Preoperative breast MRI positively impacts surgical outcomes of needle biopsy-diagnosed pure DCIS: a patient-matched analysis from the MIPA study.

OBJECTIVES: To investigate the influence of preoperative breast MRI on mastectomy and reoperation rates in patients with pure ductal carcinoma in situ (DCIS). METHODS: The MIPA observational study database (7245 patients) was searched for patients aged 18-80 years with pure unilateral DCIS diagnosed at core needle or vacuum-assisted biopsy (CNB/VAB) and planned for primary surgery. Patients who underwent preoperative MRI (MRI group) were matched (1:1) to those who did not receive MRI (noMRI group) according to 8 confounding covariates that drive referral to MRI (age; hormonal status; familial risk; posterior-to-nipple diameter; BI-RADS category; lesion diameter; lesion presentation; surgical planning at conventional imaging). Surgical outcomes were compared between the matched groups with nonparametric statistics after calculating odds ratios (ORs). RESULTS: Of 1005 women with pure unilateral DCIS at CNB/VAB (507 MRI group, 498 noMRI group), 309 remained in each group after matching. First-line mastectomy rate in the MRI group was 20.1% (62/309 patients, OR 2.03) compared to 11.0% in the noMRI group (34/309 patients, p = 0.003). The reoperation rate was 10.0% in the MRI group (31/309, OR for reoperation 0.40) and 22.0% in the noMRI group (68/309, p < 0.001), with a 2.53 OR of avoiding reoperation in the MRI group. The overall mastectomy rate was 23.3% in the MRI group (72/309, OR 1.40) and 17.8% in the noMRI group (55/309, p = 0.111). CONCLUSIONS: Compared to those going directly to surgery, patients with pure DCIS at CNB/VAB who underwent preoperative MRI had a higher OR for first-line mastectomy but a substantially lower OR for reoperation. CLINICAL RELEVANCE STATEMENT: When confounding factors behind MRI referral are accounted for in the comparison of patients with CNB/VAB-diagnosed pure unilateral DCIS, preoperative MRI yields a reduction of reoperations that is more than twice as high as the increase in overall mastectomies. KEY POINTS: • Confounding factors cause imbalance when investigating the influence of preoperative MRI on surgical outcomes of pure DCIS. • When patient matching is applied to women with pure unilateral DCIS, reoperation rates are significantly reduced in women who underwent preoperative MRI. • The reduction of reoperations brought about by preoperative MRI is more than double the increase in overall mastectomies.

Screening and diagnostic breast MRI: how do they impact surgical treatment? Insights from the MIPA study.

OBJECTIVES: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. METHODS: The MIPA observational study enrolled women aged 18-80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. RESULTS: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p < 0.001) for S-MRI, 1.0 (p = 0.957) for D-MRI, and 1.9 (p < 0.001) for P-MRI. CONCLUSIONS: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. KEY POINTS: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups.

Radiologist-Level Performance by Using Deep Learning for Segmentation of Breast Cancers on MRI Scans.

PURPOSE: To develop a deep network architecture that would achieve fully automated radiologist-level segmentation of cancers at breast MRI. MATERIALS AND METHODS: In this retrospective study, 38 229 examinations (composed of 64 063 individual breast scans from 14 475 patients) were performed in female patients (age range, 12-94 years; mean age, 52 years ± 10 [standard deviation]) who presented between 2002 and 2014 at a single clinical site. A total of 2555 breast cancers were selected that had been segmented on two-dimensional (2D) images by radiologists, as well as 60 108 benign breasts that served as examples of noncancerous tissue; all these were used for model training. For testing, an additional 250 breast cancers were segmented independently on 2D images by four radiologists. Authors selected among several three-dimensional (3D) deep convolutional neural network architectures, input modalities, and harmonization methods. The outcome measure was the Dice score for 2D segmentation, which was compared between the network and radiologists by using the Wilcoxon signed rank test and the two one-sided test procedure. RESULTS: The highest-performing network on the training set was a 3D U-Net with dynamic contrast-enhanced MRI as input and with intensity normalized for each examination. In the test set, the median Dice score of this network was 0.77 (interquartile range, 0.26). The performance of the network was equivalent to that of the radiologists (two one-sided test procedures with radiologist performance of 0.69-0.84 as equivalence bounds, P < .001 for both; n = 250). CONCLUSION: When trained on a sufficiently large dataset, the developed 3D U-Net performed as well as fellowship-trained radiologists in detailed 2D segmentation of breast cancers at routine clinical MRI.Keywords: MRI, Breast, Segmentation, Supervised Learning, Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning AlgorithmsPublished under a CC BY 4.0 license. Supplemental material is available for this article.

AI-enhanced breast imaging: Where are we and where are we heading?

Significant advances in imaging analysis and the development of high-throughput methods that can extract and correlate multiple imaging parameters with different clinical outcomes have led to a new direction in medical research. Radiomics and artificial intelligence (AI) studies are rapidly evolving and have many potential applications in breast imaging, such as breast cancer risk prediction, lesion detection and classification, radiogenomics, and prediction of treatment response and clinical outcomes. AI has been applied to different breast imaging modalities, including mammography, ultrasound, and magnetic resonance imaging, in different clinical scenarios. The application of AI tools in breast imaging has an unprecedented opportunity to better derive clinical value from imaging data and reshape the way we care for our patients. The aim of this study is to review the current knowledge and future applications of AI-enhanced breast imaging in clinical practice.

Diagnostic value of radiomics and machine learning with dynamic contrast-enhanced magnetic resonance imaging for patients with atypical ductal hyperplasia in predicting malignant upgrade.

PURPOSE: To investigate whether radiomics features extracted from magnetic resonance imaging (MRI) of patients with biopsy-proven atypical ductal hyperplasia (ADH) coupled with machine learning can differentiate high-risk lesions that will upgrade to malignancy at surgery from those that will not, and to determine if qualitatively and semi-quantitatively assessed imaging features, clinical factors, and image-guided biopsy technical factors are associated with upgrade rate. METHODS: This retrospective study included 127 patients with 139 breast lesions yielding ADH at biopsy who were assessed with multiparametric MRI prior to biopsy. Two radiologists assessed all lesions independently and with a third reader in consensus according to the BI-RADS lexicon. Univariate analysis and multivariate modeling were performed to identify significant radiomic features to be included in a machine learning model to discriminate between lesions that upgraded to malignancy on surgery from those that did not. RESULTS: Of 139 lesions, 28 were upgraded to malignancy at surgery, while 111 were not upgraded. Diagnostic accuracy was 53.6%, specificity 79.2%, and sensitivity 15.3% for the model developed from pre-contrast features, and 60.7%, 86%, and 22.8% for the model developed from delta radiomics datasets. No significant associations were found between any radiologist-assessed lesion parameters and upgrade status. There was a significant correlation between the number of specimens sampled during biopsy and upgrade status (p = 0.003). CONCLUSION: Radiomics analysis coupled with machine learning did not predict upgrade status of ADH. The only significant result from this analysis is between the number of specimens sampled during biopsy procedure and upgrade status at surgery.

Contrast-Enhanced Mammography for Screening Women after Breast Conserving Surgery.

To investigate the value of contrast-enhanced mammography (CEM) compared to full-field digital mammography (FFDM) in screening breast cancer patients after breast-conserving surgery (BCS), this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective, single-institution study included 971 CEM exams in 541 asymptomatic patients treated with BCS who underwent screening CEM between January 2013 and November 2018. Histopathology, or at least a one-year follow-up, was used as the standard of reference. Twenty-one of 541 patients (3.9%) were diagnosed with ipsi- or contralateral breast cancer: six (28.6%) cancers were seen with low-energy images (equivalent to FFDM), an additional nine (42.9%) cancers were detected only on iodine (contrast-enhanced) images, and six interval cancers were identified within 365 days of a negative screening CEM. Of the 10 ipsilateral cancers detected on CEM, four were detected on low-energy images (40%). Of the five contralateral cancers detected on CEM, two were detected on low-energy images (40%). Overall, the cancer detection rate (CDR) for CEM was 15.4/1000 (15/971), and the positive predictive value (PPV3) of the biopsies performed was 42.9% (15/35). For findings seen on low-energy images, with or without contrast, the CDR was 6.2/1000 (6/971), and the PPV3 of the biopsies performed was 37.5% (6/16). In the post-BCS screening setting, CEM has a higher CDR than FFDM.

Regional Lymph Node Involvement Among Patients With De Novo Metastatic Breast Cancer.

Importance: Regional nodal irradiation (RNI) for node-positive breast cancer reduces distant metastases and improves survival, albeit with limited reduction in regional nodal recurrences. The mechanism by which RNI robustly reduces distant metastases while modestly influencing nodal recurrences (ie, the presumed target of RNI) remains unclear. Objective: To determine whether some distant metastases putatively arise from occult regional nodal disease and whether regional recurrences otherwise remain largely undetected until an advanced cancer presentation. Design, Setting, and Participants: This cohort study examined patients presenting with de novo stage IV breast cancer to the Memorial Sloan Kettering Cancer Center in New York, New York, from 2006 to 2018. Medical records were reviewed to ascertain clinicopathological parameters, including estrogen receptor status and survival. Pretreatment positron emission tomography-computed tomography (PET-CT) imaging was reviewed to ascertain the extent of regional nodal involvement at metastatic diagnosis using standard nodal assessment criteria. A subset underwent regional lymph node biopsy for diagnostic confirmation and served to validate the radiographic nodal assessment. Data analysis was performed from October 2019 to February 2020. Exposures: Untreated metastatic breast cancer. Main Outcome and Measures: The primary outcome was the likelihood of regional nodal involvement at the time of metastatic breast cancer presentation and was determined by reviewing pretreatment PET-CT imaging and lymph node biopsy findings. Results: Among 597 women (median [interquartile range] age, 53 [44-65] years) with untreated metastatic breast cancer, 512 (85.8%) exhibited regional lymph node involvement by PET-CT or nodal biopsy, 509 (85%) had involvement of axillary level I, 328 (55%) had involvement in axillary level II, 136 (23%) had involvement in axillary level III, 101 (17%) had involvement in the supraclavicular fossa, and 96 (16%) had involvement in the internal mammary chain. Lymph node involvement was more prevalent among estrogen receptor-negative tumors (92.4%) than estrogen receptor-positive tumors (83.6%). Nodal involvement at the time of metastatic diagnosis was not associated with overall survival. Conclusions and Relevance: These findings suggest that a majority of patients with de novo metastatic breast cancer harbor regional lymph node disease at presentation, consistent with the hypothesis that regional involvement may precede metastatic dissemination. This is in alignment with the findings of landmark trials suggesting that RNI reduces distant recurrences. It is possible that this distant effect of RNI may act via eradication of occult regional disease prior to systemic seeding. The challenges inherent in detecting isolated nodal disease (which is typically asymptomatic) may account for the more modest observed benefit of RNI on regional recurrences. Alternative explanations of nodal involvement that arises concurrently or after metastatic dissemination remain possible, but do not otherwise explain the association of RNI with distant recurrence.

MRI-based machine learning radiomics can predict HER2 expression level and pathologic response after neoadjuvant therapy in HER2 overexpressing breast cancer.

BACKGROUND: To use clinical and MRI radiomic features coupled with machine learning to assess HER2 expression level and predict pathologic response (pCR) in HER2 overexpressing breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: This retrospective study included 311 patients. pCR was defined as no residual invasive carcinoma in the breast or axillary lymph nodes (ypT0/isN0). Radiomics/statistical analysis was performed using MATLAB and CERR software. After ROC and correlation analysis, selected radiomics parameters were advanced to machine learning modelling alongside clinical MRI-based parameters (lesion type, multifocality, size, nodal status). For predicting pCR, the data was split into a training and test set (80:20). FINDINGS: The overall pCR rate was 60.5% (188/311). The final model to predict HER2 heterogeneity utilised three MRI parameters (two clinical, one radiomic) for a sensitivity of 99.3% (277/279), specificity of 81.3% (26/32), and diagnostic accuracy of 97.4% (303/311). The final model to predict pCR included six MRI parameters (two clinical, four radiomic) for a sensitivity of 86.5% (32/37), specificity of 80.0% (20/25), and diagnostic accuracy of 83.9% (52/62) (test set); these results were independent of age and ER status, and outperformed the best model developed using clinical parameters only (p=0.029, comparison of proportion Chi-squared test). INTERPRETATION: The machine learning models, including both clinical and radiomics MRI features, can be used to assess HER2 expression level and can predict pCR after NAC in HER2 overexpressing breast cancer patients. FUNDING: NIH/NCI (P30CA008748), Susan G. Komen Foundation, Breast Cancer Research Foundation, Spanish Foundation Alfonso Martin Escudero, European School of Radiology.

MRI background parenchymal enhancement, fibroglandular tissue, and mammographic breast density in patients with invasive lobular breast cancer on adjuvant endocrine hormonal treatment: associations with survival.

BACKGROUND: To investigate if baseline and/or changes in contralateral background parenchymal enhancement (BPE) and fibroglandular tissue (FGT) measured on magnetic resonance imaging (MRI) and mammographic breast density (MD) can be used as imaging biomarkers for overall and recurrence-free survival in patients with invasive lobular carcinomas (ILCs) undergoing adjuvant endocrine treatment. METHODS: Women who fulfilled the following inclusion criteria were included in this retrospective HIPAA-compliant IRB-approved study: unilateral ILC, pre-treatment breast MRI and/or mammography from 2000 to 2010, adjuvant endocrine treatment, follow-up MRI, and/or mammography 1-2 years after treatment onset. BPE, FGT, and mammographic MD of the contralateral breast were independently graded by four dedicated breast radiologists according to BI-RADS. Associations between the baseline levels and change in levels of BPE, FGT, and MD with overall survival and recurrence-free survival were assessed using Kaplan-Meier survival curves and Cox regression analysis. RESULTS: Two hundred ninety-eight patients (average age = 54.1 years, range = 31-79) fulfilled the inclusion criteria. The average follow-up duration was 11.8 years (range = 2-19). Baseline and change in levels of BPE, FGT, and MD were not significantly associated with recurrence-free or overall survival. Recurrence-free and overall survival were affected by histological subtype (p < 0.0001), number of metastatic axillary lymph nodes (p < 0.0001), age (p = 0.01), and adjuvant endocrine treatment duration (p < 0.001). CONCLUSIONS: Qualitative evaluation of BPE, FGT, and mammographic MD changes cannot predict which patients are more likely to benefit from adjuvant endocrine treatment.

Improved characterization of sub-centimeter enhancing breast masses on MRI with radiomics and machine learning in BRCA mutation carriers.

OBJECTIVES: To investigate whether radiomics features extracted from MRI of BRCA-positive patients with sub-centimeter breast masses can be coupled with machine learning to differentiate benign from malignant lesions using model-free parameter maps. METHODS: In this retrospective study, BRCA-positive patients who had an MRI from November 2013 to February 2019 that led to a biopsy (BI-RADS 4) or imaging follow-up (BI-RADS 3) for sub-centimeter lesions were included. Two radiologists assessed all lesions independently and in consensus according to BI-RADS. Radiomics features were calculated using open-source CERR software. Univariate analysis and multivariate modeling were performed to identify significant radiomics features and clinical factors to be included in a machine learning model to differentiate malignant from benign lesions. RESULTS: Ninety-six BRCA mutation carriers (mean age at biopsy = 45.5 ± 13.5 years) were included. Consensus BI-RADS classification assessment achieved a diagnostic accuracy of 53.4%, sensitivity of 75% (30/40), specificity of 42.1% (32/76), PPV of 40.5% (30/74), and NPV of 76.2% (32/42). The machine learning model combining five parameters (age, lesion location, GLCM-based correlation from the pre-contrast phase, first-order coefficient of variation from the 1st post-contrast phase, and SZM-based gray level variance from the 1st post-contrast phase) achieved a diagnostic accuracy of 81.5%, sensitivity of 63.2% (24/38), specificity of 91.4% (64/70), PPV of 80.0% (24/30), and NPV of 82.1% (64/78). CONCLUSIONS: Radiomics analysis coupled with machine learning improves the diagnostic accuracy of MRI in characterizing sub-centimeter breast masses as benign or malignant compared with qualitative morphological assessment with BI-RADS classification alone in BRCA mutation carriers. KEY POINTS: • Radiomics and machine learning can help differentiate benign from malignant breast masses even if the masses are small and morphological features are benign. • Radiomics and machine learning analysis showed improved diagnostic accuracy, specificity, PPV, and NPV compared with qualitative morphological assessment alone.

Breast cancer screening in average-risk women: towards personalized screening.

Breast cancer screening is widely recognized for reducing breast cancer mortality. The objective in screening is to diagnose asymptomatic early stage disease, thereby improving treatment efficacy. Screening recommendations have been widely debated over the past years and controversies remain regarding the optimal screening frequency, age to start screening, and age to end screening. While there are no new trials, follow-up information of randomized controlled trials has become available. The American College of Physicians recently issued a new guidance statement on screening for breast cancer in average-risk women, with similar recommendations to the U.S. Preventive Services Task Force and to European guidelines. However, these guidelines differ from those ofother American specialty societies. The variations reflect differences in the organizations' values, the metrics used to evaluate screening results, and the differences in healthcare organization (individualized or state-organized healthcare). False-positive rates and overdiagnosis of biologically insignificant cancer are perceived as the most important potential harms associated with mammographic screening; however, there is limited evidence on their actual consequences. Most specialty societies agree that physicians should offer mammographic screening at age 40 years for average-risk women and discuss its benefits and potential harms to achieve a personalized screening strategy through a shared decision-making process.