Non-invasive Breast Cancer Research Articles

Abstract PO-010: Feature pyramid network for revealing tumour infiltrating lymphocyte presence and distribution in a whole slide image

Abstract Ductal Carcinoma in Situ (DCIS) is a subtype of non-invasive breast cancer contained in the ducts of the breast. DCIS is not a life-threatening condition however a small number of cases will progress to or reoccur as invasive breast cancer. Clinical workflows lack a robust biomarker to determine which patients will reoccur. Recently pathologists have turned towards investigating the tumour microenvironment to predict cancer recurrence. Machine learning models present an opportunity to analyze these features on large amounts of data with minimal requirement of pathologist time. One feature of recent interest are Tumour infiltrating lymphocytes or TILs, lymphocytes within a small region around a cancerous duct. Through a method of bootstrapping a U-Net on top of a fully convolutional network we have designed a network that is able to segment lymphocyte and malignant cells in H&E Images of Ductal Carcinoma In Situ. The original network was trained on a private set of cellularity data in breast cancer, manually annotated by pathologists to mark the centre and type of each cell in a patch. Probabilistic output from this model was used to generate segmentation maps on a much larger dataset of DCIS images from the Ontario DCIS Cohort. These segmentation maps were used as training data for a feature pyramid network. The results of this bootstrapping method was a significant increase to speed of the model in addition to much larger flexibility in the input size and shape for the model, which came at a small cost to overall model accuracy. In addition to the original segmentation target, the use of this model to generate lower resolution WSI heat-maps has been investigated for this work. This model can generate low resolution heat-maps for a 20X magnification whole slide image showing the presence of malignant cells in addition to the location and distribution of TILs around ducts. This can provide a visual overview of differences between slides and we will be examining the potential for this output to serve as information for analytical methods to process to predict recurrence free survival. Citation Format: Jonathan Mazurski, Sharon Nofech-Mozes, Dina Bassiouny, Anne L. Martel. Feature pyramid network for revealing tumour infiltrating lymphocyte presence and distribution in a whole slide image [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-010.

Abstract PS1-11: Natural transition targeted surgery

Abstract Background: Breast conserving surgery is the standard in T1-T3 primary breast cancer. The cosmetic result is very much depending on the surgeon´s experience, the tumor-size/breast ratio and the technique applied. To improve cosmetic outcome and reduce repeated surgery, we have proposed a nomogram earlier (1) which has been cited by the American Society of Breast Surgeons Consensus Conference (2). In this nomogram, we proposed 5 simple oncoplastic techniques to handle the vast majority of breast cancer cases with a good cosmetic result. However, these techniques used direct access to the mammary gland, leaving scars in the visible skin of the breast. To avoid this, we chose a more natural access to the mammary gland at the natural transitions. Methods: We conducted a prospective open-arm study including all primary invasive and non-invasive breast cancer cases of tumor stages AJCC 0-III A (Version 8.0). Access to the tumor was chosen according to the proximity of the tumor to one of the following natural transitions (Areola, Lateral Insertion of the breast, inframmary fold): Non-palpable tumors and those undergoing neoadjuvant chemotherapy had to be marked by a wireand clippes before. Intraoperative ultrasound was applied before skin incision and after removal of the tumour (ultrasound of the specimen to confirm clear margins). Resection was performed as a segmentectomy and SLN biopsy and axillary clearance was done according to current guidelines.Results: 84 patients with breast conserving NTT-surgery have been enrolled so far. 76 patients had primary surgery with stage distribution as follows: Tis (1), T1a (3), T1b (8), T1c (30), T2 (30), T3 (4) and T4b(1). 8 patients had neoadjuvant chemotherapy with stage distribution as follows: ypT0 (3), ypT1a(2), ypT1c(1) and ypT2 (2). Histopathology was predominantly invasive-ductal breast cancer (70), followed by invasive-lobular (6), ductulo-lobular (5), invasive-ductal and DCIS (1),invasive-ductal and mucinous (1) and mucinous only (1). After first surgery 77 patients had a tumor resection according to the nomogramm of NTT-surgery with free margins and 7 with involved margins, thus 91,6 % tumors were resected with free margins at first surgery. The remaining 8,4 % were margin-free after second surgery. Conclusion: Scars were not visible on the surface of the breast outside of natural transitions and rate of free margins was high at 91,6 % without impairment due to the remote access to the mammary gland. We report a high patient satisfaction. Patient-reported outcome in detail has been evaluated by validated questionnaires and will be presented onsite.

Abstract PS1-36: Outcomes and management of positive and close anterior margins following skin-sparing mastectomy

Abstract Background: Skin-sparing mastectomy (SSM) has emerged as a safe oncologic technique for extirpation of breast tissue in the context of immediate breast reconstruction (IBR). Documented rates of local recurrence are comparable for SSM and conventional mastectomy and attention to the plane of dissection is essential with removal of skin overlying the tumor when clinically indicated. The incidence of positive or close margins is greatest for peripheral tumors at the breast boundaries and will influence rates of local recurrence. Management of positive or close margins is inconsistent and this audit aimed to determine the incidence of compromised margins and their impact on local recurrence and overall survival in SSM patients. Methods: A retrospective analysis was undertaken of breast patients with invasive or non-invasive breast cancer undergoing SSM and IBR at a single tertiary referral centre between January 2006 and December 2009. A total of 150 patients were included and all underwent resection of breast tissue with a peri-areolar incision. Clinical information was extracted from a prospectively maintained database. Data was collected on patient demographics, tumor characteristics, non-surgical treatment and outcome events (recurrence and death). The definition of a negative margin on histology during the study period was tumor ≥2mm from the edge of the specimen with close margins <2mm but no ink on tumor. Results: The mean age of patients was 51 years (range 24 - 75) and median duration of follow up 140 months (range 10 - 167). Amongst these 150 SSM patients, 25 (17%) had positive or close anterior margins (<2mm) with 125 patients having negative anterior margins (>2mm). None of these patients with close or positive margins underwent re-excision following initial SSM. Twenty-four patients (16%) developed either loco-regional (n=9) or distant recurrence (n=15) with 126 patients (84%) alive at 10 years. Although more patients with positive/close compared with negative margins had recurrence (20% versus 15%), this did not reach statistical significance (p=0.55) Similar proportions of patients in each margin category received post-mastectomy radiotherapy (p=0.66) and adjuvant/neo-adjuvant chemotherapy (p=0.66). There were no statistically significant differences in rates of local recurrence or survival between patients with positive/close and negative margins but the number of events is small and may represent a type II error. Conclusion: Twenty percent of patients (5/25) with positive or close margins after SSM develop local or distant recurrence with reduction of risk by PMRT of <50%. None of the patients with positive/close margins who developed recurrence survived for 10 years. Close/positive margins after SSM may portend a worse outcome from recurrent disease and further research is required to optimize management of this group of patients in an era of skin-preserving mastectomy. Citation Format: Primeera Wignarajah, Dorin Dumitru, John R Benson. Outcomes and management of positive and close anterior margins following skin-sparing mastectomy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-36.

Altered mechanical properties of actin fibers due to breast cancer invasion: parameter identification based on micropipette aspiration and multiscale tensegrity modeling.

The biophysical properties of cells change with cancer invasion to fulfill their metastatic behavior. Cell softening induced by cancer is highly associated with alterations in cytoskeleton fibers. Changes in the mechanical properties of cytoskeletal fibers have not been quantified due to technical limitations. In this study, we used the micropipette aspiration technique to calculate and compare the viscoelastic properties of non-invasive and invasive breast cancer cells. We evaluated the mechanical properties of actin fibers and microtubules of two cancerous cell lines by using multiscale tensegrity modeling and an optimization method. Cancer invasion caused altered viscoelastic behavior of cells and the results of modeling showed changes in mechanical properties of major cytoskeleton fibers. The stiffness and viscosity constant of actin fibers in non-invasive cells were 1.28 and 2.27 times higher than those of the invasive cells, respectively. However, changes in mechanical properties of microtubules were minor. Immunofluorescent staining of fibers and their quantified distributions confirmed altered actin distribution among two cell lines, in contrast to microtubule distribution. This study highlights the function of cytoskeletal fibers in cancer progression, which could be of interest in designing therapeutic strategies to target cancer progress. Firstly, the viscoelastic behavior of non-invasive and invasive cells is examined with micropipette aspiration tests. A tensegrity model of cells is developed to mimic the viscoelastic behavior of cells, and tensegrity element stiffness is evaluated in an optimization procedure based on micropipette aspiration tests. Finally, by using immunofluorescent staining and confocal imaging, mechanical properties of actin filaments and microtubules of cancer cells are investigated during the course of metastasis.

Cytotoxic activities of zinc oxide nanoparticles on non-invasive human breast and prostate cancer cell lines

ZnO-NPs have displayed anticancer activity against a broad range of tumor cells. The present research work was planned to formulate highly pure and well-characterized ZnO-NPs, in addition, to investigate their cytotoxicity against two types of cancer cells. The cancer cells that had been investigated in the present study were breast (MCF7) and prostate (PC3) cancer cells. The aqueous sol-gel method is a powerful and cost-effective technique for the synthesis of high pure ZnO-NPs. While the anticancer activities of ZnO-NPs on both MCF7 and PC3 were determined by MTT assay. Characterizations of ZnO-NPs were fundamentally evaluated by their morphological and structural properties, in addition to their particle size distribution with the aid of SEM and EDX, respectively. ZnO NPs were successfully prepared using sol-gel method in a range of nano-scale. Scanning electron microscopy (SEM) has shown flower-like nanoparticles of zinc oxide, their nano-size has ranged from 4.497 nm. to 143.7 nm. Results of EDX characterization has exhibited a good purity of ZnO-NPs (zinc content of 50% and Oxygen content of 50 %). There was size-dependent effectiveness of ZnO-NPs as an anticancer agent on both MCF7 and PC3. In addition, there were positive correlation between anticancer activities and low toxicity with the size of ZnO-NPs. At 12.2 μg/ml, ZnO-NPs has exhibited around 51% reduction in the viability of cancerous cells. In conclusion, the results of this study have shown that there was an effective and notable dose-dependent manner in the treatment of MCF7 and PC3 with ZnO-NPs, in the cell line approaches.

Cross-platform genomic identification and clinical validation of breast cancer diagnostic biomarkers.

Introduction: Circulating non-coding RNA is an ideal source to discover novel biomarkers for non-invasive screening. However, studies for the discovery of universal miRNAs in serum and exosomes for breast cancer early diagnosis are limited.Methods: Based on bioinformatic analysis, in vitro and in vivo studies were performed to understand the role of identified hsa-miR-423-5p in cancer proliferation, migration, cancer stem cell properties. Next, global non-coding RNA expression profiles in blood serum and exosome were performed. hsa-miR-423-5p expression from a total of 356 peripheral blood samples was evaluated and the association of hsa-miR-423-5p expression with clinical characteristics, sensitivity and specificity for breast cancer diagnosis were assessed.Results: The expression of serum and exosomal hsa-miR-423-5p is abnormally increased in breast cancer. Suppression of hsa-miR-423-5p inhibited cell proliferation and invasion in both T47D and MDA-MB-231 breast cancer cell lines, and tumor growth in vivo. Compared with 113 healthy women, quantification analysis of hsa-miR-423-5p in 224 breast cancer samples confirmed the abnormal expression. Serum hsa-miR-423-5p was significantly associated with the clinical stage (P=0.001) and Ki-67 level (P=0.004).Conclusions: A translational bioinformatics analysis procedure and validation by in vitro, in vivo, and clinical samples reveal that hsa-miR-423-5p could be used as a non-invasive breast cancer biomarker.

Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells.

Simple SummaryTumor draining lymph nodes (TDLNs) are the most common metastatic sites in human cancer but are also essential sites for induction of tumor immunity. How different types of primary tumors affect the anti-tumor immune response in the LNs is not fully understood. By analyzing biobank tissue from breast cancer patients, we demonstrate that invasive breast cancer induce dramatic pre-metastatic LN changes affecting the structure and function of the specialized LN vasculature and associated stromal cells, required for recruitment of T-lymphocytes into the LNs. These changes could not be seen in patients with non-invasive breast cancer and provide new insights of how invasive tumors can disrupt essential functions within the immune system. The data also shows promise of LN stromal and vascular changes as possible future biomarkers for prediction of disease progression in human cancer.The tumor-draining lymph nodes (TDLNs) are primary sites for induction of tumor immunity. They are also common sites of metastasis, suggesting that tumor-induced mechanisms can subvert anti-tumor immune responses and promote metastatic seeding. The high endothelial venules (HEVs) together with CCL21-expressing fibroblastic reticular cells (FRCs) are essential for lymphocyte recruitment into the LNs. We established multicolor antibody panels for evaluation of HEVs and FRCs in TDLNs from breast cancer (BC) patients. Our data show that patients with invasive BC display extensive structural and molecular remodeling of the HEVs, including vessel dilation, thinning of the endothelium and discontinuous expression of the HEV-marker PNAd. Remodeling of the HEVs was associated with dysregulation of CCL21 in perivascular FRCs and with accumulation of CCL21-saturated lymphocytes, which we link to loss of CCL21-binding heparan sulfate in FRCs. These changes were rare or absent in LNs from patients with non-invasive BC and cancer-free organ donors and were observed independent of nodal metastasis. Thus, pre-metastatic dysregulation of core stromal and vascular functions within TDLNs reflect the primary tumor invasiveness in BC. This adds to the understanding of cancer-induced perturbation of the immune response and opens for prospects of vascular and stromal changes in TDLNs as potential biomarkers.

Systemic Treatment of Ductal Carcinoma In Situ of the Breast.

Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer (BC), whose diagnosis significatively increased with the diffusion of BC screening programs. DCIS actually represents roughly 20% of new BC diagnoses (1). About 70% of DCIS shows positivity for hormone receptor (HR), while HER2 is overexpressed in 25-30% of the cases (2,3). Concerning the systemic approach, the only one that should be considered for HR-positive DCIS is adjuvant endocrine therapy (ET), according to NCCN guidelines (4). In fact, the excellent prognosis of this neoplasm does not justify the utilization of more aggressive treatment strategies, such as HER2- directed therapies or chemotherapy. Here we discuss the results of the most important clinical trials enrolling DCIS patients in the adjuvant and in the preoperative setting; in addition, we report the chemoprevention studies utilizing ET which demonstrated a reduction of the risk of DCIS development. On balance, the choice to undertake or not an adjuvant ET, which is often burdened by adverse events that could impact on the quality of life of the patients and on their adherence to the therapy, should be discussed with the patient, taking into account that no survival advantage has been demonstrated so far.

Breast Cancer Statistics in Korea, 2018.

Breast cancer is the most common malignancy in Korean women, and its incidence continues to increase. The Korean Breast Cancer Society (KBCS) established a nationwide breast cancer database through its online enrollment program in 1996. This study aimed to analyze the clinical characteristics of breast cancer in Korea, and to assess the pattern of changes in breast cancer management in 2018. We analyzed the KBCS and Korea Central Cancer Registry (KCCR) databases in 2018. In 2018, 28,157 patients were newly diagnosed with breast cancer, of whom 4,510 had noninvasive breast cancer and 23,647 had invasive breast cancer. The age-standardized rate of breast cancer in 2018 was 79.0 per 100,000 women (65.6 invasive, 13.4 noninvasive). The median age of female patients diagnosed with breast cancer in 2018 was 52 years, and the incidence of breast cancer was the highest in the 40–49-years age group (9,432 patients, 33.6%). The proportion of patients with stage 0 and stage I breast cancer continued to increase, accounting for 63.8% of cases, and breast-conserving surgery was performed more often than mastectomy (66.2% vs. 33.0%). The most common subtypes of breast cancer were hormone receptor [HR]-positive and human epidermal growth factor receptor-2 (HER2)-negative types (65.9% of cases), while the HR-negative and HER2-positive types accounted for 9.2% of cases. According to the KCCR data, from 2014 to 2018, the 5-year relative survival rate of patients with breast cancer was 93.3%, which was 14.0% higher than that from 1993 to 1995 (79.3%). The clinical characteristics of breast cancer in Korea have been changing, and national databases can improve our understanding of the disease characteristics of Korean women. Therefore, updating the KBCS registry is important for the effective management of breast cancer in Korea.

Deep-inspiration breath hold radiotherapy in patients with left-sided breast cancer after partial mastectomy.

The purpose of this study was to compare the radiation dose to organs at risk for deep-inspiration breath hold (DIBH) and free-breathing (FB) radiotherapy in patients with lef-sided breast cancer undergoing adjuvant radiotherapy after partial mastectomy. Methods: One hundred patients with left-sided breast cancer underwent DIBH and FB planning computed tomography scans, and the 2 techniques were compared. Dose-volume histograms were analyzed for heart, left anterior descending coronary artery (LAD), and left lung. Results: Radiation dose to heart, LAD, and left lung was significantly lower for DIBH than for free breathing plans. The median mean heart dose for DIBH technique in comparison with FB was 1.21 Gy, and 3.22 Gy respectively; for LAD, 4.67 versus 24.71 Gy; and for left lung 8.32 Gy versus 9.99 Gy. Conclusion: DIBH is an effective technique to reduce cardiac and lung radiation exposure.

Effect of Breast Cancer Treatment on Dietary Vitamin Intake Levels.

Breast cancer is the most common tumor among women, representing the second cause of cancer deaths in women. Treatment with chemotherapy negatively interferes with nutritional status. The intake of vitamins before, during and after treatment in a pilot cohort of women with non-invasive breast cancer (type I, II) treated at the Valencian Institute of Oncology (IVO) is evaluated. A 3-day anthropometric and nutritional assessment was performed using the DIAL program. Nutritional intake is compared with the values of Estimated Average Requirements (EAR) and Dietary Reference Intake (DRI) provided by the United States Department of Agriculture (USDA) and the European Food Safety Authority (EFSA). There is an overall decrease in vitamin intake during treatment which worsens at the end of said treatment. The decrease is significant in the case of vitamins B2 (p = 0.006), B3 (p = 0.042), B5 (p = 0.001), and B8 (p = 0.021). The relative risk during and after treatment increases with respect to the reference timeframe, before treatment. Deficit risks are statistically significant in the case of vitamins B5 (p = 0.001), B8 (p = 0.001) and B12 (p = 0.001). Decreased vitamin intake during treatment suggests a negative change in the patients’ dietary behaviors during this time. Nutritional intervention and support may be beneficial to optimize overall dietary intake and maintain compliance with EAR and DRI for patients during a time in which adequate nutrition is important.

Diagnostic Accuracy of Cross-Polarization OCT and OCT-Elastography for Differentiation of Breast Cancer Subtypes: Comparative Study.

The possibility to assess molecular-biological and morphological features of particular breast cancer types can improve the precision of resection margin detection and enable accurate determining of the tumor aggressiveness, which is important for treatment selection. To enable reliable differentiation of breast-cancer subtypes and evaluation of resection margin, without performing conventional histological procedures, here we apply cross-polarization optical coherence tomography (CP-OCT) and compare it with a novel variant of compressional optical coherence elastography (C-OCE) in terms of the diagnostic accuracy (Ac) with histological verification. The study used 70 excised breast cancer specimens with different morphological structure and molecular status (Luminal A, Luminal B, Her2/Neo+, non-luminal and triple-negative cancer). Our first aim was to formulate convenient criteria of visual assessment of CP-OCT and C-OCE images intended (i) to differentiate tumorous and non-tumorous tissues and (ii) to enable more precise differentiation among different malignant states. We identified such criteria based on the presence of heterogeneities and characteristics of signal attenuation in CP-OCT images, as well as the presence of inclusions/mosaic structures combined with visually feasible assessment of several stiffness grades in C-OCE images. Secondly, we performed a blinded reader study of the Ac of C-OCE versus CP-OCT, for delineation of tumorous versus non-tumorous tissues followed by identification of breast cancer subtypes. For tumor detection, C-OCE showed higher specificity than CP-OCT (97.5% versus 93.3%) and higher Ac (96.0 versus 92.4%). For the first time, the Ac of C-OCE and CP-OCT were evaluated for differentiation between non-invasive and invasive breast cancer (90.4% and 82.5%, respectively). Furthermore, for invasive cancers, the difference between invasive but low-aggressive and highly-aggressive subtypes can be detected. For differentiation between non-tumorous tissue and low-aggressive breast-cancer subtypes, Ac was 95.7% for C-OCE and 88.1% for CP-OCT. For differentiation between non-tumorous tissue and highly-aggressive breast cancers, Ac was found to be 98.3% for C-OCE and 97.2% for CP-OCT. In all cases C-OCE showed better diagnostic parameters independently of the tumor type. These findings confirm the high potential of OCT-based examinations for rapid and accurate diagnostics during breast conservation surgery.

Innovative use of magnetic resonance imaging-guided focused ultrasound surgery for non-invasive breast cancer: a report of two cases

ObjectiveThis report describes the first clinical experience with magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) using the ExAblate 2100 system for non-invasive breast cancer.MethodsTwo women with non-invasive breast cancer underwent MRgFUS treatment. One week after the MRgFUS treatment, US-guided vacuum-assisted biopsy was performed for the ablated lesions at the same time as breast-conserving surgery.ResultsThe patients experienced good cosmetic outcomes and did not experience any severe adverse events, such as skin burns. Pathological examination of the surgical specimens revealed a few degenerated intraductal lesions around the breast biopsy markers.ConclusionPerforming MRgFUS with the new ExAblate 2100 system appears to be safe and feasible. The histopathological results revealed that adequate ultrasound energy in the appropriate location can induce tumor necrosis.

Extracellular vesicles from young women\u2019s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach

BackgroundExtracellular vesicles (EVs) are small membrane particles that contribute to cancer progression and metastases by transporting biologically significant proteins and nucleic acids. They may also serve as biomarkers of various disease states or important therapeutic targets. Breast cancer EVs have the potential to change the behavior of other cells in their microenvironment. However, the proteomic content of EVs isolated from young women’s breast cancer patients and the mechanisms underlying the influence of EVs on tumor cell behavior have not yet been reported.MethodsIn our current translational studies, we compared the proteomic content of EVs isolated from invasive breast cancer cell lines and plasma samples from young women’s breast cancer (YWBC) patients and age-matched healthy donors using mass spectrometry. We analyzed the functionality of EVs in two dimensional tumor cell invasion assays and the gene expression changes in tumor cells after incubation with EVs.ResultsWe found that treatment with EVs from both invasive breast cancer cell lines and plasma of YWBC patients altered the invasive properties of non-invasive breast cancer cells. Proteomics identified differences between EVs from YWBC patients and healthy donors that correlated with their altered function. Further, we identified gene expression changes in non-invasive breast cancer cells after treatment with EVs that implicate the Focal Adhesion Kinase (FAK) signaling pathway as a potential targetable pathway affected by breast cancer-derived EVs.ConclusionsOur results suggest that the proteome of EVs from breast cancer patients reflects their functionality in tumor motility assays and may help elucidate the role of EVs in breast cancer progression.

Discovery of novel DNA methylation biomarkers for non-invasive sporadic breast cancer detection in the Latino population.

Human diversity is one of the main pitfalls in the development of robust worldwide biomarkers in oncology. Epigenetic variability across human populations is associated with different genetic backgrounds, as well as variable lifestyles and environmental exposures, each of which should be investigated. To identify potential non-invasive biomarkers of sporadic breast cancer in the Uruguayan population, we studied genome-wide DNA methylation using Illumina methylation arrays in leukocytes of 22 women with sporadic breast cancer and 10 healthy women in a case-control study. We described a panel of 38 differentially methylated CpG positions that was able to cluster breast cancer patients (BCP) and controls, and that also recapitulated methylation differences in 12 primary breast tumors and their matched normal breast tissue. Moving forward, we simplified the detection method to improve its applicability in a clinical setting and used an independent well-characterized cohort of 80 leukocyte DNA samples from BCP and 80 healthy controls to validate methylation results at specific cancer-related genes. Our investigations identified methylation at CYFIP1 as a novel epigenetic biomarker candidate for sporadic breast cancer in the Uruguayan population. These results provide a proof-of-concept for the design of larger studies aimed at validating biomarker panels for the Latin American population.

Using Convolutional Neural Network with Cheat Sheet and Data Augmentation to Detect Breast Cancer in Mammograms.

The American Cancer Society expected to diagnose 276,480 new cases of invasive breast cancer in the USA and 48,530 new cases of noninvasive breast cancer among women in 2020. Early detection of breast cancer, followed by appropriate treatment, can reduce the risk of death from this disease. DL through CNN can assist imaging specialists in classifying the mammograms accurately. Accurate classification of mammograms using CNN needs a well-trained CNN by a large number of labeled mammograms. Unfortunately, a large number of labeled mammograms are not always available. In this study, a novel procedure to aid imaging specialists in detecting normal and abnormal mammograms has been proposed. The procedure supplied the designed CNN with a cheat sheet for some classical attributes extracted from the ROI and an extra number of labeled mammograms through data augmentation. The cheat sheet aided the CNN through encoding easy-to-recognize artificial patterns in the mammogram before passing it to the CNN, and the data augmentation supported the CNN with more labeled data points. Fifteen runs of 4 different modified datasets taken from the MIAS dataset were conducted and analyzed. The results showed that the cheat sheet, along with data augmentation, enhanced CNN's accuracy by at least 12.2% and enhanced the precision of the CNN by at least 2.2. The mean accuracy, sensitivity, and specificity obtained using the proposed procedure were 92.1, 91.4, and 96.8, respectively, while the average area under the ROC curve was 94.9.

Radiation Therapy in the Hispanic Breast Cancer Population: An Analysis of Patient Demographics and the Impact of Insurance Status on Rates of Breast Conserving Radiation Therapy.

Disparities in minority healthcare include lower rates of insurance coverage and increased morbidity and mortality from cancer. We sought to evaluate the demographics of our Hispanic breast cancer population and evaluate the impact of insurance status on rates of breast conserving radiation therapy (BCT) including whole breast radiation (WBRT) and accelerated partial breast irradiation (APBI) versus postmastectomy radiation therapy (PMRT). We performed a retrospective review of 120 women with invasive and non-invasive breast cancer receiving curative RT between the dates of January 2017 through June 2019. Women identifying as Hispanic and all women from Latin America were included. BCT included WBRT with 3D-conformal RT (3D-CRT) and APBI with either 1. 3D-CRT or 2. HDR 192Ir brachytherapy interstitial catheters or surface applicators. We defined insurance status as 1. Insured, 2. Medicaid and 3. Non-insured. Additional patient demographics including age, BMI, country of birth, and anatomical stage were reviewed. Multivariable logistic regression model was used to evaluate odds ratios for primary outcome of WBRT/APBI as a BCT event vs. PMRT. 70 Hispanic women were identified for analysis. Median age, insurance status and cancer stage are listed (Table 1). The median BMI was 29.7 (22.0, 45.3) and median age was 58.5 (33.0, 81.0). The median BMI was non-significant but slightly lower in PMRT group (29.7 vs. 30, p-value = 0.82). Multivariable model was constituted with variable: age, BMI, primary insurance, anatomic stage, and country/region of birth (USA, Caribbean, and South/Central America). There were 58 BCT events (49 WBRT and 9 APBI) which explains enough power to construction of multivariable model. In a multivariable model, the insured subjects had 17.5 times higher odds of opting for WBRT/APBI BCT [OR (95% CI) = 17.53 (1.69, 432.0)] compared to non-insured subjects which was statistically significant (p = 0.036). This association was significant [OR (95% CI) = 6.36 (1.44, 34.37), p = 0.019] in a single variable model with more than 6 times higher odds. All other associations in the multivariable model were not statistically significant. Hispanic women comprise the majority of breast cancer patients treated at our community hospital with 83% receiving BCT versus PMRT. Insured status was a significant predictor of BCT with the insured population having an almost 18-fold higher rate of receiving WBRT or APBI than the non- insured population (OR = 17.53). Although this is a single institution study and limited by a small PMRT sample size, this health care disparity warrants further investigation to better understand access to care and barriers to BCT in the Hispanic population.Tabled 1Abstract 2925; TableWBRT/APBI n = 58PMRT n = 12All n = 70Age59.553.558.5Insured35338Medicaid12315Non-insured11617Stage 010010Stage I27027Stage II181028Stage III325 Open table in a new tab

LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression.

Long intergenic non-protein coding RNA 885 (LINC00885) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by LINC00885 in non-invasive and invasive breast cancer models. We determined that LINC00885 induces premalignant phenotypic changes by increasing cell proliferation, motility, migration and altering 3D growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by LINC00885, which include bioprocesses related to TP53 signaling pathway and proliferative signatures such as activation of EREG, EGFR and FOXM1 pathways. LINC00885 silencing in breast cancer lines overexpressing this lncRNA leads to downregulation of proliferation related transcripts such as EREG, CMYC, CCND1 and to significant decrease in cell migration and motility. TCGA-BRCA data analyses show an association between high LINC00885 expression and worse overall survival in patients with primary invasive breast carcinomas (p = 0.024), suggesting that the pro-tumorigenic effects of LINC00885 overexpression persist post-invasion. We conclude that LINC00885 behaves as a positive regulator of cell growth both in normal and DCIS breast cells possibly operating as a ceRNA and representing a novel oncogenic lncRNA associated with early stage breast cancer progression.

Management of non-invasive tumours, benign tumours and breast cancer during the COVID-19 pandemic: recommendations based on a Latin American survey

IntroductionThe COVID-19 pandemic has changed health systems across the world, both in general hospitals and in oncology institutes or centres.For cancer specialists, particularly breast cancer (BC), the COVID-19 pandemic represents a combination of challenges since the hospital resources and staff have become more limited; this has obliged oncology specialists to seek a consensus and establish which patients with BC require more urgent attention and which patients can wait until there is a better control of this pandemic. The health system in Latin America has some special characteristics; in some of the countries, there are shortages which limit access to several specialities (surgery, clinical oncology and radiotherapy) in some regions.ObjectiveAfter a systematic review of the most recent literature regarding the management of BC during the COVID-19 pandemic, the main objective is to understand the position of the different Latin American Societies of Mastology in terms of available alternatives for the treatment of BC.MethodsAfter carrying out a comprehensive and exhaustive search of the most recent guides on the management of BC during the COVID-19 pandemic, the board members of the Latin American Federation of Mastology invited, via email, different specialists, all experts in BC care, to complete an anonymous survey online.The survey was distributed between 30 and 10 May 2020. The survey included 27 questions on four topics: demographic information, consultations, imaging and treatment of BC.The questionnaire was sent and then distributed to various health specialists including breast surgeons, clinical oncologists, radiation oncologists and radiologists via the Presidents of the different Latin American Societies of Mastology in 18 countries. The results are summarised as tallies based on the number of responses to each question.ResultsA total of 499 responses were received. The majority of the respondents were males (275 (55.11%)); 290 participants were over 45 years (58.11%).The questionnaire presented those surveyed with three possible answers (agree, disagree and neither agree nor disagree). The results reflect that there was consensus in the majority of situations presented. Only seven questions revealed disagreement among those responding. The results are presented as recommendations.ConclusionThe management of patients with BC presents unique challenges during the current world health situation produced by COVID-19 pandemic. Breast care specialists (surgical oncologists, breast care clinicians, clinical oncologists, radiation oncologists and radiologists) from 18 countries in Central and South America submitted through their responses and recommendations for the treatment of BC during the COVID-19 pandemic.

Diagnostic Value of Different Risk-Stratification Algorithms in Solid Breast Lesions

In the past few years, elastography has gained ground as a complementary method to ultrasonography in noninvasive breast cancer screening. Despite positive outcomes, there is a further need to refine the method, especially regarding BIRADS scores 3 and 4A, where the distinction between benignancy and malignancy is established. The aim of the present study was to evaluate the best risk-stratification system using both qualitative and semiquantitative elastographic methods for solid breast nodules. A total of 1405 solid nodules, described in 657 female patients, were examined in our endocrine unit between January 2018 and December 2019. The inclusion criterion for our retrospective study was the presence of any solid breast mass in women of all ages (mean, 40.85 ± SD 27.11), detected during ultrasound examination using a HITACHI PREIRUS machine (Hitachi Medical Corporation, Tokyo, Japan). The Breast Imaging Reporting and Data System (BIRADS)–US criteria were used in the assessment of each nodule by conventional US (gray-scale mode) and Doppler evaluation. The Ueno score and strain ratio were also measured for all the described lesions. We considered multiple algorithms for the risk reassessment of solid breast nodules: classical BIRADS–US, EFSUMB BIRADS, worst-case scenario BIRADS and BIRADS TM. There were 93 malignant nodules out of 1405. The diagnosis was based on histopathological results for all the malignant lesions. Benign lesions were diagnosed based on histopathological results, Tru-Cut biopsy, mammography and MRI. The Sensitivity (Se), Specificity (Sp), Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Accuracy (Acc) were obtained for all the proposed risk-stratification reporting systems: conventional BIRADS-US (Se, 74.23%; Sp, 63.95%; PPV, 13.53%; NPV, 97.79%; Acc, 65%); EFSUMB BIRADS (Se, 71.23%; Sp, 81.55%; PPV, 22.68%; NPV, 97.99%; Acc, 81%); worst-case scenario BIRADS (Se, 84.23%; Sp, 58.23%; PPV, 13.29%; NPV, 98.84%; Acc, 60%); BIRADS TM (Se, 81.23%; Sp, 75.84%; PPV, 20.35%; NPV, 98.81%; Acc, 77%). We found that the most efficient risk-stratification reporting system was the proposed one, BIRADS TM, which considers both upgrading and downgrading the conventional BIRADS-US, followed by the worst-case scenario BIRADS and EFSUMB BIRADS.