Sclerosing Adenosis Research Articles

Multimodal ultrasound imaging for diagnostic differentiation of sclerosing adenosis from invasive ductal carcinoma.

Sclerosing adenosis (SA) is a common proliferative benign lesion without atypia in the breast that may mimic invasive ductal carcinoma (IDC) on medical imaging, leading to it often being misdiagnosed and mistreated. Consequently, the purpose of this study was to assess the diagnostic value of multimodal ultrasound imaging in distinguishing SA from IDC. Multimodal ultrasound imaging, including automated breast volume scan (ABVS), elasticity imaging (EI), and color Doppler flow imaging (CDFI), were performed on 120 consecutive patients comprising 122 breast lesions (54 SA, 68 IDC). All lesions were pathologically confirmed. Multimodal ultrasound imaging features were compared between the two groups. Binary logistic regression analysis based on ABVS, EI, and CDFI was conducted to formulate a logistic regression equation for differentiating SA from IDC. The diagnostic performances of ABVS, EI, CDFI, and their combination were compared by the receiver operating characteristic (ROC) curve analysis. The sensitivity, specificity, and accuracy of ABVS, EI, CDFI, and their combination in differentiating SA from IDC were, respectively, 75.00%, 72.22%, and 73.77%; 86.76%, 72.22%, and 80.33%; 73.53%, 64.81%, and 69.67%; and 88.24%, 74.07%, and 81.97%. Combining multimodal ultrasound imaging yielded an area under the curve (AUC) of 0.895 (95% confidence interval: 0.827-0.943), which was higher than that of ABVS, EI, and CDFI, with AUC values of 0.736, 0.795, and 0.692, respectively, and the difference was statistically significant (ABVS vs. combined model, P<0.001; CDFI vs. combined model, P<0.001; EI vs. combined model, P<0.001). There was no significant difference in the diagnostic efficacy among the three imaging modalities (ABVS vs. EI, P=0.266; ABVS vs. CDFI, P=0.4671; EI vs. CDFI, P=0.051). Compared with those in IDC, the calcification (16.67% vs. 57.35%; P<0.001) and retraction phenomena in the coronal planes (18.52% vs. 57.35%; P<0.001) were less common in patients with SA, while circumscribed margin (38.89% vs. 5.88%; P<0.001), vascularity grade 0-I (64.81% vs. 26.47%; P<0.001), and elasticity scores 1-3 (72.22% vs. 13.24%; P<0.001) were more frequently found in patients with SA. Patients with SA were significantly younger than were patients with IDC (43±11 vs. 54±11 years; P<0.001), and the lesion size was smaller in patients with SA than in those with IDC (median size 1.0 cm; interquartile range (IQR), 0.9 cm vs. median size 1.3 cm; IQR, 1.3 cm; P<0.001). The preliminary results suggested that multimodal ultrasound imaging can improve the diagnostic accuracy of SA and provide additional information for differential diagnosis of SA and IDC.

A comparative study on the features of breast sclerosing adenosis and invasive ductal carcinoma via ultrasound and establishment of a predictive nomogram.

To analyze the clinical and ultrasonic characteristics of breast sclerosing adenosis (SA) and invasive ductal carcinoma (IDC), and construct a predictive nomogram for SA. A total of 865 patients were recruited at the Second Hospital of Shandong University from January 2016 to November 2022. All patients underwent routine breast ultrasound examinations before surgery, and the diagnosis was confirmed by histopathological examination following the operation. Ultrasonic features were recorded using the Breast Imaging Data and Reporting System (BI-RADS). Of the 865 patients, 203 (252 nodules) were diagnosed as SA and 662 (731 nodules) as IDC. They were randomly divided into a training set and a validation set at a ratio of 6:4. Lastly, the difference in clinical characteristics and ultrasonic features were comparatively analyzed. There was a statistically significant difference in multiple clinical and ultrasonic features between SA and IDC (P<0.05). As age and lesion size increased, the probability of SA significantly decreased, with a cut-off value of 36 years old and 10 mm, respectively. In the logistic regression analysis of the training set, age, nodule size, menopausal status, clinical symptoms, palpability of lesions, margins, internal echo, color Doppler flow imaging (CDFI) grading, and resistance index (RI) were statistically significant (P<0.05). These indicators were included in the static and dynamic nomogram model, which showed high predictive performance, calibration and clinical value in both the training and validation sets. SA should be suspected in asymptomatic young women, especially those younger than 36 years of age, who present with small-size lesions (especially less than 10 mm) with distinct margins, homogeneous internal echo, and lack of blood supply. The nomogram model can provide a more convenient tool for clinicians.

Deep learning radiomics of ultrasonography for differentiating sclerosing adenosis from breast cancer.

The purpose of our study is to present a method combining radiomics with deep learning and clinical data for improved differential diagnosis of sclerosing adenosis (SA)and breast cancer (BC). A total of 97 patients with SA and 100 patients with BC were included in this study. The best model for classification was selected from among four different convolutional neural network (CNN) models, including Vgg16, Resnet18, Resnet50, and Desenet121. The intra-/inter-class correlation coefficient and least absolute shrinkage and selection operator method were used for radiomics feature selection. The clinical features selected were patient age and nodule size. The overall accuracy, sensitivity, specificity, Youden index, positive predictive value, negative predictive value, and area under curve (AUC) value were calculated for comparison of diagnostic efficacy. All the CNN models combined with radiomics and clinical data were significantly superior to CNN models only. The Desenet121+radiomics+clinical data model showed the best classification performance with an accuracy of 86.80%, sensitivity of 87.60%, specificity of 86.20% and AUC of 0.915, which was better than that of the CNN model only, which had an accuracy of 85.23%, sensitivity of 85.48%, specificity of 85.02%, and AUC of 0.870. In comparison, the diagnostic accuracy, sensitivity, specificity, and AUC value for breast radiologists were 72.08%, 100%, 43.30%, and 0.716, respectively. A combination of the CNN-radiomics model and clinical data could be a helpful auxiliary diagnostic tool for distinguishing between SA and BC.

An ultrasound-based radiomics model to distinguish between sclerosing adenosis and invasive ductal carcinoma.

We aimed to develop an ultrasound-based radiomics model to distinguish between sclerosing adenosis (SA) and invasive ductal carcinoma (IDC) to avoid misdiagnosis and unnecessary biopsies. From January 2020 to March 2022, 345 cases of SA or IDC that were pathologically confirmed were included in the study. All participants underwent pre-surgical ultrasound (US), from which clinical information and ultrasound images were collected. The patients from the study population were randomly divided into a training cohort (n = 208) and a validation cohort (n = 137). The US images were imported into MaZda software (Version 4.2.6.0) to delineate the region of interest (ROI) and extract features. Intragroup correlation coefficient (ICC) was used to evaluate the consistency of the extracted features. The least absolute shrinkage and selection operator (LASSO) logistic regression and cross-validation were performed to obtain the radiomics score of the features. Based on univariate and multivariate logistic regression analyses, a model was developed. 56 cases from April 2022 to December 2022 were included for independent validation of the model. The diagnostic performance of the model and the radiomics scores were evaluated by performing the receiver operating characteristic (ROC) analysis. The calibration curve and decision curve analysis (DCA) were used for calibration and evaluation. Leave-One-Out Cross-Validation (LOOCV) was used for the stability of the model. Three predictors were selected to develop the model, including radiomics score, palpable mass and BI-RADS. In the training cohort, validation cohort and independent validation cohort, AUC of the model and radiomics score were 0.978 and 0.907, 0.946 and 0.886, 0.951 and 0.779, respectively. The model showed a statistically significant difference compared with the radiomics score (p<0.05). The Kappa value of the model was 0.79 based on LOOCV. The Brier score, calibration curve, and DCA showed the model had a good calibration and clinical usefulness. The model based on radiomics, ultrasonic features, and clinical manifestations can be used to distinguish SA from IDC, which showed good stability and diagnostic performance. The model can be considered a potential candidate diagnostic tool for breast lesions and can contribute to effective clinical diagnosis.

Value of multimodal imaging in the diagnosis of breast sclerosing adenosis associated with malignant lesions.

To explore the diagnostic value of multimodal imaging techniques, including automatic breast volume scanner (ABVS), mammography (MG), and magnetic resonance (MRI) in breast sclerosing adenosis (SA) associated with malignant lesions. From January 2018 to October 2020, 76 patients (88 lesions) with pathologically confirmed as SA associated with malignant or benign lesions were retrospective analyzed. All patients completed ABVS examination, 58 patients (67 lesions) with MG and 50 patients (62 lesions) with MRI were also completed before biopsy or surgical excision, of which, six patients (eight lesions) diagnosed as Breast Imaging Reporting and Data System (BI-RADS) category 3 by all imaging examinations underwent surgical excision without biopsy, other 70 patients (80 lesions) with BI-RADS category 4 or above by any imaging examination completed biopsy, including 65 patients (75 lesions) were further surgical excised and the other five patients (five lesions) were just followed up. All lesions were retrospectively described and classified, and were divided into benign group and malignant group according to their pathological results. Image features of different examination methods between the two groups were compared and analyzed. A ROC curve was established using the sensitivity of BI-RADS categories to predict malignant lesions in different imaging techniques as the ordinate and 1-specificity as the abscissa. 88 lesions including 26 purely SA and 45 SA associated with benign lesions were classified as benign group, and the remaining 17 SA associated with malignant lesions were classified as malignant group. On ABVS, 40 mass lesions, their heterogeneous echo, not circumscribed margin and coronal convergence signs were statistically significant for malignant lesions (p< .05), but the remain 48 nonmass lesions lack specific sonographic features. On MG, 12 showed negative results, 55 showed with microcalcification, mass, structural distortion, and asymmetric density shadow, of which 11 lesions had the above two signs at the same time, but only microcalcification had statistical difference between the two groups. 35 mass enhanced lesions and 27 nonmass enhanced lesions on MRI, but there were no significant difference between their pathological results. Time signal intensity curves showed no differences, but ADC value <1.10 × 10-3 mm2 /s is more significant in malignant lesions (p< .05). The area under the ROC curve (AUC) of BI-RADS classification of ABVS, MG, and MRI in the diagnosis of malignant lesions were 0.611, 0.474, and 0.751, respectively, and the AUC of the combined diagnosis of the three was 0.761. Mass lesions with heterogeneous echo, not circumscribed margin and coronal convergence sign on ABVS, microcalcification on MG and the ADC value <1.10× 10-3 mm2 /s on MRI are significant signs for SA associated with malignant lesions. The combined diagnosis of the three methods was the highest, and the following were MRI, ABVS, and MG. Therefore, be cognizant of significant characteristics in SA associated with malignancy showed in different imaging examinations can improve the preoperative evaluation of SA and better provide basis for subsequent clinical decision-making.

Type 2 dynamic curves: A diagnostic dilemma.

BACKGROUNDMagnetic resonance imaging (MRI) with multiparametric dynamic contrast plays a critical role in the assessment of breast lesions. Dynamic curves are a critical parameter in determining the benign or malignant nature of lesions. Dynamic curves of type 1 are known to represent benign masses, while dynamic curves of type 3 are known to identify malignant masses. Type 2 dynamic curves have a sensitivity of 42.6% and specificity of 75% for malignancy detection. AIMTo investigate the pathological diagnosis of lesions with type 2 dynamic curves.METHODSWe evaluated breast MRI examinations performed between 2020 and 2021 retrospectively and included lesions with type 2 dynamic curves. We included 38 lesions from 33 patients. The lesions were evaluated for their pathological diagnosis and morphological characteristics. RESULTSTwenty-six lesions were malignant, while twelve were benign. The most frequently encountered benign lesion (7/12, 58.3%) was sclerosing adenosis, while the most frequently encountered malignant diagnosis was invasive ductal cancer. The presence of a type 2 dynamic curve had a sensitivity of 40.2% and specificity of 73.4% for predicting malignancy. By combining type 2 curves and morphological features, the sensitivity and specificity were increased.CONCLUSIONThe high rates of malignancy detected histopathologically among patients with type 2 dynamic curves in our study are remarkable. Type 2 dynamic curves can be detected in benign breast masses, especially in sclerosing adenosis cases. Considering morphological features can increase the diagnostic accuracy in cases with type 2 dynamic curves.

Abstract SY25-02: Double-edged “soil”: Stromal microenvironment in breast cancer development

Abstract SY25-02: Double-edged “soil”: Stromal microenvironment in breast cancer development

Ultrasound characteristics of sclerosing adenosis mimicking breast carcinoma.

Sclerosing adenosis (SA) is a benign lesion with complicated pathological components and could mimic breast carcinoma in both clinical palpation and medical imaging findings. The present study was conducted to assess the value of ultrasound (US) characteristics in diagnosing SA and their differentiation from breast carcinoma. We retrospectively reviewed the medical records of 305 women (347 lesions) with invasive ductal carcinoma (IDC) and 54 women with single SA lesion, who had breast excision between April 2016 and July 2018. US BI-RADS atlas and elastography were applied and their associated characteristics were compared between SA and IDC. The mean age of SA was younger than that of IDC (43.6 ± 7.4 vs 53.2 ± 10.3, P < 0.001). Compared to IDC, SA had more frequency of parallel orientation (94.44% vs 71.76%, P < 0.001) and circumscribed margin (48.15% vs 4.90%, P < 0.001), less frequency ofirregular shape (64.81% vs 95.97%, P < 0.001), hypoechoic echotexture(88.89% vs 98.27%, P = 0.002), calcification (12.96% vs 55.04%, P < 0.001), and posterior acoustic changes (3.70% vs 53.89%, P < 0.001) or associated features (architectural distortion, 3.70% vs 59.65%, P < 0.001; duct changes, 18.52% vs 63.40%, P < 0.001). Vascularity absence was more common in SA compared to IDC (35.19% vs 6.63%, P < 0.001). And the elasticity score was lower in SA (2.38 ± 0.60 vs 3.91 ± 0.81, P < 0.001). After adjusting for age, we found spiculated margin, posterior shadowing, calcification, architectural distortion, and vascularity could independently identify the differences between these two entities. After involving elasticity score, the calcification and vascularity could still be independent indicators for differential diagnosis. Understanding SA imaging features will enable radiologists to communicate results to the referring physician consistently, which could benefit a reliable assessment and specific management recommendations. A systematic evaluation of the US BI-RADS atlas together with breast elastography may be a powerful tool to identify SA and differentiate it from breast cancer.

Carcinoma In Situ Involving Sclerosing Adenosis on Core Biopsy: Diagnostic Pearls to Aid the Practicing Clinician and Avoid Overtreatment.

IntroductionInvolvement of pre-existing benign lesions by ductal carcinoma in situ (DCIS) or lobular neoplasia (LN) can present difficult diagnostic challenges, and can easily cause misdiagnosis of invasive carcinoma and over-management of localized disease. Our objective was to gather the largest case series of DCIS and LN involving sclerosing adenosis (SA), and to report the characteristic features of these lesions, in order to provide histologic criteria for the diagnostician.MethodsOur database was searched for core biopsy material diagnosed as carcinoma in situ involving adenosis. Glass slides and pathology reports were reviewed. The cases were studied for salient features, and clinical follow-up was also obtained.ResultsThirty-one cases of DCIS or LN involving SA were obtained (12 cases of DCIS, 19 cases of LN including LCIS and ALH). Histomorphologic features commonly seen with DCIS or LN involving SA included lobulocentric architecture (31/31, 100%), myoepithelial cells visible by H&E at least focally (31/31, 100%), and separate areas of SA not involved by neoplasia (29/31, 93.5%). Features that were sometimes seen included hyaline basement membranes surrounding the lesion (14/31, 45.2%), DCIS/LN apart from the area of involvement by SA (16/31, 51.6%), and calcifications associated with DCIS/LN/SA (12/31, 38.7%). Features that were not commonly seen included desmoplasia (6/31, 19.4%), dense inflammation (4/31, 12.9%), and single epithelial cells enveloped by flattened myoepithelial cells (6/31, 19.4%). Of the ten cases of DCIS with known follow-up, four showed DCIS involving either SA or a complex SA on excision (4/10, 40%), four had only DCIS (4/10, 40%), one had DCIS with a small 1.8-mm focus of predominantly tubular carcinoma (1/10, 10%), and one showed invasive ductal carcinoma on excision (1/10, 10%). The latter case of invasive ductal carcinoma occurred in a patient who had a delay of 3 years from diagnosis to surgical resection. Of the eight cases of LN with surgical follow-up, seven had LCIS (7/8, 87.5%), and one showed only fibroadenoma and SA with no residual LN in the excised specimen (1/8, 12.5%). Importantly, no invasive carcinoma was identified in any of the resections for LN involving SA.ConclusionsIn our series of carcinoma in situ (CIS) involving sclerosing adenosis diagnosed on core biopsy, lobular lesions involving SA were more common than ductal lesions. Ductal and lobular carcinoma in situ involving adenosis were best diagnosed by the low-power appearance of a lobulocentric pattern of growth. The most helpful diagnostic feature was the observation of additional foci of carcinoma in situ away from the adenosis. Immunohistochemical stains for myoepithelial cells were useful in particularly difficult cases. The presence of stromal desmoplasia does not preclude the diagnosis of carcinoma in situ involving adenosis. Knowledge of these diagnostic pearls can reduce over-interpretation of CIS on core biopsy and subsequent overtreatment.

Conventional and contrast-enhanced ultrasound features in sclerosing adenosis and correlation with pathology.

To evaluate the efficacy of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in differential diagnosis of sclerosing adenosis (SA) from malignance and investigate the correlated features with pathology. We retrospectively enrolled 103 pathologically confirmed SA. All lesions were evaluated with conventional US while 31 lesions with CEUS. Lesions were divided into SA with or without benign lesions (Group 1, n = 81) and SA with malignancy (Group 2, n = 22). Performance of two methods were analyzed. The ultrasonographic characteristics were compared between two groups with Student's t-test for measurement and chi-squared or Fisher's exact test for count data. There were 22 lesions complicated with malignancy, and the mean age of Group 2 was higher than Group 1 (55.27 vs. 41.57, p < 0.001). The sensitivity, specificity and accuracy of conventional US and CEUS were 95.45%, 46.91%, 57.28% and 100%, 62.5%, 70.97%. Angularity (p < 0.001), spicules (p = 0.023), calcification (p = 0.026) and enlarged scope (p = 0.012) or crab claw-like enhancement (p = 0.008) in CEUS were more frequent detected in SA with malignancy. Though CEUS showed an improved accuracy, the performance of ultrasound in the diagnosis of SA was limited. Awareness and careful review of the histopathologically related imaging features can be helpful in the diagnosis of SA.

Malignant Biphasic Adenomyoepithelioma: A Rare Entity

Abstract Objectives Adenomyoepithelioma of the breast is an uncommon biphasic breast lesion characterized by a cytologically bland epithelial and myoepithelial proliferation. It is often considered benign and thought to represent a variant of intraductal papilloma. However, rare cases of adenomyoepitheliomas have been reported to show malignant transformation. Features that favor malignancy include increased mitoses, necrosis, atypia, cellular pleomorphism, and infiltrative borders. Most reported cases of malignant adenomyoepithelioma demonstrate carcinomas arising in a benign adenomyoepithelioma. Methods A 74-year-old woman presented to the hospital with an 8-month history of a palpable right breast mass. Mammogram demonstrated an irregular marginated mass, and a needle core biopsy of the mass showed atypical sclerosing adenosis. A lumpectomy revealed a firm, tan-white, ill-defined 2.7-cm mass abutting the anterior and posterior margins. Results Histologic examination showed an infiltrative proliferation of epithelial-lined tubules surrounded by myoepithelial cells with clear cytoplasm. There were focal areas of hypercellularity with marked cytologic atypia in both the epithelial and myoepithelial components. Focal necrosis and increased mitoses (12/10 HPF) were also identified. On immunohistochemical studies, the epithelial cells were positive for CK7 while the myoepithelial cells were highlighted by p63, SMMHC, SMA, and CK5/6. Ki-67 showed an increased proliferative index (35%). ER, PR, and HER-2 immunostains were negative. The overall histologic and immunohistochemical findings support a diagnosis of malignant biphasic adenomyoepithelioma. No in situ carcinoma was identified. After the diagnosis was reported, a follow-up reexcision with axillary sentinel lymph node excision was performed. Both specimens were negative for malignancy. Conclusion Malignant adenomyoepithelioma of the breast is an uncommon entity and it is strongly associated with local recurrence and distant metastases. Awareness of its distinctive histologic and immunohistochemical features will be helpful in initiating the appropriate medical management for patients with this entity, which is crucial for improving prognosis and overall survival.

Radiological and clinical findings in sclerosing adenosis of the breast.

To study the imaging and clinical features of breast sclerosing adenosis (SA), and to enhance the recognition of this disease, as well as to help the clinic to give a correct diagnosis.Imaging findings were retrospectively reviewed in 47 women with SA lesions confirmed by pathology (including 39 cases of mammography, 40 cases of ultrasound [US], and 34 cases magnetic resonance imaging [MRI]).Of 47 patients confirmed with SA, 18 cases were pure SA, and 29 cases coexist with other proliferative lesions and malignancies; the maximum diameter of SA lesions was 0.5 to 3.5 cm with an average of 1.6 cm. On the mammogram of 39 SA cases, the percentage of architectural distortion, calcifications, mass/nodular, asymmetric density, and mass combining with calcifications were 30.8%, 23.1%, 17.9%, 12.8%, and 7.7%, respectively; and 3 cases had no abnormal findings. On the sonogram (excluding 5 normal finding cases), the majority of lesions showed regular shaped (57.1%), well defined margined (60.0%), heterogenous low echoed (71.4%) nodulus. 85.3% lesions showed high signal on T2-weighted images, and all lesions were enhanced markedly, including 82.4% lesions appearing mass-like enhancement (17 star-shaped enhanced masses included); and the percentage of the time-signal intensity curve in type 1, type 2, and type 3 were 52.9%, 41.2%, and 5.9%, respectively. If the category breast imaging-reporting and data system ≥4b was considered to be a suspicious malignant lesion, the misdiagnostic rates of mammography, US, and MRI would be 17.9%, 17.5%, and 35.3%, respectively.The SA lesions are small and can occur with other diseases histologically. The majority of SA lesions showed distortion or calcifications on mammograms, low echo-level nodules with heterogenous echo on US and mass-like lesion with or without star shape on enhanced MRI.

Nodular sclerosing adenosis: Case report

Sclerosing adenosis (SA) is a benign proliferative type of breast disease affecting the acinar, myoepithelial and connective tissue in the terminal ductal lobular units. Sclerosing adenosis, which gives a nodular appearance on mammography and ultrasonography, is defined as nodular sclerosing adenosis (NSA). NSA is an atypical radiological presentation of SA. Such lesions may arouse suspicions about the reliability of the diagnosis when they receive a diagnosis of SA in the needle biopsies. Therefore, it should be kept in mind that SA may rarely be seen as a nodular mass.

Association between mammographic breast density and histologic features of benign breast disease

BackgroundOver 40% of women undergoing breast screening have mammographically dense breasts. Elevated mammographic breast density (MBD) is an established breast cancer risk factor and is known to mask tumors within the dense tissue. However, the association of MBD with high risk benign breast disease (BBD) is unknown.MethodWe analyzed data for 3400 women diagnosed with pathologically confirmed BBD in the Mayo Clinic BBD cohort from 1985–2001, with a clinical MBD measure (either parenchymal pattern (PP) or Breast Imaging Reporting and Data Systems (BI-RADS) density) and expert pathology review. Risk factor information was collected from medical records and questionnaires. MBD was dichotomized as dense (PP classification P2 or DY, or BI-RADS classification c or d) or non-dense (PP classification N1 or P1, or BI-RADS classification a or b). Associations of clinical and histologic characteristics with MBD were examined using logistic regression analysis to estimate odds ratios (ORs) with 95% confidence intervals (CIs).ResultsOf 3400 women in the study, 2163 (64%) had dense breasts. Adjusting for age and body mass index (BMI), there were positive associations of dense breasts with use of hormone therapy (HT), lack of lobular involution, presence of atypical lobular hyperplasia (ALH), histologic fibrosis, columnar cell hyperplasia/flat epithelia atypia (CCH/FEA), sclerosing adenosis (SA), cyst, usual ductal hyperplasia, and calcifications. In fully adjusted multivariate models, HT (1.3, 95% CI 1.1–1.5), ALH (1.5, 95% CI 1.0–2.2), lack of lobular involution (OR 1.6, 95% CI 1.2–2.1, compared to complete involution), fibrosis (OR 2.2, 95% CI 1.9–2.6) and CCH/FEA (OR 1.3, 95% CI 1.0–1.6) remained significantly associated with high MBD.ConclusionOur findings support an association between high risk BBD and high MBD, suggesting that risks associated with the latter may act early in breast carcinogenesis.

Sclerosing adenosis: Ultrasonographic and mammographic findings and correlation with histopathology.

The present study was conducted to evaluate the radiological findings, particularly the ultrasonographic (US) characteristics of sclerosing adenosis (SA), and their correlation with histopathological results. A retrospective review identified 191 patients with a total of 200 lesions histopathologically confirmed as SA following breast surgery between July 2009 and December 2012. Of the 191 patients, 145 (151 lesions) with SA as the major component were included for US and mammographic (MG) analysis. All 145 patients analyzed were female, with a mean age ± standard deviation of 46.8±7.8 years (range, 25–71 years). All 145 patients underwent US examination and the imaging findings included heterogeneously echogenic areas in 9.3% (14/151), masses in 51.7% (78/151), masses with calcifications in 13.9% (21/151), focal acoustic shadowing in 4.0% (6/151) and were negative in 21.2% (32/151) patients. Among the 119 lesions with visible abnormalities, 87.4% (104/119) were hypoechoic, 58.0% (69/119) were irregular in shape, 52.1% (62/119) had an ill-defined margin, calcifications were found in 17.6% (21/119) and 7.6% (9/119) were hypervascular, while none of the characteristics mentioned above were significantly correlated with histopathology. A total of 136 patients underwent MG at the Fudan University Shanghai Cancer Center, and the imaging findings included microcalcifications in 31.6% (43/136), masses in 23.5% (32/136), asymmetric focal density in 14.7% (20/136), focal architectural distortion in 22.8% (31/136), and were negative in 7.4% (10/136). The mass lesions were fewer on MG compared with US (23.5 vs. 65.6%, respectively). The area under the curve of US distinguishing between benign and malignant lesions was significantly larger compared with that of MG (0.547 vs. 0.497, respectively; P=0.036). In the 60 lesions that were overestimated by Breast Imaging Reporting and Data System US category, one or more characteristics of malignancy were found on US imaging. The most common finding of SA was masses with or without calcifications on US and microcalcifications on MG. The accuracy of US was limited, but higher compared with that of MG; however, SA mimicking the characteristics of malignancy may contribute to misdiagnosis with US.

Breast Sclerosing Adenosis and Accompanying Malignancies: A Clinicopathological and Imaging Study in a Chinese Population.

Sclerosing adenosis (SA) is a less common histopathological lesion of the breast that can coexist with proliferative lesions as well as malignancies. We aimed to analyze the clinicopathological characteristics of SA and to investigate the radiological features of SA.Patients who underwent breast surgery at our institute from 2007 to 2013 were retrospectively reviewed. A total of 815 breasts (722 patients) were included in the final analysis. Synchronous bilateral SA was defined as the detection of another SA arising in the contralateral breast within 1 month after surgery for the initial breast lesion. Baseline characteristics, imaging records (ultrasonography, mammography, and magnetic resonance imaging [MRI]), and pathology were included in the analysis.The median age at diagnosis was 47 years old. The majority of patients had unilateral non-Bc-SA (457/722). Among 102 patients with bilateral SA, 78.4% were diagnosed synchronously. In total, 26 patients suffered from synchronous bilateral breast cancer. Upon final pathological investigation, 226 cases were SA involving breast cancer (Bc-SA), most (56.2%) of which were ductal carcinoma in situ (DCIS). In addition, lobular carcinoma in situ (LCIS) and diseases that involved LCIS also comprised up to 11.1% of cases. The majority of SA cases (405; 49.7%) had no obvious symptoms except for imaging changes in mammography or ultrasound. Compared with non-Bc-SA cases, Bc-SA cases were more likely to exhibit features of mass (32.8% vs. 28.6%) and architectural distortion (20.4% vs. 13.0%) on mammography. Ultrasonography, mammography, and MRI revealed unsatisfactory sensitivity and specificity to differentiate Bc-SA from non-Bc-SA. MRI exhibited the highest sensitivity and lowest specificity, whereas the specificity of mammography was as low as 50.0%.A tendency for synchronous bilaterality in both Bc-SA and non-Bc-SA was noted. DCIS was the most commonly observed malignancy involved in Bc-SA. Although most patients with SA were asymptomatic, the ability of imaging studies to accurately differentiate non-Bc-SA from Bc-SA remained unsatisfactory.

Gene signature model for breast cancer risk prediction for women with sclerosing adenosis.

18 Background: Benign breast disease (BBD) is diagnosed in 1-2 million women/year in the US, and while these patients are known to be at substantially increased risk for subsequent development of breast cancer, existing models for risk assessment perform poorly at the individual level. Here, we describe a DNA-microarray-based transcriptional model for breast cancer risk prediction for patients with sclerosing adenosis (SA), a lesion found in ¼ of all BBD patients that is characterized by epithelial proliferation, disordered acinar architecture, and stromal fibrosis. Methods: A training set was developed from 86 patients diagnosed with sclerosing adenosis (SA), of which 27 subsequently developed cancer within 10 years (cases) and 59 remained cancer-free at 10 years (controls). A diagonal linear discriminate analysis (DLDA)-prediction model for prediction of cancer within 10 years (SA TTC10) was generated from transcriptional profiles of formalin fixed, paraffin-embedded (FFPE) biopsy-derived RNA. This model was tested on a separate validation case-control set composed of 65 SA patients. Results: The SA TTC10 gene signature model, composed of 35 gene features, achieved a clear and significant separation between case and control with receiver operating characteristic area under the curve of 0.913 in the training set and 0.836 in the validation set. Conclusions: Our results provide the first demonstration that benign breast tissue contains transcriptional alterations that indicate risk of breast cancer development, and that essential precursor biomarkers of malignancy are present many years prior to cancer development. Furthermore, the SA TTC10 gene signature model, which can be assessed on FFPE biopsies, constitutes a novel prognostic biomarker for patients with SA.

Basal cytokeratin phenotypes of myoepithelial cells indicates the origin of ductal carcinomas in situ of the breast.

Terminal duct lobular unit (TDLU) is widely accepted as the origin of ductal carcinoma in situ of breast. The differentiation states of myoepithelial cells of breast ductal system hint the development of breast hyperplastic lesions. Basal cytokeratin (CK) phenotypes indicate the differentiation of myoepithelial cells. Using antibodies of CK5/6, CK14, and CK17, this study reports the basal CK phenotypes of myoepithelial cells in 20 foci of normal breast, 20 usual ductal hyperplasias, 36 ductal carcinomas in situ (DCIS), and 28 sclerosing adenosis (SA). The results showed that the positive staining of basal CKs of myoepithelial cells in normal ducts were significantly higher than those in normal lobules. The basal CK expression of myoepithelial cells of DCIS and usual ductal hyperplasia was similar to that of normal duct, whereas that of SA was similar to that of normal lobule. We propose a modified model of TDLU origin of intraductal carcinoma that most of DCIS originate from terminal ducts of TDLU, whereas most SA originate from lobules.

Gene signature model for breast cancer risk prediction for women with sclerosing adenosis.

Benign breast disease (BBD) is diagnosed in 1–2 million women/year in the US, and while these patients are known to be at substantially increased risk for subsequent development of breast cancer, existing models for risk assessment perform poorly at the individual level. Here, we describe a DNA-microarray-based transcriptional model for breast cancer risk prediction for patients with sclerosing adenosis (SA), which represent ¼ of all BBD patients. A training set was developed from 86 patients diagnosed with SA, of which 27 subsequently developed cancer within 10 years (cases) and 59 remained cancer-free at 10 years (controls). An diagonal linear discriminate analysis-prediction model for prediction of cancer within 10 years (SA TTC10) was generated from transcriptional profiles of FFPE biopsy-derived RNA. This model was tested on a separate validation case–control set composed of 65 SA patients. The SA TTC10 gene signature model, composed of 35 gene features, achieved a clear and significant separation between case and control with receiver operating characteristic area under the curve of 0.913 in the training set and 0.836 in the validation set. Our results provide the first demonstration that benign breast tissue contains transcriptional alterations that indicate risk of breast cancer development, demonstrating that essential precursor biomarkers of malignancy are present many years prior to cancer development. Furthermore, the SA TTC10 gene signature model, which can be assessed on FFPE biopsies, constitutes a novel prognostic biomarker for patients with SA.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-015-3513-1) contains supplementary material, which is available to authorized users.

Abstract P4-14-06: Characteristics of benign breast disease and subsequent risk of breast cancer differ by age among African Americans

Abstract Introduction: A history of benign breast disease (BBD) is common and certain established pathologic features are associated with increased breast cancer risk. These associations have been reported primarily from studies of white women, where incidence of BBD peaks in the 4th or 5th decade of life. Previous work in an African American (AA) cohort of women with BBD showed AA women were younger at their first BBD diagnosis. Thus investigating whether different features of benign lesions may be associated with age and/or subsequent breast cancer risk in this population is warranted. Methods: Benign breast biopsies from 1,867 AA women with BBD diagnosed from 1997-2003 were microscopically reviewed for 15 benign features (apocrine metaplasia (AM), ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), lobular hyperplasia (LH), calcifications (Calc), cysts, duct ectasisa (DE), fibroadenoma (FA), fibrosis, intraductal papilloma (IDP), radial scar (RS), sclerosing adenosis (SA), columnar cell alterations (CC), mucocele-like tumors (MLT), and atropy), and followed for subsequent breast cancer in metropolitan Detroit, Michigan. Data from 439 women under 40 and 1,428 women 40 and older at BBD diagnosis were available for analysis, with a mean follow-up time of 14 years. Differences between age categories for BBD features were compared using chi-square tests, and risk of breast cancer was estimated with odds ratios (OR) and 95% confidence intervals (95% CI) calculated from logistic regression analysis. Results: Women 40 and over were more likely to be diagnosed with nearly all of the benign characteristics compared to younger women, including: AM, DH, Calc, cysts, CC, and ADH (all p-values &amp;lt;0.001). Younger women were more likely to present with FA (56% to 43%, p-value&amp;lt;0.001) and no atrophy (44% versus 24%, p-value&amp;lt;0.001) compared to older women. Risk of subsequent breast cancer was associated with cysts (OR=3.95, 95% CI: 1.09, 14.29) in the younger age group, but not the older (OR=1.25, 95% CI: 0.76, 2.03). CC were also associated with breast cancer risk in the young (OR=5.35, 95% CI: 1.45, 19.73) but not the older women (OR=1.44, 95% CI: 0.82, 2.50). RS were associated with increased risk in both groups, but only statistically significant for the older women (OR=3.60, 95% CI: 1.54, 8.39), and not the younger women (OR=6.64, (95% CI: 0.73, 60.67). Similarly, risk of cancer was associated with a diagnosis of ADH in both groups, but only statistically significant among older women (OR=3.02, 95% CI: 1.34, 6.79), and not younger women (OR=6.75, 95% CI: 0.71, 64.43). Conclusions: Characteristics of BBD differ by age, with more women over the age of 40 being diagnosed with various conditions. Risk of subsequent cancer also varies, although RS, CC and ADH appear to increase risk in both age groups. Citation Format: Michele L Cote, Julie J Ruterbusch, Sudeshna Bandyopadhyay, Quratulain Ahmed, Barra Alosh, Eman Abdulfatah, Haitham Arabi, Rouba Lynn Ali-Fehmi. Characteristics of benign breast disease and subsequent risk of breast cancer differ by age among African Americans [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-14-06.