Invasive Ductal Carcinoma Lesions Research Articles

Sonographic and clinicopathologic features of metaplastic breast carcinoma and infiltrating ductal carcinoma: a comparative single-center cohort study.

The rarity of metaplastic breast carcinoma (MBC) has resulted in limited sonographic data. Given the inferior prognosis of MBC compared to invasive ductal carcinoma (IDC), accurate preoperative differentiation between the two is imperative for effective treatment planning and prognostic prediction. The objective of this study was to assess the diagnostic accuracy of MBC and differentiate it from IDC by analyzing sonographic and clinicopathologic features. In this retrospective cohort study, 197 women comprising 200 IDC lesions were enrolled between January 2012 and December 2021 and 20 women comprising 20 pure MBC lesions were enrolled between January 2019 and December 2019. A comparison was made between the sonographic and clinicopathologic characteristics of MBC and IDC. The results indicated that patients with MBC had a higher proportion of tumor grade 3 (95.0% vs. 32.5%; P<0.001), high Ki-67 expression (100.0% vs. 75.0%; P<0.001), and the triple-negative subtype (90.0% vs. 13.0%; P<0.001) as compared to those with IDC. On ultrasound (US) findings, MBC lesions tended to have a larger size (≥5 cm: 45.0% vs. 1.5%; P<0.001), regular shape (45.0% vs. 1.5%, P<0.001), circumscribed margin (40.0% vs. 0.5%, P<0.001), a complex cystic and solid echo pattern (50.0% vs. 3.5%; P<0.001), and posterior acoustic enhancement (95.0% vs. 14.5%; P<0.001). Additionally, MBC was more likely to be misinterpreted as a benign lesion by sonographers than was IDC (30.0% vs. 4.5%; P<0.001). Multilayer perceptron analysis revealed posterior acoustic enhancement, circumscribed margins, and size as distinguishing factors between these two tumor types. The estimated rates of local recurrence, distant metastasis, and 5-year overall survival in 19 cases with MBC were found to be 10.5%, 31.6%, and 65.0%, respectively. MBC typically presents as a large breast mass with more benign US features in older women, findings which may facilitate its accurate diagnosis and differentiation from other breast masses.

Abstract P2-20-07: Immunotherapy becomes a treatment option in cryoablated Luminal A breast cancers

Abstract Background: Most breast cancers are not inherently immunogenic, and as a result are difficult to treat with immunotherapy. However, recent research has shown that triple-negative breast cancer (TNBC) and HER-2 positive (HER2) breast cancers can stimulate some level of an immune response. In contrast, the most common form of breast cancer, the luminal A (hormone receptor-positive (HR+)/HER-2 negative), has shown low involvement of tumor-infiltrating lymphocytes (TILs) and low expression of immune checkpoint inhibitors specifically programmed death-ligand-1 (PD-L1). Cryoablation, the destruction of cells using ultra-low temperatures, has been used as a primary treatment method for benign breast tumors and is in clinical trials to evaluate its use for invasive breast cancer. A secondary effect of cryoablation is the release of cellular proteins that can function as neoantigens and are in their native folded state We hypothesize that release of these native neoantigens might trigger an immune response capable of preventing/reducing metastasis and local relapse. In this pilot study, we evaluated biopsy material, cryoablated specimens and sentinel lymph nodes (SLN) from patients enrolled in the ACOSOG Z1072 trial at Lankenau Medical Center (LMC) [N=18] with cancers &amp;lt; 2 cm. Responses were compared to patients treated with surgical resection. Methods: After obtaining IRB approval for retrospective analyses of specimens from the ACOSOG Z1072 trial, these samples were evaluated with immunohistochemistry (IHC) using commercially available antibodies and standard techniques to determine changes in CD4, CD8, CD20, CD21, CD1c levels, as well as the immune checkpoint regulators PD-1, PD-L1 and CTLA-4, and the immune modulator IDO1. Patient samples included biopsy, surgical material, and SLN collected from the patients and were compared with patients of similar age, tumor characteristics and time to surgery. Per the ACOSOG trial protocol, tumors had to be surgically removed within 28 days of cryoablation, but the exact time was left to the surgeon’s discretion. Participating surgeons at LMC preferred to remove tumors on average 24.7 days after ablation resulting in an average time from diagnosis to surgical removal of 43.3 days. Results: Cryoablation of the tumors resulted in coagulative necrosis presenting as a gelatinous mass surrounded by a fibrous capsule. The ACOSOG trial demonstrated effective cryoablation-induced destruction of ER+ invasive ductal carcinoma lesions in 92% of patients (N=86). On IHC staining of the cryoablated samples, more CD8+ lymphocytes were identified compared to CD4+, which was consistent with pattern among non-cryoablated tumors, albeit to a lesser degree. Though no difference in percentage of PD-1 positive cells were observed between treatment modalities, positive cells in cryoablated tumors had mostly moderate-to-strong staining. We observed a 20% increase in cells positive for PD-L1 after cryoablation with predominantly strong staining. Though IDO1 had fewer positive cells in the tumor mass, the expression in SLN was higher with nearly all cells exhibiting strong staining. Compared to the patients who were treated with surgery alone, the SLNs of cryo patients had higher levels of CD20+ B cells as well as CD21+ follicular dendritic cells. CTLA-4 was seen sporadically, but with a slight preference for the surgery patients. Conclusion: We show that cryoablation of breast cancer lesions in vivo can induce an immune response in HR+ tumors, turning an immunogenically cold tumor into an immunogenically hot, tumor potentially responsive to check-point inhibitors and immune modulators. Possibly providing less toxic treatment options for elderly patients and/or patients with comorbidities All local cryo patients in the clinical trial are currently disease-free (F/U 5 - 13years), while 1 surgical patient is alive with late recurrence (11 years post-surgery). Citation Format: Zachary Aukers, Jonah Klein, Vincent Ciocca, Vlasta Zemba-Palko, Jennifer Sabol, Robin Ciocca, Laura Mandik-Nayak, Ned Carp, Margaretha Wallon. Immunotherapy becomes a treatment option in cryoablated Luminal A breast cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-20-07.

Abstract P2-21-03: Unique Collagen Peptide Signatures between Ductal Carcinoma in Situ and Invasive Breast Cancer by Mass Spectrometry Tissue Imaging

Abstract Ductal carcinoma in situ (DCIS) is characterized by inter-tumor heterogeneity that poses a therapeutic challenge due to its unpredictable recurrence and progression to invasive breast cancer (IBC). Recent publications have implicated the crucial role of the tumor microenvironment particularly stromal differences between DCIS patients who progress to IBC (progressors) and those that do not (non-progressors). However, spatial regulation of the collagen proteome has yet to be investigated in the context of disease progression in DCIS. In this study, we hypothesized that the collagen proteome was significantly altered between DCIS and IBC and that differentiating collagen peptide signatures could be related to clinical outcomes. Our initial studies investigated collagen peptide signatures in lumpectomies (n=13) annotated as DCIS, DCIS and invasive ductal carcinoma (IDC), or IDC only. We leveraged our previously published method for spatial imaging of collagen proteomics on tissue to report collagen types and collagen post-translational modifications including 40 other extracellular matrix (ECM) proteins involved in the regulation of collagen fibers. Over 1000 peaks were found to be linked to annotated pathologies or adjacent regions. Initial comparison of DCIS to IDC lesions demonstrated 63 differentially expressed peaks between these regions by unpaired, two-tailed t-test (p&amp;lt; 0.001). Image segmentation of the 315,541 pixels demonstrated 16 high-level hierarchical groups designating unique spatially localized ECM proteomic groups. Notably, these groups overlaid with histopathological features and pathological annotations. Next, we investigated collagen peptide signatures in a subset of DCIS samples from the Resource of Archival Breast Tissue (RAHBT) (n=37). Samples were histologically diverse within the tissue microarrays, with cribriform, micropapillary, papillary, solid, and comedo necrosis architectural patterns. In our preliminary analysis, we found two peptide peaks that could distinguish the solid subtype (n=22) from comedo necrosis (n=4) and one peak that could discriminate between the cribriform (n=8) and solid subtype (n=22) by area under the receiver operating curve (AUROC)≥0.75 and Wilson/Brown t-test (p&amp;lt; 0.05). Evaluated per clinical outcome, four ECM peptides showed significantly different peak intensities in progressors with IBC recurrence (n=7) compared to non-progressors (n=26) (AUROC≥0.75; Wilson/Brown t-test p&amp;lt; 0.05). One peptide had significantly different peak intensities between progressors with contralateral IBC recurrence and DCIS recurrence (n=5) and non-progressors (n=26) (AUROC≥0.75; Wilson/Brown t-test p&amp;lt; 0.05). Overall, the data suggest that unique collagen signatures in DCIS could be useful for understanding recurrence and progression to IBC. Further investigation of the spatial distribution of the collagen proteome within DCIS pathologies and relative to clinical outcome is warranted. Citation Format: Taylor S. Hulahan, Elizabeth N. Wallace, Siri H. Strand, Graham A. Colditz, E Shelley Hwang, Robert West, Laura Spruill, Jeffrey Marks, Richard R. Drake, Peggi M. Angel. Unique Collagen Peptide Signatures between Ductal Carcinoma in Situ and Invasive Breast Cancer by Mass Spectrometry Tissue Imaging [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-21-03.

Investigating the expression of cytokeratin 5/6 in benign and malignant breast lesions

Introduction: Breast cancer (BC) is the most common cancer in women, which is the second most common malignancy in terms of mortality and prevalence after lung cancer. BC is a group of very diverse diseases that can be detected at a molecular, histopathological and clinical level. Objectives: The aim of the present study was to evaluate the expression of CK5/6 and its relationship to some of the factors affecting prognosis, such as tumor grade, lymph node involvement. Patients and Methods: In this cross-sectional study with descriptive and analytical aspects, 40 malignant and 20 benign tumors were collected in 2020 from the archives of the pathology department of two educational hospitals in the city of Ahvaz. The demographic and clinical characteristics of each specimen, including age, patient, lymphovascular and perineural invasion, lymph node involvement, tumor grade and tumor type were extracted from the patients’ record. Then the expression of CK5/6 intensity staining was examined by immunohistochemistry. Results: All benign breast lesions had positive expression for CK5/6 and staining intensity between six and nine. In the malignant group, 33 samples showed negative expression of CK5/6 and only seven samples (17.5%) showed positive expression with a low-staining index. A positive expression with a low-staining index. All seven positive specimens were invasive ductal carcinoma (IDC) lesions with staining index 2, 4, and 6. Additionally, none of the ductal carcinoma in situ (DCIS) specimens which immunostained were positive for CK5/6. In the present study, all IDCs with weak expression of CK5/6 were grade III. No statistically significant relationship was observed between perineural and lymphovascular invasion and lymph node involvement with the intensity of CK5/6 expression. Conclusion: Our study showed that cytokeratin immunohistochemical intensity is able to distinguish benign lesions from malignant IDC and DCIS lesions and accordingly in determining of tumor grade after weak staining in high-grade IDC, which may be due to squamous metaplasia in these tumors; however, more extensive research with a larger sample size are required to assess its effect in lymphovascular and perineural invasion and also lymph node involvement.

Abstract P4-04-05: Development of unique immune responses triggered by cryoablation of breast cancers

Abstract Background: Breast cancers are traditionally viewed as immunologically silent. However, recent research has demonstrated that the triple-negative breast cancer (TNBC) and HER-2 positive (HER2) are capable of stimulating the immune system. In contrast, the most commonly diagnosed subtype, the luminal A (hormone receptor positive (HR+)/HER-2 negative), is associated with a lower degree of tumor infiltrating lymphocytes (TILs) and low expression level of immune checkpoint regulators such as programmed death-ligand-1 (PD-L1). Cryoablation, the destruction of cells by ultra-low temperatures, has been used to treat benign breast disease and clinical trials have been conducted to determine its utility for invasive breast cancers. The primary endpoint has been the rate of complete tumor ablation with no assessment of immunological responses. We hypothesized that neoantigens released during cryoablation might be sufficient to trigger immune responses that could aid in the prevention/reduction of metastatic spread and relapse of breast cancers.In this pilot study we evaluated biopsy material, cryoablated specimens and sentinel lymph nodes (SLN) from patients enrolled in the ACOSOG Z1072 trial at Lankenau Medical Center (LMC) [N=18] with cancers &amp;lt; 2 cm. Responses were compared to patients treated with surgical resection.Methods: After obtaining IRB approval for retrospective analyses of specimens from the ACOSOG Z1072 trial, immunohistochemical staining of archival specimens was performed. An on-going biomarker study protocol was amended to include immune markers and used to select control patients of similar age and tumor characteristics. Per trial protocol, tumors had to be be surgically removed within 28 days of cryoablation, but the exact time was left to the surgeons discretion. Participating surgeons at LMC preferred to remove tumors on average 24.7 days after ablation resulting in an average time from diagnosis to surgical removal of 43.3 days (range 25- 56 days). Although most breast surgeries are performed within two weeks of diagnosis; some patients defer their surgery for personal reasons. This allowed us to identify patients (N=26) with a comparable average time from diagnosis to surgery of 37 days (range 21 - 66 days). Sections were stained for CD4, CD8, CD20, CD21, and CD1c to assess possible changes in immune repertoire due to cryoablation. We also evaluated presence of immune check-point regulators such as PD-L1 and CTLA-4 in biopsy, surgical material and SLN together with the immune modulator IDO1 using commercially available antibodies and standard techniques. Results: Cryoablation transformed tumors in patients into a gelatinous mass surrounded by a fibrotic capsule. The ACOSOG trial demonstrated an effective cryoablation-induced destruction of ER+ invasive ductal carcinoma lesions in 92% of patients (N=86). Sections from cryoablation patients displayed a necrotic core and infiltrating lymphocytes in the microenvironment. These masses had a slightly higher presence of CD8+ lymphocytes compared to CD4+. The inverse relation was observed in non-cryoblated specimens. SLNs from cryoablated patients had an elevated presence of CD20+ B cells compared to patients treated by surgery. Follicular dendritic cells (CD21+) were also present at higher numbers in SLNs from cryoablated patients. We detected positive staining for both PD-L1 and IDO1 among surgical and cryoablated patients. Sporadic presence of CTLA-4 was identified with a slight preference for cryoabalted patients. Conclusion: Cryoablation of breast cancer lesions can induce immune responses in vivo with possible anti-tumor activity in immunologically silent tumors such as HR+ breast cancers. All local cryo patients in the clinical trial are currently disease-free (F/U 5 - 13years), while 1 surgical patient is alive with late recurrence (11 years post-surgery). Citation Format: Margaretha Wallon, Jonah D Klein, Zachary Aukers, Nolan Metz, Vibha Ahudja, Laura Mandik-Nayak, Vincenzo Ciocca, Vlasta Zemba-Palko, Robin M Ciocca, Jennifer L Sabol, Ned Z Carp. Development of unique immune responses triggered by cryoablation of breast cancers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-04-05.

Tumor-Derived Matrix Metalloproteinase-13 (MMP-13) Expression in Benign and Malignant Breast Lesions.

Introduction:Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC). Materials and Method:We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed. Results:MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells. Conclusion:This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.

Hybrid Medical Data Mining Model for Identifying Tumor Severity in Breast Cancer Diagnosis

Purpose: This study proposes a methodology for detecting tumor severity using data mining of databases relating to breast imaging modalities. In doing so, it proposes creating a software application that can serve as an efficient decision-making support system for medical practitioners, especially those in areas where there is a shortage of modern medical diagnostic devices or specialized practitioners, such as in developing countries.Method: we investigated the data of approximately 3754 screened women by using “BI-RADS” categories as a quality assessment tool to screening, measure, and identify the size and location of lesions, determine the number of lymph nodes, collect biopsy samples, determine final diagnoses, prognoses, and age which were all available from the screening registry. Result: The application of each algorithm on BI-RADS values 4 and 5 for Invasive Ductal Carcinoma lesions was assessed, and the following accuracy was acquired: CART: 84.71%. In order to get the best result, four optimum clusters based on tumor size were applied to constructing simple rules with significant confidence. Conclusion: This study presents a hybrid approach - a combination of k-means with GRI and CART decision tree - to better assess breast cancer data sets.

Fine Needle Aspiration Cytology Findings of Breast Lesions in Female Patients Presenting With Palpable Breast Lumps at Makerere University College of Health Sciences, Kampala-Uganda

Background: Palpable breast lumps are a common manifestation encountered by physicians during clinical practice. The use of fine-needle aspiration cytology (FNAC) method has proven to be quick, simple and cost-effective in the evaluation of these lumps for benign, atypical and malignant changes. This study aims to determine the type of breast lesions diagnosed by FNAC and to determine the age-wise distribution for such lesions. Methodology: A prospective study consisting of 291 females presenting with palpable breast lesions was carried out at Makerere College of Health Sciences (MakCHS) pathology laboratory from January 2019 to May 2019. FNAC results were grouped into tier five reporting categories as C1, C2, C3, C4 &amp; C5 in accordance to the International Academy of Cytology (IAC). Results: Out of the 291 cases examined, 14 (4.8%) were insufficient (C1), 192 (66%) were benign (C2), 9 (3.0%) were atypical (C3), 15 (5.2%) were suspicious of malignancy (C4) &amp; 61 (21%) were malignant (C5). In the benign category, lesions of fibroadenoma were the most commonly diagnosed constituting 110/192 (57.3%) whereas under the malignant category lesions of invasive ductal carcinoma were the most commonly diagnosed constituting 27/61(44.3%). The peak age group for benign lesions was 21-30 years whereas the peak age group for malignant lesions was 41-50 years. Conclusion: Fine-needle aspiration cytology (FNAC) was found to be an effective diagnostic tool in the categorization of palpable breast lumps into benign, malignant, atypical, suspicious and inadequate categories.

Assessment of Additional MRI-Detected Breast Lesions Using the Quantitative Analysis of Contrast-Enhanced Ultrasound Scans and Its Comparability with Dynamic Contrast-Enhanced MRI Findings of the Breast.

PurposeTo assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) for additional MR-detected enhancing lesions and to determine whether or not kinetic pattern results comparable to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast can be obtained using the quantitative analysis of CEUS.Materials and MethodsIn this single-center prospective study, a total of 71 additional MR-detected breast lesions were included. CEUS examination was performed, and lesions were categorized according to the Breast Imaging-Reporting and Data System (BI-RADS). The sensitivity, specificity, and diagnostic accuracy of CEUS were calculated by comparing the BI-RADS category to the final pathology results. The degree of agreement between CEUS and DCE-MRI kinetic patterns was evaluated using weighted kappa.ResultsOn CEUS, 46 lesions were assigned as BI-RADS category 4B, 4C, or 5, while 25 lesions category 3 or 4A. The diagnostic performance of CEUS for enhancing lesions on DCE-MRI was excellent, with 84.9% sensitivity, 94.4% specificity, and 97.8% positive predictive value. A total of 57/71 (80%) lesions had correlating kinetic patterns and showed good agreement (weighted kappa = 0.66) between CEUS and DCE-MRI. Benign lesions showed excellent agreement (weighted kappa = 0.84), and invasive ductal carcinoma (IDC) showed good agreement (weighted kappa = 0.69).ConclusionThe diagnostic performance of CEUS for additional MR-detected breast lesions was excellent. Accurate kinetic pattern assessment, fairly comparable to DCE-MRI, can be obtained for benign and IDC lesions using CEUS.

Triexponential Diffusion Analysis of Diffusion-weighted Imaging for Breast Ductal Carcinoma &lt;i&gt;in Situ&lt;/i&gt; and Invasive Ductal Carcinoma

PurposeTo obtain detailed information in breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) using triexponential diffusion analysis.MethodsDiffusion-weighted images (DWI) of the breast were obtained using single-shot diffusion echo-planar imaging with 15 b-values. Mean signal intensities at each b-value were measured in the DCIS and IDC lesions and fitted with the triexponential function based on a two-step approach: slow-restricted diffusion coefficient (Ds) was initially determined using a monoexponential function with b-values > 800 s/mm2. The diffusion coefficient of free water at 37°C was assigned to the fast-free diffusion coefficient (Df). Finally, the perfusion-related diffusion coefficient (Dp) was derived using all the b-values. Furthermore, biexponential analysis was performed to obtain the perfusion-related diffusion coefficient (D*) and the perfusion-independent diffusion coefficient (D). Monoexponential analysis was performed to obtain the apparent diffusion coefficient (ADC). The sensitivity and specificity of the aforementioned diffusion coefficients for distinguishing between DCIS and IDC were evaluated using the pathological results.ResultsThe Ds, D, and ADC of DCIS were significantly higher than those of IDC (P < 0.01 for all). There was no significant correlation between Dp and Ds, but there was a weak correlation between D* and D. The combination of Dp and Ds showed higher sensitivity and specificity (85.9% and 71.4%, respectively), compared to the combination of D* and D (81.5% and 33.3%, respectively).ConclusionTriexponential analysis can provide detailed diffusion information for breast tumors that can be used to differentiate between DCIS and IDC.

Does ARFI elastography complement B-mode ultrasonography in the radiological diagnosis of idiopathic granulomatous mastitis and invasive ductal carcinoma?

Idiopathic granulomatous mastitis (IGM) is a chronic, unpleasant autoimmune inflammatory condition and is clinically and radiologically often confused with breast malignancy. To investigate the contributions of qualitative and quantitative aspects of acoustic radiation force impulse (ARFI) elastography to the differential diagnosis between IGM and invasive ductal carcinoma (IDC) in the breast. Ninety-four women with IDC and 39 with IGM were included in the study. Shear wave velocity (SWV) was calculated for all lesions using quantitative elastography. Next, each lesion's correspondence on qualitative elastographic images to those on the B-mode images was evaluated: pattern 1, no findings on elastography images; pattern 2, lesions that were bright inside; pattern 3, lesions that contained both bright and dark areas; and pattern 4, lesions that were dark inside. Pattern 4 was subdivided into 4a (dark area same size as lesion) and 4b (dark area larger than lesion size). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. The mean SWV based on ARFI elastography was 3.78 ± 1.26 m/s for IGM and 5.34 ± 1.43 m/s for IDC lesions (P < 0.05). Based on qualitative ARFI elastography, IDC lesions were mostly classified as pattern 4b, while IGM lesions were mostly classified as pattern 1 or 2 (P = 0.01). Evaluation of both the qualitative and quantitative aspects of ARFI elastography yielded a sensitivity of 89% and specificity of 84%. ARFI elastography may facilitate the differential diagnosis between IGM and IDC.

Quantitative perfusion parameters of benign inflammatory breast pathologies: A descriptive study

PurposeWith this study, we evaluated the perfusion magnetic resonance imaging (MRI) features of benign inflammatory breast lesions for the first time and compared their Ktrans, Kep, Ve values and contrast kinetic curves to benign masses and invasive ductal carcinoma (IDC). Materials and methodsPerfusion MRIs of the benign masses (n = 42), inflammatory lesions (n = 25), and IDCs (n = 16) were evaluated retrospectively in terms of Ktrans, Kep, Ve values and contrast kinetic curves and compared by the Kruskal-Wallis, Mann-Whitney U, chi-square tests statistically. Cronbach α test was used to measure intraobserver and interobserver reliability. ResultsMean Ktrans values were 0.052 for benign masses, 0.086 for inflammatory lesions and 0.101 for IDC (p < 0.001). Mean Kep values were 0.241 for benign masses, 0.435 for inflammatory lesions and 0.530 for IDC (p < 0.001). Mean Ve values were 0.476 for benign masses, 0.318 for inflammatory lesions and 0.310 for IDC (p = 0.067). For inflammatory and IDC lesions, Ktrans and Kep values were found to be higher and Ve values were lower than benign masses (p = 0.001 for Ktrans, p = 0.001 for Kep, p = 0.045 for Ve). There were excellent or good intra-interobserver reliabilities. For the kinetic curve pattern, most of the benign lesions showed progressive (81%), inflammatory lesions progressive (64%) and IDC lesions plateau (75%) patterns (p < 0.001). ConclusionsOn T1 perfusion MRI, similar to IDC lesions, inflammatory lesions demonstrate higher Ktrans and Kep and lower Ve values than benign masses. Quantitative perfusion parameters are not helpful in differentiating them from IDC lesions.

Advanced lesions of synchronous bilateral mammary Paget\u2019s disease: a case report

BackgroundMammary Paget’s disease is an eczematous eruption on the nipple and areola with underlying breast malignancy. It is often misinterpreted as chronic dermatitis or psoriasis causing a delayed diagnosis. Synchronous bilateral mammary Paget’s disease is exceptionally rare and an advanced case with underlying invasive carcinoma might require long-term treatment and follow-up that could affect a patient’s physical, psychological, and social aspects of well-being.Case presentationA 54-year-old Javanese woman presented in our clinic with a 2-year history of itching and chronic eczema in both areolae. Bilateral nipple retraction and retro-areolar palpable lumps were observed during the first presentation. Breast ultrasound revealed hypoechoic lesions in her left and right breasts. Mammograms showed an irregular hyperdense lesion and multiple microcalcifications. Histopathology from biopsy and bilateral mastectomy demonstrated infiltration of large Paget’s cells in the epidermis of the areola with underlying lesions of invasive ductal carcinoma, diagnosed solid type with high nuclear grade and negative expression of estrogen receptor and progesterone receptor, with positive expression of human epidermal growth receptor-2(HER2) and Ki-67 (45%).ConclusionsIn a patient with suspicious chronic inflammation of the nipple and areolae, prompt biopsy should be performed to avoid a delayed diagnosis of any malignant breast lesion.

Metastatic behavior of mixed invasive ductal lobular carcinoma (mIDC/ILC).

1085 Background: Mixed invasive ductal lobular carcinoma (mIDC/ILC) is a poorly described subtype of invasive breast cancer, characterized by its composition of both ductal and lobular histopathology. It is unclear if individual or both components drive metastasis. Literature is sparse regarding sites of metastatic spread of this elusive subtype of invasive breast cancer. Methods: Cohorts of patients with mIDC/ILC, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) were identified from the UPMC Network Cancer Registry. Among these, 46 patients with mIDC/ILC, 1,131 patients with IDC, and 145 patients with ILC seen at UPMC Magee Women’s Hospital from 1990 – 2017 were found to have developed distant metastasis during the course of their disease. The metastatic pattern of spread was compared between the cohorts. Formalin-fixed, paraffin-embedded patient samples from the metastatic sites of a portion of the mIDC/ILC cases (n = 19) was acquired and evaluated by H&amp;E staining. Results: Patients with IDC were more likely than patients with ILC to have metastasis to the liver (p = 0.001) and lung (p &lt; 0.001), and less likely to have metastasis to the peritoneum (p &lt; 0.001). Patients with mIDC/ILC were more likely than patients with IDC to have peritoneal metastasis (p = 0.01), similar to patients with ILC. Compared to patients with ILC, patients with mIDC/ILC were more likely to have liver metastasis (p = 0.001), similar to patients with IDC. Evaluation of the metastatic lesions originating from mIDC/ILC displayed a spectrum of histopathology including mixed histology (n = 3), pure IDC (n = 3), pure ILC (n = 5), and indeterminate lesions with features of both IDC and ILC (n = 6). Two cases were uninterpretable due to significant crush artifact. Metastatic mIDC/ILC lesions with retained mIDC/ILC histology were found in vertebral, pleural, and skin tissues. Metastatic mIDC/ILC lesions with IDC histology were found in a cerebellar, liver, and chest wall lesion; whereas, those with ILC histology were found in bowel, omental fat, ovary, bone, and sacrum. Indeterminate histology metastatic lesions were found at liver, chest wall, cerebellar, and bone sites. Conclusions: mIDC/ILC metastasizes to a range of distant sites with a higher preference to the liver and peritoneum as compared to ILC and IDC, respectively. Metastatic lesions arising from mIDC/ILC tumors showed a spectrum of histologies, including mIDC/ILC, IDC, ILC and indeterminate lesions with features of both IDC and ILC. Ongoing genomics studies will provide further insight into development of metastases from mIDC/ILC tumors.

Predicting Axillary Lymph Node Metastasis in Patients With Breast Invasive Ductal Carcinoma With Negative Axillary Ultrasound Results Using Conventional Ultrasound and Contrast-Enhanced Ultrasound.

The purpose of this study was to establish a scoring system for predicting axillary lymph node metastasis (ALNM) in patients with breast invasive ductal carcinoma with negative axillary ultrasound (US) results. In this retrospective study, 156 breast invasive ductal carcinoma lesions from 156 women were retrospectively enrolled. The features of conventional US and contrast-enhanced ultrasound (CEUS) qualitative enhancement patterns and quantitative enhancement parameters were analyzed. Subsequently, a scoring system was created by a multivariate logistic regression analysis. The results found that 60 patients (38%) showed ALNM. A scoring system was defined as risk score = 1.75 × (if lesion size ≥20 mm) + 1.93 × (if uncircumscribed margin shown on conventional US) + 1.77 × (if coarse or twisting penetrating vessels shown on CEUS). When the risk scores were less than 1.75, 1.75 to 1.93, 1.94 to 3.70, and 3.70 or higher, the risk rates of ALNM were 0% (0 of 9), 10.7% (5 of 46), 29.2% (14 of 48) and 77.4% (41 of 53), respectively. In comparison with conventional US alone, the scoring system using the combination of conventional US and CEUS showed better discrimination ability in terms of the area under the curve (0.830 versus 0.777; P = .037). A scoring system based on conventional US and CEUS may improve the prediction of ALNM.

Differential diagnosis of plasma cell mastitis and invasive ductal carcinoma using multiparametric MRI.

Evaluate the potential of multiparametric magnetic resonance imaging (MRI) for the differential diagnosis of plasma cell mastitis (PCM) and invasive ductal carcinoma (IDC). A total of 465 female patients, including 197 PCM (42.4%) and 268 IDC (57.6%), were examined using breast MRI scanning using routine sequences, dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI) and MR spectroscopy (MRS). The MRI features of PCM and IDC lesions were analyzed and compared to the histological results. Compared to IDC, the PCM lesions were more frequent in the subareolar regions, hyperintense on T2WI (P<0.01) and showed an initial signal increase ≤90%, a persistent and plateau pattern of time-intensity curves, non-mass enhancement, multiple rim enhancements, central hyperintensity on DWI, a higher ADC value, and total choline (tCho) peak negative and tCho peak integral <29.95 AU (P<0.01). The following breast-associated findings were also observed frequently in PCM: Ipsilateral breast enlargement, nipple retraction, skin thickening, peripheral edema and axillary lymphadenopathy. However, no significant difference was observed between the two groups for the shape, border and adjacent vessel signs of the lesion. Some of the MRI features of PCM and IDC lesions were different. An integrated analysis of these multiparametric MRI features can thus assist in the differential diagnosis of PCM and IDC lesions.

Turbo Spin-echo Diffusion-weighted Imaging Compared with Single-shot Echo-planar Diffusion-weighted Imaging: Image Quality and Diagnostic Performance When Differentiating between Ductal Carcinoma in situ and Invasive Ductal Carcinoma.

Purpose:To compare the image quality between turbo spin-echo (TSE)-diffusion weighted imaging (DWI) and single-shot echo-planar imaging (EPI)-DWI, and to verify the diagnostic performance of the apparent diffusion coefficient (ADC) parameters of the two techniques by using histogram analysis in terms of differentiation between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions.Methods:Ninety-four women with 94 lesions diagnosed as breast cancer by surgery underwent IRB-approved preoperative magnetic resonance imaging, including TSE and EPI-DWI with b-values of 50 and 850 s/mm2. Twenty lesions were identified as DCIS and 74 as IDC. Image quality [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and geometric distortion] was evaluated quantitatively and compared between the TSE and EPI-DWI. A histogram analysis of the entire tumor voxel-based ADC data was performed, and the 10th, 25th, 50th, 75th, and 90th percentile values of each technique were compared between DCIS and IDC lesions.Results:The SNR and CNR of TSE-DWI were significantly higher than those of EPI-DWI (P < 0.0001 and < 0.0001). The geometric distortion of TSE-DWI was significantly lower than that of EPI-DWI (P < 0.0001). In TSE-DWI, the 10th, 25th, 50th, and 75th percentile values were significantly different between the DCIS and IDC lesions (P = 0.0010, 0.0004, 0.0008, and 0.0044, respectively). In EPI-DWI, the 50th and 75th percentile values were significantly different between the two groups (P = 0.0009 and 0.0093). There was no significant difference in the area under the curve of the receiver operating characteristic analysis of the 10th, 25th, 50th, and 75th percentile values of TSE-DWI, and the 50th and 75th percentile values of EPI-DWI (P = 0.29).Conclusion:The image quality of TSE-DWI was better than that of EPI-DWI. DCIS lesions were distinguished from IDC lesions with a wider range of percentile values in TSE-DWI than in EPI-DWI, although diagnostic performance was not significantly different between the techniques.

Long noncoding RNA BHLHE40-AS1 promotes early breast cancer progression through modulating IL-6/STAT3 signaling.

Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive breast cancer. Only a small percentage of DCIS cases are predicted to progress; however, there is no method to determine which DCIS lesions will remain innocuous from those that will become invasive disease. Therefore, DCIS is treated aggressively creating a current state of overdiagnosis and overtreatment. There is a critical need to identify functional determinants of progression of DCIS to invasive ductal carcinoma (IDC). Interrogating biopsies from five patients with contiguous DCIS and IDC lesions, we have shown that expression of the long noncoding RNA BHLHE40-AS1 increases with disease progression. BHLHE40-AS1 expression supports DCIS cell proliferation, motility, and invasive potential. Mechanistically, BHLHE40-AS1 modulates interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) activity and a proinflammatory cytokine signature, in part through interaction with interleukin enhancer-binding factor 3. These data suggest that BHLHE40-AS1 supports early breast cancer progression by engaging STAT3 signaling, creating an immune-permissive microenvironment.

Abstract P5-18-10: BHLHE40-AS1 is an enhancer associated long noncoding RNA critical to breast cancer progression

Abstract Increased emphasis on breast cancer screening has led to a dramatic increase in diagnosis of ductal carcinoma in situ (DCIS). DCIS lesions are nonobligate precursors of invasive ductal carcinoma (IDC) and thus, the current standard-of-care is aggressive therapy to prevent invasive and metastatic disease. However, only ˜40% of DCIS cases are predicted to progress leading to a current state of overtreatment and overdiagnosis. Thus, there is a critical need to identify functional determinants of progression of DCIS to IDC to allow discrimination between indolent and aggressive breast cancers and refine patient treatment strategies.We propose that long noncoding RNAs (lncRNAs) functionally drive breast cancer progression and their expression can discriminate between innocuous and potentially invasive DCIS. Using biopsies from women with tandem DCIS and IDC lesions, we identified 35 lncRNAs whose expression can distinguish between pre-invasive and invasive disease. From this candidate list, the lncRNA BHLHE40-AS1 is found enriched in multiple breast cancer progression models, in HER2+ cell lines, and HER2+ patient tumors. Functionally, BHLHE40-AS1 is found to support tumor cell cycle and motility and may serve as a clinically relevant biomarker and therapeutic target in invasive breast cancer. Further, BHLHE40-AS1 is expressed from a known super-enhancer that preliminary evidence suggests undergoes altered chromatin looping during breast cancer progression. Interestingly, over half of the candidate lncRNAs are associated with enhancer regions. Current studies are investigating super-enhancers, and associated lncRNAs that become acquired during breast cancer progression. Citation Format: DeVaux RS, Schimjawicz H, Coarfa C, Behbod F, Herschkowitz JI. BHLHE40-AS1 is an enhancer associated long noncoding RNA critical to breast cancer progression [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-18-10.

Progression Potential of Ductal Carcinoma in situ Assessed by Genomic Copy Number Profiling

Background: Ductal carcinoma in situ (DCIS) of the breast is heterogeneous in terms of the risk of progression to invasive ductal carcinoma (IDC). To treat DCIS appropriately for its progression risk, we classified individual DCIS by its profile of genomic changes into 2 groups and correlated them with clinicopathological progression factors. Methods: We used surgically resected, formalin-fixed, paraffin-embedded tissues of 22 DCIS and 30 IDC lesions. We performed immunohistochemical intrinsic subtyping, array-based comparative genomic hybridization, and unsupervised clustering. Results: The samples were divided into 2 major clusters, A and B. Cluster A showed a greater number of gene and chromosome copy number alterations, a larger IDC/DCIS ratio, a higher frequency of nonluminal subtype, a lower frequency of luminal subtype, and a higher nuclear grade, when compared with cluster B. However, there was no difference in the frequencies of lymph node metastasis between clusters A and B. We identified 9 breast-cancer-related genes, including TP53 and GATA3, that highly contributed to the discrimination of A and B clusters. Conclusion: Classification of breast tumors into rapidly progressive cluster A and the other (cluster B) may contribute to select the treatment appropriate for their progression risk.