Nariya Cho

Diffusion-weighted MR Imaging: Pretreatment Prediction of Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer

PURPOSE To evaluate the potential of diffusion-weighted (DW) magnetic resonance (MR) imaging with an apparent diffusion coefficient (ADC) map in the prediction of response to neoadjuvant chemotherapy in patients with breast cancer. MATERIALS AND METHODS This retrospective study was approved by the institutional review board, which waived the informed consent requirement. Fifty-three consecutive women (mean age, 43.7 years; median age, 42.0 years; age range, 24-65 years) with 53 invasive breast cancers (mean diameter, 5.0 cm; median diameter, 4.2 cm; diameter range, 2.0-13.3 cm) who had undergone chemotherapy were included. Both DW MR imaging (b values, 0 and 750 sec/mm(2)) and dynamic contrast material-enhanced (DCE) MR imaging were performed at 1.5 T before and after chemotherapy prior to surgery. Mean time from initiation of chemotherapy to posttreatment ADC measurement was 54 days (range, 48-62 days). Average ADC for three regions of interest per tumor on ADC maps was calculated. Patients with a reduction in tumor diameter of at least 30% after chemotherapy at DCE MR imaging were defined as responders. Pretreatment ADCs and percentage increases in ADC after chemotherapy in responders and nonresponders were compared. The best pretreatment ADC cutoff with which to differentiate between responders and nonresponders was calculated with receiver operating characteristic curve analysis. RESULTS After chemotherapy, 36 (68%) patients were classified as responders, and 17 (32%) were classified as nonresponders. Pretreatment mean ADC ([1.036 ± 0.015] × 10(-3) mm(2)/sec [standard error]) of responders was significantly lower than that of nonresponders ([1.299 ± 0.079] × 10(-3) mm(2)/sec) (P = .004). Furthermore, mean percentage ADC increase of responders (47.9% ± 4.8) was higher than that of nonresponders (18.1% ± 4.5) (P < .001). The best pretreatment ADC cutoff with which to differentiate between responders and nonresponders was 1.17 × 10(-3) mm(2)/sec, which yielded a sensitivity of 94% (95% confidence interval [CI]: 81%, 99%) and a specificity of 71% (95% CI: 44%, 90%). CONCLUSION Patients with breast cancer and a low pretreatment ADC tended to respond better to chemotherapy. Prediction of response to neoadjuvant chemotherapy with DW MR imaging might help physicians individualize treatments and avoid ineffective chemotherapy.

Nonpalpable Breast Masses: Evaluation by US Elastography

Objective To compare the diagnostic performances of conventional ultrasound (US) and US elastography for the differentiation of nonpalpable breast masses, and to evaluate whether elastography is helpful at reducing the number of benign biopsies, using histological analysis as a reference standard. Materials and Methods Conventional US and real-time elastographic images were obtained for 100 women who had been scheduled for a US-guided core biopsy of 100 nonpalpable breast masses (83 benign, 17 malignant). Two experienced radiologists unaware of the biopsy and clinical findings analyzed conventional US and elastographic images by consensus, and classified lesions based on degree of suspicion regarding the probability of malignancy. Results were evaluated by receiver operating characteristic curve analysis. In addition, the authors investigated whether a subset of lesions was categorized as suspicious by conventional US, but as benign by elastography. Results Areas under the ROC curves (Az values) were 0.901 for conventional US and 0.916 for elastography (p = 0.808). For BI-RADS category 4a lesions, 44% (22 of 50) had an elasticity score of 1 and all were found to be benign. Conclusion Elastography was found to have a diagnostic performance comparable to that of conventional US for the differentiation of nonpalpable breast masses. The authors conclude that BI-RADS category 4a lesions with an elasticity score of 1 probably do not require biopsy.

Breast Mass Evaluation: Factors Influencing the Quality of US Elastography

PURPOSE To investigate factors influencing the quality of ultrasonographic (US) elastography in the evaluation of suspicious breast masses. MATERIALS AND METHODS This prospective study was conducted with institutional review board approval; written informed consent was obtained. Between January 2009 and February 2009, real-time US elastography of 312 breast masses (245 benign, 67 malignant) was performed in 268 consecutive patients (mean age, 45.7 years ± 10.2 [standard deviation]) prior to US-guided core biopsy. Five breast radiologists who had performed the examinations assessed the quality of elasticity images as inadequate, low, or high without histologic information. Age, body mass index (BMI), mammographic density, lesion size, lesion depth, and breast thickness at US were analyzed for their association with image quality by using the χ(2) test, Student t test, and multivariate analysis. Sensitivities and specificities for the differentiation of benign from malignant masses on the basis of elastography were calculated and compared between groups of quality scores by using the logistic regression method. RESULTS The quality of elasticity images was assessed as inadequate in 21 (6.7%) cases, low in 134 (42.9%), and high in 157 (50.3%). According to univariate analysis, smaller lesion size (P = .001), shallower lesion depth (P = .005), less breast thickness where the lesion was located (P < .0001), and benign pathologic finding (P = .004) were significantly associated with higher image quality. There was no correlation of image quality with age (P = .213), BMI (P = .191), mammographic density (P = .091), or distance from the nipple (P = .100). Multivariable analysis showed that breast thickness at the location of target lesions was the most important factor influencing elasticity image quality (P = .001). There were significant differences in sensitivity between higher-quality and lower-quality images (87.0% vs 56.8%, respectively; P = .015) in the differentiation of benign from malignant masses. CONCLUSION Breast thickness at the location of the lesion was the most important factor influencing image quality at US elastography. Sensitivity for classification of benign and malignant masses improved with higher quality scores.

Sonoelastographic Strain Index for Differentiation of Benign and Malignant Nonpalpable Breast Masses

Objective. The purpose of this study was to evaluate the diagnostic potential of the sonoelastographic strain index for differentiation of nonpalpable breast masses. Methods. Ninety‐nine nonpalpable breast masses (79 benign and 20 malignant) in 94 women (mean age, 45 years; range, 21–68 years) who had been scheduled for a sonographically guided core biopsy were examined with B‐mode sonography and sonoelastography. Radiologists who had performed the biopsies analyzed the B‐mode sonograms and provided American College of Radiology Breast Imaging Reporting and Data System categories. The strain index (fat to lesion strain ratio) was calculated by dividing the strain value of the subcutaneous fat by that of the mass. The histologic result from the sonographically guided core biopsy was used as a reference standard. The diagnostic performance of the strain index and that of B‐mode sonography were compared by receiver operating characteristic (ROC) curve analysis. Results. The mean strain index values ± SD were 6.57 ± 6.62 (range, 1.29–28.69) in malignant masses and 2.63 ± 4.57 (range, 0.54–38.76) in benign masses (P = .019). The area under the ROC curve values were 0.835 (95% confidence interval [CI], 0.747–0.902) for B‐mode sonography and 0.879 (95% CI, 0.798–0.936) for the strain index (P = .490). The sensitivity, specificity, positive predictive value, and negative predictive value were 95% (19 of 20), 75% (59 of 79), 48% (19 of 39), and 98% (59 of 60), respectively, when a best cutoff point of 2.24 was used. Conclusions. The strain index based on the fat to lesion strain ratio has diagnostic performance comparable with that of B‐mode sonography for differentiation of benign and malignant breast masses.

Correlation between high resolution dynamic MR features and prognostic factors in breast cancer.

Objective To correlate high resolution dynamic MR features with prognostic factors in breast cancer. Materials and Methods One hundred and ninety-four women with invasive ductal carcinomas underwent dynamic MR imaging using T1-weighted three-dimensional fast low-angle shot (3D-FLASH) sequence within two weeks prior to surgery. Morphological and kinetic MR features were determined based on the breast imaging and reporting data system (BI-RADS) MR imaging lexicon. Histological specimens were analyzed for tumor size, axillary lymph node status, histological grade, expression of estrogen receptor (ER), expression of progesterone receptor (PR), and expression of p53, c-erbB-2, and Ki-67. Correlations between the MR features and prognostic factors were determined using the Pearson χ2 test, linear-by-linear association, and logistic regression analysis. Results By multivariate analysis, a spiculated margin was a significant, independent predictor of a lower histological grade (p < 0.001), and lower expression of Ki-67 (p = 0.007). Rim enhancement was significant, independent predictor of a higher histological grade (p < 0.001), negative expression of ER (p = 0.001), negative expression of PR (p < 0.001) and a larger tumor size (p = 0.006). A washout curve may predict a higher level of Ki-67 (p = 0.05). Most of the parameters of the initial enhancement phase cannot predict the status of the prognostic factors. Only the enhancement ratio may predict a larger tumor size (p = 0.05). Conclusion Of the BI-RADS-MR features, a spiculated margin may predict favorable prognosis, whereas rim enhancement or washout may predict unfavorable prognosis of breast cancer.

Distinguishing Benign from Malignant Masses at Breast US: Combined US Elastography and Color Doppler US—Influence on Radiologist Accuracy

PURPOSE To investigate the effect of the combined use of ultrasonographic (US) elastography and color Doppler US on the accuracy of radiologists in distinguishing benign from malignant nonpalpable breast masses and in making the decision for biopsy recommendations at B-mode US. MATERIALS AND METHODS This prospective study was conducted with institutional review board approval; written informed consent was obtained. A cohort of 367 biopsy-proved cases in 319 women (age range, 22-78 years; mean age, 48.6 years) with B-mode US, US elastographic, and Doppler US images was included. Five blinded readers independently scored the likelihood of malignancy for four data sets (ie, B-mode US alone, B-mode US and elastography, B-mode US and Doppler US, and B-mode US, US elastography, and Doppler US). The area under the receiver operating characteristic curve (A(z)) values, sensitivities, and specificities of each data set were compared. RESULTS The A(z) of B-mode US, US elastography, and Doppler US (average, 0.844; range, 0.797-0.876) was greater than that of B-mode US alone (average, 0.771; range, 0.738-0.798) for all readers (P = .001 for readers 1, 2, and 3; P < .001 for reader 4; P = .002 for reader 5). When both elastography and Doppler scores were negative, leading to strict downgrading, the specificity increased for all readers from an average of 25.3% (75.4 of 298; range, 6.4%-40.9%) to 34.0% (101.2 of 298; range, 26.5%-48.7%) (P < .001 for readers 1, 2, 4, and 5; P = .016 for reader 3) without a significant change in sensitivity. CONCLUSION Combined use of US elastography and color Doppler US increases both the accuracy in distinguishing benign from malignant masses and the specificity in decision-making for biopsy recommendation at B-mode US.

Correlation of perfusion parameters on dynamic contrast-enhanced MRI with prognostic factors and subtypes of breast cancers.

To investigate whether a correlation exists between perfusion parameters obtained from dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) and prognostic factors or immunohistochemical subtypes of breast cancers.

Preoperative Sonographic Classification of Axillary Lymph Nodes in Patients With Breast Cancer: Node-to-Node Correlation With Surgical Histology and Sentinel Node Biopsy Results

OBJECTIVE The purpose of this study was to prospectively evaluate the role of axillary lymph node classification by sonography in breast cancer patients by node-to-node correlation with surgical histology and sentinel node biopsy results. SUBJECTS AND METHODS Between June 2006 and December 2006, preoperative axillary sonography was performed in 191 consecutive breast cancer patients (median age, 46 years; age range, 24-79 years) who had been scheduled to undergo breast cancer surgery with sentinel node biopsy. The axillary lymph node that had the thickest cortex or that was closest to the primary tumor was prospectively classified and then removed through sonographically guided needle localization. Correspondence about and histologic results for the needle-localized nodes and the radioactive sentinel nodes were analyzed. The rate of malignancy, according to the sonographic classification, and the area under a receiver operating characteristic curve were analyzed. RESULTS Of the 191 needle-localized nodes, 41 (21%) had metastases and 150 (79%) did not have metastases. When a cutoff point of a cortical thickness of 2.5 mm was used, sonographic classification showed 85% (35/41) sensitivity, 78% (117/150) specificity, and an area under the curve of 0.861 (95% CI, 0.796-0.926). Of the 54 patients with metastases at sentinel node biopsy or axillary lymph node dissection, 13 (24%) had false-negative results of sonographically guided needle localization. Unsuccessful lymphatic mapping because of absent radiotracer uptake during sentinel node biopsy was found in 4% (7/191), whereas all needle-localized nodes with a cortical thickness of more than 2.5 mm were confirmed as metastases. CONCLUSION Sonographic classification of axillary lymph nodes is effective for predicting the presence of metastases to avoid sentinel node biopsy or to reduce unsuccessful lymphatic mapping during sentinel node biopsy.

Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer

IntroductionAnti-estrogen therapy has been shown to reduce mammographic breast density (MD). We hypothesized that a short-term change in breast density may be a surrogate biomarker predicting response to adjuvant endocrine therapy (ET) in breast cancer.MethodsWe analyzed data for 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET, including tamoxifen and aromatase inhibitors. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction (MDR) was defined as the absolute difference in MD of mammograms taken preoperatively and 8-20 months after the start of ET.ResultsAt a median follow-up of 68.8 months, the overall breast cancer recurrence rate was 7.5% (80/1065). Mean MDR was 5.9% (range, -17.2% to 36.9%). Logistic regression analysis showed that age < 50 years, high preoperative MD, and long interval between start of ET to follow-up mammogram were significantly associated with larger MDR (p < 0.05). In a survival analysis, tumor size, lymph node positivity, high Ki-67 (≥ 10%), and low MDR were independent factors significantly associated with recurrence-free survival (p < 0.05). Compared with the group showing the greatest MDR (≥ 10%), the hazard ratios for MDRs of 5-10%, 0-5%, and < 0% were 1.33, 1.92, and 2.26, respectively.ConclusionsMD change during short-term use of adjuvant ET was a significant predictor of long-term recurrence in women with ER-positive breast cancer. Effective treatment strategies are urgently needed in patients with low MDR despite about 1 year of ET.

Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location

Background:Colorectal cancer (CRC) is usually categorised as proximal or distal CRC. Recently, many researchers have tried to determine the molecular heterogeneity of CRCs along bowel subsites. However, the differential effects of the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) on the clinical outcome according to tumour location are not well-known.Methods:We analysed clinicopathologic and molecular characteristics, including CIMP, MSI, KRAS and BRAF mutations, in 734 CRCs according to bowel subsites. And the prognostic value of CIMP and MSI was analysed according to tumour location.Results:We found a linear increase of female predominance, T, N category, stage, differentiation, absence of luminal necrosis, tumour -infiltrating lymphocytes, Crohn’s-like lymphoid reaction, serration and mucin production from the rectum to caecum. CpG island methylator phenotype -high and MSI-high gradually increased from the rectum to caecum. CpG island methylator phenotype is a poor prognostic factor of overall survival (hazard ratio (HR): 4.13, 95% confidence interval (CI): 1.27–13.46) and disease-free survival (HR: 2.90, 95% CI: 1.04–8.08) in rectal cancers.Conclusion:Clinicopathologic and molecular profiles of CRCs gradually change along bowel subsites, and the prognostic implication of CIMP is different according to tumour location.