External validation and modification of nomogram for predicting positive resection margins before breast conserving surgery.

PURPOSE: A positive resection margin after breast conserving surgery (BCS) is the most important risk factor for tumor recurrence. In 2012, Seoul National University Hospital (SNUH) breast surgery team developed a nomogram for predicting positive resection margins before BCS to provide individual surgical plans that could reduce local recurrence without increasing re-excision rates. The purpose of this study was to validate this nomogram using an external cohort and to test if addition of surgeon-related factor could improve its use as a predictive model. METHODS: A total of 419 patients with breast cancer who underwent BCS from January to December 2018 were retrospectively reviewed. Using the SNUH BCS nomogram, risk score for positive resection margins was calculated for 343 patients. The predictive accuracy of the nomogram was assessed, and multivariable logistic regression analyses were performed to evaluate the nomogram's predictive variables. RESULTS: The positive resection margin rate of the current external validation cohort was 13.5% (46 out of 343), compared to 14.6% (151 out of 1034) of the original study. The discrimination power of the SNUH BCS nomogram as measure by area under the receiver operating characteristics curve (AUC) was 0.656 [95% confidence interval (CI) 0.576-0.735]. This result is lower than expected value of 0.823 [95% CI 0.785-0.862], the AUC of the original study. Multivariable logistic regression analysis showed that, among the five nomogram variables, presence of tumor size discrepancy greater than 0.5 cm between MRI and ultrasonography (OR 2.445, p = 0.019) and presence of ductal carcinoma in situ on needle biopsy (OR 2.066, p = 0.048) were significantly associated with positive resection margins. Finally, the nomogram score was re-calculated by adding each surgeon's resection margin positive rate as odds ratio and the AUC was increased to 0.733. CONCLUSIONS: Validation of the SNUH BCS nomogram was not successful in the current study as much as its original publication. However, we could improve its predictive power by including surgeon-related factor. Before applying a published nomogram as a preoperative predictive model, we suggest each institution to validate the model and adjust it with surgeon-related factor. Addition of new factors to currently available nomograms holds promise for improving its applicability for breast cancer patients at the actual clinical level.

Usefulness of preoperative breast magnetic resonance imaging with a dedicated axillary sequence for the detection of axillary lymph node metastasis in patients with early ductal breast cancer.

OBJECTIVE: Axillary staging of primary breast cancer is important; however, axillary staging using advanced magnetic resonance imaging (MRI) techniques is very difficult to use. Therefore, we want to evaluate the diagnostic performance of preoperative MRI with a dedicated axillary sequence for axillary lymph node (ALN) metastasis in patients with early ductal breast cancer and determine potential predictors of axillary nodal positivity. MATERIALS AND METHODS: We retrospectively reviewed the MRI findings for 74 consecutive patients diagnosed with invasive breast cancer. The diagnostic performances of axial images alone and axial + reconstructed coronal images for the detection of ALN metastasis were evaluated. The clinicopathological and MRI features of the primary breast cancer lesions were determined. RESULTS: The sensitivity (52.9% vs. 47.1%), specificity (89.5% vs. 71.9%), positive predictive value (60% vs. 33.3%), and negative predictive value (86.4% vs. 82%) for the preoperative detection of ALN metastasis were higher for axial + coronal images than for axial images. In addition, the area under the receiver operating characteristic curve value was higher for axial + coronal images than for axial images (0.595 vs. 0.712, p = 0.043). Peritumoral high signal intensity on T2-weighted images (p = 0.015) of the primary tumor was significantly associated with ALN metastasis. CONCLUSION: Our findings suggest that preoperative axial + reconstructed coronal MR images exhibit good diagnostic performance for ALN metastasis in patients with early ductal breast cancer. In addition, peritumoral high signal intensity on T2-weighted images of the primary tumor can be used as a predictor of ALN metastasis in these patients.

Additive value of diffusion-weighted MRI in the I-SPY 2 TRIAL.

BACKGROUND: The change in apparent diffusion coefficient (ADC) measured from diffusion-weighted imaging (DWI) has been shown to be predictive of pathologic complete response (pCR) for patients with locally invasive breast cancer undergoing neoadjuvant chemotherapy. PURPOSE: To investigate the additive value of tumor ADC in a multicenter clinical trial setting. STUDY TYPE: Retrospective analysis of multicenter prospective data. POPULATION: In all, 415 patients who enrolled in the I-SPY 2 TRIAL from 2010 to 2014 were included. FIELD STRENGTH/SEQUENCE: 1.5T or 3T MRI system using a fat-suppressed single-shot echo planar imaging sequence with b-values of 0 and 800 s/mm2 for DWI, followed by a T1-weighted sequence for dynamic contrast-enhanced MRI (DCE-MRI) performed at pre-NAC (T0), after 3 weeks of NAC (T1), mid-NAC (T2), and post-NAC (T3). ASSESSMENT: Functional tumor volume and tumor ADC were measured at each MRI exam; pCR measured at surgery was assessed as the binary outcome. Breast cancer subtype was defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. STATISTICAL TESTS: A logistic regression model was used to evaluate associations between MRI predictors with pCR. The cross-validated area under the curve (AUC) was calculated to assess the predictive performance of the model with and without ADC. RESULTS: In all, 354 patients (128 HR+/HER2-, 60 HR+/HER2+, 34 HR-/HER2+, 132 HR-/HER2-) were included in the analysis. In the full cohort, adding ADC predictors increased the AUC from 0.76 to 0.78 at mid-NAC and from 0.76 to 0.81 at post-NAC. In HR/HER2 subtypes, the AUC increased from 0.52 to 0.65 at pre-NAC for HR+/HER2-, from 0.67 to 0.73 at mid-NAC and from 0.72 to 0.76 at post-NAC for HR+/HER2+, from 0.71 to 0.81 at post-NAC for triple negatives. DATA CONCLUSION: The addition of ADC to standard functional tumor volume MRI showed improvement in the prediction of treatment response in HR+ and triple-negative breast cancer. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2019;50:1742-1753.

A computer-aided diagnosis system using artificial intelligence for the diagnosis and characterization of breast masses on ultrasound: Added value for the inexperienced breast radiologist.

To evaluate the value of the computer-aided diagnosis (CAD) program applied to diagnostic breast ultrasonography (US) based on operator experience.US images of 100 breast masses from 91 women over 2 months (from May to June 2015) were collected and retrospectively analyzed. Three less experienced and 2 experienced breast imaging radiologists analyzed the US features of the breast masses without and with CAD according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon and categories. We then compared the diagnostic performance between the experienced and less experienced radiologists and analyzed the interobserver agreement among the radiologists.Of the 100 breast masses, 41 (41%) were malignant and 59 (59%) were benign. Compared with the experienced radiologists, the less experienced radiologists had significantly improved negative predictive value (86.7%-94.7% vs 53.3%-76.2%, respectively) and area under receiver operating characteristics curve (0.823-0.839 vs 0.623-0.759, respectively) with CAD assistance (all P < .05). In contrast, experienced radiologists had significantly improved specificity (52.5% and 54.2% vs 66.1% and 66.1%) and positive predictive value (55.6% and 58.5% vs 64.9% and 64.9%, respectively) with CAD assistance (all P < .05). Interobserver variability of US features and final assessment by categories were significantly improved and moderate agreement was seen in the final assessment after CAD combination regardless of the radiologist's experience.CAD is a useful additional diagnostic tool for breast US in all radiologists, with benefits differing depending on the radiologist's level of experience. In this study, CAD improved the interobserver agreement and showed acceptable agreement in the characterization of breast masses.

Comparison of strain and shear wave elastography for qualitative and quantitative assessment of breast masses in the same population.

We investigated addition of strain and shear wave elastography to conventional ultrasonography for the qualitative and quantitative assessment of breast masses; cut-off points were determined for strain ratio, elasticity ratio, and visual score for differentiating between benign and malignant masses. In all, 108 masses from 94 patients were evaluated with strain and shear wave elastography and scored for suspicion of malignancy, visual score, strain ratio, and elasticity ratio. The diagnostic performance between ultrasonography alone and ultrasonography combined with either type of elastography was compared; cut-off points were determined for strain ratio, elasticity ratio, and visual score. Of the 108 masses, 44 were malignant and 64 were benign. The areas under the curves were significantly higher for strain and shear wave elastography-supplemented ultrasonography (0.839 and 0.826, respectively; P = 0.656) than for ultrasonography alone (0.764; P = 0.018 and 0.035, respectively). The diagnostic performances of strain and elasticity ratios were similar when differentiating benign from malignant masses. Cut-off values for strain ratio, elasticity ratio, and visual scores for strain and shear wave elastography were 2.93, 4, 3, and 2, respectively. Both forms of elastography similarly improved the diagnostic performance of conventional ultrasonography in the qualitative and quantitative assessment of breast masses.

Clinical significance of interval changes in breast lesions initially categorized as probably benign on breast ultrasound.

The aims of this study were to determine the malignancy rate of probably benign lesions that show an interval change on follow-up ultrasound and to evaluate the differences seen on imaging between benign and malignant lesions initially categorized as probably benign but with interval change on follow-up breast ultrasound.We retrospectively reviewed 11,323 lesions from ultrasound-guided core-biopsies performed between June 2004 and December 2014 and identified 289 lesions (266 patients) with an interval change from probably benign (Breast Imaging Reporting and Data System [BI-RADS] category 3) in the previous 2 years. Malignancy rates were compared according to the ultrasound findings and the characteristics of the interval changes, including changes in morphology and/or diameter.The malignancy rate for probably benign lesions that showed an interval change on follow-up ultrasound was 6.9% (20/289). The malignancy rate was higher for clustered cysts (33.3%) and irregular or noncircumscribed masses (12.7%) than for circumscribed oval masses (5%) or complicated cysts (5%) seen on initial ultrasound (P = 0.043). Fifty-five percent of the malignancies were found to be ductal carcinoma in situ and there was 1 case of lymph node metastasis among the patients with invasive disease in whom biopsy was delayed by 6 to 15 months. The extent of invasiveness was greater in missed cases. There was a significant difference in the maximal diameter change between the 20 malignant lesions and the 269 benign lesions (4.0 mm vs 2.7 mm, P = 0.002). The cutoff value for maximal diameter change per initial diameter was 39.0% for predicting malignancy (sensitivity 95%, specificity 53.5%). The malignancy rate for morphologically changed lesions was significantly higher than for morphologically stable lesions (13.6% vs 4.9%; P = 0.024)Our 6.9% of probably benign lesions that showed an interval change finally turned out to be malignancy was mostly DCIS. The sonographic features, interval changes in sonographic features, and lesion size might help in the recategorization of these lesions.

Does adding diffuse optical tomography to sonography improve differentiation between benign and malignant breast lesions? Observer performance study.

OBJECTIVES: The purpose of this study was to investigate the added value of diffuse optical tomographic categories combined with conventional sonography for differentiating between benign and malignant breast lesions. METHODS: In this retrospective database review, we included 145 breast lesions (116 benign and 29 malignant) from 145 women (mean age, 46 years; range, 16-86 years). Five radiologists independently reviewed sonograms with and without a diffuse optical tomographic category. Each lesion was scored on a scale of 0% to 100% for suspicion of malignancy and rated according to the American College of Radiology Breast Imaging Reporting and Data System classification. Diagnostic performance was analyzed by comparing area under receiver operating characteristic curve values. Reader agreement was assessed by intraclass correlation coefficients. RESULTS: In the multireader multicase receiver operating characteristic analysis, adding a diffuse optical tomographic category to sonography improved the diagnostic accuracy of sonography (mean areas under the curve, 0.923 for sonography alone and 0.969 for sonography with diffuse optical tomography; P = .039). The interobserver correlation was also improved (0.798 for sonography alone and 0.904 for sonography with diffuse optical tomography). The specificity increased for 4 reviewers from a mean of 19.5% to 45.8% (P < .001 for reviewers 1-4; P = .238 for reviewer 5) with no significant change in the sensitivity. When the diffuse optical tomographic category was applied strictly, the specificity increased for all reviewers from a mean of 19.5% to 68.3% (P < .001 for all reviewers) with no significant change in the sensitivity. CONCLUSIONS: The addition of diffuse optical tomographic categories to sonography may improve diagnostic performance and markedly decrease false-positive biopsy recommendations.

Comparison of sonography with sonographically guided fine-needle aspiration biopsy and core-needle biopsy for initial axillary staging of breast cancer.

OBJECTIVES: The purpose of this study was to determine the roles of sonography and sonographically guided fine-needle aspiration biopsy and core-needle biopsy for initial axillary staging of breast cancer. METHODS: Of 220 patients with breast cancer who underwent preoperative or prechemotherapy sonography for axillary staging, 52 patients who underwent sonographically guided fine-needle aspiration biopsy and core-needle biopsy for cortical thickening or a compressed hilum of lymph nodes on sonography were prospectively enrolled. Sonography and fine-needle aspiration biopsy/core-needle biopsy findings were compared with final pathologic results from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: Forty-eight patients met the final study criteria; we excluded 4 who had received primary systemic chemotherapy and showed negative fine-needle aspiration biopsy/core-needle biopsy results and negative final postoperative pathologic results. The positive predictive value of axillary sonography was 54%. The sensitivity and specificity of fine-needle aspiration biopsy were 73% and 100%, respectively, and those of core-needle biopsy were 77% and 100%. Results did not differ significantly between sonographically guided core-needle biopsy and fine-needle aspiration biopsy. The complication rates of fine-needle aspiration biopsy and core-needle biopsy were both 4%, and fine-needle aspiration biopsy and core-needle biopsy cost $180 and $350, respectively. CONCLUSIONS: Both sonographically guided fine-needle aspiration biopsy and core-needle biopsy were useful for axillary staging of breast cancer with high sensitivity. However, fine-needle aspiration biopsy is recommended based on the advantages of low cost and minimal invasiveness.

Sonoelastography for 1,786 non-palpable breast masses: diagnostic value in the decision to biopsy.

OBJECTIVES: To evaluate the diagnostic value of sonoelastography by correlation with histopathology compared with conventional ultrasound on the decision to biopsy. METHODS: Prospectively determined BI-RADS categories of conventional ultrasound and elasticity scores from strain sonoelastography of 1786 non-palpable breast masses (1,523 benign and 263 malignant) in 1,538 women were correlated with histopathology. The sensitivity and specificity of two imaging techniques were compared regarding the decision to biopsy. We also investigated whether there was a subset of benign masses that were recommended for biopsy by B-mode ultrasound but that had a less than 2% malignancy rate with the addition of sonoelastography. RESULTS: The mean elasticity score of malignant lesions was higher than that of benign lesions (2.94 ± 1.10 vs. 1.78 ± 0.81) (P < 0.001). In the decision to biopsy, B-mode ultrasound had higher sensitivity than sonoelastography (98.5% vs. 93.2%) (P < 0.001), whereas sonoelastography had higher specificity than B-mode ultrasound (42.6% vs. 16.3%) (P < 0.001). BI-RADS category 4a lesions with an elasticity score of 1 had a malignancy rate of 0.8%. CONCLUSIONS: Sonoelastography has higher specificity than B-mode ultrasound in the differentiation between benign and malignant masses and has the potential to reduce biopsies with benign results. KEY POINTS: • Sonoelastography has higher specificity than B-mode ultrasound in distinguishing benign from malignant masses. • Sonoelastography could potentially help reduce the number of biopsies with benign results. • Lesion stiffness on sonoelastography correlated with the malignant potential of the lesion.