Association of preoperative breast MRI features with locoregional recurrence after breast conservation therapy.

Background Locoregional recurrence (LRR) following breast conservation therapy (BCT) is associated with an increased risk of distant metastasis and death in patients with breast cancer. Purpose To investigate whether preoperative breast magnetic resonance imaging (MRI) features are associated with the risk of LRR in patients undergoing BCT. Material and Methods A total of 3781 women with primary invasive breast cancer underwent preoperative MRI and BCT between 2003 and 2013. Forty-eight patients who developed LRR comprised the LRR cohort and one-to-one matching (age, tumor stage, grade, and axillary nodal status) of each patient to a control participant was performed in patients who did not develop recurrence. Three readers independently reviewed MR images of the index cancer and the presence of multifocal disease was assessed. Χ2 analysis was used to compare imaging and clinical features between LRR and control cohorts, with multivariate logistic regression analysis used to identify independent features. Results Significant differences were found in the proportion of multifocal disease ( P = 0.001), background parenchymal enhancement level ( P = 0.007), and breast cancer molecular subtype ( P = 0.01) between LRR and control cohorts. Multivariate analysis showed that multifocal disease (odds ratio [OR] = 11.9; 95% confidence interval [CI] = 1.4-102.5; P = 0.02) and human epidermal growth factor receptor 2-positive subtype (OR = 12.7; 95% CI = 1.3-127.6; P = 0.03) were both independently associated with LRR. Conclusion Multifocal disease on preoperative breast MRI may indicate an increased risk of LRR in patients treated with BCT.

Association between US features of primary tumor and axillary lymph node metastasis in patients with clinical T1-T2N0 breast cancer.

Background Most patients with early-stage breast cancer have clinically negative lymph nodes (LNs). However, 15-20% of patients have axillary nodal metastasis based on the sentinel LN biopsy. Purpose To assess whether ultrasound (US) features of a primary tumor are associated with axillary LN metastasis in patients with clinical T1-T2N0 breast cancer. Material and Methods This retrospective study included 138 consecutive patients (median age = 51 years; age range = 27-78 years) who underwent breast surgery with axillary LN evaluation for clinically node-negative T1-T2 breast cancer. Three radiologists blinded to the axillary surgery results independently reviewed the US images. Tumor distance from the skin and distance from the nipple were determined based on the US report. Association between US features of a breast tumor and axillary LN metastasis was assessed using a multivariate logistic regression model after controlling for clinicopathologic variables. Results Of the 138 patients, 28 (20.3%) had nodal metastasis. At univariate analysis, tumor distance from the skin ( P = 0.019), tumor size on US ( P = 0.023), calcifications ( P = 0.036), architectural distortion ( P = 0.001), and lymphovascular invasion ( P = 0.049) were associated with axillary LN metastasis. At multivariate analysis, shorter skin-to-tumor distance (odds ratio [OR] = 4.15; 95% confidence interval [CI] = 1.01-16.19; P = 0.040) and masses with associated architectural distortion (OR = 3.80; 95% CI = 1.57-9.19; P = 0.003) were independent predictors of axillary LN metastasis. Conclusion US features of breast cancer can be promising factors associated with axillary LN metastasis in patients with clinically node-negative early-stage breast cancer.

Diagnostic performance of tomosynthesis and breast ultrasonography in women with dense breasts: a prospective comparison study.

PURPOSE: To compare the diagnostic performances of tomosynthesis and ultrasonography as adjunctives to digital mammography in women with dense breasts. METHODS: A total of 778 women with dense breasts underwent digital mammography with tomosynthesis and ultrasonography for screening and diagnostic purposes. The findings of tomosynthesis and ultrasonography were evaluated independently. The primary endpoint was overall diagnostic accuracy determined by area under the receiver operating characteristic curve (AUC). Secondary endpoints included sensitivity, specificity, and predictive values. RESULTS: Of the 778 participants, 698 women (140 breast cancers) were included in the analysis. Based on the AUC findings, the non-inferiority of tomosynthesis to ultrasonography was established in the overall group as well as in all subgroups except for that comprising women with extremely dense breast composition. There were no significant differences in AUC between tomosynthesis and ultrasonography among asymptomatic participants and participants who underwent imaging for screening (0.912 vs. 0.934 [P = 0.403] and 0.987 vs. 0.950 [P = 0.270], respectively). Tomosynthesis exhibited lower sensitivity (91.4 vs. 96.4%; P = 0.039), and higher specificity (83.9 vs. 70.4%; P < 0.001) and positive predictive value (58.7 vs. 45.0%; P < 0.001) than ultrasonography. CONCLUSIONS: Tomosynthesis exhibits comparable performance to ultrasonography as an adjunct to mammography for diagnosis of breast cancer, except among women with extremely dense breasts.

Preoperative MR Imaging in Women with Breast Cancer Detected at Screening US.

Purpose To determine additional cancer yield of magnetic resonance (MR) imaging in women with breast cancer detected at screening ultrasonography (US) and to identify a subgroup of women who are likely to benefit from preoperative MR imaging. Materials and Methods This study was approved by the institutional review board, and the requirement for informed consent was waived. A retrospective review of 374 women (median age, 48 years; age range, 30-74 years) with breast cancer detected at screening US (invasive, n = 321) who underwent preoperative breast MR imaging between 2007 and 2013 was performed. Cancer yield and positive predictive value of biopsy were calculated. Multivariate logistic regression analysis was performed to identify clinical-pathologic features associated with additional cancer detected at MR imaging. Results Of 374 women, 21 (5.6%; 95% confidence interval [CI]: 3.5%, 8.5%) were diagnosed with additional cancer (positive predictive value of biopsy, 42.0% [21 of 50 women]; 95% CI: 28%, 57%). Index invasive lobular cancer (ILC) histologic type was significantly associated with additional cancer detected at MR imaging (odds ratio, 4.0; 95% CI: 1.2, 13.6; P = .03). In women with index invasive cancer, premenopausal status (odds ratio, 5.7; 95% CI: 1.2, 35.8; P = .03) and lobular histologic type (odds ratio, 3.9; 95% CI: 1.1, 12.3; P = .03) were factors associated with additional cancer detected at MR imaging. Conclusion Preoperative MR imaging helped to detect additional sites of cancer in 5.6% of women with breast cancer detected at screening US. Women with index ILC and premenopausal women are more likely to benefit from preoperative MR imaging. © RSNA, 2016 Online supplemental material is available for this article.

Impact of prior mammograms on combined reading of digital mammography and digital breast tomosynthesis.

Background Although digital breast tomosynthesis (DBT) is an emerging technique yielding higher sensitivity and specificity compared to digital mammography (DM) alone, relative contribution of prior mammograms on the interpretation of DBT combined with DM has not been investigated. Purpose To retrospectively compare the diagnostic performances of DM, DM + DBT, and DM + DBT with prior mammograms. Material and Methods Three breast radiologists independently reviewed images of 116 patients with 24 cancers in the sequential order of DM, DM + DBT, and DM + DBT with prior mammograms using Breast Imaging Reporting and Data System (BI-RADS) assessment categories. Results The average areas under the receiver operating characteristic curve (AUC) of DM, DM + DBT, and DM + DBT with prior mammograms were 0.712, 0.777, and 0.816, respectively. Adding prior mammograms did not significantly affect the AUC of DM + DBT ( P = 0.108), whereas adding DBT significantly increased the AUC of DM ( P = 0.009). Sensitivity for DM, DM + DBT, and DM + DBT with prior mammograms was 58.3%, 69.4%, and 69.4%, and specificities were 84.1%, 85.9%, and 93.8%, respectively. Addition of DBT significantly increased the sensitivity ( P = 0.0090) of DM. Prior mammograms significantly improved the specificity of DM + DBT ( P = 0.0004), whereas adding prior mammogram did not affect sensitivity of DM + DBT ( P = 1.000). Conclusion DBT significantly increases the overall sensitivity and diagnostic performance of DM. Prior mammograms significantly increase the specificity of DM + DBT but have no significant effect on sensitivity and overall diagnostic performance.

MR and mammographic imaging features of HER2-positive breast cancers according to hormone receptor status: a retrospective comparative study.

Background Human epidermal growth factor receptor 2-positive (HER2+) breast cancer has two distinct subtypes according to hormone receptor (HR) status. Survival, pattern of recurrence, and treatment response differ between HR-/HER2+ and HR+/HER2+ cancers. Purpose To investigate imaging and clinicopathologic features of HER2+ cancers and their correlation with HR expression. Material and Methods Between 2011 and 2013, 252 consecutive patients with 252 surgically confirmed HER2+ cancers (125 HR- and 127 HR+) were included. Two experienced breast radiologists blinded to the clinicopathologic findings reviewed the mammograms and magnetic resonance (MR) images using the BI-RADS lexicon. Tumor kinetic features were acquired by computer-aided detection (CAD). The imaging and clinicopathologic features of 125 HR-/HER2+ cancers were compared with those of 127 HR+/HER2+ cancers. Association between the HR status and each feature was assessed. Results Multiple logistic regression analysis showed that circumscribed mass margin (odds ratio [OR], 4.73; P < 0.001), associated non-mass enhancement (NME) on MR images (OR, 3.29; P = 0.001), high histologic grade (OR, 3.89; P = 0.002), high Ki-67 index (OR, 3.06; P = 0.003), and older age (OR, 2.43; P = 0.006) remained independent indicators associated with HR-/HER2+ cancers. Between the two HER2+ subtypes, there were no differences in mammographic imaging presentations and calcification features and MR kinetic features by a CAD. Conclusion HER2+ breast cancers have different MR imaging (MRI) phenotypes and clinicopathologic feature according to HR status. MRI features related to HR and HER2 status have the potential to be used for the diagnosis and treatment decisions in HER2+ breast cancer patients.

Pretreatment MR Imaging Features of Triple-Negative Breast Cancer: Association with Response to Neoadjuvant Chemotherapy and Recurrence-Free Survival.

Purpose To investigate whether pretreatment breast magnetic resonance (MR) imaging features are associated with pathologic complete response (PCR) and recurrence-free survival after neoadjuvant chemotherapy (NAC) in patients with triple-negative breast cancer. Materials and Methods Identified were 132 patients with primary triple-negative breast cancers who underwent NAC and pretreatment MR imaging between 2004 and 2010. Three breast radiologists independently reviewed the MR images based on the 2013 Breast Imaging Reporting and Data System lexicon. Presence of intratumoral high signal intensity and peritumoral edema on T2-weighted images was also evaluated. Association of PCR and recurrence-free survival with MR imaging features was assessed by using logistic regression and Cox regression. Bonferroni correction was applied to the P values. Results Among 132 patients, 18 (14%) underwent PCR. Round or oval masses (odds ratio, 3.5 [95% confidence interval: 1.3, 9.7]; P = .02), the absence of intratumoral T2 high signal intensity (odds ratio, 3.8 [95% confidence interval: 1.3, 11.0]; P = .01), and the absence of peritumoral edema (odds ratio, 3.4 [95% confidence interval: 1.2, 9.5]; P = .02) were associated with PCR, but not significantly. After 54 months of median follow-up, there were 41 (31% [41 of 132]) breast cancer recurrences. Peritumoral edema was the only significant variable associated with worse recurrence-free survival (hazard ratio, 4.9 [95% confidence interval: 1.9, 12.6]; P = .001). Conclusion Pretreatment MR imaging features may be associated with PCR and recurrence-free survival in patients with triple-negative breast cancer. © RSNA, 2016 Online supplemental material is available for this article.

Early Stage Triple-Negative Breast Cancer: Imaging and Clinical-Pathologic Factors Associated with Recurrence.

PURPOSE: To determine the imaging and clinical-pathologic factors associated with recurrence in patients with early stage triple-negative breast cancer. MATERIALS AND METHODS: This study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The authors evaluated 398 patients with stage I or II triple-negative breast cancer (median age, 48 years; range, 21-81 years) who were treated between January 2003 and December 2008. Data collected included preoperative breast magnetic resonance (MR) images, mammographic density, patient age, symptoms, family history of breast cancer, histologic tumor characteristics, tumor grade, tumor size, lymphovascular invasion, lymph node involvement, surgery type, margin status, and adjuvant treatment received. Multivariate analysis was performed by using a Cox proportional hazards model, and recurrence-free survival was estimated with the adjusted Kaplan-Meier method. RESULTS: Of the 398 patients, 63 (15.8%) had recurrent disease after a median follow-up of 6.1 years. The absence of preoperative MR imaging (hazard ratio [HR] with multivariate analysis = 2.66; 95% confidence interval = 1.49, 4.75; P < .001), dense breast tissue (HR = 2.77; 95% confidence interval = 1.39, 5.51; P = .004), family history of breast cancer (HR = 2.32; 95% confidence interval = 1.10, 4.90; P = .028), and lymphovascular invasion (HR = 1.83; 95% confidence interval = 1.11, 3.03; P = .019) were found to be independently associated with recurrence. These same factors were also found to be associated with recurrence-free survival. CONCLUSION: The absence of preoperative MR imaging and the presence of dense breast tissue at mammography were associated with an increased risk of recurrence in patients with triple-negative breast cancer.

Undiagnosed Breast Cancer: Features at Supplemental Screening US.

PURPOSE: To retrospectively investigate the reasons for and features of undiagnosed cancers at previous supplemental screening ultrasonography (US) in women who subsequently received a diagnosis of breast cancer. MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived the requirement to obtain informed patient consent. The study consisted of 230 women (median age, 49 years; age range, 29-81 years) with 230 pairs of US examinations (prior and subsequent examinations) performed between December 2003 and August 2013 who were found to have cancer (median interval, 12 months; range, 2-24 months). The authors compared the clinical-pathologic features of patients with negative findings on prior images with those of patients with visible findings on prior images. Findings visible at prior US were classified as actionable or underthreshold by means of a blinded review by five radiologists. Lesions classified as Breast Imaging Reporting and Data System category 4 or 5 by fewer than three readers were determined to be underthreshold. Reasons for undiagnosed cancers and their imaging features were analyzed. RESULTS: Among the 230 prior US examinations, 72 (31.3%) showed visible findings and 158 (68.7%) showed negative findings. High-nuclear-grade cancers and triple-negative cancers were more common in patients with negative findings than in those with visible findings (P = .023 and P = .006, respectively). Blinded review revealed that 57 of the 72 visible findings (79%) were actionable. Misinterpretation (39% [28 of 72 lesions]) and multiple distracting lesions (17% [12 of 72 lesions]) were the two most common reasons for missing these actionable findings, which showed more noncircumscribed margins than did underthreshold findings (P = .028). CONCLUSION: At supplemental screening breast US, close attention should be paid to the presence of a margin that is not circumscribed, and multiple lesions should be separately assessed to reduce the number of missed breast cancers.

Heterogeneity of triple-negative breast cancer: mammographic, US, and MR imaging features according to androgen receptor expression.

OBJECTIVE: Our aim was to determine whether triple-negative breast cancers (TNBCs) with and without androgen receptor (AR) expression have distinguishing imaging features on mammography, breast ultrasound (US), and magnetic resonance (MR) imaging. METHODS: AR expression was assessed immunohistochemically in 125 patients with TNBC from a consecutive series of 1,086 operable invasive breast cancers. Two experienced radiologists blinded to clinicopathological findings reviewed all imaging studies in consensus using the BI-RADS lexicon. The imaging and pathological features of 33 AR-positive TNBCs were compared with those of 92 AR-negative TNBCs. RESULTS: The presence of mammographic calcifications with or without a mass (p < 0.001), non-mass enhancement on MR imaging (p < 0.001), and masses with irregular shape or spiculated margins on US (p < 0.001 and p = 0.002) and MR imaging (p = 0.001 and p < 0.001) were significantly associated with AR-positive TNBC. Compared with AR-negative TNBC, AR-positive TNBC was more likely to have a ductal carcinoma in situ component (59.8% vs. 90.9%, p = 0.001) and low Ki-67 expression (30.4% vs. 51.5%, p = 0.030). CONCLUSION: AR-positive and AR-negative TNBCs have different imaging features, and certain imaging findings can be useful to predict AR status in TNBC. KEY POINTS: • Triple-negative breast cancers have distinguishing imaging features according to AR expression. • AR-positive TNBC is associated with calcifications, spiculated masses, and non-mass enhancement. • Multimodality imaging can help predict androgen receptor status in TNBC.

Comparative evaluation of average glandular dose and breast cancer detection between single-view digital breast tomosynthesis (DBT) plus single-view digital mammography (DM) and two-view DM: correlation with breast thickness and density.

OBJECTIVES: To compare the average glandular dose (AGD) and diagnostic performance of mediolateral oblique (MLO) digital breast tomosynthesis (DBT) plus cranio-caudal (CC) digital mammography (DM) with two-view DM, and to evaluate the correlation of AGD with breast thickness and density. METHODS: MLO and CC DM and DBT images of both breasts were obtained in 149 subjects. AGDs of DBT and DM per exposure were recorded, and their correlation with breast thickness and density were evaluated. Paired data of MLO DBT plus CC DM and two-view DM were reviewed for presence of malignancy in a jack-knife alternative free-response ROC (JAFROC) method. RESULTS: The AGDs of both DBT and DM, and differences in AGD between DBT and DM (ΔAGD), were correlated with breast thickness and density. The average JAFROC figure of merit (FOM) was significantly higher on the combined technique than two-view DM (P = 0.005). In dense breasts, the FOM and sensitivity of the combined technique was higher than that of two-view DM (P = 0.003) with small ΔAGD. CONCLUSIONS: MLO DBT plus CC DM provided higher diagnostic performance than two-view DM in dense breasts with a small increase in AGD. KEY POINTS: • DBT has higher diagnostic performance and potential to overcome limitations of DM. • Dose differences (DBT-DM, ΔAGD) were inversely correlated with breast thickness and density. • Figure of merit of MLO-DBT/CC-DM was higher than that of two-view DM. • In dense breasts, MLO-DBT/CC-DM provides better diagnostic performance with a small AGD increase.

Quantitative MRI morphology of invasive breast cancer: correlation with immunohistochemical biomarkers and subtypes.

BACKGROUND: Breast cancer is a heterogeneous disease with intrinsic molecular subtypes. The different biology and histology of breast cancer exhibit different tumor morphology at breast magnetic resonance imaging (MRI). However, few studies have examined the quantitative relationship between the MRI morphological and immunohistochemical features in breast cancer. PURPOSE: To investigate the correlations between tumor roundness, as quantitatively assessed with MRI and biomarkers or subtypes of breast cancer. MATERIAL AND METHODS: A total of 280 women (mean age, 51 years; range, 28-79 years) with 282 invasive breast cancers (<5 cm) were included. The associations between the tumor roundness (1-100%), as measured using MRI software, and immunohistochemical (e.g. estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2], and Ki67) features were evaluated using Pearson's or Spearman's rank correlation coefficients and multiple linear regression analysis. RESULTS: An inverse correlation was observed between the ER (r = -0.408, P < 0.001) or PR (r = -0.248, P < 0.001) scores and tumor roundness, whereas a positive correlation was observed between the Ki67 index and tumor roundness (r = 0.354, P < 0.001). In multiple linear regression, the ER score (P < 0.001) and Ki67 index (P = 0.003) were independent factors determining tumor roundness. Triple-negative tumors (ER, PR, and HER2 negative) showed the highest mean roundness scores compared with the other subtypes (e.g. 67.3% for triple-negative, relative to 55.9% for HER2-enriched, 53.8% for luminal B, and 51.7% for luminal A, P < 0.001). CONCLUSION: Our results suggest that breast tumors with lower ER expression and higher cellular proliferation or biologically aggressive triple-negative tumors are likely to manifest with relatively benign morphologic features.

Background parenchymal signal enhancement ratio at preoperative MR imaging: association with subsequent local recurrence in patients with ductal carcinoma in situ after breast conservation surgery.

PURPOSE: To retrospectively investigate whether the background parenchymal features around a tumor at preoperative dynamic contrast material-enhanced magnetic resonance (MR) imaging are associated with ipsilateral breast tumor recurrence (IBTR)-free survival in patients with ductal carcinoma in situ (DCIS) after breast conservation surgery. MATERIALS AND METHODS: The institutional review board approved this study, and the requirement for informed consent was waived. Between 2004 and 2009, 215 consecutive women with pure DCIS who had undergone preoperative dynamic contrast-enhanced MR imaging and curative breast conservation surgery were identified. Clinical-pathologic features (age, menopausal status, presentation of clinical findings, biopsy method, tumor size, nuclear grade, hormonal receptor status, margin status, and adjuvant therapy) and MR imaging features (lesion size, background parenchymal enhancement grade, fibroglandular density, parenchymal signal enhancement ratio [SER] around the tumor, lesion type, and lesion kinetics) were analyzed. A Cox proportional hazards model was used to determine the association between MR imaging variables and IBTR-free survival after controlling for clinical-pathologic variables. Reproducibility of SER measurements was evaluated by using the intraclass correlation coefficient. RESULTS: There were 15 of 215 (7.0%) IBTR cases (nine DCIS cases and six invasive cases) at a median of 36 months (range, 11-61 months). Multivariate analysis showed that higher parenchymal SER (hazard ratio [HR] = 2.028, P < .001 for reader 1; HR = 1.652, P < .001 for reader 2) and larger histologic tumor size (HR = 1.360, P = .009 for reader 1; HR = 1.402, P = .006 for reader 2) were independent factors associated with worse IBTR-free survival. The intraclass correlation coefficient of SER measurements between two readers was 0.852 (95% confidence interval: 0.811, 0.885). CONCLUSION: Higher parenchymal SER around the tumor at preoperative dynamic contrast-enhanced MR imaging and larger histologic tumor size were independent factors associated with worse IBTR-free survival in patients with DCIS after breast conservation surgery.

Two-view versus single-view shear-wave elastography: comparison of observer performance in differentiating benign from malignant breast masses.

PURPOSE: To determine whether two-view shear-wave elastography (SWE) improves the performance of radiologists in differentiating benign from malignant breast masses compared with single-view SWE. MATERIALS AND METHODS: This prospective study was conducted with institutional review board approval, and written informed consent was obtained. B-mode ultrasonographic (US) and orthogonal SWE images were obtained for 219 breast masses (136 benign and 83 malignant; mean size, 14.8 mm) in 219 consecutive women (mean age, 47.9 years; range, 20-78 years). Five blinded radiologists independently assessed the likelihood of malignancy for three data sets: B-mode US alone, B-mode US and single-view SWE, and B-mode US and two-view SWE. Interobserver agreement regarding Breast Imaging Reporting and Data System (BI-RADS) category and the area under the receiver operating characteristic curve (AUC) of each data set were compared. RESULTS: Interobserver agreement was moderate (κ = 0.560 ± 0.015 [standard error of the mean]) for BI-RADS category assessment with B-mode US alone. When SWE was added to B-mode US, five readers showed substantial interobserver agreement (κ = 0.629 ± 0.017 for single-view SWE; κ = 0.651 ± 0.014 for two-view SWE). The mean AUC of B-mode US was 0.870 (range, 0.855-0.884). The AUC of B-mode US and two-view SWE (average, 0.928; range, 0.904-0.941) was higher than that of B-mode US and single-view SWE (average, 0.900; range, 0.890-0.920), with statistically significant differences for three readers (P ≤ .003). CONCLUSION: The performance of radiologists in differentiating benign from malignant breast masses was improved when B-mode US was combined with two-view SWE compared with that when B-mode US was combined with single-view SWE.