Combined Benefit of Quantitative Three-Compartment Breast Image Analysis and Mammography Radiomics in the Classification of Breast Masses in a Clinical Data Set.

Purpose To investigate the combination of mammography radiomics and quantitative three-compartment breast (3CB) image analysis of dual-energy mammography to limit unnecessary benign breast biopsies. Materials and Methods For this prospective study, dual-energy craniocaudal and mediolateral oblique mammograms were obtained immediately before biopsy in 109 women (mean age, 51 years; range, 31-85 years) with Breast Imaging Reporting and Data System category 4 or 5 breast masses (35 invasive cancers, 74 benign) from 2013 through 2017. The three quantitative compartments of water, lipid, and protein thickness at each pixel were calculated from the attenuation at high and low energy by using a within-image phantom. Masses were automatically segmented and features were extracted from the low-energy mammograms and the quantitative compartment images. Tenfold cross-validations using a linear discriminant classifier with predefined feature signatures helped differentiate between malignant and benign masses by means of (a) water-lipid-protein composition images alone, (b) mammography radiomics alone, and (c) a combined image analysis of both. Positive predictive value of biopsy performed (PPV3) at maximum sensitivity was the primary performance metric, and results were compared with those for conventional diagnostic digital mammography. Results The PPV3 for conventional diagnostic digital mammography in our data set was 32.1% (35 of 109; 95% confidence interval [CI]: 23.9%, 41.3%), with a sensitivity of 100%. In comparison, combined mammography radiomics plus quantitative 3CB image analysis had PPV3 of 49% (34 of 70; 95% CI: 36.5%, 58.9%; P < .001), with a sensitivity of 97% (34 of 35; 95% CI: 90.3%, 100%; P < .001) and 35.8% (39 of 109) fewer total biopsies (P < .001). Conclusion Quantitative three-compartment breast image analysis of breast masses combined with mammography radiomics has the potential to reduce unnecessary breast biopsies. © RSNA, 2018 Online supplemental material is available for this article.

Diffusion-weighted MRI Findings Predict Pathologic Response in Neoadjuvant Treatment of Breast Cancer: The ACRIN 6698 Multicenter Trial.

Purpose To determine if the change in tumor apparent diffusion coefficient (ADC) at diffusion-weighted (DW) MRI is predictive of pathologic complete response (pCR) to neoadjuvant chemotherapy for breast cancer. Materials and Methods In this prospective multicenter study, 272 consecutive women with breast cancer were enrolled at 10 institutions (from August 2012 to January 2015) and were randomized to treatment with 12 weekly doses of paclitaxel (with or without an experimental agent), followed by 12 weeks of treatment with four cycles of anthracycline. Each woman underwent breast DW MRI before treatment, at early treatment (3 weeks), at midtreatment (12 weeks), and after treatment. Percentage change in tumor ADC from that before treatment (ΔADC) was measured at each time point. Performance for predicting pCR was assessed by using the area under the receiver operating characteristic curve (AUC) for the overall cohort and according to tumor hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) disease subtype. Results The final analysis included 242 patients with evaluable serial imaging data, with a mean age of 48 years ± 10 (standard deviation); 99 patients had HR-positive (hereafter, HR+)/HER2-negative (hereafter, HER2-) disease, 77 patients had HR-/HER2- disease, 42 patients had HR+/HER2+ disease, and 24 patients had HR-/HER2+ disease. Eighty (33%) of 242 patients experienced pCR. Overall, ΔADC was moderately predictive of pCR at midtreatment/12 weeks (AUC = 0.60; 95% confidence interval [CI]: 0.52, 0.68; P = .017) and after treatment (AUC = 0.61; 95% CI: 0.52, 0.69; P = .013). Across the four disease subtypes, midtreatment ΔADC was predictive only for HR+/HER2- tumors (AUC = 0.76; 95% CI: 0.62, 0.89; P < .001). In a test subset, a model combining tumor subtype and midtreatment ΔADC improved predictive performance (AUC = 0.72; 95% CI: 0.61, 0.83) over ΔADC alone (AUC = 0.57; 95% CI: 0.44, 0.70; P = .032.). Conclusion After 12 weeks of therapy, change in breast tumor apparent diffusion coefficient at MRI predicts complete pathologic response to neoadjuvant chemotherapy. © RSNA, 2018 Online supplemental material is available for this article.

Screening for Breast Cancer.

The goal of screening is to detect breast cancers when still curable to decrease breast cancer-specific mortality. Breast cancer screening in the United States is routinely performed with mammography, supplemental digital breast tomosynthesis, ultrasound, and/or MR imaging. This article aims to review the most commonly used breast imaging modalities for screening, discuss how often and when to begin screening with specific imaging modalities, and examine the pros and cons of screening. By the article's end, the reader will be better equipped to have informed discussions with patients and medical professionals regarding the benefits and disadvantages of breast cancer screening.

Imaging Management of Breast Density, a Controversial Risk Factor for Breast Cancer.

BACKGROUND: Breast density is well recognized as an independent risk factor for the development of breast cancer. However, the magnitude of risk is controversial. As the public becomes increasingly aware of breast density as a risk factor, legislation and notification laws in relation to breast density have become common throughout the United States. Awareness of breast density as a risk factor for breast cancer presents new challenges for the clinician in the approach to the management and screening of women with dense breasts. METHODS: The evidence and controversy surrounding breast density as a risk factor for the development of breast cancer are discussed. Common supplemental screening modalities for breast cancer are also discussed, including tomosynthesis, ultrasonography, and magnetic resonance imaging. A management strategy for screening women with dense breasts is also presented. RESULTS: The American College of Radiology recognizes breast density as a controversial risk factor for breast cancer, whereas the American Congress of Obstetricians and Gynecologists recognizes breast density as a modest risk factor. Neither organization recommends the routine use of supplemental screening in women with dense breasts without considering additional patient-related risk factors. CONCLUSIONS: Breast density is a poorly understood and controversial risk factor for the development of breast cancer. Mammography is a screening modality proven to reduce breast cancer-related mortality rates and is the single most appropriate tool for population-based screening. Use of supplemental screening modalities should be tailored to individual risk assessment.

A comparison of the diagnostic accuracy of magnetic resonance imaging to axillary ultrasound in the detection of axillary nodal metastases in newly diagnosed breast cancer.

Patients with a diagnosis of invasive breast cancer are increasingly undergoing breast magnetic resonance imaging (MRI) for preoperative staging including evaluation of axillary lymph node metastases (ALNM). This retrospective study aims to evaluate the utility of adding axillary ultrasound (AUS) in the preoperative setting when an MRI is planned or has already been performed. This IRB approved, HIPAA compliant study reviewed a total of 271 patients with a new diagnosis of invasive breast cancer at a single institution, between June 1, 2010 and June 30, 2013. The study included patients who received both AUS and MRI for preoperative staging. Data were divided into two cohorts, patients who underwent MRI prior to AUS and those who underwent AUS prior to MRI. AUS and MRI reports were categorized according to BI-RADS criteria as "suspicious" or "not suspicious" for ALNM. In the setting of a negative MRI and subsequent positive AUS, only one out of 25 cases (4%) were positive for metastases after correlating with histologic pathology. MRI detected metastatic disease in four out of 27 (15%) patients who had false-negative AUS performed prior to MRI. Our results indicate the addition of AUS after preoperative MRI does not contribute significantly to increased detection of missed disease. MRI could serve as the initial staging imaging method of the axilla in the setting that AUS is not initially performed and may be valuable in identification of lymph nodes not identified on AUS.

Heterogeneity in intratumoral regions with rapid gadolinium washout correlates with estrogen receptor status and nodal metastasis.

PURPOSE: To evaluate heterogeneity within tumor subregions or "habitats" via textural kinetic analysis on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the classification of two clinical prognostic features; 1) estrogen receptor (ER)-positive from ER-negative tumors, and 2) tumors with four or more viable lymph node metastases after neoadjuvant chemotherapy from tumors without nodal metastases. MATERIALS AND METHODS: Two separate volumetric DCE-MRI datasets were obtained at 1.5T, comprised of bilateral axial dynamic 3D T1 -weighted fat suppressed gradient recalled echo-pulse sequences obtained before and after gadolinium-based contrast administration. Representative image slices of breast tumors from 38 and 34 patients were used for ER status and lymph node classification, respectively. Four tumor habitats were defined based on their kinetic contrast enhancement characteristics. The heterogeneity within each habitat was quantified using textural kinetic features, which were evaluated using two feature selectors and three classifiers. RESULTS: Textural kinetic features from the habitat with rapid delayed washout yielded classification accuracies of 84.44% (area under the curve [AUC] 0.83) for ER and 88.89% (AUC 0.88) for lymph node status. The texture feature, information measure of correlation, most often chosen in cross-validations, measures heterogeneity and provides accuracy approximately the same as with the best feature set. CONCLUSION: Heterogeneity within habitats with rapid washout is highly predictive of molecular tumor characteristics and clinical behavior.

Magnetic resonance imaging-guided core needle breast biopsies resulting in high-risk histopathologic findings: upstage frequency and lesion characteristics.

UNLABELLED: Analysis of magnetic resonance imaging-guided breast biopsies yielding high-risk histopathologic features at a single institution found an overall upstage rate to malignancy of 14% at surgical excision. All upstaged lesions were associated with atypical ductal hyperplasia. Flat epithelial atypia and atypical lobular hyperplasia alone or with lobular carcinoma in situ were not associated with an upstage to malignancy. INTRODUCTION: The purpose of the present study w as to determine the malignancy upstage rates and imaging features of high-risk histopathologic findings resulting from magnetic resonance imaging (MRI)-guided core needle breast biopsies. These features include atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), flat epithelial atypia (FEA), and lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: A retrospective medical record review was performed on all MRI-guided core needle breast biopsies at a single institution from June 1, 2007 to December 1, 2013 to select biopsies yielding high-risk histopathologic findings. The patient demographics, MRI lesion characteristics, and histopathologic features at biopsy and surgical excision were analyzed. RESULTS: A total of 257 MRI-guided biopsies had been performed, and 50 yielded high-risk histopathologic features (19%). Biopsy site and surgical excision site correlation was confirmed in 29 of 50 cases. Four of 29 lesions (14%) were upstaged: 1 case to invasive ductal carcinoma and 3 cases to ductal carcinoma in situ. ADH alone had an overall upstage rate of 7% (1 of 14), mixed ADH/ALH a rate of 75% (3 of 4), ALH alone or with LCIS a rate of 0% (0 of 7), and FEA a rate of 0% (0 of 4). Only mixed ADH/ALH had a statistically significant upstage rate to malignancy compared with the other high-risk histopathologic subtypes combined. No specific imaging characteristics on MRI were associated with an upstage to malignancy on the statistical analysis. CONCLUSION: MRI-guided breast biopsies yielding high-risk histopathologic features were associated with an overall upstage to malignancy rate of 14% at surgical excision. All upstaged lesions were associated with ADH. FEA and ALH alone or with LCIS were not associated with an upstage to malignancy.

Short-term imaging follow-up of patients with concordant benign breast core needle biopsies: is it really worth it?

PURPOSE: Women with histologically proven concordant benign breast disease are often followed closely after biopsy for a period of two years, and they are considered to be at high-risk for cancer development. Our goal was to evaluate the utility of short-term (six-month) imaging follow-up and determine the incidence of breast cancer development in this population. METHODS: Retrospective review of concordant benign breast pathology was performed in 558 patients who underwent multimodality breast core biopsy. A total of 339 patients (60.7%) with 393 biopsies qualified for the study. The six-, 12-, and 24-month incidence rates of breast cancer development were estimated with 95% confidence intervals (CI), using the exact method binomial proportions. RESULTS: No cancer was detected in 285 of 339 patients (84.1%) returning for the six-month follow-up. No cancer was detected in 271 of 339 patients (79.9%) returning for the 12-month follow-up. Among 207 follow-up exams (61.1%) performed at 24 months, three patients were detected to have cancer in the ipsilateral breast (1.45% [95% CI, 0.30%-4.18%]) and two patients were detected to have cancer in the contralateral breast (0.97% [95% CI, 0.12%-3.45%]). Subsequent patient biopsy rate was 30 of 339 (8.85%, [95% CI, 6.05%-12.39%]). Three ipsilateral biopsies occurred as a sole result of the six-month follow-up of 285 patients (1.05%, [95% CI, 0.22%-3.05%]). CONCLUSION: Short-term imaging follow-up did not contribute to improved breast cancer detection, as all subsequent cancers were detected on annual mammography. Annual diagnostic mammography after benign breast biopsy may be sufficient.

Early experience with ultrasound features after intrabeam intraoperative radiation for early stage breast cancer.

BACKGROUND: Intraoperative radiation therapy (IORT) is an emerging option for partial breast radiotherapy in select women with early stage breast cancer. We assessed short-term clinical and sonographic findings after breast conservation (BCT) and IORT. METHODS: An IRB-approved, single institution retrospective chart review was conducted of patients (pts) treated with BCT/IORT from 1/2011 to 6/2012. Follow-up clinical breast exams and ultrasounds (US) obtained 6 and 12 months after BCT/IORT were retrospectively reviewed by a single breast radiologist (JD) for sonographic findings. P values were calculated using McNemar's test, Wilcoxon Rank Sum Test, and Chi-square. RESULTS: Seventy-one pts underwent BCT/IORT and 38 pts had an US. All 38 pts had a seroma, 10/38 (26%) pts were symptomatic. Eighteen pts had deep tissue closure (DTC) of the lumpectomy cavity with 5/18 (28%) DTC pts being symptomatic at follow-up versus 5/33 (15%) without DTC (P = 0.296). At 6 months, DTC resulted in smaller seroma cavity volumes compared to those without DTC (P = 0.03). CONCLUSION: Presence of a seroma is commonplace post BCT/IORT; symptomatic seromas are uncommon. DTC generated smaller seromas. Longer follow-up with serial US performed in all BCT/IORT pts could be considered to document natural progression/regression of symptoms and seromas.

Mammographic quantitative image analysis and biologic image composition for breast lesion characterization and classification.

PURPOSE: To investigate whether biologic image composition of mammographic lesions can improve upon existing mammographic quantitative image analysis (QIA) in estimating the probability of malignancy. METHODS: The study population consisted of 45 breast lesions imaged with dual-energy mammography prior to breast biopsy with final diagnosis resulting in 10 invasive ductal carcinomas, 5 ductal carcinomain situ, 11 fibroadenomas, and 19 other benign diagnoses. Analysis was threefold: (1) The raw low-energy mammographic images were analyzed with an established in-house QIA method, "QIA alone," (2) the three-compartment breast (3CB) composition measure-derived from the dual-energy mammography-of water, lipid, and protein thickness were assessed, "3CB alone", and (3) information from QIA and 3CB was combined, "QIA + 3CB." Analysis was initiated from radiologist-indicated lesion centers and was otherwise fully automated. Steps of the QIA and 3CB methods were lesion segmentation, characterization, and subsequent classification for malignancy in leave-one-case-out cross-validation. Performance assessment included box plots, Bland-Altman plots, and Receiver Operating Characteristic (ROC) analysis. RESULTS: The area under the ROC curve (AUC) for distinguishing between benign and malignant lesions (invasive and DCIS) was 0.81 (standard error 0.07) for the "QIA alone" method, 0.72 (0.07) for "3CB alone" method, and 0.86 (0.04) for "QIA+3CB" combined. The difference in AUC was 0.043 between "QIA + 3CB" and "QIA alone" but failed to reach statistical significance (95% confidence interval [-0.17 to + 0.26]). CONCLUSIONS: In this pilot study analyzing the new 3CB imaging modality, knowledge of the composition of breast lesions and their periphery appeared additive in combination with existing mammographic QIA methods for the distinction between different benign and malignant lesion types.

Beyond mammography: new frontiers in breast cancer screening.

Breast cancer screening remains a subject of intense and, at times, passionate debate. Mammography has long been the mainstay of breast cancer detection and is the only screening test proven to reduce mortality. Although it remains the gold standard of breast cancer screening, there is increasing awareness of subpopulations of women for whom mammography has reduced sensitivity. Mammography also has undergone increased scrutiny for false positives and excessive biopsies, which increase radiation dose, cost, and patient anxiety. In response to these challenges, new technologies for breast cancer screening have been developed, including low-dose mammography, contrast-enhanced mammography, tomosynthesis, automated whole breast ultrasound, molecular imaging, and magnetic resonance imaging. Here we examine some of the current controversies and promising new technologies that may improve detection of breast cancer both in the general population and in high-risk groups, such as women with dense breasts. We propose that optimal breast cancer screening will ultimately require a personalized approach based on metrics of cancer risk with selective application of specific screening technologies best suited to the individual's age, risk, and breast density.

MR imaging assessment of the breast after breast conservation therapy: distinguishing benign from malignant lesions.

Dynamic contrast material-enhanced magnetic resonance (MR) imaging has emerged as a valuable tool in evaluation of women who have undergone lumpectomy and whole-breast radiation therapy for breast cancer. Early diagnosis of local recurrence by means of close clinical and imaging follow-up is an important component of a breast-conserving strategy, as it may improve survival. In the post-breast conservation therapy (BCT) breast, resolving edema, fat necrosis, a small focal area of non-masslike enhancement (NMLE), and thin linear NMLE at the lumpectomy site can all be expected findings. In contrast, masslike enhancement or NMLE of ductal or segmental distribution can indicate recurrence. Therefore, at MR imaging of the post-BCT breast, it is important to identify lesions that are benign or appropriate for short-interval imaging surveillance to minimize unnecessary intervention, as well as to discern suspicious lesions and optimize the diagnosis of recurrence.

Clinical and imaging surveillance following breast cancer diagnosis.

Breast cancer is the most common malignancy affecting women worldwide. Women have a 1 in 8 lifetime risk of breast cancer. Breast conservation therapy (BCT) is the most common method of definitive treatment. Patients who previously have had to undergo mastectomy may be now eligible for BCT or a multitude of options for reconstruction, either immediate or delayed. Surveillance imaging after a breast cancer diagnosis is important because there is an increased risk of recurrence developing in patients, and early detection has been shown to improve survival. There is currently no consensus on a protocol for imaging the postoperative breast. In patients who have undergone mastectomy, detection of recurrence has mostly been via clinical symptoms and physical exam, often at a later stage. New imaging modalities, such as magnetic resonance imaging (MRI), ultrasound (US), and positron emission mammography (PEM) are changing the way we image the postsurgical breast. MRI, coupled with physical exam and mammography, approaches 100% sensitivity and high specificity for the identification of recurrent disease. We present a review of major academic institutions' imaging protocols and discuss the advantages of including MRI in traditional mammographic and clinical exams.