Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing.

PURPOSE: Triple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC. METHODS: A kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three non-Asian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy). The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation. RESULTS: The significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively). CONCLUSION: Comprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.

Artificial Intelligence-based Radiomics in the Era of Immuno-oncology.

The recent, rapid advances in immuno-oncology have revolutionized cancer treatment and spurred further research into tumor biology. Yet, cancer patients respond variably to immunotherapy despite mounting evidence to support its efficacy. Current methods for predicting immunotherapy response are unreliable, as these tests cannot fully account for tumor heterogeneity and microenvironment. An improved method for predicting response to immunotherapy is needed. Recent studies have proposed radiomics-the process of converting medical images into quantitative data (features) that can be processed using machine learning algorithms to identify complex patterns and trends-for predicting response to immunotherapy. Because patients undergo numerous imaging procedures throughout the course of the disease, there exists a wealth of radiological imaging data available for training radiomics models. And because radiomic features reflect cancer biology, such as tumor heterogeneity and microenvironment, these models have enormous potential to predict immunotherapy response more accurately than current methods. Models trained on preexisting biomarkers and/or clinical outcomes have demonstrated potential to improve patient stratification and treatment outcomes. In this review, we discuss current applications of radiomics in oncology, followed by a discussion on recent studies that use radiomics to predict immunotherapy response and toxicity.

Impact of birth season on second-to-fourth digit ratio, prostate volume, and prostate cancer.

PURPOSE: The second-to-fourth digit ratio (digit ratio), which is determined in utero, is associated with exposure to visible sunlight during early pregnancy and the season of birth. The digit ratio is also associated with benign prostatic hyperplasia (BPH) and prostate cancer. This suggests that BPH and prostate cancer may be related to the birth season. Therefore, this study aimed to determine whether prostate volume and prostate cancer were related to the birth season. MATERIALS AND METHODS: A total of 858 male patients with lower urinary tract symptoms were enrolled. The right digit ratio was measured, and the month of birth was surveyed. Serum prostate-specific antigen (PSA) levels were measured, and prostate volumes were measured by transrectal ultrasonography. Patients with suspected prostate cancer underwent prostate biopsy. RESULTS: The mean age, digit ratio, prostate volume, and serum PSA level of 858 patients were 61.6 years, 0.947, 36.2 mL, and 4.24 ng/mL, respectively. Age, serum PSA levels, prostate biopsy rates, and cancer detection rates did not differ significantly according to the birth season. However, compared with the summer birth group, the winter birth group had lower digit ratios (0.951±0.040 vs. 0.941±0.040; p=0.014), larger prostate volumes (33.4±14.9 mL vs. 38.2±20.7 mL; p=0.008), and more prostate cancer (5.3% vs. 11.3%; p=0.031). Multivariate analysis showed that birth season independently predicted prostate cancer. CONCLUSIONS: The relationships of birth season with prostate volume and prostate cancer may be due to differences in the amount of light exposure during early pregnancy.

Fabrication of 2D and 3D Cell Cluster Arrays Using a Cell-Friendly Photoresist.

Cells in 3D behave differently than cells in 2D. We develop a new method for the fabrication of 2D and 3D cell cluster arrays on an identical substrate using a cell-friendly photoresist, which enables comparative study between cells in 2D and 3D cell clusters. The fabricated cell cluster arrays maintain their structure up to 3 days with good viability. Using this method, 2D and 3D cancer cell clusters with comparable sizes are fabricated, and natural killer (NK) cell cytotoxicity assays are performed to assess how dimensionality of cancer cell clusters influence their susceptibility to immune cell-mediated killing.

Overcoming acquired resistance to PD-1 inhibitor with the addition of metformin in small cell lung cancer (SCLC).

Metformin has been widely used as the treatment of type II diabetes mellitus for its anti-hyperglycemic effect. In recent years, it has also been extensively studied for its anti-cancer effect as it diminishes immune exhaustion of CD8 + tumor-infiltrating lymphocytes (TILs). It decreases apoptosis of CD8 + TILs, thereby enhancing T cell-mediated immune response to tumor cells. Here, we present a unique case of a patient with small cell lung cancer (SCLC) who exhibited an overall partial response as per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) since starting metformin in combination with nivolumab therapy. Our patient had been treated with nivolumab monotherapy for 2 years until she had progression of disease. After she was started on metformin along with nivolumab therapy, she has shown a significant durable response for over 6 months. Many patients develop resistance to immunotherapy such as antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Tumor hypoxia is one of the resistance factors. Signals activated by hypoxic environments in tumors are associated with decreased sensitivity to the PD-1 blockade. Metformin inhibits oxygen consumption in tumor cells in vitro and in vivo, reducing intratumoral hypoxia. These data suggest that metformin can improve susceptibility to anti-PD-1 treatment. To the best of our knowledge, our case is the first reported example demonstrating a proof-of-concept that metformin can contribute to overcoming acquired resistance to PD-1 inhibitors.

Development and Validation of a Next-Generation Sequencing-Based Multigene Assay to Predict the Prognosis of Estrogen Receptor-Positive, HER2-Negative Breast Cancer.

PURPOSE: Multigene assays provide useful prognostic information regarding hormone receptor (HR)-positive breast cancer. Next-generation sequencing (NGS)-based platforms have numerous advantages including reproducibility and adaptability in local laboratories. This study aimed to develop and validate an NGS-based multigene assay to predict the distant recurrence risk. EXPERIMENTAL DESIGN: In total, 179 genes including 30 reference genes highly correlated with the 21-gene recurrence score (RS) algorithm were selected from public databases. Targeted RNA-sequencing was performed using 250 and 93 archived breast cancer samples with a known RS in the training and verification sets, respectively, to develop the algorithm and NGS-Prognostic Score (NGS-PS). The assay was validated in 413 independent samples with long-term follow-up data on distant metastasis. RESULTS: In the verification set, the NGS-PS and 21-gene RS displayed 91.4% concurrence (85/93 samples). In the validation cohort of 413 samples, area under the receiver operating characteristic curve plotted using NGS-PS values classified for distant recurrence was 0.76. The best NGS-PS cut-off value predicting distant metastasis was 20. Furthermore, 269 and 144 patients were classified as low- and high-risk patients in accordance with the cut-off. Five- and 10-year estimates of distant metastasis-free survival (DMFS) for low- versus high-risk groups were 97.0% versus 77.8% and 93.2% versus 64.4%, respectively. The age-related HR for distant recurrence without chemotherapy was 9.73 (95% CI, 3.59-26.40) and 3.19 (95% CI, 1.40-7.29) for patients aged ≤50 and >50 years, respectively. CONCLUSIONS: The newly developed and validated NGS-based multigene assay can predict the distant recurrence risk in ER-positive, HER2-negative breast cancer.

Prediction of pathologic complete response using image-guided biopsy after neoadjuvant chemotherapy in breast cancer patients selected based on MRI findings: a prospective feasibility trial.

PURPOSE: Accurate prediction of pathologic complete response (pCR) in breast cancer using magnetic resonance imaging (MRI) and ultrasound (US)-guided biopsy may aid in selecting patients who forego surgery for breast cancer. We evaluated the accuracy of US-guided biopsy aided by MRI in predicting pCR in the breast after neoadjuvant chemotherapy (NAC). METHODS: After completion of NAC, 40 patients with near pCR (either tumor size ≤ 0.5 cm or lesion-to-background signal enhancement ratio (L-to-B SER) ≤ 1.6 on MRI) and no diffused residual microcalcifications were prospectively enrolled at a single institution. US-guided multiple core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) of the tumor bed, followed by standard surgical excision, was performed. Matched biopsy and surgical specimens were compared to assess pCR. The negative predictive value (NPV), accuracy, and false-negative rate (FNR) were analyzed. RESULTS: pCR was confirmed in 27 (67.5%) surgical specimens. Preoperative biopsy had an NPV, accuracy, and FNR of 87.1%, 90.0%, and 30.8%, respectively. NPV for hormone receptor-negative and hormone receptor-positive tumors were 83.3% and 100%, respectively. Obtaining at least 5 biopsy cores based on tumor size ≤ 0.5 cm and an L-to-B SER of ≤ 1.6 on MRI (27 patients) resulted in 100% NPV and accuracy. No differences in accuracy were noted between CNB and VAB (90% vs. 90%). CONCLUSIONS: Investigation using stringent MRI criteria and ultrasound-guided biopsy could accurately predict patients with pCR after NAC. A larger prospective clinical trial evaluating the clinical safety of breast surgery omission after NAC in selected patients will be conducted based on these findings.

Dynamic Contrast-enhanced Breast MRI for Evaluating Residual Tumor Size after Neoadjuvant Chemotherapy.

Purpose To investigate the accuracy of dynamic contrast material-enhanced (DCE) breast MRI for determining residual tumor size after neoadjuvant chemotherapy (NAC). Materials and Methods For this retrospective study, 487 consecutive women (mean age, 47.0 years ± 10.3 [standard deviation]; range, 24-78 years) underwent preoperative DCE MRI following NAC and subsequent surgeries between 2008 and 2011. Tumor size was measured at early-phase, conventional delayed-phase, and late delayed-phase MRI (90, 360, and 590 seconds after contrast material injection, respectively). At histopathologic examination, total tumor size (both invasive and in situ) and the size of invasive tumor alone were separately recorded. Absolute agreement between tumor size at MRI and histopathologic examination was assessed by using intraclass correlation coefficient (ICC) analysis. Factors affecting size discrepancy were assessed by using multiple linear regression analysis. Results Compared with tumor size at histopathologic examination, total tumor sizes showed higher agreement at conventional delayed-phase MRI than at early-phase MRI (ICC, 0.76 vs 0.56; P ˂ .001) and comparable agreement at conventional and late delayed-phase MRI (ICC, 0.76 vs 0.74; P = .55). Lobular histologic features and tumor subtype were independently associated with greater size discrepancy (P ˂ .001). Lobular cancers were underestimated in size compared with ductal cancers (mean size discrepancy, -2.8 cm ± 3.2 vs -0.3 cm ± 1.8; P = .004). Estrogen receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative cancers were underestimated compared with HER2-positive cancers (-0.8 cm ± 2.0 vs -0.3 cm ± 1.7, P = .006) and triple-negative cancers (-0.8 cm ± 2.0 vs 0.3 cm ± 1.7, P ˂ .001). Conclusion Delayed-phase MRI is more accurate than early-phase MRI for evaluating residual breast tumor size after neoadjuvant chemotherapy. Lobular or estrogen receptor-positive/human epidermal growth factor receptor 2-negative cancers are underestimated in size at MRI compared with ductal or other subtypes. © RSNA, 2018 Online supplemental material is available for this article.

Integrated 18F-FDG PET/MRI in breast cancer: early prediction of response to neoadjuvant chemotherapy.

PURPOSE: To explore whether integrated 18F-FDG PET/MRI can be used to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. METHODS: Between November 2014 and April 2016, 26 patients with breast cancer who had received NAC and subsequent surgery were prospectively enrolled. Each patient underwent 18F-FDG PET/MRI examination before and after the first cycle of NAC. Qualitative MRI parameters, including morphological descriptors and the presence of peritumoral oedema were assessed. Quantitatively, PET parameters, including maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis (TLG), and MRI parameters, including washout proportion and signal enhancement ratio (SER), were measured. The performance of the imaging parameters singly and in combination in predicting a pathological incomplete response (non-pCR) was assessed. RESULTS: Of the 26 patients, 7 (26.9%) exhibited a pathological complete response (pCR), and 19 (73.1%) exhibited a non-pCR. No significant differences were found between the pCR and non-pCR groups in the qualitative MRI parameters. The mean percentage reductions in TLG30% on PET and SER on MRI were significantly greater in the pCR group than in the non-pCR group (TLG30% -64.8 ± 15.5% vs. -25.4 ± 48.7%, P = 0.005; SER -34.6 ± 19.7% vs. -8.7 ± 29.0%, P = 0.040). The area under the receiver operating characteristic curve for the percentage change in TLG30% (0.789, 95% CI 0.614 to 0.965) was similar to that for the percentage change in SER (0.789, 95% CI 0.552 to 1.000; P = 1.000).The specificity of TLG30% in predicting pCR) was 100% (7/7) and that of SER was 71.4% (5/7). The sensitivity of TLG30% in predicting non-pCR was 63.2% (12/19) and that of SER was 84.2% (16/19). When the combined TLG30% and SER criterion was applied, sensitivity was 100% (19/19), and specificity was 71.4% (5/7). CONCLUSION: 18F-FDG PET/MRI can be used to predict non-pCR after the first cycle of NAC in patients with breast cancer and has the potential to improve sensitivity by the addition of MRI parameters to the PET parameters.

Patients with Concordant Triple-Negative Phenotype between Primary Breast Cancers and Corresponding Metastases Have Poor Prognosis.

PURPOSE: We investigated the prognostic impact of discordance between the receptor status of primary breast cancers and corresponding metastases. METHODS: A total 144 patients with breast cancer and distant metastasis were investigated. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of primary tumor and corresponding metastases were assessed. Tumor phenotype according to receptor status was classified as triple-negative phenotype (TNP) or non-TNP. Concordance and discordance was determined by whether there was a change in receptor status or phenotype between primary and metastatic lesions. RESULTS: The rates of discordance between primary breast cancer and metastatic lesions were 18.1%, 25.0%, and 10.3% for ER, PR, and HER2, respectively. The rates of concordant non-TNP, concordant TNP and discordant TNP were 65.9%, 20.9%, and 13.2%, respectively. Patients with concordant ER/PR-negative status had worse postrecurrence survival (PRS) than patients with concordant ER/PR-positive and discordant ER/PR status (p=0.001 and p=0.021, respectively). Patients who converted from HER2-positive to negative after distant metastasis had worst PRS (p=0.040). Multivariate analysis showed that concordant TNP was statistically significant factor for worse PRS (p<0.001). CONCLUSION: Discordance in receptor status and tumor phenotype between primary breast cancer and corresponding metastatic lesions was observed. Patients with concordant TNP had worse long-term outcomes than patients with concordant non-TNP and discordant TNP between primary and metastatic breast cancer. Identifying the receptor status of metastatic lesions may lead to improvements in patient management and survival.

Features of Pure Lobular Carcinoma In Situ on Magnetic Resonance Imaging Associated with Immediate Re-Excision after Lumpectomy.

PURPOSE: To evaluate imaging features of pure lobular carcinoma in situ (LCIS) on magnetic resonance imaging (MRI) in patients who underwent immediate re-excision after lumpectomy. METHODS: Twenty-six patients (46.1±6.7 years) with 28 pure LCIS lesions, who underwent preoperative MRI and received curative surgery at our institution between 2005 and 2013, were included in this study. Clinicopathologic features associated with immediate re-excision were reviewed and analyzed using Fisher exact test or the Wilcoxon signed rank test. RESULTS: Of the 28 lesions, 21.4% (6/28, six patients) were subjected to immediate re-excision due to resection margin involvement by LCIS. Nonmass lesions and moderate-to-marked background parenchymal enhancement on MRI were more frequently found in the re-excision group than in the single operation group (100% [6/6] vs. 40.9% [9/22], p=0.018; 83.3% [5/6] vs. 31.8% [7/22], p=0.057, respectively). The median lesion size discrepancy observed between magnetic resonance images and histopathology was greater in the re-excision group than in the single operation group (-0.82 vs. 0.13, p=0.018). There were no differences in the mammographic or histopathologic findings between the two groups. CONCLUSION: Nonmass LCIS lesions or moderate-to-marked background parenchymal enhancements on MRI can result in an underestimation of the extent of the lesions and are associated with subsequent re-excision due to resection margin involvement.

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.

Early prediction of response to neoadjuvant chemotherapy in breast cancer patients: comparison of single-voxel (1)H-magnetic resonance spectroscopy and (18)F-fluorodeoxyglucose positron emission tomography.

OBJECTIVES: To prospectively compare performances of single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting pathologic response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Thirty-five breast cancer patients who received NAC and subsequent surgery were prospectively enrolled. MRS and FDG-PET were performed before and after the 1st NAC cycle. Percentage changes of total choline-containing compounds (tCho) via MRS, and maximum and peak standardized uptake values (SUVmax, SUVpeak) and total lesion glycolysis (TLG) via FDG-PET were measured, and their performances in predicting pathologic complete response (pCR) were compared. RESULTS: Of the 35 patients, 6 showed pCR and 29 showed non-pCR. Mean % reductions of tCho, SUVmax, SUVpeak, and TLG of the pCR group were larger than those of the non-pCR group (-80.3 ± 13.9 % vs. -32.1 ± 49.4 %, P = 0.025; -54.7 ± 22.1 % vs. -26.3 ± 33.7 %, P = 0.058; -60.7 ± 18.3 % vs. -32.3 ± 23.3 %, P = 0.009; -89.5 ± 8.5 % vs. -52.6 ± 36.2 %, P = 0.020). Diagnostic accuracy (area under ROC curve; Az, 0.911) of the % reduction of tCho was comparable to those of %SUVmax (0.822), SUVpeak (0.862), and TLG (0.879) in distinguishing pCR from non-pCR (all P > 0.05). CONCLUSION: MRS showed comparable performance to FDG-PET in early prediction of pCR in breast cancer patients. KEY POINTS: • MRS can predict response to NAC in breast cancer post-1 (st) cycle. • Changes in tCho and SUV after NAC reflect tumour cellularity changes. • MRS can be an alternative to FDG-PET in predicting response to NAC.

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.

Magnetic resonance imaging findings of mucinous borderline ovarian tumors: comparison of intestinal and endocervical subtypes.

PURPOSE: The purpose of this study is to compare the MRI features of intestinal and endocervical mucinous borderline ovarian tumors (MBOT). METHODS: Fifty seven and 17 patients with histologically proven intestinal (n = 62) and endocervical (n = 22) MBOT, respectively, underwent preoperative MRI which were reviewed by two radiologists blinded to histology. An array of MRI features and clinical factors (age, cancer antigen 125 [CA-125]) were compared between intestinal and endocervical subtypes using the t test and Chi-square test. Univariate and multivariate logistic regression analyses were performed to evaluate for significant predictors of subtype. RESULTS: There was no significant difference in patient age of intestinal and endocervical MBOT (P = 0.423). CA-125 levels were higher in endocervical MBOT (P = 0.022). Regarding MR features, intestinal MBOT was larger, had more septations, more frequently demonstrated honeycomb loculi, and signal intensity discrepancy while endocervical MBOT was more frequently bilateral with papillary projections (P < 0.05). At multivariate analysis, higher CA-125 (odds ratio [OR] 1.015, P = 0.034) and the presence of papillary projections (OR 11.441, P = 0.024) were the only independent predictive factors of endocervical MBOT. CONCLUSION: Intestinal and endocervical subtypes of MBOT demonstrated significantly different features on MRI. The presence of papillary projection was the only independent MRI feature predictive of endocervical MBOT.

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.

Recurrent Pseudomonas aeruginosa Infection in Chronic Lung Diseases: Relapse or Reinfection?

BACKGROUND: Pseudomonas aeruginosa infection is particularly associated with progressive and ultimately chronic recurrent respiratory infections in chronic obstructive pulmonary disease, bronchiectasis, chronic destroyed lung disease, and cystic fibrosis. Its treatment is also very complex because of drug resistance and recurrence. METHODS: Forty eight cultures from 18 patients with recurrent P. aeruginosa pneumonia from 1998 to 2002 were included in this study. Two or more pairs of sputum cultures were performed during 2 or more different periods of recurrences. The comparison of strains was made according to the phenotypic patterns of antibiotic resistance and chromosomal fingerprinting by pulsed field gel electrophoresis (PFGE) using the genomic DNA of P. aeruginosa from the sputum culture. RESULTS: Phenotypic patterns of antibiotic resistance of P. aeruginosa were not correlated with their prior antibiotic exposition. Fifteen of 18 patients (83.3%) had recurrent P. aeruginosa pneumonia caused by the strains with same PFGE pattern. CONCLUSION: These data suggest that the most of the recurrent P. aeruginosa infections in chronic lung disease occurred due to the relapse of prior infections. Further investigations should be performed for assessing the molecular mechanisms of the persistent colonization and for determining how to eradicate clonal persistence of P. aeruginosa.

A New Isolated Mediastinal Lymph Node or Small Pulmonary Nodule Arising during Breast Cancer Surveillance Following Curative Surgery: Clinical Factors That Differentiate Malignant from Benign Lesions.

PURPOSE: A newly isolated mediastinal lymph node (LN) or a small pulmonary nodule, which appears during breast cancer surveillance, may pose a diagnostic dilemma with regard to malignancy. We conducted this study to determine which clinical factors were useful for the differentiation of malignant lesions from benign lesions under these circumstances. MATERIALS AND METHODS: We enrolled breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule that arose during surveillance, and whose lesions were pathologically confirmed. Tissue diagnosis was made by mediastinoscopy, video-assisted thoracic surgery or thoracotomy. RESULTS: A total of 43 patients were enrolled (mediastinal LN, 13 patients; pulmonary nodule, 30 patients). Eighteen patients (41.9%) were pathologically confirmed to have a benign lesion (benign group), and 25 patients (58.1%) were confirmed to have malignant lesion (malignant group). Between the two groups, the initial tumor size (p=0.096) and N stage (p=0.749) were similar. Hormone receptor negativity was more prevalent in the malignant group (59.1% vs. 40.9%, p=0.048). The mean lesion size was larger in the malignant group than in the benign group (20.8 mm vs. 14.4 mm, p=0.024). Metastatic lesions had a significantly higher value of maximal standardized uptake (mSUV) than that of benign lesions (6.4 vs. 3.4, p=0.021). CONCLUSION: Hormone receptor status, lesion size, and mSUV on positron emission tomography are helpful in the differentiation of malignant lesions from benign lesions in breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule during surveillance.

Low rates of additional cancer detection by magnetic resonance imaging in newly diagnosed breast cancer patients who undergo preoperative mammography and ultrasonography.

PURPOSE: We evaluated the efficacy of breast magnetic resonance imaging (MRI) for detecting additional malignancies in breast cancer patients newly diagnosed by breast ultrasonography and mammography. METHODS: We retrospectively reviewed the records of 1,038 breast cancer patients who underwent preoperative mammography, bilateral breast ultrasonography, and subsequent breast MRI between August 2007 and December 2010 at single institution in Korea. MRI-detected additional lesions were defined as those lesions detected by breast MRI that were previously undetected by mammography and ultrasonography and which would otherwise have not been identified. RESULTS: Among the 1,038 cases, 228 additional lesions (22.0%) and 30 additional malignancies (2.9%) were detected by breast MRI. Of these 228 lesions, 109 were suspected to be malignant (Breast Imaging-Reporting and Data System category 4 or 5) on breast MRI and second-look ultrasonography and 30 were pathologically confirmed to be malignant (13.2%). Of these 30 lesions, 21 were ipsilateral to the main lesion and nine were contralateral. Fourteen lesions were in situ carcinomas and 16 were invasive carcinomas. The positive predictive value of breast MRI was 27.5% (30/109). No clinicopathological factors were significantly associated with additional malignant foci. CONCLUSION: Breast MRI was useful in detecting additional malignancy in a small number of patients who underwent ultrasonography and mammography.