339 | PMC:PMC9117043 | DOI:10.1155/2022/9166873

Comput Math Methods Med. 2022 May 12;2022:2299852. doi: 10.1155/2022/2299852. eCollection 2022.

ABSTRACT

OBJECTIVE: To evaluate the diagnostic value of the nanometer carbon suspension tracer staining technique in sentinel lymph node biopsy of breast cancer is the objective of this study.

METHODS: The PubMed, Embase, Cochrane Library (Central), and Web of Science (SCI Expanded), and Chinese databases (CNKI, VIP, Wan Fang, and CBM) were systematically searched for studies on the diagnostic value of nanocarbon suspension in sentinel lymph node biopsy of breast cancer. Two reviewers independently assessed the methodological quality of each study using the QUADAS-2 tool. The extracted valid data were calculated using Meta-Disc1.4 software and tested for heterogeneity. STATA14.0 software was selected for sensitivity analysis of the included studies, and publication bias was assessed using Deeks' forest plot asymmetry test.

RESULTS: A total of 10 studies were obtained. The pooled data were as follows: sensitivity, 0.92 (0.88~0.95); specificity, 0.99 (0.98~1.00); positive likelihood ratio, 69.24 (30.34~158.02); negative likelihood ratio, 0.09 (0.06~0.13); and the combined diagnostic odds ratio, 747.40 (285.77~1954.76), AUC = 0.9881. Nanocarbon suspension tracers have an accuracy rate of 98.81% in the diagnosis of sentinel lymph nodes in breast cancer.

CONCLUSION: Tracer staining technology based on nanocarbon suspension can accurately assess the status of lymph nodes in sentinel lymph node biopsy of breast cancer and has good stability and operability, which is worthy of clinical promotion.

PMID:35602338 | PMC:PMC9119750 | DOI:10.1155/2022/2299852

Front Public Health. 2022 May 6;10:838579. doi: 10.3389/fpubh.2022.838579. eCollection 2022.

ABSTRACT

OBJECTIVE: To document breast cancer (BC) knowledge, awareness, and attitudes among female undergraduate students studying at health and non-health colleges.

METHODS: A 3-month cross-sectional study was conducted among female undergraduate students studying at health and non-health subject colleges affiliated to a public university. Convenience sampling was employed, and a previously validated questionnaire available in English and Arabic languages was used. Multiple linear regression was used to report the predictors of BC knowledge. A two-tailed p-value of < 0.05 was considered significant. The study was approved by an ethics committee.

RESULTS: A total of 506 responses were analyzed. The mean knowledge score was 13.98 ± 4.1. The findings of the surveyed students suggested that more than 55% of the students had an acceptable level of knowledge. By education sector, approximately 70% and 40% of health and non-health college students, respectively, had an acceptable level of knowledge. The mean difference in knowledge scores between students of health and non-health colleges was significant (p < 0.001) as students at health colleges had a higher score. Age, college type and the presence of the disease in family/relatives were significant predictors of students' BC knowledge (p < 0.05).

CONCLUSION: By comparing it with previous evidence, the knowledge of BC has improved. The role of awareness campaigns as an information medium for students from non-health backgrounds is greatly appreciated. Moreover, the internet and electronic media have emerged as new sources of information for non-health college students, and therefore, more efforts are needed to utilize this medium in empowering this student population in understanding of this disease.

PMID:35602142 | PMC:PMC9120525 | DOI:10.3389/fpubh.2022.838579

Int J Gen Med. 2022 May 14;15:4959-4974. doi: 10.2147/IJGM.S354826. eCollection 2022.

ABSTRACT

OBJECTIVE: We used bioinformatics analysis to identify potential biomarker genes and their relationship with breast cancer (BC).

MATERIALS AND METHODS: We used a weighted gene co-expression network analysis (WGCNA) to create a co-expression network based on the top 25% genes in the GSE24124, GSE33926, and GSE86166 datasets obtained from the Gene Expression Omnibus. We used the DAVID online platform to perform GO and KEGG pathway enrichment analyses and the Cytoscape CytoHubba plug-in to screen the potential genes. Then, we related the genes to prognostic values in BC using the Oncomine, GEPIA, and Kaplan-Meier Plotter databases. Findings were validated by immunohistochemical (IHC) staining in the Human Protein Atlas and the TCGA-BRCA cohort. LinkedOmics identified the interactive expressions of hub genes. We used UALCAN to evaluate the methylation levels of these hub genes. MethSurv and SurvivalMeth were used to assess the multilevel prognostic value. Finally, we assessed hub gene association with immune cell infiltration using TIMER.

RESULTS: The mRNA levels of MKI67, UBE2C, GTSE1, CCNA2, and MND1 were significantly upregulated in BC, whereas ESR1, THSD4, TFF1, AGR2, and FOXA1 were significantly downregulated. The DNA methylation signature analysis showed a better prognosis in the low-risk group. Further subgroup analyses revealed that MND1 might serve as an independent risk factor for unfavorable BC prognosis. Additionally, MND1 expression levels positively correlate with the immune infiltration statuses of CD4+ T cells, CD8+ T cells, B cells, neutrophils, dendritic cells, and macrophages.

CONCLUSION: Our results indicate that the ten hub genes may be involved in BC's carcinogenesis, development, or metastasis, and MND1 may be a potential biomarker and therapeutic target for BC.

PMID:35601002 | PMC:PMC9117423 | DOI:10.2147/IJGM.S354826

Breast Dis. 2022;41(1):261-266. doi: 10.3233/BD-210080.

ABSTRACT

INTRODUCTION: Postmastectomy radiotherapy reduces the risk of locoregional recurrence in breast cancer patients. The first results on accelerated radiotherapy in five fractions after breast conserving surgery are promising. The data on postmastectomy radiotherapy in five or six fractions is limited. We now present the data on acute and one-year toxicity and health related quality of life (HRQoL) after postmastectomy radiotherapy in patients of sixty years or older.

METHODOLOGY: 119 patients received five fractions of 5.7 Gy to the chest wall and five fractions of 5.4 Gy to the lymph nodes over ten to twelve days. Physician-assessed toxicity were scored using the Common Terminology Criteria for Adverse Events version 4.03 toxicity scoring system and the LENT-SOMA scale. Fatigue was measured by the Multidimensional Fatigue Inventory (MFI-206). HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire the breast cancer specific module and the BREAST-Q questionnaire.

RESULTS: Fatigue and edema were the most frequently observed physician-assessed toxicities. One year after radiotherapy only 12.9% experienced a clinically important deterioration in chest wall symptoms and in 22.9% of the patients were improved. Future perspective at one year after radiotherapy was improved in 40.0% of the patients. Patient-reported fatigue showed the greatest improvement.

CONCLUSION: Accelerated radiotherapy should be considered to minimize the burden of breast cancer treatment, especially in older patients.

PMID:35599462 | DOI:10.3233/BD-210080

Breast Dis. 2022;41(1):267-272. doi: 10.3233/BD-210062.

ABSTRACT

PURPOSE: Immediate autologous breast reconstruction (IABR) offers fewer surgeries with better psychosocial, quality of life and aesthetic outcomes. In high-risk patients or those with locally advanced breast cancer (LABC), adjuvant postmastectomy radiotherapy decreases local recurrence and improves survival. However, it has negative effects on the reconstructed flap. Reversing the treatment protocol using neoadjuvant radiotherapy may minimise the negative effects on the reconstructed breast in women requesting IABR. We assessed the safety and efficacy of women who underwent mastectomy and IABR post-neoadjuvant chemoradiotherapy (NACRT) for LABC.

METHODOLOGY: A cohort study using a retrospective and prospective analysis was performed on women with LABC who underwent mastectomy and IABR post-NACRT between 1998 and 2018. All reconstructions were performed by oncoplastic breast surgeons from a single unit. Outcome measures analysed included surgical complications, flap failure, loco-regional recurrence, overall and disease-free survival. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This study was approved by the institutional review board.

RESULTS: A total of 28 women with a median age of 50 (33-64) were included. 25% underwent TRAM flap and 75% underwent LD flap reconstruction. The median period of follow-up was 61 months. Post-NACRT, 35.7% achieved complete pathological response (PCR). 3/28 (10.7%) had early complications (2 implant and 1 donor site infection). 7% underwent revision surgery. There was no flap loss. 1/28 (3.5%) had loco-regional recurrence, 3.2% had distant metastasis, and 2.5% had breast cancer related mortality.

CONCLUSION: In women with LABC, NACRT followed by mastectomy and IABR is safe and may not compromise oncological and cosmetic outcomes. If offers the benefits of immediate breast reconstruction and avoids delaying adjuvant therapy.

PMID:35599461 | DOI:10.3233/BD-210062

Breast Dis. 2022;41(1):255-260. doi: 10.3233/BD-210041.

ABSTRACT

Inflammatory breast cancer (IBC) is a rare variety of breast cancer accounting for two percent of breast cancer diagnoses in the United States. It is characterized by peau d'orange, breast edema and erythema on physical examination and dermal lymphatic invasion by tumor emboli on histological examination. Micrometastases to lymphatics and bone marrow at the time of diagnosis and angiogenic properties of IBC explain the high propensity of this cancer to relapse and metastasize, its aggressiveness and poor prognosis. Preoperative sequential anthracycline and taxane (plus trastuzumab and pertuzumab if HER2-positive) based chemotherapy is the current standard of care for IBC. We herein report a case of stage IIIC triple-negative IBC treated with pembrolizumab plus chemotherapy based neoadjuvant therapy with a complete clinical and complete pathological response. This is the first case of triple-negative IBC treated with this regimen reported in the literature, thereby providing clinical data on the tolerability and efficacy of pembrolizumab plus chemotherapy based neoadjuvant regimen for the treatment of IBC.

PMID:35599460 | DOI:10.3233/BD-210041

Med Oncol. 2022 May 23;39(5):99. doi: 10.1007/s12032-022-01692-1.

ABSTRACT

Intensive investigation for novel antiproliferative and cytotoxic effective chemical compounds is currently concentrated on structurally modified agents of natural or synthetic source. The selenium derivative of triorganotin compound, triphenyltin isoselenocyanate (TPT-NCSe) caused higher cytotoxicity in hormone sensitive MCF 7 (IC 50-250 nM) in comparison with triple-negative MDA-MB-231 breast carcinoma cell line (IC 50-450 nM) as determined by MTT assay. Measurement of DNA damage showed presence of crosslinks in both cell lines treated by increasing TPT-NCSe concentrations. This compound decreased mitochondrial membrane potential shown by JC-1 staining in a concentration-dependent manner in both cell lines. Activation of caspases-3/7 was observed in MDA-MB-231 cells and was significant only by concentrations causing significant level of crosslinks. On the other hand, migration assay revealed inhibitory effect of viability keeping 100 nM concentration of TPT-NCSe on migration of MDA-MB-231 cells. Our data has shown that this selenium containing triorganotin molecule exerts DNA damage-linked antineoplastic activity in breast carcinoma cell lines studied.

PMID:35599282 | DOI:10.1007/s12032-022-01692-1

Med Oncol. 2022 May 23;39(5):100. doi: 10.1007/s12032-022-01701-3.

ABSTRACT

Microtubule-associated serine/threonine kinase-like (MASTL) regulates mitotic progression and is an attractive target for the development of new anticancer drugs. In this study, novel inhibitory molecules were screened against MASTL kinase, a protein involved in cell proliferation in breast cancer. Natural source-derived drugs Enzastaurin and Palbociclib were selected to identify their role as MASTL kinase inhibitors. Cytotoxic activity, kinase activity, and other cell-based assays of Enzastaurin and Palbociclib were evaluated on human breast cancer (MCF-7) cells. The potential natural compounds caused cytotoxicity in MCF-7 cells in a dose- and time-dependent manner. Further analysis by Annexin V and PI staining indicated that both drugs are potent inducers of apoptosis. Enzastaurin induced G2/M phase arrest, while Palbociclib caused G1 arrest. MASTL kinase activity was significantly abrogated with both the compounds showing EC₅₀ values of 17.13 µM and 10.51 µM, respectively. Taken together, these data strongly suggest that Enzastaurin and Palbociclib possess the ability to inhibit MASTL kinase activity and induce cell death in breast cancer cells, thus exhibiting significant therapeutic potential.

PMID:35599277 | DOI:10.1007/s12032-022-01701-3

Sci Rep. 2022 May 22;12(1):8625. doi: 10.1038/s41598-022-12352-9.

ABSTRACT

Patients with early breast cancer are affected by metastasis to axillary lymph nodes. Metastasis to these nodes is crucial for staging and quality of surgery. Sentinel Lymph Node Biopsy that is currently used to assess lymph node metastasis is not effective. This necessitates identification of biomarkers that can flag metastasis. Early stage breast cancer patients were recruited. Surgical resection of breast was followed by identification of sentinel lymph nodes. Fresh frozen section biopsy was used to assign metastatic and non-metastatic sentinel lymph nodes. Discovery phase included iTRAQ proteomics coupled with mass spectrometric analysis to identify differentially expressed proteins. Data is available via ProteomeXchange with identifier PXD027668. Validation was done by bioinformatic analysis and ELISA. There were 2398 unique protein groups and 109 differentially expressed proteins comparing metastatic and non-metastatic lymph nodes. Forty nine proteins were up-regulated, and sixty proteins that were down regulated in metastatic group. Bioinformatic analysis showed ECM-receptor interaction pathways to be implicated in lymph node metastasis. ELISA confirmed up-regulation of ECM proteins in metastatic lymph nodes. ECM proteins have requisite parameters to be developed as a diagnostic tool to assess status of sentinel lymph nodes to guide surgical intervention in early breast cancer.

PMID:35599267 | DOI:10.1038/s41598-022-12352-9

Nihon Hoshasen Gijutsu Gakkai Zasshi. 2022;78(5):531-534. doi: 10.6009/jjrt.2022-2022.

NO ABSTRACT

PMID:35598963 | DOI:10.6009/jjrt.2022-2022

Oncologist. 2022 May 22:oyac064. doi: 10.1093/oncolo/oyac064. Online ahead of print.

ABSTRACT

The management of breast cancer brain metastases (BCBM) has historically involved local therapies. However, as novel systemic treatments have become more effective in controlling visceral disease, BCBM have also been better controlled. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in brain metastases in patients with lung cancer and melanoma and represent a promising option for patients with triple negative BCBM, a group with limited systemic therapy options. In this review we summarize current data about the role of ICIs in the treatment BCBM. We identified 15 clinical trials that evaluated ICIs ± chemotherapy in patients with breast cancer. The studies were mostly focused on triple negative breast cancer (TNBC). Of these trials, 4 excluded patients with BCBM, while 11 allowed patients with stable, treated or asymptomatic BCBM. In total, 2692 patients were enrolled in the identified clinical trials, but only 91 trial patients (3.3%) had BCBM. Furthermore, only 2 of these clinical trials reported BCBM-specific outcomes and none of the clinical trials reported BCBM-specific adverse events. Up to 45% of patients with TNBC will develop BCBM; however, only 3.3% of the patients included in the clinical trials that led to the U.S. Food and Drug Administration approvals for ICIs in advanced breast cancer had brain metastases. This review reinforces that efficacy data are greatly needed for patients with BCBM-this is an area of unmet need in oncology. More inclusive clinical trials and real-world data that evaluate the safety and efficacy of ICIs in patients with BCBM are greatly needed.

PMID:35598254 | DOI:10.1093/oncolo/oyac064

BMC Health Serv Res. 2022 May 21;22(1):683. doi: 10.1186/s12913-022-08090-3.

ABSTRACT

BACKGROUND: In 2018 Translating Research Into Practice (TRIP), an evidence-based patient navigation intervention aimed at addressing breast cancer care disparities, was implemented across six Boston hospitals. This study assesses patient navigator team member perspectives regarding implementation barriers and facilitators one year post-study implementation.

METHODS: We conducted in-depth qualitative interviews at the six sites participating in the pragmatic TRIP trial from December 2019 to March 2021. Navigation team members involved with breast cancer care navigation processes at each site were interviewed at least 12 months after intervention implementation. Interview questions were designed to address domains of the Consolidated Framework for Implementation Research (CFIR), focusing on barriers and facilitators to implementing the intervention that included 1) rigorous 11-step guidelines for navigation, 2) a shared patient registry and 3) a social risk screening and referral program. Analysis was structured using deductive codes representing domains and constructs within CFIR.

RESULTS: Seventeen interviews were conducted with patient navigators, their supervisors, and designated clinical champions. Participants identified the following benefits provided by the TRIP intervention: 1) increased networking and connections for navigators across clinical sites (Cosmopolitanism), 2) formalization of the patient navigation process (Goals and Purpose, Access to Knowledge and Information, and Relative Advantage), and 3) flexibility within the TRIP intervention that allowed for diversity in implementation and use of TRIP components across sites (Adaptability). Barriers included those related to documentation requirements (Complexity) and the structured patient follow up guidelines that did not always align with the timeline of existing site navigation processes (Relative Priority).

CONCLUSIONS: Our analysis provides data using real-world experience from an intervention trial in progress, identifying barriers and facilitators to implementing an evidence-based patient navigation intervention for breast cancer care. We identified core processes that facilitated the navigators' patient-focused tasks and role on the clinical team. Barriers encountered reflect limitations of navigator funding models and high caseload.

TRIAL REGISTRATION: Clinical Trial Registration Number NCT03514433 , 5/2/2018.

PMID:35597947 | PMC:PMC9123866 | DOI:10.1186/s12913-022-08090-3

Cell Death Dis. 2022 May 21;13(5):485. doi: 10.1038/s41419-022-04939-x.

ABSTRACT

We present a multiscale agent-based model of ductal carcinoma in situ (DCIS) to study how key phenotypic and signaling pathways are involved in the early stages of disease progression. The model includes a phenotypic hierarchy, and key endocrine and paracrine signaling pathways, and simulates cancer ductal growth in a 3D lattice-free domain. In particular, by considering stochastic cell dedifferentiation plasticity, the model allows for study of how dedifferentiation to a more stem-like phenotype plays key roles in the maintenance of cancer stem cell populations and disease progression. Through extensive parameter perturbation studies, we have quantified and ranked how DCIS is sensitive to perturbations in several key mechanisms that are instrumental to early disease development. Our studies reveal that long-term maintenance of multipotent stem-like cell niches within the tumor are dependent on cell dedifferentiation plasticity, and that disease progression will become arrested due to dilution of the multipotent stem-like population in the absence of dedifferentiation. We have identified dedifferentiation rates necessary to maintain biologically relevant multipotent cell populations, and also explored quantitative relationships between dedifferentiation rates and disease progression rates, which may potentially help to optimize the efficacy of emerging anti-cancer stem cell therapeutics.

PMID:35597788 | PMC:PMC9124196 | DOI:10.1038/s41419-022-04939-x

Sci Rep. 2022 May 21;12(1):8607. doi: 10.1038/s41598-022-12504-x.

ABSTRACT

Re-operation due to disease being inadvertently close to the resection margin is a major challenge in breast conserving surgery (BCS). Indocyanine green (ICG) fluorescence imaging could be used to visualize the tumor boundaries and help surgeons resect disease more efficiently. In this work, ICG fluorescence and color images were acquired with a custom-built camera system from 40 patients treated with BCS. Images were acquired from the tumor in-situ, surgical cavity post-excision, freshly excised tumor and histopathology tumour grossing. Fluorescence image intensity and texture were used as individual or combined predictors in both logistic regression (LR) and support vector machine models to predict the tumor extent. ICG fluorescence spectra in formalin-fixed histopathology grossing tumor were acquired and analyzed. Our results showed that ICG remains in the tissue after formalin fixation. Therefore, tissue imaging could be validated in freshly excised and in formalin-fixed grossing tumor. The trained LR model with combined fluorescence intensity (pixel values) and texture (slope of power spectral density curve) identified the tumor's extent in the grossing images with pixel-level resolution and sensitivity, specificity of 0.75 ± 0.3, 0.89 ± 0.2.This model was applied on tumor in-situ and surgical cavity (post-excision) images to predict tumor presence.

PMID:35597783 | PMC:PMC9124184 | DOI:10.1038/s41598-022-12504-x

BMC Anesthesiol. 2022 May 20;22(1):155. doi: 10.1186/s12871-022-01688-4.

ABSTRACT

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed drugs worldwide. However, the effect of NSAIDS on postoperative renal function is still unclear. Few studies have assessed the effects of parecoxib on renal function. Our aim is to investigate a correlation between parecoxib and the presence or absence of AKI postoperatively after a breast cancer surgery operation.

METHODS: This was a retrospective cohort study that we performed on our hospitalized database. From January 2012 to August 2021, 3542 female patients undergoing radical mastectomy were enrolled, all data including the patients' information and laboratory results were obtained from electronic medical system. The main outcome was the incidence of AKI postoperatively. AKI was defined in accordance with the KDIGO criteria. Study groups were treated with or without parecoxib. Univariable and multivariable logistic regression analyses were performed.

RESULTS: In our study, about 5.76% experienced AKI. The incidence rate of postoperative AKI (3.49%) within 7 days in the parecoxib group was lower than that in the control group (6.00%, P = 0.05). Compared to the control group, the AKI's incidence was reduced by 49% (OR = 0.46; 95%CI 0.27-0.97) in parecoxib group in multivariable logistic regression analysis. There was a reduction in the incidence of postoperative AKI in other three subgroups: preoperative eGFR < 90 mL/min·1.73/m2 (OR = 0.52; 95%CI 0.27-0.97), blood loss < 1000 ml (OR = 0.48; 95%CI 0.24-0.96) and non-diabetes (OR = 0.51; 95%CI 0.26-0.98).

CONCLUSIONS: Parecoxib was associated with incidence of postoperative acute kidney injury.

PMID:35596129 | PMC:PMC9121548 | DOI:10.1186/s12871-022-01688-4

Commun Biol. 2022 May 20;5(1):478. doi: 10.1038/s42003-022-03422-9.

ABSTRACT

Increasing evidence highlights approaches targeting metabolism as potential adjuvants to cancer therapy. Sodium-glucose transport protein 2 (SGLT2) inhibitors are the newest class of antihyperglycemic drugs. To our knowledge, SGLT2 inhibitors have not been applied in the neoadjuvant setting as a precision medicine approach for this devastating disease. Here, we treat lean breast tumor-bearing mice with the SGLT2 inhibitor dapagliflozin as monotherapy and in combination with paclitaxel chemotherapy. We show that dapagliflozin enhances the efficacy of paclitaxel, reducing tumor glucose uptake and prolonging survival. Further, the ability of dapagliflozin to enhance the efficacy of chemotherapy correlates with its effect to reduce circulating insulin in some but not all breast tumors. Our data suggest a genetic signature for breast tumors more likely to respond to dapagliflozin in combination with paclitaxel. In the current study, tumors driven by mutations upstream of canonical insulin signaling pathways responded to this combined treatment, whereas tumors driven by mutations downstream of canonical insulin signaling did not. These data demonstrate that dapagliflozin enhances the response to chemotherapy in mice with breast cancer and suggest that patients with driver mutations upstream of canonical insulin signaling may be most likely to benefit from this neoadjuvant approach.

PMID:35595952 | PMC:PMC9122928 | DOI:10.1038/s42003-022-03422-9

Sci Rep. 2022 May 20;12(1):8520. doi: 10.1038/s41598-022-12614-6.

ABSTRACT

Breast-conserving surgery has become the preferred treatment method for breast cancer. Surgical margin assessment is performed during surgery, as it can reduce local recurrence in the preserved breast. Development of reliable and lower-cost ex vivo cancer detection methods would offer several benefits for patient care. Here, a practical and quantitative evaluation method for the ex vivo fluorescent diagnosis of breast lesions was developed and confirmed through a three-step clinical study. Gamma-glutamyl-hydroxymethyl rhodamine green (gGlu-HMRG) has been reported to generate fluorescence in breast lesions. Using this probe, we constructed a reliable and reproducible procedure for the quantitative evaluation of fluorescence levels. We evaluated the reliability of the method by considering reproducibility, temperature sensitivity, and the effects of other clinicopathological factors. The results suggest that the fluorescence increase of gGlu-HMRG is a good indicator of the malignancy of breast lesions. However, the distributions overlapped. A 5 min reaction with this probe could be used to distinguish at least part of the normal breast tissue. This method did not affect the final pathological examination. In summary, our results indicate that the methods developed in this study may serve as a feasible intraoperative negative-margin assessment tool during breast-conserving surgery.

PMID:35595810 | PMC:PMC9122917 | DOI:10.1038/s41598-022-12614-6

Sci Rep. 2022 May 20;12(1):8547. doi: 10.1038/s41598-022-12480-2.

ABSTRACT

Only up to 25% of the cases in which there is a familial aggregation of breast and/or ovarian cancer are explained by germline mutations in the well-known BRCA1 and BRCA2 high-risk genes. Recently, the BRCA1-associated ring domain (BARD1), that partners BRCA1 in DNA repair, has been confirmed as a moderate-risk breast cancer susceptibility gene. Taking advantage of next-generation sequencing techniques, and with the purpose of defining the whole spectrum of possible pathogenic variants (PVs) in this gene, here we have performed a comprehensive mutational analysis of BARD1 in a cohort of 1946 Spanish patients who fulfilled criteria to be tested for germline pathogenic mutations in BRCA1 and BRCA2. We identified 22 different rare germline variants, being 5 of them clearly pathogenic or likely pathogenic large deletions, which account for 0.26% of the patients tested. Our results show that the prevalence and spectrum of mutations in the BARD1 gene might vary between different regions of Spain and expose the relevance to test for copy number variations.

PMID:35595798 | PMC:PMC9122922 | DOI:10.1038/s41598-022-12480-2

Cell Death Dis. 2022 May 20;13(5):482. doi: 10.1038/s41419-022-04945-z.

ABSTRACT

Androgen receptor (AR) signaling plays important roles in breast cancer progression. We show here that Kindlin-2, a focal adhesion protein, is critically involved in the promotion of AR signaling and breast cancer progression. Kindlin-2 physically associates with AR and Src through its two neighboring domains, namely F1 and F0 domains, resulting in formation of a Kindlin-2-AR-Src supramolecular complex and consequently facilitating Src-mediated AR Tyr-534 phosphorylation and signaling. Depletion of Kindlin-2 was sufficient to suppress Src-mediated AR Tyr-534 phosphorylation and signaling, resulting in diminished breast cancer cell proliferation and migration. Re-expression of wild-type Kindlin-2, but not AR-binding-defective or Src-binding-defective mutant forms of Kindlin-2, in Kindlin-2-deficient cells restored AR Tyr-534 phosphorylation, signaling, breast cancer cell proliferation and migration. Furthermore, re-introduction of phosphor-mimic mutant AR-Y534D, but not wild-type AR reversed Kindlin-2 deficiency-induced inhibition of AR signaling and breast cancer progression. Finally, using a genetic knockout strategy, we show that ablation of Kindlin-2 from mammary tumors in mouse significantly reduced AR Tyr-534 phosphorylation, breast tumor progression and metastasis in vivo. Our results suggest a critical role of Kindlin-2 in promoting breast cancer progression and shed light on the molecular mechanism through which it functions in this process.

PMID:35595729 | PMC:PMC9122951 | DOI:10.1038/s41419-022-04945-z

JCO Glob Oncol. 2022 May;8:e2100357. doi: 10.1200/GO.21.00357.

ABSTRACT

PURPOSE: An expert panel on breast cancer and COVID-19 disease was convened to address the impact of the COVID-19 pandemic for early breast cancer (eBC) management.

METHODS: To ensure that the most clinically relevant information was addressed, essential information was drawn from several of the latest national and international guidelines and another technical document. The expert panel met in five virtual closed sessions from November 2020 to May 2021 to consult on the relevant data from evidence-based results. The data gathered were discussed on an online platform.

RESULTS: This article reports the expert panel's highlights of these meetings' discussions. In addition, it provides practical recommendations covering topics regarding diagnosis, treatment, and management of patients with eBC in clinical settings routinely encountered by health care professionals amid the COVID-19 pandemic.

CONCLUSION: This article provided guidance on several topics regarding eBC management amid the COVID-19 pandemics to inform safer care practices.

PMID:35594492 | DOI:10.1200/GO.21.00357

Cancer J. 2022 May-Jun 01;28(3):246-253. doi: 10.1097/PPO.0000000000000593.

ABSTRACT

This article focuses on the value of a unique graphic/image designed to communicate health risks and benefits related to the administration of hormone replacement therapy. It will demonstrate why equations, technical terms, and confusing rhetoric need not be used for communication to patients and others. The use of a "familiar" theater graphic (given the name Benefit/Risk Characterization Theater) will allow physicians and patients to share decision-making by visualizing tradeoffs through the use of a clearer format: example Benefit/Risk Characterization Theaters: breast cancer risks associated with hormone replacement therapy, effectiveness of estrogen in treating menopausal symptoms, and thromboembolic risk of taking estrogen for postmenopausal women. The article describes a practical, simple methodology that can be used in many countries to facilitate doctor-patient communication.

PMID:35594472 | DOI:10.1097/PPO.0000000000000593

Cancer J. 2022 May-Jun 01;28(3):224-240. doi: 10.1097/PPO.0000000000000596.

ABSTRACT

PURPOSE: Current concepts regarding estrogen and its mechanistic effects on breast cancer in women are evolving. This article reviews studies that address estrogen-mediated breast cancer development, the prevalence of occult tumors at autopsy, and the natural history of breast cancer as predicted by a newly developed tumor kinetic model.

METHODS: This article reviews previously published studies from the authors and articles pertinent to the data presented.

RESULTS: We discuss the concepts of adaptive hypersensitivity that develops in response to long-term deprivation of estrogen and results in both increased cell proliferation and apoptosis. The effects of menopausal hormonal therapy on breast cancer in postmenopausal women are interpreted based on the tumor kinetic model. Studies of the administration of a tissue selective estrogen complex in vitro, in vivo, and in patients are described. We review the various clinical studies of breast cancer prevention with selective estrogen receptor modulators and aromatase inhibitors. Finally, the effects of the underlying risk of breast cancer on the effects of menopausal hormone therapy are outlined.

DISCUSSION: The overall intent of this review is to present data supporting recent concepts, discuss pertinent literature, and critically examine areas of controversy.

PMID:35594470 | DOI:10.1097/PPO.0000000000000596

Cancer J. 2022 May-Jun 01;28(3):204-207. doi: 10.1097/PPO.0000000000000592.

ABSTRACT

This narrative review analyzes the customization of menopause hormone therapy (MHT) for osteoporosis prevention and treatment in the context of the patients' age and menopausal age. In short, MHT is indicated in most women suffering from menopause before the age of 45 years except for breast cancer survivors. These women should be treated with MHT until the age of 50 years. For women who have entered menopause at around the age of 50 years, risks associated with MHT are low, and MHT is a safe option, provided there is an indication for it. We suggest that pursuing MHT entails different risks than initiating it, after the age of 60 years. In both cases, advantages and risks should be evaluated. We suggest using risk calculators to assess the magnitude of these risks and choosing regimens that entail the lowest breast and thrombosis risks.

PMID:35594468 | DOI:10.1097/PPO.0000000000000592

Cancer J. 2022 May-Jun 01;28(3):183-190. doi: 10.1097/PPO.0000000000000595.

ABSTRACT

This article reviews the decades of evidence supporting the reproducible benefits of HRT for menopausal symptom control, improved cardiac health, prevention of hip fracture, reduction in the risk and pace of cognitive decline, and enhanced longevity. It quantifies the increased risk of thromboembolism associated with oral, though not transdermal, HRT. It evaluates the repeated claims that HRT is associated with an increased risk of breast cancer development, and, when administered to breast cancer survivors, an increased risk of breast cancer recurrence. Twenty-five studies of HRT after a breast cancer diagnosis, published between 1980 and 2013, are discussed, as are the 20 reviews of those studies published between 1994 and 2021. Only 1 of the 25 studies, the HABITS trial, demonstrated an increased risk of recurrence, which was limited to local or contralateral, and not distant, recurrence. None of the studies, including HABITS, reported increased breast cancer mortality associated with HRT. Even in the HABITS trial, the absolute increase in the number of women who had a recurrence (localized only) associated with HRT administration was 22. It is on the basis of these 22 patients that HRT, with its demonstrated benefits for so many aspects of women's health, is being denied to millions of breast cancer survivors around the world.

PMID:35594465 | DOI:10.1097/PPO.0000000000000595

Cancer J. 2022 May-Jun 01;28(3):176-182. doi: 10.1097/PPO.0000000000000599.

ABSTRACT

Survivorship has become a crucial component in breast cancer care. For women who have not completed their family planning, conceiving at the end of anticancer treatments should not be discouraged but might be challenging. Oncofertility counseling should be offered at the time of diagnosis to all patients, in order to inform them about the potential treatment-induced gonadotoxicity as well as the available strategies for fertility preservation, thus allowing to increase the chances of a future pregnancy. This article reports an updated overview on the current state of the art on pregnancy in women with prior breast cancer diagnosis and treatment, with a main focus on the issues faced by patients with history of hormone receptor-positive disease and BRCA carriers.

PMID:35594464 | DOI:10.1097/PPO.0000000000000599

Cancer J. 2022 May-Jun 01;28(3):169-175. doi: 10.1097/PPO.0000000000000601.

ABSTRACT

Associations of estrogen-alone and estrogen plus progestin with breast cancer incidence and related mortality are reviewed from observational studies (The Collaborative Group on Hormonal Factors in Breast Cancer and The Million Women Study, 2019) and the Women's Health Initiative's (2020) two randomized trials evaluating conjugated equine estrogen alone, for women with prior hysterectomy or with medroxyprogesterone acetate. Findings are generally concordant for estrogen plus progestin use with both observational and randomized studies reporting higher breast cancer incidence. Findings are discordant for estrogen-alone use where, in the WHI randomized trial, a lower incidence and lower breast cancer mortality was seen. In contrast, in the observational studies, estrogen-alone use was associated with higher breast cancer incidence and higher breast cancer mortality. Although these discordant findings are difficult to fully reconcile, we conclude with a discussion of public health implications of the available evidence on menopausal hormone therapy and breast cancer.

PMID:35594463 | DOI:10.1097/PPO.0000000000000601

Cancer J. 2022 May-Jun 01;28(3):163-168. doi: 10.1097/PPO.0000000000000600.

ABSTRACT

In 1971, Sir Alexander Haddow et al. delivered the inaugural David A. Karnofsky lecture at the American Society for Clinical Oncology. This award was designated American Society for Clinical Oncology's highest, as he had used translational research to identify the first clinical therapy, that is, synthetic estrogens to treat breast cancer. His lecture was entitled "Thoughts on Chemical Therapy." For 40 years, high-dose synthetic estrogens were used as palliative therapy, for some advanced breast cancer patients 5 years following menopause. Mechanisms were unknown. Tamoxifen, a failed "morning-after pill," is an antiestrogen in estrogen receptor-positive breast cancer, which was subsequently used to treat all stages of breast cancer and to prevent breast cancer. In 2008, Jordan was selected to present the 38th Karnofsky lecture entitled: "The Paradoxical Action of Estrogen in Breast Cancer-Survival or Death?" Unexpectedly, through a study of acquired resistance to long-term tamoxifen therapy, estrogen-induced apoptosis in long-term estrogen-deprived breast cancer was deciphered in Jordan's laboratory. These data and the biological rules established under laboratory conditions provided molecular mechanisms to aid in the interpretation of the Women's Health initiative in the United States and the Million Women Study in the United Kingdom. In addition, by establishing laboratory models to understand mechanisms of estrogen-induced apoptosis, new estrogen derivatives were successfully evaluated in the laboratory and tested as candidates for women after the therapeutic failure of antiestrogenic strategies to treat breast cancer. For the future, the knowledge obtained about estrogen-induced apoptosis in cancer holds the promise of discovering new therapies to control or cure cancer in general.

PMID:35594462 | DOI:10.1097/PPO.0000000000000600

Sci Adv. 2022 May 20;8(20):eabk2746. doi: 10.1126/sciadv.abk2746. Epub 2022 May 20.

ABSTRACT

Anti-HER2 therapies have markedly improved prognosis of HER2-positive breast cancer. However, different mechanisms play a role in treatment resistance. Here, we identified AXL overexpression as an essential mechanism of trastuzumab resistance. AXL orchestrates epithelial-to-mesenchymal transition and heterodimerizes with HER2, leading to activation of PI3K/AKT and MAPK pathways in a ligand-independent manner. Genetic depletion and pharmacological inhibition of AXL restored trastuzumab response in vitro and in vivo. AXL inhibitor plus trastuzumab achieved complete regression in trastuzumab-resistant patient-derived xenograft models. Moreover, AXL expression in HER2-positive primary tumors was able to predict prognosis. Data from the PAMELA trial showed a change in AXL expression during neoadjuvant dual HER2 blockade, supporting its role in resistance. Therefore, our study highlights the importance of targeting AXL in combination with anti-HER2 drugs across HER2-amplified breast cancer patients with high AXL expression. Furthermore, it unveils the potential value of AXL as a druggable prognostic biomarker in HER2-positive breast cancer.

PMID:35594351 | DOI:10.1126/sciadv.abk2746

PLoS One. 2022 May 20;17(5):e0267308. doi: 10.1371/journal.pone.0267308. eCollection 2022.

ABSTRACT

INTRODUCTION: Breast cancer patients in low- and middle-income countries often present at an advanced stage. This qualitative study elicited views regarding the challenges and opportunities for breast cancer screening and early detection among women in a low-income semi-rural community in Segamat district, Malaysia.

METHODS: Individual semi-structured interviews with 22 people (health professionals, cancer survivors, community volunteers and member from a non-governmental organization) and four focus group discussions (n = 22 participants) with women from a local community were conducted. All participants were purposively sampled and female residents registered with the South East Asia Community Observatory aged ≥40 years were eligible to participate in the focus group discussions. Data were transcribed verbatim and analyzed using thematic analysis.

RESULTS: The thematic analysis illuminated barriers, challenges and opportunities across six domains: (i) personal experiences and barriers to help-seeking as well as financial and travel access barriers; (ii) primary care challenges (related to delivering clinical breast examination and teaching breast-self-examination); (iii) secondary care challenges (related to mammogram services); (iv) disconnection between secondary and primary care breast cancer screening pathways; and (v) opportunities to improve breast cancer early detection relating to community civil service society activities (i.e. awareness raising, support groups, addressing stigma/embarrassment and encouraging husbands to support women) and vi) links between public healthcare personnel and community (i.e. improving breast self-examination education, clinical breast examination provision and subsidised mammograms).

CONCLUSION: The results point to a variety of reasons for low uptake and, therefore, to the complex nature of improving breast cancer screening and early detection. There is a need to adopt a systems approach to address this complexity and to take account of the socio-cultural context of communities in order, in turn, to strengthen cancer control policy and practices in Malaysia.

PMID:35594267 | PMC:PMC9122189 | DOI:10.1371/journal.pone.0267308

Cell Mol Life Sci. 2022 May 20;79(6):306. doi: 10.1007/s00018-022-04333-y.

ABSTRACT

Although type I interferons (IFNs) play multifaceted roles during tumorigenesis and cancer treatment, the interplay between type I IFNs and estrogen signaling in breast cancer (BC) microenvironment is not well understood. Here, we report a novel function of type I IFNs in inducing aromatase expression in adipose tissues surrounding BC, which potentiates the E₂-dependent growth of estrogen receptor (ER)-positive BC. First, we found that expression levels of type I IFNs correlate negatively with clinical outcome but positively with tumor grade in patients with ER-positive BC. Levels of type I IFNs were elevated in cocultured media of immune cells and BC cells, which increased aromatase expression and E₂ production in Simpson-Golabi-Behmel syndrome preadipocytes. The type I IFN-induced aromatase expression was dependent on IFN-γ-inducible protein 16 (IFI16), which is encoded by an interferon-stimulated gene. At the molecular level, type I IFNs led to recruitment of HIF1α-IFI16-PRMT2 complex to the hypoxia-response element located in the aromatase PI.3/PII promoter. Next, we generated an adipocyte-specific Ifi204, which is a mouse ortholog of human IFI16, knockout mouse (Ifi204-AKO). IFNβ induced E₂ production in the preadipocytes isolated from the control mice, but such E₂ production was far lower in the Ifi204-AKO preadipocytes. Importantly, the growth of orthotopically inoculated E0771 ER-positive mammary tumors was reduced significantly in the Ifi204-AKO mice. Taken together, our findings provide novel insights into the crosstalk between type I IFNs and estrogen signaling in the progression of ER-positive BC.

PMID:35593921 | PMC:PMC9122892 | DOI:10.1007/s00018-022-04333-y

Integr Cancer Ther. 2022 Jan-Dec;21:15347354221096868. doi: 10.1177/15347354221096868.

ABSTRACT

Propolis is a resinous beehive product that has a wide range of biological activities, namely antimicrobial, antioxidant, and anti-inflammatory properties. Propolis is collected by the bees from plant resin and exudates to protect hives and maintain hive homeostasis. The aim of the present systematic scoping review is to explore the potential and suitability of propolis as an adjunctive treatment in breast cancers, based on the latest available experimental evidence (2012-2021). After applying the exclusion criteria, a total of 83 research publications were identified and retrieved from Scopus, Web of Science, and Pubmed. Several relevant key themes identified from the included studies were cytotoxicity, synergistic/combination treatment, improvement in bioavailability, human clinical trials, and others. A majority of the studies identified were still in the in vitro and in vivo stages. Nonetheless, we managed to identify 4 human clinical trials that demonstrated the successful use of propolis in alleviating side effects of chemotherapy and radiotherapy while increasing the quality of life of breast cancer patients, with minimal adverse effects. In conclusion, propolis, as an adjunctive treatment, may have therapeutic benefits in alleviating symptoms related to breast cancers. However, further clinical trials, preferably with higher number of participants/subjects/patients, are urgently needed.

PMID:35593403 | DOI:10.1177/15347354221096868

Ugeskr Laeger. 2022 May 9;184(19):V10210813.

ABSTRACT

The use of a sentinel lymph node procedure (SN) in various cancer treatments including breast cancer is well examined. Little is known however, regarding the use of SN in colorectal cancer treatment. In this review, we explain the use of SN and its implications for future colorectal cancer treatment.

PMID:35593370

Natl Med J India. 2022 Sep-Oct;34(5):271-275. doi: 10.25259/NMJI_222_18.

ABSTRACT

Background As breast epithelium is affected by vitamin D, it may have a direct effect on breast density and the risk of breast cancer. Our aim was to study the serum levels of vitamin D in patients with malignant and benign breast disease, and to study the association, if any, between vitamin D levels, mammographic breast density (MD) and molecular subtypes of breast cancer. Methods In this cross-sectional, observational study, we enrolled 162 consecutive adult women with benign and malignant breast masses subjected to mammography and core-needle biopsy. Serum levels of vitamin D were estimated and correlated with MD and with immunohistochemical subtyping of breast cancer. Results The mean vitamin D level in these 162 patients was 12.44 (5.88) ng/ml, with vitamin D deficiency seen in 98%. The mean (SD) vitamin D level in MD type 1 was 16.19 (4.62) ng/ml and it decreased to 7.54 (2.58) ng/ml in MD type 4. High MD was associated with significantly lower vitamin D levels. The mean vitamin D level in patients with benign breast disease (n=102) was 13.73 (5.68) ng/ml, while it was significantly lower in patients with breast cancer (n=60) at 10.26 (5.61) ng/ml. Among patients with breast cancer, the good prognosis luminal A molecular subtype had mean vitamin D level of 12.94 (6.16) ng/ml, whereas the poor prognosis triple-negative subtype had a significantly lower value of 7.68 (3.42) ng/ml. Conclusion Our study shows that vitamin D deficiency has a significant relationship with breast cancer (v. benign breast disease), high MD (showing increased breast cancer risk) and poor prognosis triple-negative breast cancer. Vitamin D deficiency could be an important, potentially modifiable, risk factor for the prevention of breast cancer in susceptible populations.

PMID:35593250 | DOI:10.25259/NMJI_222_18

Natl Med J India. 2022 Sep-Oct;34(5):285-286. doi: 10.25259/NMJI_338_21.

NO ABSTRACT

PMID:35593237 | DOI:10.25259/NMJI_338_21

J Med Screen. 2022 May 20:9691413221101807. doi: 10.1177/09691413221101807. Online ahead of print.

ABSTRACT

OBJECTIVE: The ongoing COVID-19 pandemic has caused an indefinite delay to cancer screening programs worldwide. This study aims to explore the impact on breast cancer screening outcomes such as mammography and diagnosis rates.

METHODS: We searched Ovid MEDLINE, Ovid Embase, medRxiv and bioRxiv between January 2020 to October 2021 to identify studies that reported on the rates of screening mammography and breast cancer diagnosis before and during the pandemic. The effects of 'lockdown' measures, age and ethnicity on outcomes were also examined. All studies were assessed for risk of bias using the Newcastle-Ottawa Scale (NOS). Rate ratios were calculated for all outcomes and pooled using standard inverse-variance random effects meta-analysis.

RESULTS: We identified 994 articles, of which 7 registry-based and 24 non-registry-based retrospective cohort studies, including data on 4,860,786 and 629,823 patients respectively across 18 different countries, were identified. Overall, breast cancer screening and diagnosis rates dropped by an estimated 41-53% and 18-29% respectively between 2019 and 2020. No differences in mammogram screening rates depending on patient age or ethnicity were observed. However, countries that implemented lockdown measures were associated with a significantly greater reduction in mammogram and diagnosis rates between 2019 and 2020 in comparison to those that did not.

CONCLUSION: The pandemic has caused a substantial reduction in the screening and diagnosis of breast cancer, with reductions more pronounced in countries under lockdown restrictions. It is early yet to know if delayed screening during the pandemic translates into higher breast cancer mortality.

PMID:35593115 | DOI:10.1177/09691413221101807

Comput Intell Neurosci. 2022 May 10;2022:4601696. doi: 10.1155/2022/4601696. eCollection 2022.

ABSTRACT

Assessing the extent of cancer spread by histopathological analysis of sentinel axillary lymph nodes is an important part of breast cancer staging. With the maturity and prevalence of deep learning technology, building auxiliary medical systems can help to relieve the burden of pathologists and increase the diagnostic precision and accuracy during this process. However, such histopathological images have complex patterns that are difficult for ordinary people to understand and require professional medical practitioners to annotate. This increases the cost of constructing such medical systems. To reduce the cost of annotating and improve the performance of the model as much as possible, in other words, using as few labeled samples as possible to obtain a greater performance improvement, we propose a deep learning framework with a three-stage query strategy and novel model update strategy. The framework first trains an auto-encoder with all the samples to obtain a global representation in a low-dimensional space. In the query stage, the unlabeled samples are first selected according to uncertainty, and then, coreset-based methods are employed to reduce sample redundancy. Finally, distribution differences between labeled samples and unlabeled samples are evaluated and samples that can quickly eliminate the distribution differences are selected. This method achieves faster iterative efficiency than the uncertainty strategies, representative strategies, or hybrid strategies on the lymph node slice dataset and other commonly used datasets. It reaches the performance of training with all data, but only uses 50% of the labeled. During the model update process, we randomly freeze some weights and only train the task model on new labeled samples with a smaller learning rate. Compared with fine-tuning task model on new samples, large-scale performance degradation is avoided. Compared with the retraining strategy or the replay strategy, it reduces the training cost of updating the task model by 79.87% and 90.07%, respectively.

PMID:35592722 | PMC:PMC9113892 | DOI:10.1155/2022/4601696

Int J Nanomedicine. 2022 May 13;17:2165-2187. doi: 10.2147/IJN.S360161. eCollection 2022.

ABSTRACT

PURPOSE: Triple negative breast cancer (TNBC) is challenging for effective remission due to its very aggressive, extremely metastatic and resistant to conventional chemotherapy. Herein, a multifunctional theranostic nanoparticle was fabricated to enhance tumor targeted imaging and promote focused ultrasound (FUS) ablation and chemotherapy and sonodynamic therapy (SDT). A multi-modal synergistic therapy can improve the therapeutic efficacy and prognosis of TNBC.

METHODS: AS1411 aptamer modified PEG@PLGA nanoparticles encapsulated with perfluorohexane (PFH) and anti-cancer drug doxorubicin (DOX) were constructed (AS1411-DOX/PFH-PEG@PLGA) to enhance tumor targeted imaging to guide ablation and synergistic effect of FUS/chemotherapy. FUS was utilized to trigger the co-release of doxorubicin and simultaneously PFH phase transition and activate DOX for SDT effect. The physicochemical, phase-changeable imaging capability, biosafety of nanoparticles and multi-mode synergistic effects on growth of TNBC were thoroughly evaluated in vivo and in vitro.

RESULTS: The synthesized AS1411-DOX/PFH-PEG@PLGA (A-DPPs) nanoparticles are uniformly round with an average diameter of 306.03 ± 5.35 nm and the zeta potential of -4.05 ± 0.13 mV, displaying high biosafety and FUS-responsive drug release in vitro and in vivo. AS1411 modified NPs specifically bind to 4T1 cells and elevate the ultrasound contrast agent (UCA) image contrast intensity via PFH phase-transition after FUS exposure. Moreover, the combined treatment of A-DPPs nanoparticles with FUS exhibited significantly higher apoptosis rate, stronger inhibitory effect on 4T1 cell invasion in vitro, induced more reactive oxygen species (ROS), and enhanced anti-tumor effect compared to a single therapy (p < 0.05). Additionally, the joint strategy resulted in more intense cavitation effect and larger ablated areas and reduced energy efficiency factor (EEF) both in vitro and in vivo.

CONCLUSION: The multifunctional AS1411-DOX/PFH-PEG@PLGA nanoparticles can perform as a marvelous synergistic agent for enhanced FUS/chemotherapy, promote real-time contrast enhanced US imaging and improve the therapeutic efficacy and prognosis of TNBC.

PMID:35592098 | PMC:PMC9113557 | DOI:10.2147/IJN.S360161

Sensors (Basel). 2022 May 9;22(9):3594. doi: 10.3390/s22093594.

ABSTRACT

BACKGROUND: Cone-beam breast computed tomography (CBBCT) and digital breast tomosynthesis (DBT) remain the main 3D modalities for X-ray breast imaging. This study aimed to systematically evaluate and meta-analyze the comparison of diagnostic accuracy of CBBCT and DBT to characterize breast cancers.

METHODS: Two independent reviewers identified screening on diagnostic studies from 1 January 2015 to 30 December 2021, with at least reported sensitivity and specificity for both CBBCT and DBT. A univariate pooled meta-analysis was performed using the random-effects model to estimate the sensitivity and specificity while other diagnostic parameters like the area under the ROC curve (AUC), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were estimated using the bivariate model.

RESULTS: The pooled sensitivity specificity, LR+ and LR- and AUC at 95% confidence interval are 86.7% (80.3-91.2), 87.0% (79.9-91.8), 6.28 (4.40-8.96), 0.17 (0.12-0.25) and 0.925 for the 17 included studies in DBT arm, respectively, while, 83.7% (54.6-95.7), 71.3% (47.5-87.2), 2.71 (1.39-5.29), 0.20 (0.04-1.05), and 0.831 are the pooled sensitivity specificity, LR+ and LR- and AUC for the five studies in the CBBCT arm, respectively.

CONCLUSIONS: Our study demonstrates that DBT shows improved diagnostic performance over CBBCT regarding all estimated diagnostic parameters; with the statistical improvement in the AUC of DBT over CBBCT. The CBBCT might be a useful modality for breast cancer detection, thus we recommend more prospective studies on CBBCT application.

PMID:35591290 | PMC:PMC9101306 | DOI:10.3390/s22093594

Sensors (Basel). 2022 Apr 25;22(9):3279. doi: 10.3390/s22093279.

ABSTRACT

Dielectrophoresis (DEP) refers to a type of electrical motion of dielectric particles. Because DEP is caused by particle polarization, it has been utilized to characterize particles. This study investigated the DEP of three types of exosomes, namely bovine milk, human breast milk, and human breast cancer exosomes. Exosomes are kinds of extracellular vesicles. The crossover frequencies of the exosomes were determined by direct observation of their DEPs. Consequently, bovine and human milk exosomes showed similar DEP properties, whereas the cancer exosomes were significantly different from the others. The membrane capacitance and conductivity of the exosomes were estimated using determined values. A significant difference was observed between bovine and human milk exosomes on their membrane capacitance. It was revealed that the membrane capacitances of human breast milk and human breast cancer exosomes were almost identical to those of their host cells and the conductivity of the exosomes were much lower than that of the host cell. Based on these results, DEP separation of the human breast milk and cancer exosomes was demonstrated. These results imply that DEP can be utilized to separate and identify cancer exosomes rapidly. Additionally, our method can be utilized to estimate the electric property of other types of extracellular vesicles.

PMID:35590969 | PMC:PMC9101962 | DOI:10.3390/s22093279

Med (N Y). 2021 Sep 10;2(9):996-998. doi: 10.1016/j.medj.2021.08.010.

ABSTRACT

Adjuvant endocrine therapy has transformed outcomes for patients with early-stage, hormone receptor-positive, HER2-negative breast cancer; however, the optimal duration remains undefined. In a recent issue of The New England Journal of Medicine, Gnant et al. report the results of the ABCSG-16/SALSA trial that investigated the optimal duration of extended adjuvant aromatase inhibition and found that 5 years was not more beneficial than a 2-year extension.¹.

PMID:35590193 | DOI:10.1016/j.medj.2021.08.010