Early Breast Tumors Research Articles

Copy number alterations in metastatic and early breast tumours: prognostic and acquired biomarkers of resistance to CDK4/6 inhibitors

BackgroundCopy number alterations (CNA) are acquired during the evolution of cancers from their early stage to metastatic stage. This study aims at analysing the clinical value of the identified metastasis-associated CNAs both in metastatic breast cancers (mBCs) and early breast cancers (eBCs).MethodsSingle-nucleotide polymorphism (SNP)-array was performed on 926 biopsies from mBC patients, enrolled in SAFIR02-BREAST prospective trial. CNA profiles of eBCs from The Cancer Genome Atlas Breast Invasive Carcinoma (n = 770), Molecular Taxonomy of Breast Cancer International Consortium (n = 1620) and PACS04 trial (n = 243) cohorts were used as references for comparing mBCs and eBCs CNA profiles. Overall survival was the considered survival endpoint.ResultsAmong the twenty-one genes frequently altered in ER + /HER2− mBCs: focal amplification of TERT was associated with poor outcome in the ER + /HER2− mBC population. Among the ER + /HER2− mBCs patients for whom CDK4/6 inhibitors information before biopsies collection was available: we identified seven genes on post-treatment biopsies, including the cyclin-dependent kinase 4 (CDK4), which was amplified in 9.8% of the ER + /HER2− mBCs pretreated population, as compared to 1.5% in the ER + /HER2− mBCs unpretreated population (P = 2.82E-04) as well as the 3 eBC populations. CDK4 amplification was associated with poor outcome in the ER + /HER2− eBCs.ConclusionsThis study provides insights into the biology of mBCs and identifies clinically useful genomic features for future improvement of breast cancer patient management.

Comparative effectiveness of treatment approaches for early invasive breast cancer

BackgroundRandomized controlled trials (RCTs) suggested breast conserving therapy (BCT) and mastectomy have similar survival for early-stage breast cancer, whereas observational studies reported survival advantage for BCT. We aimed to address biases in observational studies to compare the effect of BCT and mastectomy on survival. MethodsWe emulated a target trial using institutional cancer registry. We included adult women diagnosed with early invasive first primary breast tumors ≤ 5 cm between July 2011 and December 2017. We used cloning, censoring, and weighting to estimate risk differences (RDs) and risk ratios (RRs) for all-cause mortality and recurrence or all-cause mortality between BCT and mastectomy (reference). ResultsOur study population comprised 534 observations with breast cancer. Median age was 56 years and 65 % were racial/ethnic minorities. The 8-year RD was 1.5 % (95 % confidence limits [CL]: −7.0 %, 9.8 %) and RR was 1.1 (95 % CL: 0.57, 2.2) for all-cause mortality. Results for recurrence or mortality were similar. ConclusionsOur results suggest that target trial emulation to mitigate selection and immortal-time biases in observational studies may generate estimates that are more compatible with RCTs when comparing the effects of BCT and mastectomy on survival. Studies with longer follow-up and more events are needed to confirm our findings.

Molecular profiling after short-term preoperative endocrine therapy to identify oestrogen receptor positive (ER+)/HER2+ early breast tumours with favourable prognosis.

560 Background: The impeded anti-proliferative response of Estrogen Receptor positive (ER+) HER2+ breast cancer (BC) to endocrine therapy (ET) has been considered negated by treatment with anti-HER2 therapies but residual disease after anti-HER2 therapy remains at risk of recurrence. Studying the molecular changes (MolC) of ER+HER2+ BC in response to ET will provide clinical insights to treatment options. Methods: POETIC was a phase III trial of post-menopausal patients with ER+ BC randomized 2:1 to 2-weeks of peri-operative aromatase inhibitors (POAI) vs control, followed by standard-of-care. Paired pre-treatment (B) and on-treatment (2wk) samples from 313 ER+HER2+ BC (213 POAI/100 controls) were gene expression profiled (BC 360 codeset; NanoString). Association of MolC with Early biological response to AI was assessed by residual Ki672wk (low ≤10%; high >10%) by T-test, multiple testing corrected by Benjamini & Hochberg (FDR); with time to recurrence (TTR) was estimated using multivariable Cox regression models adjusted for post-surgery clinicopathological variables and age as adjuvant treatment surrogate. Results: In POAI tumours, immunity-related signatures and mammary stemness were significantly upregulated in responders while proliferation, DNA-damage repair (DDR), TP53mutational status and ER-signaling were downregulated (FDR<0.05). Controls had exclusive downregulation of PDL1 and upregulation of hypoxia (FDR < 0.05). We previously identified 5 new molecular subgroups based on baseline gene expression (1- Immune high, ESR1 low; 2- ECM, ESR1 low, highest ERBB2; 3- DDR deficiency, 4- Endocrine signalling high and 5- Endocrine and PI3K/MAPK/RAS signalling high) which were associated with different response to AI and differential outcome. Endocrine-signalling, PI3K/MAPK/RAS signalling, tumour-immunity and chemokines were upregulated at a higher magnitude in AI sensitive subgroups (3 and 4) while the molecular subgroup with early resistance to AI and poorer outcome at baseline (2) did not show significant changes. Intrinsic subtype (IS) shifting was significantly more prevalent in treated (37%, 79/213) than in controls (14%, 14/100) (p <0.001). In POAI most Luminal B (LumB) shifted to Luminal A (LumA; 79%, 59/75), driven by a reduction in proliferation. LumA2wk was associated with better outcome compared to LumB2wk (HR 0.2; CI95% 0.06-0.72, p=0.01). IS2wk provides additional information predicting TTR, than ISB (AIC value = 217.2 vs 221.6). Conclusions: We provide a comprehensive picture on how ER+HER2+ BC gene expression profile changes in response to ET. Most LumB BC shift to LumA, being LumA2wk IS significantly associated with better outcome. There is a clinical utility of peri-operative ET for ER+HER2+ BC, guiding who would have good prognosis for adjuvant ET and who may need additional therapy. Clinical trial information: NCT02338310 .

Association of Gene Polymorphisms with Breast Cancer Risk in the Kazakh Population.

The research aim is analyzing and identify reliable genetic markers of breast cancer risk in the Kazakh population. The databases were analyzed with the selection of polymorphisms associated with the development of breast cancer and further genotypic study of a group of women with a confirmed diagnosis of breast adenocarcinoma (group No. 1) and a group of relatively healthy women (group No. 2). The research presents the results of a study on the frequency of certain single-nucleotide polymorphisms in patients with breast cancer in the Republic of Kazakhstan. The frequency of single-nucleotide polymorphisms rs4646, rs1065852, rs4244285, rs67376798, rs6504950, rs2229774, rs1800056, rs16942, rs4987047 is statistically significant compared to the control group of patients. These polymorphisms in the Kazakh population have a direct association with an increased risk of breast cancer in women and may be used as cancer indicators during the genetic screening of patients with a complicated family history. Single-nucleotide polymorphisms such as rs55886062, rs3918290, rs12721655, rs4987117, rs2229774, rs11203289, rs137852576, rs11571833, rs80359062 and rs11571746 were found in more than 40. Zero percent of patients with breast cancer may be used as markers for detecting patients at increased risk of breast malignancy in the Kazakh population without a history of poor family history. The usage of the data obtained in a set of state programs for early screening of patients will improve the rates of early breast tumor detection, form groups of patients with a high risk of disease development and improve the quality and expectancy of life.

The Clinicopathological Features and Prognostic Significance of HER2-Low in Early Breast Tumors Patients Prognostic Comparison of HER-Low and HER2-Negative Breast Cancer Stratified by Hormone Receptor Status

Introduction. There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations. Methods. We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records. Results. Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival ( p = 0.003 ) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival ( p < 0.001 ). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors ( p = 0.008 ). Conclusion. Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses.

Exploring the Relationship Between CD 166 Expression and Breast Imaging Reporting and Data System (BI-RADS) Scores in Breast Cancer Patients and Healthy Volunteers.

This research embarked on a crucial endeavor to clarify the connection between levels of CD166 expression and the established Breast Imaging Reporting and Data System (BI-RADS) grading system. Through a comprehensive exploration of this correlation, the objective was to ascertain if CD166 could function as an additional biomarker, enhancing the predictive effectiveness of the BI-RADS classification. This prospective observational study involved 81 women with histopathologically confirmed early breast tumors and 81 radiologically confirmed healthy breast volunteers. The BI-RADS scores of all the participants included in the study were recorded. Before starting treatment, serum, saliva, and urine samples were collected. The CD166 levels were quantified using an enzyme-linked immunosorbent assay. The study involved the analysis and comparison of the mean and standard deviations of CD166 expression in serum, saliva, and urine across various BI-RADS categories. Notably, statistically significant differentiation was found (p=0.00) across all samples spanning the spectrum of BI-RADS categories. A progressive rise in CD166 concentration coincides with the increasing gradient of the BI-RADS category, implying a possible link between CD166 and breast cancer progression and severity.

Differences in the Tumor Molecular and Microenvironmental Landscape between Early (Non-Metastatic) and De Novo Metastatic Primary Luminal Breast Tumors.

Background: The molecular mechanisms underlying the de novo metastasis of luminal breast cancer (dnMBC) remain largely unknown. Materials and Methods: Newly diagnosed dnMBC patients (grade 2/3, ER+, PR+/-, HER2-), with available core needle biopsy (CNB), collected from the primary tumor, were selected from our clinical-pathological database. Tumors from dnMBC patients were 1:1 pairwise matched (n = 32) to tumors from newly diagnosed patients who had no distant metastases at baseline (eBC group). RNA was extracted from 5 × 10 µm sections of FFPE CNBs. RNA sequencing was performed using the Illumina platform. Differentially expressed genes (DEG)s were assessed using EdgeR; deconvolution was performed using CIBERSORTx to assess immune cell fractions. A paired Wilcoxon test was used to compare dnMBC and eBC groups and corrected for the false discovery rate. Results: Many regulatory DEGs were significantly downregulated in dnMBC compared to eBC. Also, immune-related and hypoxia-related signatures were significantly upregulated. Paired Wilcoxon analysis showed that the CCL17 and neutrophils fraction were significantly upregulated, whereas the memory B-cell fraction was significantly downregulated in the dnMBC group. Conclusions: Primary luminal tumors of dnMBC patients display significant transcriptomic and immunological differences compared to comparable tumors from eBC patients.

Molecular intrinsic subtypes, genomic, and immune landscapes of BRCA-proficient but HRD-high ER-positive/HER2-negative early breast cancers

PurposeThe vast majority of research studies that have described the links between DNA damage repair or homologous recombination deficiency (HRD) score, and tumor biology, have concerned either triple negative breast cancers or cancers with mutation of BRCA 1/2. We hypothesized that ER + /HER2- early breast tumors without BRCA 1/2 mutation could have high HRD score and aimed to describe their genomic, transcriptomic, and immune landscapes.Patients and methodsIn this study, we reported BRCA 1/2 mutational status, HRD score, and mutational signature 3 (S3) expression, in all early breast cancer (eBC) subtypes from the TCGA database, with a particular focus in ER + /HER2-. In this subtype, bioinformatics analyses of tumor transcriptomic, immune profile, and mutational landscape were performed, according to HRD status. Overall survival (OS), progression free-interval (PFI), and variables associated with outcome were also evaluated.ResultsAmong the 928 tumor samples analyzed, 46 harbored BRCA 1/2 mutations, and 606 were ER + /HER2- (of which 24 were BRCA 1/2 mutated). We found a subset of BRCA-proficient ER + /HER2— eBC, with high HRD score. These tumors displayed significantly different immune, mutational, and tumor molecular signatures landscapes, compared to BRCA-mutated and BRCA-proficient HRD-low tumors. Outcome did not significantly differ between these 3 groups, but biological factors associated with survival are not the same across the 3 entities.ConclusionThis study highlights possible novel biological differences among ER + /HER2- breast cancer related to HRD status. Our results could have important implications for translational research and/or the design of future clinical trials, but require prospective clinical evaluation.

A compact ultrawideband slotted patch antenna for early stage breast tumor detection applications

AbstractThis paper presents a compact ultrawideband slotted patch antenna for early stage tumor detection applications using microwave breast imaging systems. In order to reduce any reflections between the antenna and breast, the antenna is designed and optimized inside a coupling medium with electrical properties similar to that of normal breast tissue as a coupling medium. The wideband performance of the antenna is obtained by adding a rectangular slit and L-shaped sleeves on the ground plane. While the added rectangular slit mainly improves the matching, the L-shaped sleeves improve both the matching and the bandwidth. The antenna operates from 0.9 to 9.6 GHz with a fractional bandwidth of ~165$\%$, providing a good penetration and resolution. In addition, the proposed antenna has a very compact size of 16 × 16 mm2. Furthermore, an antenna array consisting of 31 antennas is formed around a realistic breast phantom in the simulation environment to demonstrate the imaging of a spherical tumor with a diameter of 5 mm inside the breast. The results confirm that the proposed antenna can be used for early stage breast tumor detection purposes.

Automatic Breast Tumor Screening of Mammographic Images with Optimal Convolutional Neural Network

Mammography is a first-line imaging examination approach used for early breast tumor screening. Computational techniques based on deep-learning methods, such as convolutional neural network (CNN), are routinely used as classifiers for rapid automatic breast tumor screening in mammography examination. Classifying multiple feature maps on two-dimensional (2D) digital images, a multilayer CNN has multiple convolutional-pooling layers and fully connected networks, which can increase the screening accuracy and reduce the error rate. However, this multilayer architecture presents some limitations, such as high computational complexity, large-scale training dataset requirements, and poor suitability for real-time clinical applications. Hence, this study designs an optimal multilayer architecture for a CNN-based classifier for automatic breast tumor screening, consisting of three convolutional layers, two pooling layers, a flattening layer, and a classification layer. In the first convolutional layer, the proposed classifier performs the fractional-order convolutional process to enhance the image and remove unwanted noise for obtaining the desired object’s edges; in the second and third convolutional-pooling layers, two kernel convolutional and pooling operations are used to ensure the continuous enhancement and sharpening of the feature patterns for further extracting of the desired features at different scales and different levels. Moreover, there is a reduction of the dimensions of the feature patterns. In the classification layer, a multilayer network with an adaptive moment estimation algorithm is used to refine a classifier’s network parameters for mammography classification by separating tumor-free feature patterns from tumor feature patterns. Images can be selected from a curated breast imaging subset of a digital database for screening mammography (CBIS-DDSM), and K-fold cross-validations are performed. The experimental results indicate promising performance for automatic breast tumor screening in terms of recall (%), precision (%), accuracy (%), F1 score, and Youden’s index.

ASO Visual Abstract: Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT)

ASO Visual Abstract: Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT)

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT).

IntroductionIntraoperative radiotherapy (IORT) permits accurate delivery of radiation therapy directly to the tumor bed. We report local, regional, and distant recurrence data along with overall and breast cancer-specific survival for 1400 tumors treated with x-ray IORT.MethodsA total of 1367 patients with 1400 distinct tumors were enrolled in a registry trial. All received breast conservation surgery and low-energy 50 kV x-ray IORT. To be eligible for excision plus IORT as the only local treatment, histopathology had to confirm tumor size ≤30 mm, margins ≥2 mm, negative lymph nodes, and no extensive lymphovascular invasion. Patients who failed any parameters were referred for additional surgery and/or whole breast radiation therapy (WBRT).ResultsThere were 64 ipsilateral local recurrences, 60 were in the IORT only group, 7 axillary recurrences, and 7 distant recurrences. Forty-one local recurrences were within the same quadrant as the index cancer. Twenty-three were in different quadrants. With 62 months of median follow-up, the 5-year Kaplan–Meier probability of any event for all 1400 tumors was 5.27%. For 1175 patients who received IORT only, it was 5.98%. For favorable subtypes, it ranged from 2.41 to 4.31%. Multivariate analysis revealed that biologic subtype luminal A and the addition of WBRT significantly reduced the risk of local recurrence.ConclusionsThe local, regional, and distant recurrence rates observed were comparable to those reported in the literature for IORT but higher than those reported for standard forms of WBRT, hypofractionated treatment, or APBI. IORT benefits include convenience, decreased exposure to medical environments, and low complication rates.

Path to Clonal Theranostics in Luminal Breast Cancers.

Integrating tumor heterogeneity in the drug discovery process is a key challenge to tackle breast cancer resistance. Identifying protein targets for functionally distinct tumor clones is particularly important to tailor therapy to the heterogeneous tumor subpopulations and achieve clonal theranostics. For this purpose, we performed an unsupervised, label-free, spatially resolved shotgun proteomics guided by MALDI mass spectrometry imaging (MSI) on 124 selected tumor clonal areas from early luminal breast cancers, tumor stroma, and breast cancer metastases. 2868 proteins were identified. The main protein classes found in the clonal proteome dataset were enzymes, cytoskeletal proteins, membrane-traffic, translational or scaffold proteins, or transporters. As a comparison, gene-specific transcriptional regulators, chromatin related proteins or transmembrane signal receptor were more abundant in the TCGA dataset. Moreover, 26 mutated proteins have been identified. Similarly, expanding the search to alternative proteins databases retrieved 126 alternative proteins in the clonal proteome dataset. Most of these alternative proteins were coded mainly from non-coding RNA. To fully understand the molecular information brought by our approach and its relevance to drug target discovery, the clonal proteomic dataset was further compared to the TCGA breast cancer database and two transcriptomic panels, BC360 (nanoString®) and CDx (Foundation One®). We retrieved 139 pathways in the clonal proteome dataset. Only 55% of these pathways were also present in the TCGA dataset, 68% in BC360 and 50% in CDx. Seven of these pathways have been suggested as candidate for drug targeting, 22 have been associated with breast cancer in experimental or clinical reports, the remaining 19 pathways have been understudied in breast cancer. Among the anticancer drugs, 35 drugs matched uniquely with the clonal proteome dataset, with only 7 of them already approved in breast cancer. The number of target and drug interactions with non-anticancer drugs (such as agents targeting the cardiovascular system, metabolism, the musculoskeletal or the nervous systems) was higher in the clonal proteome dataset (540 interactions) compared to TCGA (83 interactions), BC360 (419 interactions), or CDx (172 interactions). Many of the protein targets identified and drugs screened were clinically relevant to breast cancer and are in clinical trials. Thus, we described the non-redundant knowledge brought by this clone-tailored approach compared to TCGA or transcriptomic panels, the targetable proteins identified in the clonal proteome dataset, and the potential of this approach for drug discovery and repurposing through drug interactions with antineoplastic agents and non-anticancer drugs.

Three-Dimensional H-Scan Ultrasound Imaging of Early Breast Cancer Response to Neoadjuvant Therapy in a Murine Model.

Three-dimensional (3D) H-scan is a new ultrasound (US) technique that images the relative size of acoustic scatterers. The goal of this research was to evaluate use of 3D H-scan US imaging for monitoring early breast cancer response to neoadjuvant therapy using a preclinical murine model of breast cancer. Preclinical studies were conducted using luciferase-positive breast cancer-bearing mice (n = 40). Anesthetized animals underwent US imaging at baseline before administration with an apoptosis-inducing drug or a saline control. Image data were acquired using a US scanner equipped with a volumetric transducer following either a shorter- or longer-term protocol. The later included bioluminescent imaging to quantify tumor cell viability. At termination, tumors were excised for ex vivo analysis. In vivo results showed that 3D H-scan US imaging is considerably more sensitive to tumor changes after apoptosis-inducing drug therapy as compared with traditional B-scan US. Although there was no difference at baseline (P > 0.99), H-scan US results from treated tumors exhibited progressive decreases in image intensity (up to 62.2% by day 3) that had a significant linear correlation with cancer cell nuclear size (R2 > 0.51, P < 0.001). Results were validated by histological data and a secondary longitudinal study with survival as the primary end point. Experimental results demonstrate that noninvasive 3D H-scan US imaging can detect an early breast tumor response to apoptosis-inducing drug therapy. Local in vivo H-scan US image intensity correlated with cancer cell nuclear size, which is one of the first observable changes of a cancer cell undergoing apoptosis and confirmed using histological techniques. Early imaging results seem to provide prognostic insight on longer-term tumor response. Overall, 3D H-scan US imaging is a promising technique that visualizes the entire tumor and detects breast cancer response at an early stage of therapy.

1331 An Observational Study Investigating the Role of Therapeutic Mammoplasty in Breast Tumours Greater Than 40mm

Abstract Aim For large breast tumours, therapeutic mammoplasty (TM) provides a breast-conserving approach to the conventional mastectomy. The prevalence and outcomes following TM in larger breast tumours is relatively unknown. This study aims to analyse the short-term outcomes and local recurrence rate following TM for breast tumours of varying sizes. Method Single-centre retrospective analysis of data from all patients undergoing a TM between June 2016-October 2019. Variables reviewed included age, imaging, tumour size, pre-operative histology, adjuvant chemotherapy and radiotherapy, post-operative pathology, post-operative complications, and recurrence rates. Results 192 patients undergoing a TM procedure were included, 126 (66%) patients had tumours &amp;lt;40mm and 66 (34%) patients had tumours &amp;gt;40mm. The average age of participants was 61 years with a mean follow-up of 31 months. The mean size of tumours &amp;gt;40mm was 56.8mm, of these patients 15% had positive margins, 2 (3%) patients required a further mastectomy and 8 (12%) underwent margin re-excisions. In lesions &amp;gt;40mm there were six episodes (9%) of T-junction delayed wound healing with two requiring surgical management, two episodes (3%) of wound infections requiring antibiotics and four episodes (6%) of seroma with one requiring surgery for an infected seroma. Two patients were found to have metastatic disease and no patients were found to have local recurrence at the most recent follow-up. Conclusions Our study demonstrated TM offers a surgical option with suitable cosmetic and oncological outcomes for women with early breast tumours above 40mm. These results warrant further study into the long-term outcomes for patients undergoing TM with tumours &amp;gt;40mm.

CD1a- and CD83-positive dendritic cells as prognostic markers of metastasis development in early breast cancer patients.

Dendritic cells (DCs) are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response in different types of cancer. However, the prognostic significance of the accumulation of these cells in human early breast tumors is not totally clear. The aim of this study is to evaluate the prognostic relevance of CD1a( +) and CD83( +) dendritic cells in early breast cancer patients. We conducted immunohistochemical assays to determine the number of stromal CD1a( +) and CD83( +) DCs in primary tumors from early invasive ductal breast cancer patients, and analyzed their association with clinico-pathological characteristics. Patients with high CD1a( +) DC number had lower risk of bone metastatic occurrence, as well as, longer disease-free survival (DFS), bone metastasis-free survival (BMFS) and overall survival (OS). Moreover, CD1a( +) DC number was an independent prognostic factor for BMFS and OS. In contrast, we found that patients with high number of CD83( +) DCs had lower risk of mix (bone and visceral)-metastatic occurrence. Likewise, these patients presented better prognosis with longer DFS, mix-MFS and OS. Furthermore, CD83( +) DC number was an independent prognostic factor for DFS and OS. The quantification of the stromal infiltration of DCs expressing CD1a or CD83 in early invasive breast cancer patients serves to indicate the prognostic risk of developing metastasis in a specific site.

Non Monte Carlo Method for Intrinsic Investigation of the Potential Use of Modified Uniformly Redundant Arrays (Muras) Coded Apertures for Early Breast Tumor Imaging

This is a continuous investigation of a possible application of Coded Aperture (CA) for breast tumor imaging. This paper describes a novel non-Monte Carlo method that based on a simple attractive approach called Binary Mask Shift.

Precise detection of early breast tumor using a novel EEMD-based feature extraction approach by UWB microwave.

The accurate detection of early breast cancer is of great significance to each patient. In recent years, breast cancer non-invasive detection technology based on Ultra-Wideband (UWB) microwave has been proposed and developed extensively, which is complementary to the existing methods. In this paper, a novel approach is proposed for tumor existence detection based on feature extraction algorithm. Firstly, the breast features are obtained by Ensemble Empirical Mode Decomposition (EEMD) and valid correlation Intrinsic Mode Function (IMF) selection. Secondly, raw feature datasets are constructed and then simplified by Principal Component Analysis (PCA) or Recursive Feature Elimination (RFE). Finally, the detection is realized by Support Vector Machines (SVM). The influence of different kernel functions and feature selection methods on detection results is compared. In this study, 11,232 sets of backscatter signals from simulation results of four different categories' breast models are utilized. And feature dataset is constructed by 24 specific features from each signal's four valid components. The results demonstrate that the proposed method can extract representative features and detect the early breast cancer effectively with the accuracy of 84.8%.

Abstract PS6-61: Survivin immunoexpression: An independent prognostic marker of recurrence in early-stage breast cancer

Abstract Survivin is a small protein member of the inhibitor of apoptosis protein family. Its expression occurs in G2/M phase of cell cycle, acting inhibiting apoptosis blocking caspases cascade directly or indirectly, and also controlling cell division. Survivin was found to be overexpressed in breast cancer, and its expression have been associated mostly with poor outcome. The aim of this case-control study was to evaluate the prognostic value of Survivin immunoexpression in early stage (pT1pN0 or pT2pN0) breast cancer. The study was conducted collecting data from 170 women with invasive breast carcinoma. The case group (n=57) and control group (n=113) consisted of patients with and without tumor recurrence, respectively. Immunohistochemical Tissue Microarray analyses were conducted to detect Survivin expression. In addition, molecular classification was done based on immunohistochemistry, and classic clinical and histological breast cancer variables were collected. The findings were submitted to the chi-square test and Fisher’s exact test, followed by multivariate analysis with multinomial logistic regression. The level of statistical significance was set at 5% (p&amp;lt;0.05). Median follow-up time was 6 years, ranging from 4 to 13 years. In the univariate analysis, patients with recurrence presented a higher histologic grade (p=0.005), percentage of tumor cells expressing survivin (p=0.006) and stronger immunostaining for this protein (p=0.021). In the multivariate analysis, stronger immunostaining for survivin (OR 1.850; p=0.023) and greater percentage of survivin expression (OR 2.290; p=0.016) persisted independently associated which higher rates of recurrence. Higher immunoexpression of survivin was independently associated with recurrence in early stage invasive breast tumors. Multinomial logistic regression model. In the first model, variables with p &amp;lt;0.200 were used in order to highlight the first order factors independently associated with disease-free survival. In the second model, variables with a significant association in model 1 were excluded in order to highlight second order factors independently associated with disease-free survival. In the third model, there were no factors independently associated with disease-free survival. Table 1 - Clinical-pathological characterization of the 170 cases of early stage breast cancer patients with and without recurrence.RecurrenceTotalNoYespAge≤ 55 years8658280,78650,6%51,3%49,1%&amp;gt; 55 years84552949,4%48,7%50,9%Histological subtypeDuctal158104540,24492,9%92,0%94,7%Lobular5502,9%4,4%,0%Others7434,1%3,5%5,3%StagespT1a7520,9024,1%4,4%3,5%pT1b2113812,4%11,5%14,0%pT1c65452038,2%39,8%35,1%pT277502745,3%44,2%47,4%Histological gradeI332850,00519,4%24,8%8,8%II75492644,1%43,4%45,6%III41192224,1%16,8%38,6%Ignored2117412,4%15,1%7,0%Breast surgeryMastectomy8557281,00050,0%50,4%49,1%Conservative85562950,0%49,6%50,9%Sentinel lymph node biopsyNo3220120,35318,82%17,7%18,2%Yes137934481,5%82,3%80,0%Ignored1010,6%0,0%1,8%ChemotherapyNo5135160,69730,0%31,0%28,1%Yes119784170,0%69,0%71,9%TrastuzumabNo156105510,76192,3%92,9%91,1%Yes13857,7%7,1%8,9%Hormone therapyNo2918110,58117,1%15,9%19,3%Yes141954682,9%84,1%80,7% Table 2 - Patterns of Survivin expression in tumors of patients with breast cancer with and without recurrence.RecurrenceTotal**NoYespSubcellular localizationAbsent4220,9422,7%2,1%3,8%Cytoplasmic89573260,1%60,0%60,4%Nuclear2315815,5%15,8%15,1%Cytoplasmic and Nuclear32211121,6%22,1%20,8%IntensityAbsent4220,0212,7%2,1%3,8%Weak7353*2049,3%55,8%37,7%Moderate62382441,9%40,0%45,3%Strong927*6,1%2,1%13,2%Percentage of expression≤ 50%10977320,00673,6%81,1%60,4%&amp;gt; 50%39182126,4%18,9%39,6%*p&amp;lt;0,05** 22 patients (12,9%) of sample loss in tissue microarray. Table 3 - Cox survival regression model of patients diagnosed and treated for invasive breast carcinoma.p-ValorAdjusted ORModel 1Histological grade*0,0072,108Survivin - intensity*0,0231,850Survivin - percentage of expression0,1001,876Breast cancer subtype classified by immunohistochemistry0,2631,126Model 2Survivin - percentage of expression*0,0162,290Breast cancer subtype classified by immunohistochemistry0,0931,170Model 3Breast cancer subtype classified by immunohistochemistry0,2411,107 Citation Format: Heloisa OM Belchior, Victor P Andrade, Marcos VA Lima, Maria do PSS Cunha, Monique BC Lemos, Paulo GB Silva, Isabelle JL Silva-Fernandes. Survivin immunoexpression: An independent prognostic marker of recurrence in early-stage breast cancer [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 PS6-61.

Abstract PS15-11: Intraoperative radiation therapy (IORT) for1200 early breast tumors

Abstract Introduction: Two prospective randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy (IORT) to be a safe alternative with a low-risk of local recurrence compared to whole breast radiation therapy following breast conserving surgery for selected low-risk patients. We report the first 1200 tumors treated with this modality at our facility.Methods: 1200 distinct breast cancers in 1169 patients (31 bilateral) were treated with breast conserving surgery and X-ray IORT, using the Xoft Accent System from June 2010 to November 2018. Patients were enrolled in an IORT registry trial and data were collected at 1 week, 1 month, 6 months, 1 year, and yearly thereafter. The primary endpoint was local recurrence.Results: To date, there have been 61 events in 54 patients: 50 ipsilateral local recurrences (14 DCIS and 36 invasive), 7 regional nodal recurrences and 4 distant recurrences. Of local recurrences, 9 were within the IORT field, 21 outside of the IORT field but within the same quadrant as the index cancer, and 20 were new cancers in different quadrants. There has been no breast cancer related deaths and 27 non-breast cancer deaths. Currently, with a median follow-up of 52 months, Kaplan Meier analysis projects 5.2 % local recurrence rate at 5 years. In the table below, the five-year probability of local recurrence is analyzed by quadrant and/or type of recurrence (all recurrences or just invasive). Using the 2017, ASTRO Categories, 520 patients (43%) were suitable for IORT, 415 (35%) were cautionary, and 265 (22%) were unsuitable for IORT after final histopathology was evaluated.Conclusion: IORT is profoundly convenient. When used as the only adjuvant breast irradiation, it eliminates approximately 15-35 outpatient visits. This has become increasingly important during the current COVID-19 pandemic. In the group of patients described here, more that 100,000 patient-hours were saved. The local, regional, and distant recurrence rates observed in this trial were slightly higher than those of the prospective randomized TARGIT-A and ELIOT Trials. This may be explained by 22% of our patients being considered unsuitable for IORT by ASTRO Criteria. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of X-ray IORT in women with low-risk breast cancer. Citation Format: Melinda Epstein, Melvin Silverstein, Peter Chen, Kevin Lin, Brian Kim, Sadia Khan, Lincoln Snyder, Lisa E. Guerra, Colleen Coleman. Intraoperative radiation therapy (IORT) for1200 early breast tumors [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 PS15-11.