The blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancer.

BACKGROUND: There is a long-time unmet need for a means to detect breast cancer (BC) using blood. Although mammography is accepted as the gold standard for screening, a blood-based diagnostic can complement mammography and assist in the accurate detection of BC in the diagnostic process period of early diagnosis. We have previously reported the possible use of thioredoxin 1 (Trx1) in serum as a novel means to detect BC. In the present study, we validated the clinical utility of Trx1 to identify BC by testing sera from biopsy-confirmed cancer patients and women without cancer. METHODS: We have generated monoclonal antibodies against Trx1 and developed an ELISA kit that can quantitate Trx1 in sera. The level of Trx1 was determined in each serum from women without cancer (n = 114), as well as in serum from patients with BC (n = 106) and other types of cancers (n = 74), including cervical, lung, stomach, colorectal, and thyroid cancer. The sera from BC patients were collected and classified by the subjects' age and cancer stage. In addition to the Trx1 levels of BC patients, several pathological and molecular aspects of BC were analyzed. Test results were retrospectively compared to those from mammography. Each test was duplicated, and test results were analyzed by ROC analysis, one-way ANOVA tests, and unpaired t-tests. RESULTS: The mean level of Trx1 from women without cancer was 5.45 ± 4.16 (±SD) ng/ml, that of the other malignant cancer patient group was 2.70 ± 2.01 ng/ml, and that from the BC group was 21.96 ± 6.79 ng/ml. The difference among these values was large enough to distinguish BC sera from non-BC control sera with a sensitivity of 97.17% and specificity of 94.15% (AUC 0.990, p < 0.0001). Most Trx1 levels from BC patients' sera were higher than the cut-off value of 11.4 ng/ml regardless of age, stage, histological grade, type, and specific receptors' expression profile of BC. The level of Trx1 could rescue women from most cases of misread or incomplete mammography diagnoses. CONCLUSION: These results indicated that the blood level of Trx1 could be an effective and accurate means to assist the detection of BC during the early diagnosis period.

Dynamic contrast enhanced-MRI and diffusion-weighted image as predictors of lymphovascular invasion in node-negative invasive breast cancer.

BACKGROUND: Lymphovascular invasion (LVI) is an important risk factor for prognosis of breast cancer and an unfavorable prognostic factor in node-negative invasive breast cancer patients. The purpose of this study was to evaluate the association between LVI and pre-operative features of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) in node-negative invasive breast cancer. METHODS: Data were collected retrospectively from 132 cases who had undergone pre-operative MRI and had invasive breast carcinoma confirmed on the last surgical pathology report. MRI and DWI data were analyzed for the size of tumor, mass shape, margin, internal enhancement pattern, kinetic enhancement curve, high intratumoral T2-weighted signal intensity, peritumoral edema, DWI rim sign, and apparent diffusion coefficient (ADC) values. We calculated the relationship between presence of LVI and various prognostic factors and MRI features. RESULTS: Pathologic tumor size, mass margin, internal enhancement pattern, kinetic enhancement curve, DWI rim sign, and the difference between maximum and minimum ADC were significantly correlated with LVI (p < 0.05). CONCLUSIONS: We suggest that DCE-MRI with DWI would assist in predicting LVI status in node-negative invasive breast cancer patients.

Associations Between Apparent Diffusion Coefficient Values and the Prognostic Factors of Breast Cancer.

OBJECTIVES: Breast imaging can offer great information about breast cancer heterogeneity. The purpose of this study was to analyze the relationship between apparent diffusion coefficient (ADC) values and various prognostic factors and investigate whether ADC values are useful for breast cancer diagnosis, evaluation of treatment response, and determination of prognosis. METHODS: A total of 111 cases of breast cancer were included in this study. Magnetic resonance findings were recorded according to the Breast Imaging Reporting and Data System magnetic resonance imaging lexicon. Diffusion-weighted imaging rim sign and minimum, maximum, and difference ADC values (ADCdiff) were also evaluated. RESULTS: ADCdiff was related to all prognostic factors such as histological grade, Ki-67, tumor size, molecular subtype, axillary node metastasis, lymphvascular invasion, internal enhancement pattern, intratumoral high T2 signal, peritumoral edema, and diffusion-weighted imaging rim sign, whereas minimum and maximum ADC values showed variable associations. CONCLUSIONS: Apparent diffusion coefficient values were shown to be correlated with many proven or possible prognostic factors of breast cancer. In particular, ADCdiff can reflect tumor heterogeneity and showed higher correlation.

Associations Between Magnetic Resonance Imaging Findings and Clincopathologic Factors in Triple-Negative Breast Cancer.

OBJECTIVE: The aim of the study was to evaluate the magnetic resonance imaging findings associated with clinicopathologic factors in patients with triple-negative breast cancer. METHODS: One hundred one patients with surgically confirmed triple-negative breast cancer who underwent preoperative breast magnetic resonance imaging with diffusion-weighted imaging (DWI) were included in this study. Presence of rim enhancement on contrast-enhanced T1-weighted imaging and hyperintense rim on DWI were visually assessed. Pathologic data about presence of recurrence and presence of lymphovascular invasion (LVI) were reviewed. Statistics for relative risk of recurrence carried out. RESULTS: Of the 101, 13 cases (12.9%) were recurred after a median follow-up of 18.5 months. Rim enhancement was more frequently seen in the LVI-positive group (P = 0.046). Hyperintense rim on DWI and apparent diffusion coefficient values showed no significant relationship with clinical-pathologic factors. CONCLUSIONS: Rim enhancement was significantly associated with positive LVI status in patients with triple-negative breast cancer. Our study suggests that rim enhancement may be useful to predict the prognosis.

Effective factors to raise diagnostic performance of breast MRI for diagnosing pathologic complete response in breast cancer patients after neoadjuvant chemotherapy.

BACKGROUND: Although MRI is a highly effective tool in evaluating residual disease after neoadjuvant chemotherapy (NAC), there are many reports of discordance between the response of MRI and pathology. To increase MR accuracy, additional methods, which reflect post-NAC changes, should be considered in diagnosis. PURPOSE: To evaluate effective methods that raise the diagnostic performance of MRI for predicting pathologic complete response (pCR) in breast cancer after neoadjuvant chemotherapy (NAC). MATERIAL AND METHODS: For 98 invasive breast carcinoma patients, chemotherapeutic response to MRI was evaluated for the following parameters: tumor size, tumor distribution pattern, kinetic curve analysis, and background parenchymal enhancement pattern (BPE). BPE was categorized as "minimal", "mild", "moderate", or "marked", according to the ACR BI-RADS criteria. RESULTS: After NAC, the mean size of tumors decreased by 40% in non-pCR and by 59% in pCR groups, respectively. The sensitivity, specificity, false positive rate and false negative rate of MRI were 96% (78/81), 53% (9/17), 47% (8/17), and 4% (3/81), respectively. At pre-NAC MRI, the most common kinetic curve was delayed washout pattern (68%, 67/98); however, at post-NAC MRI the persistent pattern (55%, 47/86). Grouped lesion was the most common tumor distribution pattern on pre-NAC MRI (28%, 27/98), while on post-NAC solitary mass (40%, 34/86). The most common BPE at pre- and post-NAC MRI was mild and minimal enhancement, respectively. CONCLUSION: To improve the diagnostic accuracy of MRI, we should consider additional factors including: tumor distribution pattern, BPE, kinetic curve analysis, and tumor size.

Invasive cribriform carcinoma of the breast: mammographic, sonographic, MRI, and 18 F-FDG PET-CT features.

BACKGROUND: Invasive cribriform carcinoma (ICC) of the breast is a rare type of invasive carcinoma which shows a favorable prognosis and a lower frequency of axillary nodal metastases. Few imaging findings related to ICC have been reported. PURPOSE: To evaluate imaging findings with multiple imaging techniques in ICC of the breast. MATERIAL AND METHODS: Twenty-eight cases of histopathologically proven ICC of the breast were gathered for this study. We retrospectively reviewed the mammographic, sonographic, and magnetic resonance imaging (MRI) findings of ICC according to the American College of Radiology (ACR) breast imaging reporting and data system (BI-RADS) lexicon. 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET-CT) findings were also evaluated. Microscopic slides of surgical specimens were reviewed by a breast pathologist. RESULTS: The mean age of the patients was 51 years. The most common mammographic findings were irregular shape (72.8%), spiculated margin (63.7%), and a high density (81.8%) mass. Microcalcifications were noted in 9/28 cases. The most common shape was pleomorphic (66.7%). The most common sonographic findings were irregular shape (77.8%), spiculated margin (29.6%), hypoechogenicity (81.5%), and no posterior acoustic features (85.2%). On MRI, most ICCs presented as irregular shaped mass (62.0%) and irregular (42.9%) margin. All four patients (16.0%) who presented with non-mass-like enhancement pattern showed a segmental distribution. The 18 F-FDG PET-CT showed a mean maximum standardized uptake value (SUVmax) of 5.90. Axillary nodal metastases were found in 17.9% (5/28) of the surgical specimens. Immunohistochemical studies showed a high positivity for estrogen and progesterone receptor (100% and 87.5%, respectively). CONCLUSION: The imaging features of invasive cribriform carcinoma are highly suggestive of malignancy and are not distinguishable from those of other breast cancers like infiltrating ductal carcinoma.

Associations between the standardized uptake value of (18)F-FDG PET/CT and the prognostic factors of invasive lobular carcinoma: in comparison with invasive ductal carcinoma.

BACKGROUND: The aims of this study were to evaluate the associations between the maximum standardized uptake value (SUVmax) and prognostic factors in invasive lobular carcinoma (ILC) and to compare these results with those in invasive ductal carcinoma (IDC). METHODS: The study included pathologically confirmed ILCs (n = 32) and IDCs (n = 73). We retrospectively evaluated the preoperative (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and measured the SUVmax. The pathologic results were reviewed regarding the size, histological type, histological grade, estrogen receptor (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and Ki-67 of the primary tumor. We also compared the associations between the SUVmax and prognostic factors. RESULTS: The mean SUVmax of the ILCs was significantly lower compared with that of the IDCs (P = 0.032). The SUVmax increased with tumor grade (P < 0.001) and was higher with ER negativity compared with ER positivity (P = 0.007) in IDC. The SUVmax was higher with EGFR positivity compared with EGFR negativity (P = 0.013) in IDC and higher with Ki-67 positivity compared with Ki-67 negativity in IDC and ILC (P < 0.001 and P = 0.002, respectively). The SUVmax was not significantly different regarding PR or HER2 for both tumor groups. The correlation between the tumor size and the SUVmax was demonstrated for IDCs (r = 0.57), but not for ILCs (r = 0.25). CONCLUSIONS: The SUVmax was significantly different according to the tumor grade, ER, EGFR, and Ki-67 for IDCs. The SUVmax exhibited a positive association with Ki-67 in ILC; however, it was not significantly different with other factors, which suggests that the role of (18)F-FDG PET/CT may be limited in ILC.

Metaplastic carcinoma of the breast: multimodality imaging and histopathologic assessment.

BACKGROUND: Metaplastic carcinomas are ductal carcinomas that display metaplastic transformation of the glandular epithelium to non-glandular mesenchymal tissue. Metaplastic carcinoma has a poorer prognosis than most other breast cancers, so the differential diagnosis is important. Although many clinical and pathologic findings have been reported, to our knowledge, few imaging findings related to metaplastic carcinoma have been reported. PURPOSE: To investigate whole-breast imaging findings, including mammography, sonography, MRI, and pathologic findings, including immunohistochemical studies of metaplastic carcinomas of the breast. MATERIAL AND METHODS: We analyzed 33 cases of metaplastic carcinoma between January 2001 and January 2011. Mammography, ultrasonography, and MRI were recorded retrospectively using the American College of Radiology (ACR) breast imaging reporting and data system (BI-RADS) lexicon. Immunohistochemical studies of estrogen receptor (ER), progesterone receptor (PR), p53, and C-erbB-2 were performed. RESULTS: The most common mammographic findings were oval shape (37%), circumscribed margin (59%), and high density (74%). The most common sonographic findings were irregular shape (59.4%), microlobulated margin (41%), complex echogenicity (81%), parallel orientation (97%), and posterior acoustic enhancement (50%). Axillary lymph node metastases were noted for 25% of the sonographic examinations. On MRI, the most common findings of margin and shape were irregularity (57% and 52.4%, respectively). High signal intensity was the most common finding on T2-weighted images (57%). Immunohistochemical profile was negative for ER (91%, 29/32) and PR (81%, 26/32). CONCLUSION: Metaplastic carcinomas might display more benign features and less axillary lymph node metastasis than IDC. High signal intensity on T2 MRI images and hormone receptor negativity would be helpful in differentiating this tumor from other breast cancers.

Diffusion-weighted imaging and FDG PET/CT: predicting the prognoses with apparent diffusion coefficient values and maximum standardized uptake values in patients with invasive ductal carcinoma.

BACKGROUND: FDG PET/CT and DWI are both functional modalities that indirectly represent the biological characteristics of cancer, but there are few studies exploring the association between the two modalities and prognostic factors. Our study attempted to evaluate the mutual association by comparing the prognostic factors, SUV(max) value of PET/CT, and ADC values associated with diffusion imaging in invasive ductal carcinoma (IDC) patients. METHODS: Patients with pathologically confirmed IDC were recruited. There were 118 patients who underwent MRI, including DWI, FDG PET/CT, and immunohistochemical staining of the surgical specimen. Histologic analysis was done on tumor size, lymph node metastasis, expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and epidermal growth factor receptors (EGFR). The relationship among ADC values, SUV(max) and prognostic factors were evaluated. RESULTS: There was significant association between the ADC value and ER-positive and HER2-negative expression. Significant associations were noted between SUV(max) and tumor size, lymph node metastasis, histologic grade, ER and PR expression, EGFR and Ki-67. However, there was no significant correlation between the ADC value and SUV(max). CONCLUSIONS: Even though there was no correlation between ADC and SUV(max), both indexes are useful for predicting the prognosis of IDC.

Lobular lesions of the breast: imaging findings of lobular neoplasia and invasive lobular carcinoma.

The clinical and radiological diagnoses of lobular neoplasia (LN) and invasive lobular carcinoma (ILC) are difficult because they have no specific findings. The purpose of this study is to illustrate the imaging and pathological features of LN and ILC. For lobular lesions, imaging is the basic and essential diagnostic tool, so the understanding and effective use of multimodality imaging findings are important. This article shows imaging findings of LN, which are seldom known, and ILC as well as their characteristic histopathological features.

Radiologic findings of lobular carcinoma in situ: mammography and ultrasonography.

PURPOSE: The purpose was to evaluate the mammographic and sonographic (US) features of lobular carcinoma in situ (LCIS). Methods. Mammographic and US findings of nine lesions diagnosed pathologically as pure LCIS were analyzed retrospectively according to the American College of Radiology breast imaging reporting and data system (BI-RADS) lexicon. RESULTS: With regards to mammographic findings of LCIS, there were no lesions demonstrated in six cases and a mass in three cases, two of which contained microcalcifications. The most common US findings of LCIS were irregular shape (five cases), ill-defined margins (eight cases), and hypoechogenicity (seven cases). All cases had an elongated shape parallel to the skin or were round (no lesion had a taller-than-wide shape). Two cases were associated with microcalcifications. The final BI-RADS categories were category 3 (probably benign finding) in one case, category 4A (low suspicion of malignancy) in two cases, and category 4B (intermediate suspicion of malignancy) in six cases. CONCLUSIONS: LCIS is frequently mammographically occult, and an incidental finding on routine screening mammograms, usually because of microcalcifications. LCIS, a high-risk lesion, can mimic invasive carcinoma on US.

Effectiveness of ADC Difference Value on Pre-neoadjuvant Chemotherapy MRI for Response Evaluation of Breast Cancer.

Background: Neoadjuvant chemotherapy (NAC) is known to be a suitable treatment and first-line defense for locally advanced breast cancer. However, the NAC response may include unexpected outcomes, and it is not easy to predict the NAC response precisely. Especially, early detection of those patients who do not benefit from NAC is needed to reduce unnecessary therapy and side effects. Objective: The purpose of this study was to determine whether the pretreatment apparent diffusion coefficient (ADC) value is effective for predicting the response of breast cancer to NAC. Method: Forty-nine breast cancer cases with pre- and post-NAC breast MRI were enrolled. MRI was performed using a 1.5-T scanner with the basic protocol including diffusion-weighted imaging. ADC difference value (ADC-diff) was calculated in all cases. Results: ADC-diff was high in complete response and partial response cases (p < .05). ADC-diff correlated with the DWI rim sign, with a positive DWI rim sign being associated with a higher ADC-diff (p < .05). Conclusion: High-ADC difference value on the pretreatment MRI can provide information for a better response of NAC on breast cancer.

Basal-like Breast Cancer: Comparison of Imaging Characteristics.

BACKGROUND: Basal-like carcinoma is one of the breast subtypes that lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). It has a poor prognosis and aggressive behavior. It is in a heterogeneous group with various other types of cancer, including metaplastic carcinoma, carcinomas with medullary features, medullary carcinoma, adenoid cystic carcinoma, secretory carcinoma, and invasive carcinoma arising in the setting of BRCA1 mutations. Imaging features of basal-like cancers have not been uniform, and there are no studies with imaging comparisons between basal-like carcinomas. OBJECTIVES: To compare imaging features of basal-like carcinomas and to understand their characteristics. METHODS: By using our radiologic database, we retrospectively searched 37 cases of metaplastic carcinoma and 44 cases of invasive carcinoma with medullary features (ICMF). Two radiologists reviewed images according to ACR BI-RADS lexicon. RESULTS: The higher Ki-67 and absence of calcifications were statistically significant in ICMF than in metaplastic carcinoma. Metaplastic carcinoma demonstrated oval shape and parallel orientation more frequently. ICMF showed more irregular shape and angular margin on ultrasound, irregular or spiculated margin on breast MRI. ICMF showed more delayed washout pattern of enhancement than metaplastic carcinoma. Intratumoral T2, a very high signal was noted more in metaplastic carcinoma. CONCLUSION: Our study presents variable imaging features observed between basal-like carcinomas. Although it is not sufficient to predict clinical progress, aggressiveness or prognosis of basal-like carcinomas, the results of this study will be helpful in understanding and diagnosing various basallike carcinomas.

Association between MRI Features and Standardized Uptake Value of 18F-FDG PET/CT in Triple-Negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a breast cancer subgroup that lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Certain magnetic resonance imaging (MRI) features of TNBC might reflect the poor prognosis of TNBC. Standardized uptake value (SUV) of [18F]fluorodeoxyglucose positron emission tomography/computed tomography is 1 of predictive prognostic factors for breast cancer. The purpose of this study was to correlate MRI features of TNBC with SUVmax to determine whether MRI findings in TNBC could be helpful for predicting prognosis. METHODS: We analyzed MRI findings of TNBC according to breast imaging reporting and data system (BI-RADS) MRI lexicon. We also assessed intratumoral high signal intensity on T2-weighted MRI, time-intensity curve analysis and peritumoral edema. The relationship between MRI features of TNBC and SUVmax was then statistically analyzed. RESULTS: Significant correlations of SUVmax with the internal enhancement pattern, intratumoral high signal intensity on T2-weighted images, and peritumoral edema were noted. There was no significant correlation of SUVmax with mass shape, margin, or kinetics. CONCLUSION: Certain MRI features of TNBC such as heterogeneous or rim enhancement, intratumoral very high signal intensity on T2 images, and peritumoral edema might be useful in predicting the prognosis of patients with TNBC.

Correlation of Prognostic Factors of Invasive Lobular Carcinoma with ADC Value of DWI and SUVMax of FDG-PET.

Invasive lobular carcinoma (ILC) is the second most common kind of breast cancer. Diffusion weighted imaging (DWI) and positron emission tomography/computed tomography (PET/CT) are functional modalities for presenting the biological characteristics of breast cancer. The purpose of this article is to study the relationship between DWI or PET/CT and ILC's prognostic factors. The relationship between the apparent diffusion coefficient (ADC) values, standard uptake value (SUV)max and prognostic factors of ILC were statistically evaluated. The ADC values were lower in mass types of ILC. SUVmax was statistically higher in grade 3 and 4 background parenchymal enhancement and positive lymph node metastasis. ADC values of DWI and SUVmax of PET/CT can be helpful in the prediction of the prognosis of ILC.

MR differentiation of low-grade chondrosarcoma from enchondroma.

PURPOSE: To evaluate magnetic resonance (MR) imaging for the discrimination between low-grade chondrosarcoma and enchondroma. MATERIALS AND METHODS: MR images of 34 patients who were confirmed with low-grade chondrosarcoma or enchondroma were retrospectively reviewed. After review of medical records, MR findings in 18 patients with low-grade chondrosarcoma and 16 patients with enchondroma were compared. MR images were retrospectively reviewed for the lesion location (central or eccentric; epiphysis, metaphysic, or diaphysis), margin, contour, mineralized matrix, endosteal scalloping, cortical expansion, cortical destruction, soft tissue mass formation, and periosteal reaction. Signal intensity, the patterns of contrast enhancement (unilocular or multilobular), soft tissue mass, and adjacent abnormal bone marrow and soft tissue signal were also reviewed. Statistical analysis was performed with chi-square test. RESULTS: The patients with low-grade chondrosarcoma had a significantly higher incidence of MR findings (P<.05): predominantly intermediate signal on T1-weighted images [72% (13/18) in low-grade chondrosarcoma vs. 25% (4/16) in enchondroma], multilocular appearance on contrast-enhanced T1-weighted images [83% (15/18) vs. 44% (7/16)], cortical destruction [33% (6/18) vs. 0% (0/16)], a soft tissue mass [28% (5/18) vs. 0% (0/16)], adjacent bone marrow and soft tissue abnormal signal [22% (4/18) vs. 0% (0/16)], and an involvement of the epiphysis or flat bone [56% (10/18) vs. 19% (3/16)]. CONCLUSION: MR imaging shows helpful features for differentiating low-grade chondrosarcoma from enchondroma.

Imaging findings of invasive micropapillary carcinoma of the breast.

PURPOSE: The purpose of this study is to evaluate imaging and histopathologic findings including the immunohistochemical characteristics of invasive micropapillary carcinoma (IMPC) of the breast. METHODS: Twenty-nine patients diagnosed with IMPC were included in the present study. Mammographic, sonographic, and magnetic resonance imaging (MRI) findings were analyzed retrospectively according to the American College of Radiology Breast Imaging Reporting and Data System lexicon. (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings were also evaluated. Microscopic slides of surgical specimens were reviewed in consensus by two pathologists with a specialty in breast pathology. RESULTS: Most IMPCs presented as a high density irregular mass with a non-circumscribed margin associated with microcalcifications on mammography, as an irregular hypoechoic mass with a spiculated margin on ultrasound, and as irregular spiculated masses with washout patterns on MRI. PET-CT showed a high maximum standardized uptake value (SUVmax) (mean, 11.2). Axillary nodal metastases were identified in 65.5% of the patients. Immunohistochemical studies showed high positivities for estrogen receptor and c-erbB-2 (93.1% and 51.7µ, respectively). CONCLUSION: Even though the imaging characteristics of IMPCs are not distinguishable from typical invasive ductal carcinomas, this tumor type frequently results in nodal metastases and high positivities for both estrogen receptor and c-erbB-2. The high SUVmax value that is apparent on PET-CT might be helpful in the diagnosis of IMPC.