MRI-based breast cancer radiogenomics using RNA profiling: association with subtypes in a single-center prospective study.

BACKGROUND: There are few prospective studies on the correlations between MRI features and whole RNA-sequencing data in breast cancer according to molecular subtypes. The purpose of our study was to explore the association between genetic profiles and MRI phenotypes of breast cancer and to identify imaging markers that influences the prognosis and treatment according to subtypes. METHODS: From June 2017 to August 2018, MRIs of 95 women with invasive breast cancer were prospectively analyzed, using the breast imaging-reporting and data system and texture analysis. Whole RNA obtained from surgical specimens was analyzed using next-generation sequencing. The association between MRI features and gene expression profiles was analyzed in the entire tumor and subtypes. Gene networks, enriched functions, and canonical pathways were analyzed using Ingenuity Pathway Analysis. The P value for differential expression was obtained using a parametric F test comparing nested linear models and adjusted for multiple testing by reporting Q value. RESULTS: In 95 participants (mean age, 53 years ± 11 [standard deviation]), mass lesion type was associated with upregulation of CCL3L1 (sevenfold) and irregular mass shape was associated with downregulation of MIR421 (sixfold). In estrogen receptor-positive cancer with mass lesion type, CCL3L1 (21-fold), SNHG12 (11-fold), and MIR206 (sevenfold) were upregulated, and MIR597 (265-fold), MIR126 (12-fold), and SOX17 (fivefold) were downregulated. In triple-negative breast cancer with increased standard deviation of texture analysis on precontrast T1-weighted imaging, CLEC3A (23-fold), SRGN (13-fold), HSPG2 (sevenfold), KMT2D (fivefold), and VMP1 (fivefold) were upregulated, and IGLC2 (73-fold) and PRDX4 (sevenfold) were downregulated (all, P < 0.05 and Q < 0.1). Gene network and functional analysis showed that mass type estrogen receptor-positive cancers were associated with cell growth, anti-estrogen resistance, and poor survival. CONCLUSION: MRI characteristics are associated with the different expressions of genes related to metastasis, anti-drug resistance, and prognosis, depending on the molecular subtypes of breast cancer.

Value of Breast MRI and Nomogram After Negative Axillary Ultrasound for Predicting Axillary Lymph Node Metastasis in Patients With Clinically T1-2 N0 Breast Cancer.

BACKGROUND: There are increasing concerns about that sentinel lymph node biopsy (SLNB) could be omitted in patients with clinically T1-2 N0 breast cancers who has negative axillary ultrasound (AUS). This study aims to assess the false negative result (FNR) of AUS, the rate of high nodal burden (HNB) in clinically T1-2 N0 breast cancer patients, and the diagnostic performance of breast magnetic resonance imaging (MRI) and nomogram. METHODS: We identified 948 consecutive patients with clinically T1-2 N0 cancers who had negative AUS, subsequent MRI, and breast conserving therapy between 2013 and 2020 from two tertiary medical centers. Patients from two centers were assigned to development and validation sets, respectively. Among 948 patients, 402 (mean age ± standard deviation, 57.61 ± 11.58) were within development cohort and 546 (54.43 ± 10.02) within validation cohort. Using logistic regression analyses, clinical-imaging factors associated with lymph node (LN) metastasis were analyzed in the development set from which nomogram was created. The performance of MRI and nomogram was assessed. HNB was defined as ≥ 3 positive LNs. RESULTS: The FNR of AUS was 20.1% (81 of 402) and 19.2% (105 of 546) and the rates of HNB were 1.2% (5/402) and 2.2% (12/546), respectively. Clinical and imaging features associated with LN metastasis were progesterone receptor positivity, outer tumor location on mammography, breast imaging reporting and data system category 5 assessment of cancer on ultrasound, and positive axilla on MRI. In validation cohorts, the positive predictive value (PPV) and negative predictive value (NPV) of MRI and clinical-imaging nomogram was 58.5% and 86.5%, and 56.0% and 82.0%, respectively. CONCLUSION: The FNR of AUS was approximately 20% but the rate of HNB was low. The diagnostic performance of MRI was not satisfactory with low PPV but MRI had merit in reaffirming negative AUS with high NPV. Patients who had low probability scores from our clinical-imaging nomogram might be possible candidates for the omission of SLNB.

Machine learning with multiparametric breast MRI for prediction of Ki-67 and histologic grade in early-stage luminal breast cancer.

OBJECTIVES: To investigate whether machine learning-based prediction models using 3-T multiparametric MRI (mpMRI) can predict Ki-67 and histologic grade in stage I-II luminal cancer. METHODS: Between 2013 and 2019, consecutive women with luminal cancers who underwent preoperative MRI with diffusion-weighted imaging (DWI) and surgery were included. For prediction models, morphology, kinetic features using computer-aided diagnosis (CAD), and apparent diffusion coefficient (ADC) at DWI were evaluated by two radiologists. Logistic regression analysis was used to identify mpMRI features for predicting Ki-67 and grade. Diagnostic performance was assessed using eight machine learning algorithms incorporating mpMRI features and compared using the DeLong method. RESULTS: Of 300 women, 203 (67.7%) had low Ki-67 and 97 (32.3%) had high Ki-67; 242 (80.7%) had low grade and 58 (19.3%) had high grade. In multivariate analysis, independent predictors for higher Ki-67 were washout component > 13.5% (odds ratio [OR] = 4.16; p < 0.001) and intratumoral high SI on T2-weighted image (OR = 1.89; p = 0.022). Those for higher grade were washout component > 15.5% (OR = 7.22; p < 0.001), rim enhancement (OR = 2.59; p = 0.022), and ADC value < 0.945 × 10-3 mm2/s (OR = 2.47; p = 0.015). Among eight models using these predictors, six models showed the equivalent performance for Ki-67 (area under the receiver operating characteristic curve [AUC]: 0.70) and Naive Bayes classifier showed the highest performance for grade (AUC: 0.79). CONCLUSIONS: A prediction model incorporating mpMRI features shows good diagnostic performance for predicting Ki-67 and histologic grade in patients with luminal breast cancers. KEY POINTS: • Among multiparametric MRI features, kinetic feature of washout component >13.5% and intratumoral high signal intensity on T2-weighted image were associated with higher Ki-67. • Washout component >15.5%, rim enhancement, and mean apparent diffusion coefficient value < 0.945 × 10-3 mm2/s were associated with higher histologic grade. • Machine learning-based prediction models incorporating multiparametric MRI features showed good diagnostic performance for Ki-67 and histologic grade in luminal breast cancers.

Radiomic machine learning for predicting prognostic biomarkers and molecular subtypes of breast cancer using tumor heterogeneity and angiogenesis properties on MRI.

OBJECTIVES: To investigate machine learning approaches for radiomics-based prediction of prognostic biomarkers and molecular subtypes of breast cancer using quantification of tumor heterogeneity and angiogenesis properties on magnetic resonance imaging (MRI). METHODS: This prospective study examined 291 invasive cancers in 288 patients who underwent breast MRI at 3 T before treatment between May 2017 and July 2019. Texture and perfusion analyses were performed and a total of 160 parameters for each cancer were extracted. Relationships between MRI parameters and prognostic biomarkers were analyzed using five machine learning algorithms. Each model was built using only texture features, only perfusion features, or both. Model performance was compared using the area under the receiver-operating characteristic curve (AUC) and the DeLong method, and the importance of MRI parameters in prediction was derived. RESULTS: Texture parameters were associated with the status of hormone receptors, human epidermal growth factor receptor 2, and Ki67, tumor size, grade, and molecular subtypes (p < 0.002). Perfusion parameters were associated with the status of hormone receptors and Ki67, grade, and molecular subtypes (p < 0.003). The random forest model integrating texture and perfusion parameters showed the highest performance (AUC = 0.75). The performance of the random forest model was the best with a special scale filter of 0 (AUC = 0.80). The important parameters for prediction were texture irregularity (entropy) and relative extracellular extravascular space (Ve). CONCLUSIONS: Radiomic machine learning that integrates tumor heterogeneity and angiogenesis properties on MRI has the potential to noninvasively predict prognostic factors of breast cancer. KEY POINTS: • Machine learning, integrating tumor heterogeneity and angiogenesis properties on MRI, can be applied to predict prognostic biomarkers and molecular subtypes in breast cancer. • The random forest model showed the best predictive performance among the five machine learning models (logistic regression, decision tree, naïve Bayes, random forest, and artificial neural network). • The most important MRI parameters for predicting prognostic factors in breast cancer were texture irregularity (entropy) among texture parameters and relative extracellular extravascular space (Ve) among perfusion parameters.

Simultaneous Multislice Readout-Segmented Echo Planar Imaging for Diffusion-Weighted MRI in Patients With Invasive Breast Cancers.

BACKGROUND: In diffusion-weighted imaging (DWI) of breast MRI, simultaneous multislice acceleration techniques can be used for readout-segmented echo planar imaging (rs-EPI) to shorten the scan time. PURPOSE: To compare the image quality, apparent diffusion coefficient (ADC) value, and scan time of rs-EPI and simultaneous multislice rs-EPI (SMS rs-EPI) sequences. STUDY TYPE: Retrospective. SUBJECTS: In all, 134 consecutive women (mean age: 55.3 years) with invasive breast cancer who underwent preoperative MRI. FIELD STRENGTH/ SEQUENCES: 3.0T; rs-EPI sequence, prototypic SMS rs-EPI sequence and dynamic contrast-enhanced MRI (DCE-MRI) sequence ASSESSMENT: For quantitative comparison, two radiologists independently measured the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), lesion contrast, and apparent diffusion coefficient (ADC). For qualitative comparison, image quality, lesion conspicuity, and reader preference were assessed with a reference of DCE-MRI. STATISTICAL TESTS: Paired t-tests and Mann-Whitney tests were used. RESULTS: For SNR and CNR, there were no differences between the sequences (P = 0.342 and 0.665 for reader 1; P = 0.606 and P = 0.116 for reader 2). Lesion contrast of SMS rs-EPI was higher than that of rs-EPI (P < 0.05 for both reader 1 and reader 2). Mean tumor ADC was similar in rs-EPI and SMS rs-EPI sequences (0.98 ± 0.22 vs. 1.00 ± 0.22; P = 0.291 for reader 1, 0.98 ± 0.21 vs. 1.00 ± 0.22; P = 0.418 for reader 2). Regarding qualitative comparison, image quality and lesion conspicuity were higher in SMS rs-EPI than in rs-EPI (both P < 0.05 for both readers). The two readers regarded SMS rs-EPI as superior or equal to rs-EPI in over 90% of cases. The acquisition time was 4:30 minutes for rs-EPI and 2:31 minutes for SMS rs-EPI. DATA CONCLUSION: The SMS rs-EPI sequence resulted in a similar ADC value and better image quality than the rs-EPI sequence in a 44.1% reduced scan time. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: 3.

Radiogenomic Analysis of Breast Cancer by Using B-Mode and Vascular US and RNA Sequencing.

Background Radiogenomic investigations for breast cancer provide an understanding of tumor heterogeneity and discover image phenotypes of genetic variation. However, there is little research on the correlations between US features of breast cancer and whole-transcriptome profiling. Purpose To explore US phenotypes reflecting genetic alteration relevant to breast cancer treatment and prognosis by comparing US images of tumor with their RNA sequencing results. Materials and Methods From January to October 2016, B-mode and vascular US images in 31 women (mean age, 49 years ± 9 [standard deviation]) with breast cancer were prospectively analyzed. B-mode features included size, shape, echo pattern, orientation, margin, and calcifications. Vascular features were evaluated by using microvascular US and contrast agent-enhanced US: vascular index, vessel morphologic features, distribution, penetrating vessels, enhancement degree, order, margin, internal homogeneity, and perfusion defect. RNA sequencing was conducted with total RNA obtained from a surgical specimen by using next-generation sequencing. US features were compared with gene expression profiles, and ingenuity pathway analysis was used to analyze gene networks, enriched functions, and canonical pathways associated with breast cancer. The P value for differential expression was extracted by using a parametric F test comparing nested linear models. Results Thirteen US features were associated with various patterns of 340 genes (P < .05). Nonparallel orientation at B-mode US was associated with upregulation of TFF1 (log twofold change [log2FC] = 4.0; P < .001), TFF3 (log2FC = 2.5; P < .001), AREG (log2FC = 2.6; P = .005), and AGR3 (log2FC = 2.6; P = .003). Complex vessel morphologic structure was associated with upregulation of FZD8 (log2FC = 2.0; P = .01) and downregulation of IGF1R (log2FC = -2.0; P = .006) and CRIPAK (log2FC = -2.4; P = .01). The top networks with regard to orientation or vessel morphologic structure were associated with cell cycle, death, and proliferation. Conclusion Compared with RNA sequencing, B-mode and vascular US features reflected genomic alterations associated with hormone receptor status, angiogenesis, or prognosis in breast cancer. © RSNA, 2020 Online supplemental material is available for this article.

Intravoxel incoherent motion diffusion-weighted MRI of invasive breast cancer: Correlation with prognostic factors and kinetic features acquired with computer-aided diagnosis.

BACKGROUND: As both intravoxel incoherent motion (IVIM) modeling and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provide perfusion parameters, IVIM-derived perfusion parameters might be expected to correlate with the kinetic features from DCE-MRI. PURPOSE: To investigate the association between IVIM parameters and prognostic factors and to evaluate the correlation between IVIM parameters and kinetic features in invasive breast cancer patients using computer-aided diagnosis (CAD). STUDY TYPE: Retrospective. POPULATION: Eighty-five patients (invasive cancers; mean size, 1.8 cm; range, 0.8-4.8 cm) who underwent diffusion-weighted imaging with 12 b-values (0-1000 s/mm2 ). FIELD STRENGTH/SEQUENCE: 3.0T MRI axial, IVIM-DWI epi-sequence, and DCE-MRI. ASSESSMENT: Two radiologists measured the apparent diffusion coefficient (ADC), diffusion coefficient, pseudodiffusion coefficient, and perfusion fraction (f) using IVIM modeling. Kinetic features such as peak enhancement and early and delayed enhancement profiles were acquired using CAD. STATISTICAL TESTS: The correlation between the IVIM parameters and kinetic features and the association between the IVIM parameters and prognostic factors were investigated using Mann-Whitney test and Spearman correlation test. RESULTS: There were no significant associations between IVIM parameters and prognostic factors. When IVIM parameters were correlated with kinetic features by CAD, both the ADC and f values showed correlations with delayed enhancement profiles. The ADC values were lower in tumors with lower persistent components (P = 0.013) and higher washout components (P = 0.045) and showed a positive correlation with persistent proportion (Spearman's rho (r) = 0.222, P = 0.041). The f value was higher in tumors with higher persistent components (P = 0.021) and showed a positive correlation with persistent proportion (r = 0.227, P = 0.029). DATA CONCLUSION: This analysis revealed that IVIM-derived ADC and f values showed correlations with kinetic features at the delayed phase as assessed by CAD. These results indicate the potential of IVIM imaging biomarkers to provide information on the biological and kinetic properties of breast cancers without a contrast agent. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:118-130.

Incidence and risk factors for congestive heart failure in patients with early breast cancer who received anthracycline and/or trastuzumab: a big data analysis of the Korean Health Insurance Review and Assessment service database.

PURPOSE: We aimed to analyze the incidence, time to occurrence, and congestive heart failure (CHF) risk factors for early breast cancer patients treated with anthracycline (AC)-based chemotherapy and/or trastuzumab (T) therapy in Korea. METHODS: We included female patients > 19 years old from the Health Insurance Review and Assessment Service database who had no prior CHF history and had been diagnosed with early breast cancer between January 2007 and October 2016. RESULTS: We included 83,544 patients in our analysis. In terms of crude incidence for CHF, AC followed by T showed the highest incidence (6.3%). However, 3.1 and 4.2% of the patients had CHF due to AC-based chemotherapy and non-AC followed by T, respectively. The median times to occurrence of CHF were different according to adjuvant treatments, approximately 2 years (701.0 days) in the AC-based chemotherapy group vs 1 year (377.5 days) AC followed by T group. T therapy was associated with earlier development of CHF irrespective of previous chemotherapy, but late risk of CHF 1.2 years after T therapy rapidly decreased in both chemotherapy groups. Multivariate Cox regression analysis revealed that the adjusted hazard ratio for CHF was increased in the group of older patients (≥ 65 years old) who underwent AC followed by T therapy, with Charlson comorbidity index scores of ≥ 2. CONCLUSIONS: Our study showed that neo-/adjuvant chemotherapy using T irrespective of previous chemotherapy (AC or non-AC) was associated with significantly increased risk of CHF compared with AC-based chemotherapy in Korean patients with early breast cancer.

Additional value of diffusion-weighted imaging to evaluate multifocal and multicentric breast cancer detected using pre-operative breast MRI.

OBJECTIVES: To investigate whether diffusion-weighted imaging (DWI) aids pre-operative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to evaluate additional lesions in breast cancer patients. METHODS: DCE-MRI and DWI were performed on 131 lesions, with available histopathological results. The apparent diffusion coefficient (ADC) of each lesion was measured, and the cut-off value for differentiation between malignant and benign lesions was calculated. A protocol combining the ADC cut-off value with DCE-MRI was validated in a cohort of 107 lesions in 77 patients. RESULTS: When an ADC cut-off value of 1.11 × 10-3 mm2/s from the development cohort was applied to the additional lesions in the validation cohort, the specificity increased from 18.9% to 67.6% (P < 0.001), and the diagnostic accuracy increased from 61.7% to 82.2% (P = 0.05), without significant loss of sensitivity (98.6% vs. 90.0%, P = 0.07). The negative predictive values of lesions in the same quadrant had decreased, as had those of lesions ≥1 cm in diameter. The ADC cut-off value in the validation cohort was 1.05 × 10-3 mm2/s. CONCLUSIONS: Additional implementation of DWI for breast lesions in pre-operative MRI can help to obviate unnecessary biopsies by increasing specificity. However, to avoid missing cancers, clinicians should closely monitor lesions located in the same quadrant or lesions ≥1 cm. KEY POINTS: • DWI can be used to further differentiate lesions during pre-operative cancer staging. • ADC cut-off values were similar in the development and validation cohorts. • DWI improves both PPV and NPV in cases of multicentric lesions. • DWI improves both PPV and NPV in lesions <1 in diameter. • NPVs are decreased in multifocal lesions and lesions ≥1 cm in diameter.

The sonographic "coffee bean" sign helps distinguish an axillary neurofibroma from a lymphadenopathy.

Axillary masses may represent various soft tissue tumors or lymphadenopathy. Neurofibromas are benign peripheral nerve sheath tumors and, while they are very uncommon, it is important to remember that neurogenic tumors arising from brachial plexus can develop in the axilla. We describe an axillary neurofibroma arising from the brachial plexus that presented with a "coffee bean sign" on sonography that distinguished it from axillary lymphadenopathy.

Unusual US Findings of Diffuse Large B-Cell Lymphoma of the Breast: A Case Report.

Lymphoma is an uncommon type of breast malignancy, with low prevalence. The ultrasonographic findings of breast lymphoma have been described as nonspecific. Breast lymphoma most commonly appears as a solitary hypoechoic mass on US, and usually shows hypervascularity on color Doppler US. Herein, we report an unusual case of breast lymphoma that presented as multiple bilateral hyperechoic nodules on US.

Tumor Heterogeneity of Breast Cancer Assessed with Computed Tomography Texture Analysis: Association with Disease-Free Survival and Clinicopathological Prognostic Factor.

Breast cancer is a heterogeneous disease, and computed tomography texture analysis (CTTA), which reflects the tumor heterogeneity, may predict the prognosis. We investigated the usefulness of CTTA for the prediction of disease-free survival (DFS) and prognostic factors in patients with invasive breast cancer. A total of 256 consecutive women who underwent preoperative chest CT and surgery in our institution were included. The Cox proportional hazards model was used to determine the relationship between textural features and DFS. Logistic regression analysis was used to reveal the relationship between textural features and prognostic factors. Of 256 patients, 21 (8.2%) had disease recurrence over a median follow-up of 60 months. For the prediction of shorter DFS, higher histological grade (hazard ratio [HR], 6.12; p < 0.001) and lymphovascular invasion (HR, 2.93; p = 0.029) showed significance, as well as textural features such as lower mean attenuation (HR, 4.71; p = 0.003) and higher entropy (HR, 2.77; p = 0.036). Lower mean attenuation showed a correlation with higher tumor size, and higher entropy showed correlations with higher tumor size and Ki-67. In conclusion, CTTA-derived textural features can be used as a noninvasive imaging biomarker to predict shorter DFS and prognostic factors in patients with invasive breast cancer.

Comparison of CT- and MRI-Based Quantification of Tumor Heterogeneity and Vascularity for Correlations with Prognostic Biomarkers and Survival Outcomes: A Single-Center Prospective Cohort Study.

BACKGROUND: Tumor heterogeneity and vascularity can be noninvasively quantified using histogram and perfusion analyses on computed tomography (CT) and magnetic resonance imaging (MRI). We compared the association of histogram and perfusion features with histological prognostic factors and progression-free survival (PFS) in breast cancer patients on low-dose CT and MRI. METHODS: This prospective study enrolled 147 women diagnosed with invasive breast cancer who simultaneously underwent contrast-enhanced MRI and CT before treatment. We extracted histogram and perfusion parameters from each tumor on MRI and CT, assessed associations between imaging features and histological biomarkers, and estimated PFS using the Kaplan-Meier analysis. RESULTS: Out of 54 histogram and perfusion parameters, entropy on T2- and postcontrast T1-weighted MRI and postcontrast CT, and perfusion (blood flow) on CT were significantly associated with the status of subtypes, hormone receptors, and human epidermal growth factor receptor 2 (p < 0.05). Patients with high entropy on postcontrast CT showed worse PFS than patients with low entropy (p = 0.053) and high entropy on postcontrast CT negatively affected PFS in the Ki67-positive group (p = 0.046). CONCLUSIONS: Low-dose CT histogram and perfusion analysis were comparable to MRI, and the entropy of postcontrast CT could be a feasible parameter to predict PFS in breast cancer patients.

Prediction of Axillary Lymph Node Metastasis in Early-stage Triple-Negative Breast Cancer Using Multiparametric and Radiomic Features of Breast MRI.

RATIONALE AND OBJECTIVES: To investigate whether machine learning (ML) approaches using breast magnetic resonance imaging (MRI)-derived multiparametric and radiomic features could predict axillary lymph node metastasis (ALNM) in stage I-II triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Between 2013 and 2019, 86 consecutive patients with TNBC who underwent preoperative MRI and surgery were enrolled and divided into ALNM (N = 27) and non-ALNM (n = 59) groups according to histopathologic results. For multiparametric features, kinetic features using computer-aided diagnosis (CAD), morphologic features, and apparent diffusion coefficient (ADC) values at diffusion-weighted images were evaluated. For extracting radiomic features, three-dimensional segmentation of tumors using T2-weighted images (T2WI) and T1-weighted subtraction images were respectively performed by two radiologists. Each predictive model using three ML algorithms was built using multiparametric features or radiomic features, or both. The diagnostic performances of models were compared using the DeLong method. RESULTS: Among multiparametric features, non-circumscribed margin, peritumoral edema, larger tumor size, and larger angio-volume at CAD were associated with ALNM in univariate analysis. In multivariate analysis, larger angio-volume was the sole statistically significant predictor for ALNM (odds ratio = 1.33, P = 0.008). Regarding ADC values, there were no significant differences according to ALNM status. The area under the receiver operating characteristic curve for predicting ALNM was 0.74 using multiparametric features, 0.77 using radiomic features from T1-weighted subtraction images, 0.80 using radiomic features from T2WI, and 0.82 using all features. CONCLUSION: A predictive model incorporating breast MRI-derived multiparametric and radiomic features may be valuable in predicting ALNM preoperatively in patients with TNBC.

Therapy-related myeloid neoplasm in early breast cancer patients treated with adjuvant chemotherapy.

BACKGROUND: Long-term complications are becoming more important as the survival rate of breast cancer improves. Treatment-related myeloid neoplasm is an important long-term complication in breast cancer survivors as it has a poor prognosis. OBJECTIVE: We evaluated the incidence and risk factors for the development of treatment-related acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS) in patients treated with early breast cancer. METHODS: We accessed the national Korean database to identify 153,565 patients diagnosed with breast cancer between January 2007 and October 2016 who underwent surgery for breast cancer. We estimated the cumulative incidence of AML/MDS and analysed the risk factors for developing AML/MDS. RESULTS: Of 153,575 patients, 79,321 received anthracycline-based adjuvant therapy, 14,317 received adjuvant therapy without anthracyclines and 46,657 did not receive adjuvant chemotherapy. Overall, 120 developed AML (105 in the anthracycline group, 9 in the non-anthracycline group and 6 in the control group), and 128 developed MDS (96, 9 and 23 in each group). The 10-year cumulative incidence of AML/MDS was the highest in the anthracycline group (0.221% and 0.199%), followed by the non-anthracycline group (0.122% and 0.163%) and the control group (0.024% and 0.089%). The risk of developing AML/MDS was significantly higher in patients treated with anthracyclines (hazard ratio [HR] 9.531; p < 0.0001 for AML and HR 2.559; p < 0.0001 for MDS) compared to patients in the control group. CONCLUSION: This study found that anthracycline-based adjuvant therapy significantly increased the risk of AML/MDS in Korean breast cancer patients, with the risk persisting for at least 10 years. While the cumulative incidence was low, the long-term risks of AML/MDS should be taken into account considering the poor outcomes associated with these neoplasms.

PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients.

PURPOSE: Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer. Materials and Methods: We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment. RESULTS: Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors. CONCLUSION: Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

Association between vascular ultrasound features and DNA sequencing in breast cancer: a preliminary study.

There are few radiogenomic studies to correlate ultrasound features of breast cancer with genomic changes. We investigated whether vascular ultrasound phenotypes are associated with breast cancer gene profiles for predicting angiogenesis and prognosis. We prospectively correlated quantitative and qualitative features of microvascular ultrasound (vascular index, vessel morphology, distribution, and penetrating vessel) and contrast-enhanced ultrasound (time-intensity curve parameters and enhancement pattern) with genomic characteristics in 31 breast cancers. DNA obtained from breast tumors and normal tissues were analyzed using targeted next-generation sequencing of 105 genes. The single-variant association test was used to identify correlations between vascular ultrasound features and genomic profiles. Chi-square analysis was used to detect single nucleotide polymorphisms (SNPs) associated with ultrasound features by estimating p values and odds ratios (ORs). Eight ultrasound features were significantly associated with 9 SNPs (p < 0.05). Among them, four ultrasound features were positively associated with 5 SNPs: high vascular index with rs1136201 in ERBB2 (p = 0.04, OR = 7.75); large area under the curve on contrast-enhanced ultrasound with rs35597368 in PDGFRA (p = 0.04, OR = 4.07); high peak intensity with rs35597368 in PDGFRA (p = 0.049, OR = 4.05) and rs2305948 in KDR (p = 0.04, OR = 5.10); and long mean transit time with rs2275237 in ARNT (p = 0.02, OR = 10.25) and rs755793 in FGFR2 (p = 0.02, OR = 10.25). We identified 198 non-silent SNPs in 71 various cancer-related genes. Vascular ultrasound features can reflect genomic changes associated with angiogenesis and prognosis in breast cancer.

Granular Cell Tumor Originating from the Pectoral Muscle: A Rare Extramammary Finding on Mammography.

A granular cell tumor (GCT) is a rare soft tissue tumor that usually arises from the striated muscle of the tongue. Few literatures have reported pectoral muscle involvement of the GCT. Herein, we report a rare case of a GCT originating from the pectoral muscle below the breast with multimodal imaging appearance.

Diagnostic Performance of Digital Breast Tomosynthesis with the Two-Dimensional Synthesized Mammogram for Suspicious Breast Microcalcifications Compared to Full-Field Digital Mammography in Stereotactic Breast Biopsy.

Purpose: To evaluate the diagnostic performance of digital breast tomosynthesis (DBT) with the two-dimensional synthesized mammogram (2DSM), compared to full-field digital mammography (FFDM), for suspicious microcalcifications in the breast ahead of stereotactic biopsy and to assess the diagnostic image visibility of the images. Materials and Methods: This retrospective study involved 189 patients with microcalcifications, which were histopathologically verified by stereotactic breast biopsy, who underwent DBT with 2DSM and FFDM between January 8, 2015, and January 20, 2020. Two radiologists assessed all cases of microcalcifications based on Breast Imaging Reporting and Data System (BI-RADS) independently. They were blinded to the histopathologic outcome and additionally evaluated lesion visibility using a five-point scoring scale. Results: Overall, the inter-observer agreement was excellent (0.9559). Under the setting of category 4A as negative due to the low possibility of malignancy and to avoid the dilution of malignancy criteria in our study, McNemar tests confirmed no significant difference between the performances of the two modalities in detecting microcalcifications with a high potential for malignancy (4B, 4C, or 5; p = 0.1573); however, the tests showed a significant difference between their performances in detecting microcalcifications with a high potential for benignancy (4A; p = 0.0009). DBT with 2DSM demonstrated superior visibility and diagnostic performance than FFDM in dense breasts. Conclusion: DBT with 2DSM is superior to FFDM in terms of total diagnostic accuracy and lesion visibility for benign microcalcifications in dense breasts. This study suggests a promising role for DBT with 2DSM as an accommodating tool for stereotactic biopsy in female with dense breasts and suspicious breast microcalcifications.