Publications by authors named "Hee-Jung Shin"

112 Publications

Diffusion-Weighted Magnetic Resonance Imaging for Breast Cancer Screening in High-Risk Women: Design and Imaging Protocol of a Prospective Multicenter Study in Korea.

J Breast Cancer 2021 Apr;24(2):218-228

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Purpose: Interest in unenhanced magnetic resonance imaging (MRI) screening for breast cancer is growing due to concerns about gadolinium deposition in the brain and the high cost of contrast-enhanced MRI. The purpose of this report is to describe the protocol of the Diffusion-Weighted Magnetic Resonance Imaging Screening Trial (DWIST), which is a prospective, multicenter, intraindividual comparative cohort study designed to compare the performance of mammography, ultrasonography, dynamic contrast-enhanced (DCE) MRI, and diffusion-weighted (DW) MRI screening in women at high risk of developing breast cancer.

Methods: A total of 890 women with mutation or family history of breast cancer and lifetime risk ≥ 20% are enrolled. The participants undergo 2 annual breast screenings with digital mammography, ultrasonography, DCE MRI, and DW MRI at 3.0 T. Images are independently interpreted by trained radiologists. The reference standard is a combination of pathology and 12-month follow-up. Each image modality and their combination will be compared in terms of sensitivity, specificity, accuracy, positive predictive value, rate of invasive cancer detection, abnormal interpretation rate, and characteristics of detected cancers. The first participant was enrolled in April 2019. At the time of manuscript submission, 5 academic medical centers in South Korea are actively enrolling eligible women and a total of 235 women have undergone the first round of screening. Completion of enrollment is expected in 2022 and the results of the study are expected to be published in 2026.

Discussion: DWIST is the first prospective multicenter study to compare the performance of DW MRI and conventional imaging modalities for breast cancer screening in high-risk women. DWIST is currently in the patient enrollment phase.

Trial Registration: ClinicalTrials.gov Identifier: NCT03835897.
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http://dx.doi.org/10.4048/jbc.2021.24.e19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090809PMC
April 2021

Preoperative Breast MRI in Women 35 Years of Age and Younger with Breast Cancer: Benefits in Surgical Outcomes by Using Propensity Score Analysis.

Radiology 2021 Apr 20:204124. Epub 2021 Apr 20.

From the Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-Gil, Songpa-Gu, Seoul 05505, Republic of Korea.

Background The role of preoperative MRI in women 35 years of age or younger with breast cancer remains controversial. Purpose To determine the association between preoperative MRI and surgical outcomes in women aged 35 years or younger with breast cancer by using propensity score (PS) analysis to investigate the impact of preoperative MRI. Materials and Methods Women 35 years of age or younger diagnosed with breast cancer between 2007 and 2017 who had or had not undergone preoperative breast MRI were retrospectively identified. The MRI detection rate of additional suspicious lesions was analyzed, and changes in surgical management were recorded. Inverse probability weighting (IPW) and PS matching were used to adjust 19 variables and to create a balance between the two groups. Surgical outcomes were compared by using univariable logistic regression. Results Among 964 women (mean age ± standard deviation, 32 years ± 3), 665 (69%) had undergone preoperative MRI (MRI group; mean age, 32 years ± 3) and 299 (31%) had not (no-MRI group; mean age, 32 years ± 3). In the MRI group, additional suspicious lesions were found in 178 of the 665 women (27%), with 88 of those 178 women (49%) having malignant lesions. The surgical management was changed in 99 of the 665 women (15%) due to MRI findings, which was appropriate for 62 of those 99 women (63%). In the IPW analysis, the MRI group showed lower odds of repeat surgery (odds ratio [OR], 0.13; 95% CI: 0.07, 0.21; < .001) and higher odds of initial mastectomy (OR, 1.62; 95% CI: 1.17, 2.25; = .004). However, there was no difference in the overall mastectomy rate (OR, 1.24; 95% CI: 0.91, 1.68; = .17) compared with the no-MRI group. These results were consistent when using the PS matching method. Conclusion Preoperative MRI in young women with breast cancer is useful for detecting additional malignancy and improving surgical outcomes by reducing the repeat surgery rate, with a similar likelihood of overall mastectomy. © RSNA, 2021
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http://dx.doi.org/10.1148/radiol.2021204124DOI Listing
April 2021

Automated breast US as the primary screening test for breast cancer among East Asian women aged 40-49 years: a multicenter prospective study.

Eur Radiol 2021 Mar 29. Epub 2021 Mar 29.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Objectives: To prospectively evaluate the diagnostic performance of screening ABUS as the primary screening test for breast cancer among Korean women aged 40-49 years.

Methods: This prospective, multicenter study included asymptomatic Korean women aged 40-49 years from three academic centers between February 2017 and October 2019. Each participant underwent ABUS without mammography, and the ABUS images were interpreted at each hospital with double-reading by two breast radiologists. Biopsy and at least 1 year of follow-up was considered the reference standard. Diagnostic performance of ABUS screening and subgroup analyses according to patient and tumor characteristics were evaluated.

Results: Reference standard data were available for 959 women. The recall rate was 9.8% (95% confidence interval [CI]: 7.9%, 11.7%; 94 of 959 women) and the cancer detection yield was 5.2 per 1000 women (95% CI: -0.6, 11.1; 5 of 959 women). There was only one interval cancer. The sensitivity was 83.3% (95% CI: 53.5%, 100%; 5 of 6 cancers) and the specificity was 90.7% (95% CI: 88.8%, 92.5%; 864 of 95. women). The positive predictive values of biopsies performed (PPV) was 20.0% (95% CI: 4.3%, 35.7%; 5 of 25 women). Women with heterogeneous background echotexture had a higher recall rate (p = .009) and lower specificity (p = .036). Women with body mass index values < 25 kg/m had a higher mean recall rate (p = .046).

Conclusion: In East Asia, screening automated breast US may be an alternative to screening mammography for detecting breast cancers in women aged 40-49 years.

Key Points: • Automated breast US screening for breast cancer in asymptomatic women aged 40-49 is effective with 5.2 per 1000 cancer detection yield. • Women with heterogeneous background echotexture had a higher recall rate and lower specificity. • Women with body mass index < 25 kg/m had a higher recall rate.
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http://dx.doi.org/10.1007/s00330-021-07864-3DOI Listing
March 2021

Association between Oncotype DX recurrence score and dynamic contrast-enhanced MRI features in patients with estrogen receptor-positive HER2-negative invasive breast cancer.

Clin Imaging 2021 Jan 20;75:131-137. Epub 2021 Jan 20.

Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.

Background: Oncotype DX is a multigene assay used in breast cancer, and the result provided as a 'recurrence score (RS)' corresponds to the risk of a cancer recurrence and the chemotherapeutic benefit in estrogen receptor (ER)-positive human epidermal growth factor receptor (HER)2-negative invasive breast cancer. However, its accessibility is limited.

Purpose: To evaluate whether magnetic resonance imaging (MRI) could be used to predict Oncotype DX RS in patients with ER-positive HER2-negative invasive breast cancer.

Material And Methods: We enrolled 473 patients with ER-positive HER2-negative invasive breast cancer who underwent a preoperative MRI and Oncotype DX assay between January 2015 and December 2018. The MRI was reviewed and associations between Oncotype DX RS values were evaluated. Logistic regression analysis was used to identify independent predictors of high and low RS.

Results: Of the 485 cancers, 288 (59.4%) had low (<18), 155 (31.9%) had intermediate (18-30), and 42 (8.7%) had high (≥31) RS. Multiple logistic regression analysis revealed that a round shape (odds ratio [OR] = 2.554, P = 0.089) and low proportion of washout component (OR = 1.011, P = 0.014) were associated with low RS and that heterogeneously dense (OR = 3.205, P = 0.007) or scattered fibroglandular (OR = 3.776, P = 0.005) breast tissue, a non-spiculated margin (OR = 5.435, P = 0.007), and low proportion of persistent component (OR = 1.012, P = 0.036) were associated with high RS.

Conclusion: MRI features showed the potential for the discrimination of Oncotype DX RS in patients with ER-positive HER2-negative invasive breast cancer.
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http://dx.doi.org/10.1016/j.clinimag.2021.01.021DOI Listing
January 2021

Association of mammography and ultrasound features with MammaPrint in patients with estrogen receptor-positive, HER2-negative, node-positive invasive breast cancer.

Acta Radiol 2020 Dec 10:284185120980003. Epub 2020 Dec 10.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, 65526Asan Medical Center, Seoul, Republic of Korea.

Background: MammaPrint is a 70-gene signature microarray assay that predicts the likelihood of recurrence of breast cancer and chemotherapeutic benefits.

Purpose: To investigate the association between mammography and ultrasound (US) features and MammaPrint results in patients with estrogen receptor (ER)-positive, HER2-negative, node-positive invasive breast cancer, and to identify the predictive factors for high risk of recurrence.

Material And Methods: This retrospective study included 251 patients with ER-positive, HER2-negative, 1-3 node-positive invasive breast cancer. Mammography and US findings were reviewed according to the BI-RADS criteria. The association between MammaPrint results and the clinicopathological and imaging features was evaluated. Logistic regression analysis was performed to identify independent predictors for high risk of recurrence.

Results: Of the patients, 143 (57.0%) and 108 (43.0%) had low and high risks for recurrence on MammaPrint, respectively. Young age (odds ratio [OR] 1.08; 95% confidence interval (CI) 1.04-1.12; <0.001), posterior enhancement on US (OR 2.45; 95% CI 1.16-5.20;  = 0.019), absence of posterior shadowing on US (OR 3.19; 95% CI 1.17-8.62;  = 0.023), high histologic grade (OR 113.36; 95% CI 6.79-1893.53;  = 0.001), and high Ki-67 level (OR 4.90; 95% CI 2.62-9.17; <0.001) were independently associated with high risk of recurrence on multivariate logistic regression analysis.

Conclusion: Posterior features in US may predict a high risk of recurrence in patients with ER-positive, HER2-negative, node-positive invasive breast cancer, which may be useful in enhancing the diagnostic value of MammaPrint and aid in the decision-making process regarding treatment.
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http://dx.doi.org/10.1177/0284185120980003DOI Listing
December 2020

Association between reproductive years and insulin resistance in middle-aged and older women: A 10-year prospective cohort study.

Maturitas 2020 Dec 10;142:31-37. Epub 2020 Jul 10.

Department of Family Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea; Department of Medicine, Graduate School of Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Family Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea. Electronic address:

Objectives: We hypothesized that reproductive years, a marker of total estrogen exposure, may play an important role in insulin resistance.

Study Design: A total of 3327 middle-aged and older women (age range 40-69 years) from the Korean Genome and Epidemiology Study were included in this large prospective cohort study with a mean follow-up of 10.8 years.

Main Outcome Measures: Insulin resistance and sensitivity were calculated using the homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). A linear mixed model for a repeated-measures covariance pattern with unstructured covariance within participants was used to assess longitudinal associations between baseline reproductive years and subsequent changes in HOMA-IR and QUICKI. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for new-onset insulin resistance according to quartiles of reproductive years.

Results: Changes in HOMA-IR were significantly greater in Q1 (fewest reproductive years) than in Q4 (most reproductive years) (beta[SE] = 0.038[0.016]; p-value = 0.022), while changes in QUICKI were significantly smaller in Q1 than in Q4 (beta[SE] = -0.001[0.000]; p-value = 0.048) after adjusting for possible confounders over time. Compared with Q1, HRs (95 % CIs) for the incidence of new-onset insulin resistance were 0.807 (0.654-0.994) for Q2, 0.793 (0.645-0.974) for Q3, and 0.770 (0.622-0.953) for Q4 after adjusting for possible confounders.

Conclusion: A short reproductive period is associated with elevated levels on the HOMA-IR and decreased levels on the QUICKI over time. The lowest quartile of reproductive years was significantly associated with a higher risk of new-onset insulin resistance.
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http://dx.doi.org/10.1016/j.maturitas.2020.07.004DOI Listing
December 2020

Predictive Role of TP53, PIK3CA and MLL2 in ER+ HER2+ Breast Bancer: Biomarker Analysis of Neo-ALL-IN [NCT 01275859].

Anticancer Res 2020 Oct;40(10):5883-5893

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

Background/aim: Somatic mutations were investigated in 21 patients with postmenopausal estrogen receptor (ER)-positive and human epidermal growth factor receptor-2 (HER-2)-positive (ER+HER2+) breast cancer (BC) treated with neoadjuvant letrozole and lapatinib, to identify their distinct molecular landscape.

Patients And Methods: We used tissue samples of 21 patients from phase II Neo ALL-IN cohort, and somatic alterations were examined using targeted exome sequencing performed in Foundation Medicine, Inc. (FMI).

Results: TP53 (61.9%) and PIK3CA (57.1%) were the two most frequently mutated genes that were inter-correlated (p=0.026). They were associated with unfavorable clinical outcomes, particularly when accompanying PIK3CA mutations at exon 9 in helical domains. Meanwhile, MLL2 alteration was negatively associated with mutations of TP53 or PIK3CA, and it tended to be present in patients with low KI-67 levels and no initial nodal involvement. Moreover, patients with MLL2 mutations numerically showed more favorable overall response rates (ORR) (80% vs. 56.2%) and better 5-year event-free survival (EFS) rates (100% vs. 87.5%) compared to the wild-type.

Conclusion: Mutations in TP53 and PIK3CA hotspot at exon 9 may be potential negative predictors of ER+HER2+ BC treated with neoadjuvant letrozole and lapatinib, while MLL2 inactivating mutation might confer therapeutic benefit in these patients.
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http://dx.doi.org/10.21873/anticanres.14608DOI Listing
October 2020

Calcifications with suspicious morphology at mammography: should they all be considered with the same clinical significance?

Eur Radiol 2021 Apr 22;31(4):2529-2538. Epub 2020 Sep 22.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Objectives: To evaluate the positive predictive values (PPVs) of calcifications with suspicious morphology by incorporating distribution and clinical factors in two separate cohorts to provide more practical guidance for management.

Methods: This retrospective study included 1076 consecutive women from two cohorts (cohort A, 556; cohort B, 520), with calcifications of suspicious morphology seen on mammography that were pathologically confirmed or followed with mammography. Reader-averaged PPVs of the calcifications were analyzed and compared by logistic regression using the generalized estimating equation. Multivariate logistic regression analysis was performed to evaluate independent factors associated with the PPVs of suspicious calcifications.

Results: Overall reader-averaged PPVs of suspicious calcifications were 16.8% and 15.2% in cohort A and B, respectively. Reader-averaged PPVs according to morphology in cohort A and B were as follows: amorphous 9.1%, 6.4%; coarse heterogeneous 16.1%, 22.1%; fine pleomorphic 78.8%, 44.7%; and fine linear branching 78.6%, 85.1%, respectively (p < 0.001). PPVs for diffuse amorphous combinations were 2.6% and 2.6%, and for regional amorphous calcifications, 3.6% and 3.1%, respectively. Among diffuse amorphous calcifications, the PPVs for women ≥ 50 years and women without a personal history of breast cancer ranged from 0.0 to 1.9%.

Conclusions: Amorphous calcifications have lower reader-averaged PPVs compared to calcifications with other suspicious morphology, falling into the BI-RADS 4a assessment (PPV 2-10%). Amorphous calcifications with diffuse distributions detected in women > 50 years old and without a personal history of breast cancer have reader-averaged PPVs < 2.0%. Further prospective studies are necessary to confirm if these patients can be managed with imaging follow-up.

Key Points: • In two cohorts, reader-averaged positive predictive values (PPVs) for suspicious calcifications showed lower rates for amorphous calcifications. • In two separate cohorts, reader-averaged PPVs showed lower rates for diffuse amorphous calcifications, falling into the BI-RADS 4a assessment category (PPV 2-10%). • Diffuse amorphous calcifications detected in women > 50 years old and without a personal history of breast cancer have reader-averaged PPVs < 2.0%.
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http://dx.doi.org/10.1007/s00330-020-07215-8DOI Listing
April 2021

Diffusion-Weighted Magnetic Resonance Imaging of the Breast: Standardization of Image Acquisition and Interpretation.

Korean J Radiol 2021 01 28;22(1):9-22. Epub 2020 Aug 28.

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Diffusion-weighted (DW) magnetic resonance imaging (MRI) is a rapid, unenhanced imaging technique that measures the motion of water molecules within tissues and provides information regarding the cell density and tissue microstructure. DW MRI has demonstrated the potential to improve the specificity of breast MRI, facilitate the evaluation of tumor response to neoadjuvant chemotherapy and can be employed in unenhanced MRI screening. However, standardization of the acquisition and interpretation of DW MRI is challenging. Recently, the European Society of Breast Radiology issued a consensus statement, which described the acquisition parameters and interpretation of DW MRI. The current article describes the basic principles, standardized acquisition protocols and interpretation guidelines, and the clinical applications of DW MRI in breast imaging.
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http://dx.doi.org/10.3348/kjr.2020.0093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772373PMC
January 2021

Added Value of the Vascular Index on Superb Microvascular Imaging for the Evaluation of Breast Masses: Comparison With Grayscale Ultrasound.

J Ultrasound Med 2021 Apr 20;40(4):715-723. Epub 2020 Aug 20.

Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Objectives: To evaluate the value of the vascular index (VI) on Superb Microvascular Imaging (SMI; Canon Medical Systems Corporation, Tokyo, Japan) in comparison with grayscale ultrasound (US) alone for assessing breast masses.

Methods: We evaluated a total of 70 breast masses (36 malignant and 34 benign lesions) in 70 consecutive patients using grayscale US and SMI. Two breast radiologists analyzed grayscale US alone and the combination of grayscale US and SMI. They also measured the VI based on SMI. The diagnostic performance of grayscale US alone and the combination of grayscale US and SMI was compared. The VI was compared between benign and malignant masses, and the optimal cutoff value was determined. In addition, the interobserver agreement in imaging analyses and the VI was assessed.

Results: The interobserver agreements in imaging analyses and the VI were almost perfect. The VI of malignant breast masses was significantly higher than that of benign lesions (P < .001). The optimal cutoff value of the VI for differentiating between malignant and benign breast masses was 2.95, with sensitivity of 86.1% and specificity of 91.2%. The diagnostic performance values of grayscale US alone and the combination of grayscale US and SMI were 0.824 and 0.912, respectively, for reader 1 (P = .028) and 0.795 and 0.853 for reader 2 (P = .101).

Conclusions: The VI on SMI was significantly higher for malignant breast masses than for benign lesions, with high interobserver agreement. Our study suggests that the combination of grayscale US and SMI with the VI could improve the characterization of breast masses.
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http://dx.doi.org/10.1002/jum.15441DOI Listing
April 2021

The role of MRI and clinicopathologic features in predicting the invasive component of biopsy-confirmed ductal carcinoma in situ.

BMC Med Imaging 2020 08 12;20(1):95. Epub 2020 Aug 12.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.

Background: The upgrade rate of biopsy-confirmed ductal carcinoma in situ (DCIS) to invasive carcinoma is up to 50% on final pathology. We investigated MRI and clinicopathologic predictors of the invasive components of DCIS diagnosed by preoperative biopsy and then compared MRI features between patients with DCIS, microinvasive ductal carcinoma (mIDC), and invasive ductal carcinoma (IDC) diagnosed on final pathology.

Methods: Two hundred and one patients with 206 biopsy-confirmed DCIS lesions were enrolled. MRI and clinicopathologic features were used to predict either mIDC or IDC via a cumulative logistic regression analysis. For the lesions detected on MRI, morphologic and kinetic analyses were performed using the Chi-square, Fisher's exact, and Kruskal-Wallis tests.

Results: Of all the lesions, 112 (54.4%) were diagnosed as DCIS, 50 (24.3%) were upgraded to mIDC, and 44 (21.4%) to IDC. The detection on MRI as mass (Odds ratio (OR) = 8.84, 95% confidence interval (CI) = 1.05-74.04, P = 0.045) or non-mass enhancement (NME; OR = 11.17, 95% CI = 1.35-92.36, P = 0.025), negative progesterone receptor (PR; OR = 2.40, 95% CI = 1.29-4.44, P = 0.006), and high Ki-67 level (OR = 2.42, 95% CI = 1.30-4.50, P = 0.005) were significant independent predictors of histologic upgrade. On MRI, 87 (42.2%) lesions appeared as mass and 107 (51.9%) as NME. Irregularly shaped, not-circumscribed, heterogeneous, or rim-enhancing masses with intratumoral high signal intensity or peritumoral edema, clumped or clustered ring-enhancing NMEs, and high peak enhancement were significantly associated with histologic upgrade (P < 0.001).

Conclusion: MRI detection, negative PR, and high Ki-67 levels are associated with a histologic upgrade in patients with biopsy-confirmed DCIS. Suspicious MRI features are more frequent in such patients.
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http://dx.doi.org/10.1186/s12880-020-00494-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424652PMC
August 2020

Clinicopathological and Imaging Features Predictive of Clinical Outcome in Metaplastic Breast Cancer.

Curr Med Imaging 2020 ;16(6):729-738

Department of Radiology, School of Medicine, Kangwon National University, Baengnyeong-Ro 156, Chuncheon-Si, Kangwon-Do 24289, South Korea.

Background: Metaplastic breast cancer (MC) is a rare disease, thus it is difficult to study its clinical outcomes.

Objectives: To investigate whether any clinicopathological or imaging features were associated with clinical outcome in MC.

Methods: We retrospectively evaluated the clinicopathological and imaging findings, and the clinical outcomes of seventy-two pathologically confirmed MCs. We then compared these parameters between triple-negative (TNMC) and non-TNMCs (NTNMC).

Results: Oval or round shape, and not-circumscribed margin were the most common findings on mammography, ultrasound (US), and magnetic resonance imaging (MRI). It was mostly a mass without calcification on mammography, and revealed complex or hypoechoic echotexture, and posterior acoustic enhancement on US, and rim enhancement, wash-out kinetics, peritumoral edema, and intratumoral necrosis on MRI. Of all 72, 64 were TNMCs, and eight were NTNMCs. Clinicopathological and imaging findings were similar between the two groups, except that MRI showed peritumoral edema more frequently in TNMCs than NTNMCs (p=0.045). There were 21 recurrences and 13 deaths. Multivariable analysis showed that larger tumor size and co-existing DCIS were significantly predictive of Disease free survival (DFS), and larger tumor size and neoadjuvant chemotherapy were significantly predictive of overall survival (OS).

Conclusion: MC showed characteristic imaging findings, and some variables associated with survival outcome may help to predict prognosis.
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http://dx.doi.org/10.2174/1573405615666190219105810DOI Listing
January 2020

Analysis of false-negative findings of breast cancer on previous magnetic resonance imaging.

Acta Radiol 2020 Jul 19:284185120941830. Epub 2020 Jul 19.

Department of Radiology, Research Institute of Radiology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

Background: Despite the excellent contribution of contrast-enhanced breast magnetic resonance imaging (MRI), there are variable false-negative cases on MRI.

Purpose: To evaluate the false-negative findings of breast cancer on previous MRI.

Material And Methods: Between 2012 and 2016, we collected 132 patients who underwent surgery for a second primary cancer and had both current and previous MRI at an interval of <3 years. We included 45 patients; we excluded 38 patients who could not find a second cancer in the previous MRI and 49 patients who had a second cancer near to the original cancer and within within the same quadrant. Compared with current MRI, we retrospectively assessed the second primary cancer on previous MRI according to BI-RADS and analyzed the reasons of misinterpretation.

Results: Analysis of previous MRI revealed 26 (57.8%) masses (mean size 7.7 ± 2.25 mm), 12 (26.7%) non-mass enhancements (mean size 14.7 ± 4.76 mm), and 7 (15.5%) foci. At first reading, 24 (53.3%) were missed, 17 (37.8%) were assessed as BI-RADS category 2 or 3, and 4 (8.9%) were assessed as category 4. On current MRI, 39 (86.7%) lesions showed an increase in size and 22 (48.9%) showed a change in kinetics to wash-out pattern.

Conclusion: On previous MRI, missed or misinterpreted cancers show variable findings of mass and non-mass enhancements with any types of kinetics. Careful application of BI-RADS is necessary as well as an appropriate biopsy. Any lesion that increases in size and changes in kinetics should not be underestimated.
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http://dx.doi.org/10.1177/0284185120941830DOI Listing
July 2020

Recurrence of Breast Carcinoma as Paget's Disease of the Skin along the Core Needle Biopsy Tract after Skin-Sparing Mastectomy.

J Breast Cancer 2020 Apr 17;23(2):224-229. Epub 2020 Feb 17.

Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.

We report a case of recurrence as Paget's disease at the core needle biopsy (CNB) entry site in a patient with microinvasive ductal carcinoma who underwent nipple-areola-skin sparing mastectomy (NASSM) and autologous reconstruction. Clinically diagnosed recurrences associated with previous needle procedures for malignant breast lesions are rare and usually occur in patients who have not received radiation therapy. The present case involved local recurrence at the skin puncture site of a patient diagnosed based on CNB findings who underwent NASSM without receiving radiation therapy. Although the removal of the CNB tract with resected breast tissue is not always emphasized, the skin puncture site should be recorded to detect abnormal skin changes after surgery for the timely detection and management of complications.
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http://dx.doi.org/10.4048/jbc.2020.23.e16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192744PMC
April 2020

Diagnostic performance of standard breast MR imaging compared to dedicated axillary MR imaging in the evaluation of axillary lymph node.

BMC Med Imaging 2020 05 1;20(1):45. Epub 2020 May 1.

Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, South Korea.

Background: Breast magnetic resonance (MR) imaging does not usually assess axillary lymph nodes -using dedicated axillary sequence. The additional utility of dedicated axillary sequence is poorly understood. We evaluated the diagnostic performance of dedicated axillary imaging sequence for evaluation of axillary lymph node.

Methods: In this retrospective study from January 2018 to March 2018, 750 consecutive women underwent breast MR imaging. 263 patients were excluded, due to neoadjuvant chemotherapy (n = 235), incomplete histopathological information (n = 14) and follow-up loss (n = 14), 487 women were included. Two radiologists scored lymph node on confidence level scale from 0 (definitely benign) to 4 (definitely malignant), -using standard MR and dedicated axillary imaging sequences. Diagnostic performance parameters were compared and calculated correlation coefficient of quantitative features (largest dimension, cortical thickness, and the ratio of cortical thickness to largest dimension of lymph node).

Results: 68 (14.0%) were node-positive and 419 (86.0%) were node-negative. The sensitivity, specificity, positive, negative predictive values and accuracy were respectively, 66.2, 93.3, 61.6, 94.4, and 89.5% for dedicated axillary sequence and 64.7, 94.0, 63.8, 94.3, 89.9% for standard MR sequence The dedicated axillary and standard sequences s did not exhibit significant differences in detection of positive lymph nodes (AUC, 0.794 for standard and 0.798 for dedicated axillary sequence, P = 0.825). The cortical thickness appeared to be the most discriminative quantitative measurement using both axillary (AUC, 0.846) and standard sequences (AUC, 0.823), with high correlation coefficient (0.947).

Conclusion: Evaluation of axillary nodal status using standard breast MR imaging is comparable to dedicated axillary MR imaging.
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http://dx.doi.org/10.1186/s12880-020-00449-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195753PMC
May 2020

Male patients with unilateral breast symptoms: an optimal imaging approach.

Eur Radiol 2020 Aug 3;30(8):4242-4250. Epub 2020 Apr 3.

Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

Objectives: To evaluate the usefulness of bilateral mammography in male patients with unilateral breast symptoms, including investigation of the diagnostic performance of unilateral and bilateral reviews and the average glandular dose (AGD) per exposure.

Methods: Two hundred seventy-one consecutive male patients (mean age, 57 years) with unilateral breast symptoms underwent bilateral mammography. Image interpretation was performed in two ways, first with a unilateral review of the symptomatic breast and then with a bilateral review. A modified BI-RADS scale (from 1 to 5) was used. The diagnostic performance of unilateral and bilateral reviews was compared, and contralateral breast abnormalities and the AGD per exposure were recorded. We also analyzed ultrasound (US) results and compared them with mammography.

Results: Of 271 male patients, 29 were pathologically diagnosed with breast cancer. There was no bilateral breast cancer. The sensitivity, specificity, positive and negative predictive values, and accuracy were 96.6%, 96.7%, 77.8%, 99.6%, and 96.7%, respectively, for unilateral review, and 96.6%, 95.9%, 73.7%, 99.6%, and 95.9% for bilateral review. Receiver operator characteristic analysis showed excellent diagnostic performance for both methods: the area under the curve (AUC) was 0.966 for unilateral review and 0.962 for bilateral review (p = 0.415). The mean AGD per exposure was 1.10 ± 0.29 mGy for symptomatic breast and 1.04 ± 0.30 mGy for contralateral breast (p < 0.001). Diagnostic performance parameters of US were not significantly different from bilateral or unilateral review of mammography.

Conclusion: The diagnostic performance of unilateral mammography is comparable with bilateral mammography in male patients with unilateral breast symptoms. Unilateral mammography also has the advantage of reducing radiation exposure.

Key Points: • There is limited knowledge about standardized guidelines or recommendations for imaging the male breast. • Unilateral mammography for male patients with unilateral breast symptoms showed comparable diagnostic performance with bilateral mammography. • Both unilateral and bilateral mammography showed excellent diagnostic performance in the assessment of male patients with unilateral breast symptoms.
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http://dx.doi.org/10.1007/s00330-020-06828-3DOI Listing
August 2020

Surgical Outcomes for Ductal Carcinoma in Situ: Impact of Preoperative MRI.

Radiology 2020 05 17;295(2):296-303. Epub 2020 Mar 17.

From the Department of Radiology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea (G.Y.Y.); and Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea (G.Y.Y., W.J.C., H.H.K., J.H.C., H.J.S., E.Y.C.).

Background The role of preoperative MRI for predicting surgical outcomes in patients diagnosed with ductal carcinoma in situ (DCIS) remains uncertain. Purpose To investigate the associations between preoperative MRI and surgical outcomes in DCIS confirmed by using US-guided core-needle biopsy (CNB) and to evaluate clinical-pathologic variables associated with a benefit from MRI. Materials and Methods Women with DCIS confirmed by using US-guided CNB between January 2012 and December 2016 were included in this retrospective study. Propensity score matching using 18 confounding covariates was used to create matched groups with MRI and without MRI, and surgical outcomes were compared. Clinical-pathologic variables were evaluated to determine women who benefited from MRI. Results A total of 541 women (mean age ± standard deviation, 50 years ± 10) were evaluated. Among 430 women who underwent MRI, 67 additional lesions (16%) were depicted, with 25 (37%) of the 67 additional lesions being malignant. Fifty-seven (13%) of the 430 women had a change in surgical plan because of their MRI findings; the change was appropriate for 31 (54%) women. In matched groups, the MRI group was associated with lower odds of positive resection margin (odds ratio [OR], 0.39; 95% confidence interval [CI]: 0.16, 0.93; = .03) and repeat surgery (OR, 0.33; 95% CI: 0.12, 0.92; = .03) compared with the non-MRI group. There was no difference in likelihood of initial mastectomy (OR, 1.2; 95% CI: 0.7, 2.0; = .59) and overall mastectomy (OR, 0.93; 95% CI: 0.5, 1.6; = .79). In the MRI group, low nuclear grade (90% [28 of 31] vs 69% [275 of 399]; = .01), progesterone receptor positivity (81% [25 of 31] vs 61% [244 of 399]; = .03), and human epidermal growth factor receptor 2 negativity (90% [28 of 31] vs 68% [270 of 399]; = .01) were associated with a benefit from MRI versus no MRI. Conclusion Preoperative MRI depicted additional malignancy and reduced positive surgical margins and repeat surgery for ductal carcinoma in situ confirmed at US-guided biopsy without a higher mastectomy rate. © RSNA, 2020 See also the editorial by Pinker in this issue.
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http://dx.doi.org/10.1148/radiol.2020191535DOI Listing
May 2020

Salivary Duct Cancer Metastasis Mimicking Primary Breast Cancer: A Case Report and Review.

J Breast Cancer 2019 Dec 30;22(4):653-660. Epub 2019 Sep 30.

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Secondary breast malignancy is a rare occurrence, accounting for less than 2% of all breast malignancies. Salivary duct carcinoma (SDC) metastasizing to the breast has not been reported previously. This report presents the case of a woman who was initially diagnosed with and treated for parotid carcinoma. Two years later, during a follow-up visit, a breast lump was discovered, which was diagnosed as primary breast cancer and managed surgically. After surgery, hematoxylin and eosin and immunohistochemical staining revealed that the breast tumor had the same features as her primary SDC. Here, we present a confusing case of SDC metastasis to the breast that mimicked triple-negative breast cancer.
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http://dx.doi.org/10.4048/jbc.2019.22.e45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933031PMC
December 2019

Feasibility of supine MRI (Magnetic Resonance Imaging)-navigated ultrasound in breast cancer patients.

Asian J Surg 2020 Aug 2;43(8):787-794. Epub 2019 Dec 2.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea. Electronic address:

Objective: The purpose of this study was to evaluate the feasibility of image fusion between US and supine MRI in breast cancer patients, and to evaluate differences in tumor location between prone and supine positions.

Methods: This prospective study included 88 patients who underwent an additional supine MRI (MRsup) sequence following routine prone MRI (MRpro) for breast cancer between May 2016 and December 2017. The location of the tumor and discrepancies in the distances from nipple to lesion (NLD), skin to lesion (SLD), and chest wall to lesion (CLD) were evaluated between MRpro and MRsup (MRpro-sup), MRpro and MRsup-navigated US (MRpro-USnav), and MRsup and USnav (MRsup-USnav). Associations between breast thickness and measurement discrepancies were analyzed.

Results: Total 91 index lesions were evaluated. The intraclass correlation coefficients (ICCs) for the location of MRpro and MRsup compared with USnav were 0.994 (range: 0.990-0.996) and 0.998 (range: 0.996-0.999), respectively. The mean MRpro-sup and MRpro-USnav measurement discrepancies were greater than those of MRsup-USnav, significantly. Most outer locations showed greater mean measurement discrepancies than inner locations, and each NLD, SLD, and CLD mean measurement discrepancy showed different tendencies according to location (upper or lower) and lesion depth (superficial, middle, or deep). High breast thickness showed significantly greater mean measurement discrepancies than low breast thickness.

Conclusion: Image fusion between US and supine MRI is feasible in breast cancer patients, although there is a considerable difference in tumor location measurements between prone and supine positions, especially with thicker breasts.
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http://dx.doi.org/10.1016/j.asjsur.2019.09.007DOI Listing
August 2020

Diffusion-weighted MRI for Unenhanced Breast Cancer Screening.

Radiology 2019 12 8;293(3):504-520. Epub 2019 Oct 8.

From the Department of Breast Imaging, University of Massachusetts Memorial Medical Center, Worcester, Mass (N.A.); Medical Imaging and Radiology-Cancer Prevention, German Cancer Research Center, Heidelberg, Germany (S.B.); Department of Radiology, Asan Medical Center, University of Ulsan, Seoul, South Korea (H.J.S.); Department of Radiology, University of Washington, 825 Eastlake Ave E, G2-600, Seattle, WA 98109 (M.D., H.R., S.C.P.); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY (K.P.); and Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria (K.P.).

Diffusion-weighted (DW) MRI is a rapid technique that measures the mobility of water molecules within tissue, reflecting the cellular microenvironment. At DW MRI, breast cancers typically exhibit reduced diffusivity and appear hyperintense to surrounding tissues. On the basis of this characteristic, DW MRI may offer an unenhanced method to detect breast cancer without the costs and safety concerns associated with dynamic contrast material-enhanced MRI, the current reference standard in the setting of high-risk screening. This application of DW MRI has not been widely explored but is particularly timely given the growing health concerns related to the long-term use of gadolinium-based contrast material. Moreover, increasing breast density notification legislation across the United States is raising awareness of the limitations of mammography in women with dense breasts, emphasizing the need for additional cost-effective supplemental screening examinations. Preliminary studies suggest unenhanced MRI with DW MRI may provide higher sensitivity than screening mammography for the detection of breast malignancies. Larger prospective multicenter trials are needed to validate single-center findings and assess the performance of DW MRI for generalized breast cancer screening. Standardization of DW MRI acquisition and interpretation is essential to ensure reliable sensitivity and specificity, and an optimal approach for screening using readily available techniques is proposed here.
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http://dx.doi.org/10.1148/radiol.2019182789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884069PMC
December 2019

Imaging and Clinicopathologic Features Associated With Pathologic Complete Response in HER2-positive Breast Cancer Receiving Neoadjuvant Chemotherapy With Dual HER2 Blockade.

Clin Breast Cancer 2020 02 21;20(1):25-32. Epub 2019 Aug 21.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: In human epidermal growth factor receptor 2-positive (HER2) breast cancer, the incorporation of a dual HER2 blockade into neoadjuvant chemotherapy (NAC) has been shown to induce a higher rate of pathologic complete response (pCR). The purpose of this study was to investigate whether pretreatment imaging and clinicopathologic features show any association with pCR in HER2 breast cancer receiving NAC plus dual blockade.

Materials And Methods: This retrospective study evaluated 94 consecutive patients (mean age, 49.8 ± 9.9 years) with HER2 breast cancer who underwent NAC plus dual blockade with trastuzumab and pertuzumab between April 2016 and June 2018. All patients underwent mammography, ultrasound, and magnetic resonance imaging prior to NAC. Clinicopathologic and imaging features acquired before NAC were evaluated for their ability to predict the pathologic response after surgery. Multivariate analysis was used to identify independent predictors of pCR.

Results: Fifty patients (53.2%) showed pCR and 44 (46.8%) did not. According to a univariate analysis, fine pleomorphic/fine linear or linear-branching calcification morphology on mammography, parallel orientation on ultrasound, intratumoral high signal intensity on T2-weighted magnetic resonance imaging, progesterone receptor negativity, and high levels of tumor-infiltrating lymphocytes were associated with pCR. On multivariate analysis, fine pleomorphic/fine linear or linear-branching calcification morphology on mammography (odds ratio [OR], 7.23), progesterone receptor negativity (OR, 6.76), and a high tumor-infiltrating lymphocyte level (OR, 5.92) remained significant independent factors associated with pCR.

Conclusion: Several pretreatment imaging and clinicopathologic features were shown to be independent variables predicting pCR in patients with HER2 breast cancer receiving NAC with dual blockade.
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http://dx.doi.org/10.1016/j.clbc.2019.06.015DOI Listing
February 2020

Complete response on MR imaging after neoadjuvant chemotherapy in breast cancer patients: Factors of radiologic-pathologic discordance.

Eur J Radiol 2019 Sep 21;118:114-121. Epub 2019 Jun 21.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea. Electronic address:

Purpose: To evaluate the radiologic and clinicopathologic factors in radiologic-pathologic discordance (false-negative results) in breast cancer patients who demonstrate radiologic complete response (rCR) in MR imaging after neoadjuvant chemotherapy (NAC).

Method: Our institutional review board approved this retrospective study. We included 209 consecutive patients who showed rCR in MR imaging after NAC. rCR was diagnosed when the original lesion site showed no enhancement. Pathologic CR (pCR) was defined as the complete absence of both invasive cancer and ductal carcinoma in situ in the breast upon pathology. Clinicopathologic and radiologic factors affecting the radiologic-pathologic correlation were analyzed.

Results: pCR was noted in 108 patients (51.7%); the remaining 101 (48.3%) had residual lesion on pathology. False negative rCR findings were significantly more frequent in cases of 1 or 2 histologic grade (p = 0.001), low tumor-infiltrating lymphocytes (p = 0.004), and luminal A or B subtype (p < 0.001). Multivariate analysis of radiologic findings to identify predictors of false negative findings found calcifications in mammography (p = 0.037), multifocal multicentric lesions (p = 0.004), and non-mass enhancement in pretreatment MR imaging (p = 0.023) to be significantly associated with false-negative findings.

Conclusions: Patients with calcification in mammography, multifocal multicentric lesions, and non-mass enhancement in pretreatment MR imaging are significantly associated with false-negative results who showed rCR on MR imaging after NAC. These patient populations should be interpreted with caution.
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http://dx.doi.org/10.1016/j.ejrad.2019.06.017DOI Listing
September 2019

Comparison of Pathologic Response Evaluation Systems After Neoadjuvant Chemotherapy in Breast Cancers: Correlation With Computer-Aided Diagnosis of MRI Features.

AJR Am J Roentgenol 2019 10 25;213(4):944-952. Epub 2019 Jun 25.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 Gil, Songpa-Gu, Seoul 05505, Korea.

The objective of our study was to compare pathologic response assessment systems with dynamic contrast-enhanced MRI (DCE-MRI) features and evaluate the predictive performance of DCE-MRI features relative to different pathologic response assessment systems after neoadjuvant chemotherapy (NAC). This retrospective study included 223 women (mean age, 47.2 years; age range, 31-71 years) who underwent DCE-MRI before and after completing NAC before definitive surgery between January and December 2015. Six MRI features (i.e., tumor size; angio volume; peak enhancement; and persistent, plateau, and washout enhancing components) were measured and correlated with the Miller-Payne grading system, residual cancer burden (RCB) class, and modified in-breast RCB index. Percentage changes in MRI features were correlated with pathologic assessment systems using the Spearman rank correlation test; ROC curves were analyzed to predict pathologic outcomes. All six MRI features correlated most strongly with the in-breast RCB index ( = -0.75 to -0.51, < 0.001) followed by the Miller-Payne system ( = 0.47-0.72, < 0.001) and RCB class ( = -0.58 to -0.41, < 0.001). The in-breast RCB index correlated most strongly with the angio volume reduction rate ( = -0.75, < 0.001) followed by maximum diameter ( = -0.69, < 0.001), peak enhancement ( = -0.67, < 0.001), washout component ( = -0.60, < 0.001), plateau component ( = -0.59, < 0.001), and persistent component ( = -0.51, < 0.001). The in-breast RCB index correlated best with changes in DCE-MRI features, and the MRI-measured angio volume reduction rate correlated best with pathologic tumor responses.
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http://dx.doi.org/10.2214/AJR.18.21016DOI Listing
October 2019

Mammography, US, and MRI to Assess Outcomes of Invasive Breast Cancer with Extensive Intraductal Component: A Matched Cohort Study.

Radiology 2019 08 28;292(2):299-308. Epub 2019 May 28.

From the Department of Radiology, Research Institute of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (S.M.H.); and Department of Radiology, Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43 Gil, Songpa-Gu, Seoul 05505, Republic of Korea (J.H.C., H.J.S., E.Y.C., W.J.C., H.H.K.).

Background An extensive intraductal component (EIC) in breast cancer is an independent risk factor for local recurrence after surgery, especially in young, premenopausal women. Few studies have analyzed long-term outcomes or imaging features of EIC-positive breast cancer. Purpose To assess the prognostic value of EIC on recurrence-free and overall survival in breast cancer and evaluate imaging features of EIC-positive breast cancer by using mammography, US, and MRI. Materials and Methods A retrospective study of 6816 consecutive women with surgically diagnosed invasive breast cancer between January 2007 and December 2012 was performed. After individual matching, women were allocated into either an EIC-positive or an EIC-negative group. Imaging factors associated with prognosis were investigated. The recurrence-free and overall survival rates were compared. Univariable and multivariable analyses were performed to analyze the effect of EIC. Results Among 6136 included women (mean age, 48.9 years ± 9.8), 1800 EIC-positive and 4336 EIC-negative breast cancers were identified. After matching according to EIC presence was performed, 1551 women were allocated into each group. The mean follow-up period was 79.9 months. The local-regional recurrence rate in the EIC-positive group was higher than that in the EIC-negative group (39.4% [63 of 160] vs 25.5% [37 of 145]; = .001). However, there were no significant differences in total recurrence rate (hazard ratio [HR]: 1.2; 95% confidence interval [CI]: 0.9, 1.4; = .21) or death (HR: 1.1; 95% CI: 0.8, 1.5; = .45). EIC was not a significant independent factor for recurrence-free survival (HR: 1.1; 95% CI: 0.9, 1.4; = .45) or death (HR: 1.1; 95% CI: 0.8, 1.6; = .44) in multivariable analyses. Calcification and non-mass lesions were more commonly seen at US and MRI in the EIC-positive group than in the EIC-negative group ( < .001). Conclusion The presence of an extensive intraductal component in women with invasive breast cancer did not affect overall survival or recurrence-free survival. © RSNA, 2019 See also the editorial by Eby in this issue.
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http://dx.doi.org/10.1148/radiol.2019182762DOI Listing
August 2019

Correlation between magnetic resonance imaging and the level of tumor-infiltrating lymphocytes in patients with estrogen receptor-negative HER2-positive breast cancer.

Acta Radiol 2020 Jan 20;61(1):3-10. Epub 2019 May 20.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

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http://dx.doi.org/10.1177/0284185119851235DOI Listing
January 2020

Comparison of invasive micropapillary and invasive ductal carcinoma of the breast: a matched cohort study.

Acta Radiol 2019 Nov 21;60(11):1405-1413. Epub 2019 Mar 21.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.

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http://dx.doi.org/10.1177/0284185119834689DOI Listing
November 2019

Diagnostic accuracy and safety of 16α-[F]fluoro-17β-oestradiol PET-CT for the assessment of oestrogen receptor status in recurrent or metastatic lesions in patients with breast cancer: a prospective cohort study.

Lancet Oncol 2019 04 4;20(4):546-555. Epub 2019 Mar 4.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address:

Background: A biopsy of first recurrence or metastatic disease is recommended to re-evaluate oestrogen receptor status in patients with breast cancer and to select appropriate treatment. However, retesting for oestrogen receptor status with rebiopsy is not always feasible, depending on lesion location and the risk associated with biopsy, and in these cases clinicians continue to treat patients according to the oestrogen receptor status of the primary tumour. Consequently suboptimal therapy might be offered to these patients. We assessed the diagnostic accuracy and safety of 16α-[F]fluoro-17β-oestradiol (F-FES) PET-CT to assess oestrogen receptor status in patients with recurrent or metastatic breast cancer.

Methods: We did a prospective cohort study at the Asan Medical Center, Seoul, South Korea. Eligible patients had breast cancer, with first recurrence or metastatic disease at presentation, were 19 years or older, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary objective was to show the agreement between qualitative F-FES PET-CT interpretation and the results of oestrogen receptor expression by immunohistochemical assay, a non-reference standard test. Whole-body F-FES PET-CT imaging was done after intravenous injection of 111-222 MBq of F-FES, with dosing primarily determined by radiation dosimetry analysis. F-FES uptake above background intensity was interpreted as positive. Efficacy was assessed in all patients with histologically confirmed recurrent or metastatic breast cancer who received F-FES and had PET-CT images available (intention-to-diagnose analysis), and safety was assessed in all patients who received F-FES. This study is registered with ClinicalTrials.gov, number NCT01986569.

Findings: Between Nov 27, 2013, and Nov 10, 2016, 93 patients were enrolled. Of the 85 patients included in the efficacy analysis, 47 (55%) were oestrogen receptor-positive and 38 (45%) were oestrogen receptor-negative. Positive status percent agreement between the F-FES PET-CT results and oestrogen receptor status by immunohistochemical assay was 76·6% (95% CI 62·0-87·7) and the negative status percent agreement was 100·0% (90·8-100·0). Patients who were oestrogen receptor-positive and had a positive F-FES PET-CT result had a significantly higher progesterone receptor expression than those who were oestrogen receptor-positive and had a negative F-FES PET-CT result (23 [68%] of 34 patients vs 0 of 11 patients; p<0·0001). The most common adverse event was procedural pain in nine (10%) of 90 patients injected with F-FES. No adverse events were related to the study drug except injection site pain in one (1%) patient. No serious adverse events were recorded.

Interpretation: The high negative percent agreement between F-FES PET-CT and oestrogen receptor status by immunohistochemical assay in this cohort suggests that positive F-FES uptake by recurrent or metastatic oestrogen receptor-positive breast cancer lesions could be an alternative to oestrogen receptor assays in this setting. Staging assessment should include F-FES PET-CT when retesting oestrogen receptor status is not feasible.

Funding: Asan Institute for Life Sciences, Ministry of Health and Welfare, South Korea.
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http://dx.doi.org/10.1016/S1470-2045(18)30936-7DOI Listing
April 2019

Long-term survival outcomes in invasive lobular carcinoma patients with and without preoperative MR imaging: a matched cohort study.

Eur Radiol 2019 May 7;29(5):2526-2534. Epub 2019 Jan 7.

Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, South Korea.

Objective: To investigate and compare the effect of preoperative breast magnetic resonance (MR) imaging on recurrence-free survival (RFS) and overall survival (OS) outcomes among patients with invasive lobular carcinoma (ILC).

Methods: A total of 287 ILC patients between January 2005 and December 2012 were included. One hundred twenty (41.8%) had undergone preoperative breast MR imaging (MR group) and 167 (58.2%) had not (no MR group). Two groups were matched for 21 covariates in terms of patient demographics, tumor characteristics, and clinical features. We compared unmatched variables between the patients with and without breast MR imaging using the chi-square or Student's t test. Comparisons of matched data were performed with McNemar's test or test of symmetry for categorical variables and paired t test for continuous variables. The RFS and OS outcomes were compared using the Kaplan-Meier estimates. MR effects were estimated after adjusting for significant potential confounders of specific outcomes in the multivariable modeling.

Results: In the matched cohort, no statistically significant association was observed between MR imaging and total recurrence (hazard ratio [HR], 1.096; p = 0.821), loco-regional recurrence (HR, 1.204; p = 0.796), contralateral breast recurrence (HR, 0.945; p = 0.952), or distant recurrence (HR, 1.020; p = 0.973). MR imaging was associated with improved OS with 51% reduction, but not significantly (HR, 0.485; p = 0.231). Analysis with multivariable Cox regression model indicated that MR imaging was not significant independent factor for better RFS (HR, 0.823; p = 0.586) or improved OS (HR, 0.478; p = 0.168).

Conclusion: Preoperative MR imaging is not significant prognostic factor and produces no apparent recurrence or survival outcome benefits in ILC patients.

Key Points: • Preoperative breast MR imaging in invasive lobular carcinoma was associated with a better overall survival with 51% reduction, but not statistically significant. • Preoperative breast MR imaging does not show significant prognostic value in invasive lobular carcinoma as there is no apparent benefit in terms of recurrence or survival outcomes.
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http://dx.doi.org/10.1007/s00330-018-5952-7DOI Listing
May 2019

Screening mammography for second breast cancers in women with history of early-stage breast cancer: factors and causes associated with non-detection.

BMC Med Imaging 2019 01 5;19(1). Epub 2019 Jan 5.

Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea.

Background: The aim of our study was to identify the factors and causes associated with non-detection for second breast cancers on screening mammography in women with a personal history of early-stage breast cancer.

Methods: Between January 2000 and December 2008, 7976 women with early-stage breast cancer underwent breast surgery in our institution. The inclusion criteria of our study were patients who had: (a) subsequent in-breast recurrence, (b) surveillance mammography within 1 year before recurrence. Retrospective analysis of mammography was performed. Non-detection was defined as second breast cancers that were not visible on screening mammography. Imaging features, demographics, primary breast cancer (PBC) characteristics, and clinical features were evaluated to determine its association with non-detection. Univariate and multivariate logistic regression analyses were also performed to identify the factors related to non-detection.

Results: We identified 188 patients that met the criteria. Among them, 39% of patients showed non-detection (n = 74). Of the 74 patients with non-detection, 53 (72%) were classified as having no detectable mammographic abnormality (i.e., true negative) due to overlapping dense breast tissue (n = 32), obscured by postoperative scar (n = 12) or difficult anatomic location / poor positioning (n = 9). The remaining 21 patients were categorized as having subtle findings (n = 11) or missed cancer (n = 10). Non-detection for second breast cancers were significantly associated with mammographic breast density (p = 0.001, OR = 2.959) and detectability of PBC on mammography (p = 0.011, OR = 3.013).

Conclusion: Non-detection of second breast cancer in women with a personal history of early-stage breast cancer were associated with mammographic dense breast and lower detectability of PBC on mammography.
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http://dx.doi.org/10.1186/s12880-018-0303-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321714PMC
January 2019

Prognostic factors predicting recurrence in invasive breast cancer: An analysis of radiological and clinicopathological factors.

Asian J Surg 2019 May 11;42(5):613-620. Epub 2018 Dec 11.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.

Background/objective: The purpose of this study was to perform a comprehensive analysis of the radiological and clinicopathological factors that could predict recurrence of invasive breast cancer who underwent curative surgery without neoadjuvant chemotherapy.

Methods: Three hundred and sixty-four consecutive women who underwent preoperative mammography, ultrasound, and breast magnetic resonance imaging for newly diagnosed invasive breast cancers and curative surgery between January and December 2010 were included. We analyzed the radiological findings of each modality and reviewed the histopathological features. A Cox proportional hazards model was used to determine the association between the radiological and clinicopathological parameters and disease-free survival (DFS).

Results: During the median follow-up period of 5.3 years, 23 patients (6.3%) developed recurrences: locoregional recurrence in six patients, contralateral breast recurrence in three patients, and distant recurrences in 14 patients. Microcalcifications on mammography showed a tendency towards worse DFS. The multivariate Cox regression analysis showed that presence of lymphovascular invasion (LVI) (p = 0.006), negative progesterone receptor (PR) status (p < 0.001), and positive CK5/6 expression (p = 0.015) were independent significant variables predictive of worse DFS.

Conclusion: Understanding the prognostic factors in patients with invasive breast cancer may provide considerable practical information about future treatment strategies.
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http://dx.doi.org/10.1016/j.asjsur.2018.10.009DOI Listing
May 2019