High-risk Benign Lesions Research Articles

Discrimination Between Benign and Malignant Lesions With Restriction Spectrum Imaging MRI in an Enriched Breast Cancer Screening Cohort.

Breast cancer screening with dynamic contrast-enhanced MRI (DCE-MRI) is recommended for high-risk women but has limitations, including variable specificity and difficulty in distinguishing cancerous (CL) and high-risk benign lesions (HRBL) from average-risk benign lesions (ARBL). Complementary non-invasive imaging techniques would be useful to improve specificity. To evaluate the performance of a previously-developed breast-specific diffusion-weighted MRI (DW-MRI) model (BS-RSI3C) to improve discrimination between CL, HRBL, and ARBL in an enriched screening population. Prospective. Exactly 187 women, either with mammography screening recommending additional imaging (N = 49) or high-risk individuals undergoing routine breast MRI (N = 138), before the biopsy. Multishell DW-MRI echo planar imaging sequence with a reduced field of view at 3.0 T. A total of 72 women had at least one biopsied lesion, with 89 lesions categorized into ARBL, HRBL, CL, and combined CLs and HRBLs (CHRLs). DW-MRI data were processed to produce apparent diffusion coefficient (ADC) maps, and estimate signal contributions (C1, C2, and C3-restricted, hindered, and free diffusion, respectively) from the BS-RSI3C model. Lesion regions of interest (ROIs) were delineated on DW images based on suspicious DCE-MRI findings by two radiologists; control ROIs were drawn in the contralateral breast. One-way ANOVA and two-sided t-tests were used to assess differences in signal contributions and ADC values among groups. P-values were adjusted using the Bonferroni method for multiple testing, P = 0.05 was used for the significance level. Receiver operating characteristics (ROC) curves and intra-class correlations (ICC) were also evaluated. C1, √C1C2, and were significantly different in HRBLs compared with ARBLs (P-values < 0.05). The had the highest AUC (0.821) in differentiating CHRLs from ARBLs, performing better than ADC (0.696), especially in non-mass enhancement (0.776 vs. 0.517). This study demonstrated the BS-RSI3C could differentiate HRBLs from ARBLs in a screening population, and separate CHRLs from ARBLs better than ADC. 2.

Abstract P6-04-12: Differential diagnoses of breast biopsies by spatial parametric modeling of histological structures and explainable AI

Abstract Background: Pathologists typically diagnose the breast tissue slides under a microscope by examining: (i) lumen and ductal morphology, (ii) nuclei size, shape, and spatial arrangement and their combinations, (iii) intraductal architecture, and (iv) textural properties. These features may be subtle and can overlap between diagnoses which contribute to inter- and intra-observer variability. We aim to mitigate this arbitrary nature of breast diagnoses with an exemplar-driven precision pathology pipeline based on spatial parametric modeling of histological structures. Methods: For our study, we consider a broad spectrum of breast biopsies including: (i) invasive breast cancer, (ii) three high-risk benign lesions: ductal carcinoma in-situ, atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and (iii) three low-risk benign lesions: usual ductal hyperplasia, columnar cell change and Normal; where the risk is indicated by the relative chance of developing breast cancer. We build spatial parametric models for a dictionary of histological structures that pathologists frequently use (also documented in the standard reference book from WHO on the classification of tumors) in making complex diagnostic decisions. These models enable our precision pathology pipeline to simultaneously identify distinct exemplar images to account for inter-class heterogeneity, and learn the relative importance of lumen/ductal morphology (LD), intraductal structures including nuclei morphology and spatial arrangements (ID) and textural features (T) from automatically identified exemplar images in assigning diagnostic labels. In doing so, we assert that the assignment of relative importances to LD, ID, and T features is driven by similar looking ducts (‘exemplars’) which were previously encountered during pathology training or clinical practice. Results: We evaluated the inferential power of our exemplar-driven precision pathology pipeline on two separate breast core biopsy image datasets, i) dataset containing 4539 regions of interest (ROIs) images extracted from 387 whole slide images (WSIs, 40x), and ii) dataset containing 1237 ROI images extracted from 93 WSIs (20x). Our precision pathology pipeline shows significant improvement (~20%) in the overall classification performance compared to state-of-the-art black box deep learning methods (e.g., graphical neural networks) on both datasets. In particular, while our performance in detecting invasive lesions is comparable to baseline methods, we show a significant improvement (p&amp;lt; 0.01) in detecting diagnostically important high-risk ADH and FEA ROIs compared to the baseline methods, where inter- and intra-observer variability is a problem. Conclusions: A key highlight of our method is in its ability to provide pathologist friendly diagnostic explanations without largely compromising on the classification performance. The strategy outlined in this work can be generalized to other tissue histologies from other organs as defined in the WHO Classification of Tumors books. Further, our approach can facilitate a communication platform between pathologists and computational scientists to interact and develop AI-driven algorithmic tools that can enhance patient care in a clinical setting. Our framework provides pathologist-friendly explanations paving the way for better, transparent, and trustworthy diagnostic tools. Differential diagnoses of breast biopsies Differential diagnoses of breast biopsies The precision pathology pipeline optimizes the identification of a broad spectrum of breast biopsies (invasive, DCIS, benign), including difficult borderline cases (e.g., ADH, FEA, etc.). It provides pathologist-friendly explanations integrated into a clinical workflow for better, transparent, and trustworthy diagnostic aid. This approach sddresses the limitations of standard black-box AI in building trust with pathologists. Citation Format: Akif Burak Tosun, S. Chakra Chennubhotla. Differential diagnoses of breast biopsies by spatial parametric modeling of histological structures and explainable AI [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 P6-04-12.

Can shear wave elastography be utilized as an additional tool for the assessment of non-mass breast lesions?

We aimed to describe shear wave elastography parameters of non-mass lesions of the breast and to assess the measures of diagnostic accuracy of shear wave elastography in the differentiation of non-mass lesions compared with conventional ultrasound, using histopathologic results as the reference standard. This retrospective study included breast ultrasound-detected non-mass lesions with a confirmed pathologic diagnosis during a two-year study period. B-mode ultrasound and shear wave elastography were performed for all lesions before biopsy. Ultrasound features, shear wave elastography parameters (mean elasticity and maximum stiffness color), as well as Breast Imaging-Reporting and Data System categories were recorded for each lesion. Measures of diagnostic accuracy of ultrasound and ultrasound + shear wave elastography were also assessed. From a total of 567 breast lesions requiring core-needle biopsy, 49 (8.6%) were considered as non-mass lesions. Based on histopathologic reports, 32 patients (65.3%) had non-high-risk benign lesions, five (10.2%) had high-risk benign lesions, five (10.2%) had ductal carcinoma in situ, and seven (14.3%) had invasive carcinoma. There was no significant difference in patients' age and palpability between benign and malignant lesions (p = 0.16 and p = 0.12, respectively). Mean elasticity values and Breast Imaging-Reporting and Data System categories were significantly higher among malignant lesions compared with benign non-mass lesions (both p < 0.001). Furthermore, the addition of shear wave elastography to grayscale ultrasound increased the specificity, positive predictive value, and diagnostic accuracy. The complementary use of shear wave elastography with conventional ultrasound might help in the differentiation of non-mass breast lesions and has the potential to decrease the frequency of unnecessary biopsies performed for benign non-mass lesions.

Benign Breast Intraductal Papillomas Without Atypia at Core Needle Biopsies: Is Surgical Excision Necessary?

The aim of this study was to determine the upgrade rate of image-guided core needle biopsy (CNB)-proven benign breast intraductal papillomas (IDPs) without atypia to high-risk benign lesions or malignancy after surgical excision. A retrospective database search at a single institution identified 102 adult female patients with benign breast IDPs without atypia diagnosed on imaging-guided CNBs who subsequently had surgical excisions between 2011 and 2016. Patient characteristics, imaging features, biopsy techniques, and the pathology reports from imaging-guided CNBs and subsequent surgical excisions were reviewed. The upgrade rate to malignancies or high-risk benign lesions was determined at the patient level. The upgrade rate to malignancy was 2.9% (3/102), including two cases of ductal carcinoma in situ (DCIS) and one case of microinvasive (< 1mm) ductal carcinoma arising from DCIS. The upgrade rate to high-risk benign lesions was 7.8% (8/102), with seven cases of atypical ductal hyperplasia and one case of atypical lobular hyperplasia. A personal history of breast cancer and a larger mean lesion size were significantly associated with an upgrade to malignancy (p < 0.05). The management of benign breast IDPs without atypia detected on imaging-guided CNBs is controversial. Our results suggest risk stratification is important in approaching these patients. Although surgical excision should be considered for all benign breast IDPs without atypia, observation with serial imaging may be appropriate in selected low-risk patients. This approach will save many women from surgeries and decrease the cost of medical care.

Breast Biopsy Intensity and Findings Following Breast Cancer Screening in Women With and Without a Personal History of Breast Cancer

There is little evidence on population-based harms and benefits of screening breast magnetic resonance imaging (MRI) in women with and without a personal history of breast cancer (PHBC). To evaluate biopsy rates and yield in the 90 days following screening (mammography vs magnetic resonance imaging with or without mammography) among women with and without a PHBC. Observational cohort study of 6 Breast Cancer Surveillance Consortium (BCSC) registries. Population-based sample of 812 164 women undergoing screening, 2003 through 2013. A total of 2 048 994 digital mammography and/or breast MRI screening episodes (mammogram alone vs MRI with or without screening mammogram within 30 days). Biopsy intensity (surgical greater than core greater than fine-needle aspiration) and yield (invasive cancer greater than ductal carcinoma in situ greater than high-risk benign greater than benign) within 90 days of a screening episode. We computed age-adjusted rates of biopsy intensity (per 1000 screening episodes) and biopsy yield (per 1000 screening episodes with biopsies). Outcomes were stratified by PHBC and by BCSC 5-year breast cancer risk among women without PHBC. We included 101 103 and 1 939 455 mammogram screening episodes in women with and without PHBC, respectively; MRI screening episodes included 3763 with PHBC and 4673 without PHBC. Age-adjusted core and surgical biopsy rates (per 1000 episodes) doubled (57.1; 95% CI, 50.3-65.1) following MRI compared with mammography (23.6; 95% CI, 22.4-24.8) in women with PHBC. Differences (per 1000 episodes) were even larger in women without PHBC: 84.7 (95% CI, 75.9-94.9) following MRI and 14.9 (95% CI, 14.7-15.0) following mammography episodes. Ductal carcinoma in situ and invasive biopsy yield (per 1000 episodes) was significantly higher following mammography compared with MRI episodes in women with PHBC (mammography, 404.6; 95% CI, 381.2-428.8; MRI, 267.6; 95% CI, 208.0-337.8) and nonsignificantly higher, but in the same direction, in women without PHBC (mammography, 279.3; 95% CI, 274.2-284.4; MRI, 214.6; 95% CI, 158.7-280.8). High-risk benign lesions were more commonly identified following MRI regardless of PHBC. Higher biopsy rates and lower cancer yield following MRI were not explained by increasing age or higher 5-year breast cancer risk. Women with and without PHBC who undergo screening MRI experience higher biopsy rates coupled with significantly lower cancer yield findings following biopsy compared with screening mammography alone. Further work is needed to identify women who will benefit from screening MRI to ensure an acceptable benefit-to-harm ratio.

Most lobular carcinoma in situ and atypical lobular hyperplasia diagnosed on core needle biopsy can be managed clinically with radiologic follow‐up in a multidisciplinary setting

We evaluated the efficacy of using standard radiologic and histologic criteria to guide the follow-up of patients with lobular carcinoma in situ (LCIS), lobular neoplasia (LN), or atypical lobular hyperplasia (ALH). Patients with high-risk benign lesions diagnosed on biopsy were presented and reviewed in a multidisciplinary clinical management conference from 1 November 2003 through September 2011. Associations between patient characteristics and rates of upgrade were determined by univariate and multivariate logistic models, and times to diagnosis carcinoma were calculated. Of 853 cases reviewed, 124 (14.5%) were lobular neoplasms. In all, 104 patients were clinically and/or radiographically monitored. In 20 patients, who were found to have LN on core biopsy and were recommended to have immediate surgical excision, a more significant lesion was identified in 8 (40%) of the excised specimens. Factors associated with a more significant lesion on excisional biopsy included whether the lobular lesion had been targeted for biopsy and whether the extent of disease involved three or more terminal duct lobular units. Of the 104 patients radiographically and clinically monitored, the median follow-up time was 3.4 years with a range of 0.44–8.6 years. Five patients under surveillance were subsequently diagnosed with breast malignancy (three of the five at a site unrelated to the initial biopsy). Patients with incidental lobular lesions identified on percutaneous core needle biopsy have a small risk of upgrade and may not require an excisional biopsy. Clinical management of low-volume lobular lesions in a multidisciplinary setting is an efficacious alternative to surgical excision when radiologic and histologic characteristics are well-defined.

What information do public organizations provide to Belgian women on primary prevention of breast cancer?

Women need to be adequately informed about risk factors and risk reduction strategies for breast cancer to seek optimal primary prevention care. The aim of this study was to determine the amount and content of written information published by Belgian health services and related to primary prevention of breast cancer. We collected all available French language brochures and leaflets related to breast cancer primary prevention and analyzed which risk factors and risk reduction strategies were mentioned. Risk factors and prevention strategies were seldom mentioned. Among the 21 selected leaflets, pertinent to the patient, alcohol was mentioned in eight leaflets; age and genetic predisposition in five; overweight/obesity, personal history of breast cancer, and exercise in four; hormonal treatment in three; family history in two; earlier high-risk benign lesions in one, and ethnicity, breast density, and earlier chest radiation therapy in none. Lifestyle modifications were described in nine, but not one mentioned chemoprevention and risk reduction surgeries. As breast cancer risk reduction now represents an achievable medical objective for women, available written information to women must be improved to help them make an informed choice regarding risk reduction strategies.

Molecular Cloning of hMena (ENAH) and Its Splice Variant hMena+11a: Epidermal Growth Factor Increases Their Expression and Stimulates hMena+11a Phosphorylation in Breast Cancer Cell Lines

hMena (ENAH), an actin regulatory protein involved in the control of cell motility and adhesion, is modulated during human breast carcinogenesis. In fact, whereas undetectable in normal mammary epithelium, hMena becomes overexpressed in high-risk benign lesions and primary and metastatic tumors. In vivo, hMena overexpression correlates with the HER-2(+)/ER(-)/Ki67(+) unfavorable prognostic phenotype. In vitro, neuregulin-1 up-regulates whereas Herceptin treatment down-modulates hMena expression, suggesting that it may couple tyrosine kinase receptor signaling to the actin cytoskeleton. Herein, we report the cloning of hMena and of a splice variant, hMena(+11a), which contains an additional exon corresponding to 21 amino acids located in the EVH2 domain, from a breast carcinoma cell line of epithelial phenotype. Whereas hMena overexpression consistently characterizes the transformed phenotype of tumor cells of different lineages, hMena(+11a) isoform is concomitantly present only in epithelial tumor cell lines. In breast cancer cell lines, epidermal growth factor (EGF) treatment promotes concomitant up-regulation of hMena and hMena(+11a), resulting in an increase of the fraction of phosphorylated hMena(+11a) isoform only. hMena(+11a) overexpression and phosphorylation leads to increased p42/44 mitogen-activated protein kinase (MAPK) activation and cell proliferation as evidenced in hMena(+11a)-transfected breast cancer cell lines. On the contrary, hMena knockdown induces reduction of p42/44 MAPK phosphorylation and of the proliferative response to EGF. The present data provide new insight into the relevance of actin cytoskeleton regulatory proteins and, in particular, of hMena isoforms in coupling multiple signaling pathways involved in breast cancer.

The Role of the Use of US-guided Vacuum-Assisted Breast Biopsy for the Total Removal of Sonographic Evidence in Low- and High-Risk Benign and Malignant Breast Lesions

Purpose: To determine the role of the use of a US-guided vacuum-assisted biopsy for the removal of sonographic evidence (excisional mammotome) for low- and high-risk benign and malignant breast lesions. Materials and Methods: We retrospectively reviewed the pathological results of 678 excisional mammotomes (611 low- and 46 high-risk benign and 21 malignant lesions). We compared the pathological results of the excisional mammotomes and the corresponding subsequent surgery of 27 high-risk benign (7/46 cases) and malignant (20/21 cases) lesions. We also reviewed the follow-up US findings of low- (306/611 cases) and high-risk benign lesions (33/39 cases). Results: Fifteen of 27 (55.6%) surgical cases revealed a residual lesion on the excisional mammotome. There was no case of upgrade pathology seen for a surgical specimen. Follow-up sonography of 306 low-risk benign lesions showed a negative finding for 231 (75.2%) cases, post-biopsy changes in 56 (17.8%) cases, and residual lesions in 19 (5.7%) cases. None of the lesion was palpable. Follow-up sonography of 33 high-risk benign lesions revealed a negative finding in 28 (85%) cases, a post-biopsy scar in 4 (12%) cases, and a local recurrence in 1 (3%) case; none of the cases showed a residual lesion. Conclusion: We suggest that an excisional mammotome can replace surgical excision for low-risk cases and may avoid the immediate surgery for high-risk benign lesions; however, surgery is crucial for a malignancy.

Analyse rétrospective multivariée de la corrélation radio-anatomopathologique de lésions infracliniques du sein. Expérience de l'hôpital Saint-Louis

Several studies have demonstrated that systematic breast cancer screening increases overall survival. We report our experience regarding diagnosis of breast lesions detected using mammography. Case reports of patients operated on in either 1992 or 1993 were retrospectively reviewed. A multivariate analysis of the clinico-pathological correlation was performed. Four hundred fifty seven patients representing on total 544 procedures, were included in the study. Mean age was 50.5 years (range 19-80 years). Most of the patients had no previous history of mammary lesion. Mammography was performed with prophylactic intent in more than 60% of the cases. Four hundred twelve (75.7%) benign lesions were diagnosed. Main lesions were: adenofibroma (15.7%), fibrocystic mastopathy (66.3%), adenosis (26.2%), ductal hyperplasia (23.9%), lobular hyperplasia (10.7%), and combined ductal and lobular hyperplasia (8.5%). Hyperplasia accompanied by cytonuclear atypia was observed in 49 (11%) cases. One hundred thirty two (24.3%) malignant lesions were reported, including 69 (52.3%) invasive carcinomas and 63 (47.7%) in situ carcinomas. Only nine axillary lymph node dissections were positive and 75 minimal breast cancers were diagnosed. The multivariate analysis showed that only radiological signs are a risk factor for cancer. The relative risk for cancer when focus of irregular and vermicular microcalcifications are diagnosed is 4.2 (2.0-8.5). It is 5.6 (2.5-12.5) in case of spiculated opacity. Exeresis following radiological prophylactic screening allows diagnosis of high-risk benign lesions and low-stage breast cancer. Radiological parameters are the most powerful predictive factors for malignancy.