Radiomics Analysis of Contrast-Enhanced Breast MRI for Optimized Modelling of Virtual Prognostic Biomarkers in Breast Cancer.

Objective: Breast cancer clinical stage and nodal status are the most clinically significant drivers of patient management, in combination with other pathological biomarkers, such as estrogen receptor (ER), progesterone receptor or human epidermal growth factor receptor 2 (HER2) receptor status and tumor grade. Accurate prediction of such parameters can help avoid unnecessary intervention, including unnecessary surgery. The objective was to investigate the role of magnetic resonance imaging (MRI) radiomics for yielding virtual prognostic biomarkers (ER, HER2 expression, tumor grade, molecular subtype, and T-stage). Materials and Methods: Patients with primary invasive breast cancer who underwent dynamic contrast-enhanced (DCE) breast MRI between July 2013 and July 2016 in a single center were retrospectively reviewed. Age, N-stage, grade, ER and HER2 status, and Ki-67 (%) were recorded. DCE images were segmented and Haralick texture features were extracted. The Bootstrap Lasso feature selection method was used to select a small subset of optimal texture features. Classification of the performance of the final model was assessed with the area under the receiver operating characteristic curve (AUC). Results: Median age of patients (n = 209) was 49 (21-79) years. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the model for differentiating N0 vs N1-N3 was: 71%, 79%, 76%, 74%, 75% [AUC = 0.78 (95% confidence interval (CI) 0.72-0.85)], N0-N1 vs N2-N3 was 81%, 59%, 24%, 95%, 62% [AUC = 0.74 (95% CI 0.63-0.85)], distinguishing HER2(+) from HER2(-) was 79%, 48%, 34%, 87%, 56% [AUC = 0.64 (95% CI 0.54-0.73)], high nuclear grade (grade 2-3) vs low grade (grades 1) was 56%, 88%, 96%, 29%, 61% [AUC = 0.71 (95% CI 0.63-0.80)]; and for ER (+) vs ER(-) status the [AUC=0.67 (95% CI 0.59-0.76)]. Radiomics performance in distinguishing triple-negative vs other molecular subtypes was [0.60 (95% CI 0.49-0.71)], and Luminal A [0.66 (95% CI 0.56-0.76)]. Conclusion: Quantitative radiomics using MRI contrast texture shows promise in identifying aggressive high grade, node positive triple negative breast cancer, and correlated well with higher nuclear grades, higher T-stages, and N-positive stages.

Machine Learning Prediction of Lymph Node Metastasis in Breast Cancer: Performance of a Multi-institutional MRI-based 4D Convolutional Neural Network.

Purpose To develop a custom deep convolutional neural network (CNN) for noninvasive prediction of breast cancer nodal metastasis. Materials and Methods This retrospective study included patients with newly diagnosed primary invasive breast cancer with known pathologic (pN) and clinical nodal (cN) status who underwent dynamic contrast-enhanced (DCE) breast MRI at the authors' institution between July 2013 and July 2016. Clinicopathologic data (age, estrogen receptor and human epidermal growth factor 2 status, Ki-67 index, and tumor grade) and cN and pN status were collected. A four-dimensional (4D) CNN model integrating temporal information from dynamic image sets was developed. The convolutional layers learned prognostic image features, which were combined with clinicopathologic measures to predict cN0 versus cN+ and pN0 versus pN+ disease. Performance was assessed with the area under the receiver operating characteristic curve (AUC), with fivefold nested cross-validation. Results Data from 350 female patients (mean age, 51.7 years ± 11.9 [SD]) were analyzed. AUC, sensitivity, and specificity values of the 4D hybrid model were 0.87 (95% CI: 0.83, 0.91), 89% (95% CI: 79%, 93%), and 76% (95% CI: 68%, 88%) for differentiating pN0 versus pN+ and 0.79 (95% CI: 0.76, 0.82), 80% (95% CI: 77%, 84%), and 62% (95% CI: 58%, 67%), respectively, for differentiating cN0 versus cN+. Conclusion The proposed deep learning model using tumor DCE MR images demonstrated high sensitivity in identifying breast cancer lymph node metastasis and shows promise for potential use as a clinical decision support tool. Keywords: MR Imaging, Breast, Breast Cancer, Breast MRI, Machine Learning, Metastasis, Prognostic Prediction Supplemental material is available for this article. Published under a CC BY 4.0 license.

A Tale of Two Hospitals: Effect of Access to Care Through a Safety Net Hospital on Adjuvant Therapy, Imaging Compliance and 5-Year Survival Rates Compared to the University Hospital Served by the Same Breast Cancer Clinical Teams.

RATIONALE AND OBJECTIVES: To compare rates of guideline-concordant care, imaging surveillance, recurrence and survival outcomes between a safety-net (SNH) and tertiary-care University Hospital (UH) served by the same breast cancer clinical teams. MATERIALS AND METHODS: 647 women with newly diagnosed breast cancer treated in affiliated SNH and UH between 11.1.2014 and 3.31.2017 were reviewed. Patient demographics, completion of guideline-concordant adjuvant chemotherapy, radiation and hormonal therapy were recorded. Two multivariable logistic regression models were performed to investigate the effect of hospital and race on cancer stage. Kaplan-Meier log-rank and Cox-regression were used to analyze five-year recurrence-free (RFS) and overall survival (OS) between hospitals and races, (p < 0.05 significant). RESULTS: Patients in SNH were younger (mean SNH 53.2 vs UH 57.9, p < 0.001) and had higher rates of cT3/T4 disease (SNH 19% vs UH 5.5%, p < 0.001). Patients in the UH had higher rates of bilateral mastectomy (SNH 17.6% vs UH 40.1% p < 0.001) while there was no difference in the positive surgical margin rate (SNH 5.0% vs UH 7.6%, p = 0.20), completion of adjuvant radiation (SNH 96.9% vs UH 98.7%, p = 0.2) and endocrine therapy (SNH 60.8% vs UH 66.2%, p = 0.20). SNH patients were less compliant with mammography surveillance (SNH 64.1% vs UH 75.1%, p = 0.02) and adjuvant chemotherapy (SNH 79.1% vs UH 96.3%, p < 0.01). RFS was lower in the SNH (SNH 54 months vs UH 57 months, HR 1.90, 95% CI: 1.18-3.94, p = 0.01) while OS was not significantly different (SNH 90.5% vs UH 94.2%, HR 1.78, 95% CI: 0.97-3.26, p = 0.06). CONCLUSION: In patients experiencing health care disparities, having access to guideline-concordant care through SNH resulted in non-inferior OS to those in tertiary-care UH.

Imaging Challenges in Diagnosing Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) refers to a heterogeneous group of carcinomas that have more aggressive biologic features, faster growth, and a propensity for early distant metastasis and recurrence compared with other breast cancer subtypes. Due to the aggressiveness and rapid growth of TNBCs, there are specific imaging challenges associated with their timely and accurate diagnosis. TNBCs commonly manifest initially as circumscribed masses and therefore lack the typical features of a primary breast malignancy, such as irregular shape, spiculated margins, and desmoplastic reaction. Given the potential for misinterpretation, review of the multimodality imaging appearances of TNBCs is important for guiding the radiologist in distinguishing TNBCs from benign conditions. Rather than manifesting as a screening-detected cancer, TNBC typically appears clinically as a palpable area of concern that most commonly corresponds to a discrete mass at mammography, US, and MRI. The combination of circumscribed margins and hypoechoic to anechoic echogenicity may lead to TNBC being misinterpreted as a benign fibroadenoma or cyst. Therefore, careful mammographic and sonographic evaluation with US image optimization can help avoid misinterpretation. Radiologists should recognize the characteristics of TNBCs that can mimic benign entities, as well as the subtle features of TNBCs that should raise concern for malignancy and aid in timely and accurate diagnosis. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Radial Scars Without Atypia Diagnosed at Percutaneous Core Needle Breast Biopsy: Support for Imaging Surveillance.

Objective: Radial scar (RS) is a low-risk breast lesion that can be associated with or mimic malignancy. Management guidelines remain controversial for patients with RS without atypia on core needle biopsy (CNB). The aim was to evaluate the upgrade rate of these lesions and factors associated with malignancy risk and excision rate to more definitively guide management. Materials and Methods: In this retrospective study, 123 patients with RS without atypia, diagnosed with CNB between January 2008 to December 2014 who were either referred for surgical excision or followed-up with imaging, were reviewed. The differences in clinical presentation, imaging features, and biopsy technique among the benign RS patients and those upgraded, as well as the excised versus the observed patients were compared. Results: Of 123 RS reviewed, 93 cases of RS without atypia as the highest-grade lesion in the ipsilateral breast and with either 24-month imaging follow-up or surgical correlation were included. Seventy-four (79.6%) lesions were surgically excised and 19 (20.4%) were followed-up for at least 24 months. A single upgrade to malignancy (1%) and 15 upgrades to high-risk lesions (16%) were found. There was no association of any upgraded lesion with presenting symptoms or imaging features. The use of vacuum-assistance and larger biopsy needles, along with obtaining a higher number of samples, was associated with fewer upgrades and lower surgical excision rates. Conclusion: The upgrade rate of RS without atypia in our population was low, regardless of the imaging features and biopsy technique utilized. Close imaging surveillance is an acceptable alternative to surgical excision in these patients.

Outcome of Imaging and Biopsy of BI-RADS Category 3 Lesions: Follow-Up Compliance, Biopsy, and Malignancy Rates in a Large Patient Cohort.

OBJECTIVES: To identify biopsy rates and indications for BI-RADS 3 lesions in a large cohort of patients and compare with follow-up compliance and malignancy outcomes. METHODS: We retrospectively reviewed all BI-RADS category-3 lesions seen on mammography and/or ultrasound between 2013 and 2015. Patient age, lesion size, follow-up rates at 6-, 12-, and 24-months were collected. Biopsy timing, indication, and outcomes (malignant vs benign) were recorded using at least 2-year follow-up or biopsy pathology as endpoint. RESULTS: Of 2319 BI-RADS 3 lesions in 2075 women analyzed, biopsy was performed in 173 (7.5%). Most biopsies were performed upfront (99, 57.2%), followed by at 6 (44, 25.4%), 12 (21, 12.1%), and 24-month follow-up (9, 5.2%; P < .001). Palpable (P < .001) and larger (median 1.4 vs 1.0 cm, P < .001) lesions in women <40 years (15.2% vs 4.8%, P < .001) were more likely to undergo biopsy. Most biopsies were prompted by patient/physician desire (64.5%, P < .001). Of 783 lesions with available endpoint, 5 (0.6%) were cancer. All cancers were identified either at presentation (in 0-5 months, n = 1) or 6-month follow-up (in 5-9 months, n = 4) with biopsy prompted by either morphology change (n = 3) or lesion growth (n = 2). Of the 1855 lesions which were expected for follow up, only 310 (16.7%) underwent all follow-ups, while 482 (26.1%) had two, 489 (26.5%) one, and 565 (30.6%) had no follow-up. CONCLUSIONS: In our cohort, BI-RADS category 3 lesions had significantly higher biopsy rates compared with the small malignancy rate, all of which were identified at baseline or first follow-up. Overall patient follow-up compliance low. Imaging follow-up, especially at first 6-month time point, should be encouraged in BI-RADS 3 lesions, instead of upfront biopsies.

Performance of a clinical and imaging-based multivariate model as decision support tool to help save unnecessary surgeries for high-risk breast lesions.

PURPOSE: To investigate the performance of an imaging and biopsy parameters-based multivariate model in decreasing unnecessary surgeries for high-risk breast lesions. METHODS: In an IRB-approved study, we retrospectively reviewed all high-risk lesions (HRL) identified at imaging-guided biopsy in our institution between July 1, 2014-July 1, 2017. Lesions were categorized high-risk-I (HR-I = atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ and atypical papillary lesion) and II (HR-II = Flat epithelial atypia, radial scar, benign papilloma). Patient risk factors, lesion features, detection and biopsy modality, excision and cancer upgrade rates were collected. Reference standard for upgrade was either excision or at least 2-year imaging follow-up. Multiple logistic regression analysis was performed to develop a multivariate model using HRL type, lesion and biopsy needle size for surgical cancer upgrade with performance assessed using ROC analysis. RESULTS: Of 699 HRL in 652 patients, 525(75%) had reference standard available, and 48/525(9.1%) showed cancer at surgical excision. Excision (84.5% vs 51.1%) and upgrade (17.6%vs1.8%) rates were higher in HR-I compared to HR-II (p < 0.01). In HR-I, small needle size < 12G vs ≥ 12G [32.1% vs 13.2%, p < 0.01] and less cores [< 6 vs ≥ 6, 28.6%vs13.7%, p = 0.01] were significantly associated with higher cancer upgrades. Our multivariate model had an AUC = 0.87, saving 28.1% of benign surgeries with 100% sensitivity, based on HRL subtype, lesion size(mm, continuous), needle size (< 12G vs ≥ 12G) and biopsy modality (US vs MRI vs stereotactic) CONCLUSION: Our multivariate model using lesion size, needle size and patient age had a high diagnostic performance in decreasing unnecessary surgeries and shows promise as a decision support tool.

Contrast-Enhanced Digital Mammography: Technique, Clinical Applications, and Pitfalls.

OBJECTIVE. Contrast-enhanced digital mammography (CEDM) combines the high spatial resolution of mammography with the improved enhancement provided by contrast medium. In this article, CEDM technique-the current and potential clinical applications and current challenges-will be reviewed. CONCLUSION. CEDM is a promising technique in the supplemental evaluation of patients with mammographically inconclusive findings and potentially in the screening of women with mammographically dense breasts. CEDM is emerging as a cost-effective alternative to dynamic contrast-enhanced MRI to stage newly diagnosed breast cancer and evaluate response to neoadjuvant chemotherapy.

Benign breast papillomas without atypia diagnosed with core needle biopsy: Outcome of surgical excision and imaging follow-up.

PURPOSE: To evaluate the surgical upgrade rate to malignancy and high-risk lesions in cases of papilloma without atypia diagnosed with imaging-guided percutaneous core needle biopsy (CNB) and to determine whether any lesion imaging features, biopsy techniques, and pathological factors can predict lesion upgrade to help guide clinical management. MATERIALS AND METHODS: Benign papillomas without atypia (n = 399) diagnosed with CNB were retrospectively reviewed. The surgical upgrade rate to malignancy or high-risk lesion (atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in-situ, flat epithelial atypia and atypical papilloma) was determined. Detection modality (i.e. mammography, ultrasonography (US), magnetic resonance imaging (MRI)), lesion type and size, biopsy-guidance modality (US, stereotactic, MRI), biopsy needle size (<14 G vs ≥14 G), use of vacuum assistance, and presenting symptoms were statistically analyzed. The reference standard for evaluation of upgrade was either excision or at least 24 months of imaging follow-up. Chi Square test and Fisher exact tests were performed for categorical variables, and the Mann-Whitney-U test was used for continuous variables. RESULTS: Ultrasound was the predominant biopsy modality (78.4 %, p < 0.001). Of the 399 benign papilloma lesions in 329 women, 239 (59.9 %) were excised and 93 others were followed for at least 24 months (total of 332). Of these 332 lesions, 7 (2.1 %) were upgraded to ductal carcinoma in-situ and 41 (12.3 %) to high-risk lesions at excision. Larger lesion size (≥15 mm, p = 0.009), smaller biopsy needle size (≥14 G, p = 0.027), and use of spring-loaded biopsy device (p = 0.012) were significantly associated with upgrade to atypia. Only lesion size (≥15 mm, p = 0.02) was associated with upgrade to cancer. CONCLUSION: Upgrade to malignancy of biopsy-proven benign papillomas without atypia at the time of surgery was sufficiently low (2.1 %) to support non-operative management. Surgery may be performed for selected cases- those with larger lesion size and those whose biopsies were performed with smaller spring-loaded biopsy needles.