Ku Sang Kim

The effect of chromosome 17 polysomy on HER-2/neu status in breast cancer

Aim: To investigate the effect of polysomy 17 on HER-2 status as evaluated by immunohistochemistry (IHC), dual-colour fluorescence in situ hybridisation (FISH) and chromogenic in situ hybridisation (CISH). Methods: Dual-probe FISH and single-probe CISH were performed to detect HER-2 gene amplification, and IHC to detect HER-2 expression, on 309 invasive breast cancers. Results: Polysomy 17 was detected in 32.0% of the total number of breast cancers; it was detected in 12.3% of the IHC 0 or 1+ cases, 42.8% of the IHC 2+ cases and 66.0% of the IHC 3+ cases (p<0.001). In addition, there was a substantially higher rate of polysomy 17 in the IHC 2+ or 3+/FISH-negative cases than in the IHC 0 or 1+ cases (40.8% vs 12.3%; p<0.001). The FISH and CISH results were concordant in 299 cases (96.8%). Of the 10 discordant cases, FISH suggested amplification in five with disomy 17 and one with monosomy 17, whereas CISH pointed to borderline copy numbers in each of these six cases. The remaining four cases had high polysomy 17; CISH, but not FISH, indicated amplification. Conclusions: Results suggest that an increase of HER-2 gene copy number secondary to polysomy 17 leads to HER-2 overexpression in some IHC 2+/3+ breast cancers, without gene amplification. The high level of concordance between FISH and CISH suggests that CISH is a valid alternative to FISH for assessing HER-2 gene amplification. However, cases in which CISH indicates the presence of borderline copy numbers or low levels of amplification may need FISH to rule out polysomy 17 and to determine HER-2 gene amplification status accurately.

The accuracy of preoperative core biopsy in determining histologic grade, hormone receptors, and human epidermal growth factor receptor 2 status in invasive breast cancer

BACKGROUND Proper determination of histologic type and biomarkers in a core biopsy specimen is important before preoperative systemic therapy. The purpose of this study was to determine the accuracy of preoperative core biopsy through comparative analysis of histologic grade (HG), hormone receptors, and human epidermal growth factor receptor 2 (HER-2) status in both the core biopsy and surgical specimens. METHODS We identified 104 patients with invasive ductal cancer who underwent core biopsy and definitive surgery in our institution. The histologic type, HG, estrogen receptor (ER), progesterone receptor (PR), and HER-2 status were determined in both the core biopsy and surgical specimens by one pathologist. RESULTS The mean age of the 104 patients was 50 +/- 9.9 years and the mean number of core biopsies was 5.1 +/- .9. The concordance rates for histologic type, HG, ER, PR, and HER-2 status were 100%, 80.8%, 99%, 97.1%, and 86.5%, respectively. CONCLUSIONS Core biopsy can predict histologic type, HG, ER, PR and HER-2 status preoperatively in breast cancer when used properly.

The Korean Hereditary Breast Cancer (KOHBRA) Study: Protocols and Interim Report

AIMS The primary aims of the Korean Hereditary Breast Cancer (KOHBRA) study are to estimate the prevalence of BRCA1/2 mutations and ovarian cancer among a high-risk group of patients with hereditary breast cancer and their families. MATERIALS AND METHODS The KOHBRA study is a prospective multicentre cohort identifying cases and their families. Between May 2007 and May 2010, the KOHBRA study enrolled up to 2000 subjects. All participants received genetic counselling and BRCA genetic testing; the clinical information and blood samples for blood banking were collected. An interim analysis of the prevalence of BRCA1/2 mutations and ovarian cancer in Korean subjects was determined from the initial 975 patients who presented to 33 centres. RESULTS By April 2009, a total of 167 mutation carriers among 853 probands were identified. The prevalence of the BRCA mutation was as follows: 24.8% (106/428) for breast cancer patients with a family history of breast/ovarian cancers; 11.3% (24/212) for patients with early-onset (<35 years) breast cancer without a family history; 22.1% (15/68) for patients with bilateral breast cancer; male breast cancer in 8.3% (1/12); and 33.4% (1/3) for patients with breast and ovarian cancer. CONCLUSIONS The results of this study suggest that the prevalence of BRCA mutations in Korean subjects is similar to the prevalence reported among Western cohorts. However, weak family history and non-familial early-onset of breast cancer were significant factors associated with carrying the BRCA mutation in Korean breast cancer patients. Completion of the KOHBRA study is needed to confirm these findings.

Differential diagnosis in idiopathic granulomatous mastitis and tuberculous mastitis.

Purpose Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease of unknown etiology. The diagnosis of IGM requires that other granulomatous lesions in the breast be excluded. Tuberculous mastitis (TM) is also an uncommon disease that is often difficult to differentiate from IGM. The purpose of this study is to develop a new algorithm for the differential diagnosis and treatment of IGM and TM. Methods Medical records of 68 patients (58 with IGM and 10 with TM) between July 1999 and February 2009 were retrospectively reviewed. Results The mean age of the patients was 33.5 (IGM) and 40 (TM) years (p=0.018). The median follow-up was 84 months. Of the total 10 patients with TM, 5 patients had a history of pulmonary tuberculosis. The most common symptoms of the diseases were breast lump and pain. However, axillary lymphadenopathy was more seen in TM (50%) compared to IGM (20.6%) (p=0.048). TM showed more cancer-mimicking findings on radiologic study (p=0.028). In IGM, 48 patients (82.7%) underwent surgical wide excision and 21 patients (36.2%) were managed with corticosteroid therapy and antibiotics. All of the TM patients received anti-tuberculosis medications and 9 patients (90%) underwent wide excision. The mean treatment duration was 2.8 months in IGM and 8.4 months in TM. Recurrence developed in 5 patients (8.6%) in IGM and 1 patient (10%) in TM. Conclusion This study shows different characteristics between IGM and TM. The IGM patients were younger and had more mastalgia symptoms than the TM patients. Axillary lymphadenopathy was seen more often in TM patients. Half of the TM patients had pulmonary tuberculosis or tuberculosis lymphadenitis. Surgical wide excision might be both therapeutic and useful for providing an exact diagnosis.

Nation-Wide Korean Breast Cancer Data from 2008 Using the Breast Cancer Registration Program

Purpose Since 1996, the Korean Breast Cancer Society has collected nation-wide breast cancer data and analyzed the data using their online registration program biannually. The purpose of this study was to evaluate the characteristics of Korean breast cancer from 2008 and examine chronological based patterns. Methods Data were collected from 38 medical schools (67 hospitals), 20 general hospitals, and 10 private clinics. The data on the total number, gender, and age distribution were collected through a questionnaire as well as other detailed data analyzed via the online registration program. Results In 2008, there were 13,908 patients who were newly diagnosed with breast cancer. The crude incidence rate of female breast cancer was 57.3 among 100,000 and the median age was 49 years. The age distribution had not changed since the initial survey; however the proportion of postmenopausal patients had increased and median age was older than the past. In staging distribution, the proportion of early breast cancer (stage 0, I) was 47.2% with, breast-conserving surgery performed in 58% and mastectomy in 39.5%. Conclusion Compared to past data, the incidence of breast cancer in Korea continues to rise. Furthermore, the proportion of those detected by screening and breast conservation surgery has increased remarkably. To understand the patterns of Korean breast cancer, the nation-wide data should continuously investigated.

Magnetic resonance imaging patterns of tumor regression after neoadjuvant chemotherapy in breast cancer patients: correlation with pathological response grading system based on tumor cellularity

Purpose The objectives of the study were to analyze the tumor shrinkage pattern on magnetic resonance imaging (MRI) after neoadjuvant chemotherapy and to evaluate whether there is any difference in shrinkage pattern between pathological responder and nonresponder groups. In addition, we wanted to compare tumor diameter obtained from MRI with histological diameter according to the tumor shrinkage pattern. Methods Between July 2008 and December 2010, 55 consecutive patients (56 lesions) with pathologically proven breast cancer who underwent neoadjuvant chemotherapy followed by surgery were retrospectively enrolled. The shrinkage pattern was classified into 4 categories: I (concentric shrinkage without surrounding lesion), II (concentric shrinkage with surrounding lesions), III (shrinkage with residual multinodular lesions, and IV (diffuse contrast enhancement in whole quadrants). Histological regression was scored on a 5-point scale regarding tumor cellularity reduction (Miller-Payne grading system). Patients with Miller-Payne grade 1 or 2 were classified into the nonresponder group, and patients with grade 3, 4, or 5 were in the responder group. Results Of 56 lesions, pattern I was seen in 29 lesions, pattern II in 13 lesions, pattern III in 5 lesions, and pattern IV in 4 lesions. Three lesions were not visualized on MRI after neoadjuvant chemotherapy, and 2 lesions were increased in size. There was a statistically significant difference in the tumor shrinkage pattern between responder and nonresponder groups (P = 0.017). All 5 lesions with type III shrinkage pattern were found in the responder group, and all 4 lesions with pattern IV were in the nonresponder group. Magnetic resonance imaging diameter of lesions with types I, II, and IV patterns showed significant correlation with the histological diameter. Among them, the correlation factor was highest in pattern IV (&rgr; = 0.94, P < 0.001) followed by pattern I (&rgr; = 0.67, P < 0.01) and pattern II (&rgr; = 0.502, P = 0.08). However, in type III shrinkage pattern, tumor size measured on MRI was not significantly correlated with histological size (P = 0.87). Conclusions Types III and I shrinkage patterns were more frequently observed in the pathological responder group, and type IV was more frequently noted in the nonresponder group. Tumor diameter measured on MRI showed strong correlation with histological diameter in lesions with types I and IV shrinkage patterns, whereas lesions with type III did not show significant correlation. Type II pattern showed similar frequencies between the 2 groups and moderate correlation between sizes obtained from MRI and histology.

Is there any correlation between model-based perfusion parameters and model-free parameters of time-signal intensity curve on dynamic contrast enhanced MRI in breast cancer patients?

ObjectiveTo find out any correlation between dynamic contrast-enhanced (DCE) model-based parameters and model-free parameters, and evaluate correlations between perfusion parameters with histologic prognostic factors.MethodsModel-based parameters (Ktrans, Kep and Ve) of 102 invasive ductal carcinomas were obtained using DCE-MRI and post-processing software. Correlations between model-based and model-free parameters and between perfusion parameters and histologic prognostic factors were analysed.ResultsMean Kep was significantly higher in cancers showing initial rapid enhancement (P = 0.002) and a delayed washout pattern (P = 0.001). Ve was significantly lower in cancers showing a delayed washout pattern (P = 0.015). Kep significantly correlated with time to peak enhancement (TTP) (ρ = −0.33, P < 0.001) and washout slope (ρ = 0.39, P = 0.002). Ve was significantly correlated with TTP (ρ = 0.33, P = 0.002). Mean Kep was higher in tumours with high nuclear grade (P = 0.017). Mean Ve was lower in tumours with high histologic grade (P = 0.005) and in tumours with negative oestrogen receptor status (P = 0.047). TTP was shorter in tumours with negative oestrogen receptor status (P = 0.037).ConclusionsWe could acquire general information about the tumour vascular physiology, interstitial space volume and pathologic prognostic factors by analyzing time-signal intensity curve without a complicated acquisition process for the model-based parameters.Key points• Kep mainly affected the initial and delayed curve pattern in time–signal intensity curve.• There is significant correlation between model-based and model-free parameters.• We acquired information about tumour vascular physiology, interstitial space volume and prognostic factors.

Prognostic role of MRI enhancement features in patients with breast cancer: value of adjacent vessel sign and increased ipsilateral whole-breast vascularity.

OBJECTIVE The purpose of this study was to compare adjacent vessel sign, increased ipsilateral whole-breast vascularity, and various MRI features as described in the American College of Radiology BI-RADS MRI lexicon with histopathologic predictors in patients with unilateral breast cancer. MATERIALS AND METHODS We retrospectively evaluated breast MRI examinations of 249 patients with histologically confirmed breast cancer. In addition to the BI-RADS MRI lexicon, the adjacent vessel sign and increased ipsilateral whole-breast vascularity of the cancer-bearing breast were evaluated by two independent observers. MRI features were then correlated with histopathologic prognostic factors. RESULTS The adjacent vessel sign was significantly (p=0.023 to p<0.001) associated with tumor size, lymph node metastasis, distant metastasis, nuclear grade, and expression of estrogen and progesterone receptors. Increased ipsilateral whole-breast vascularity was significantly associated with all histopathologic predictors (p=0.017 to p<0.001). In multivariate analysis, the significant and independent predictors were a spiculated margin and rim enhancement for negative estrogen and progesterone receptors, a kinetic curve type for higher histologic grade, and an increased ipsilateral whole-breast vascularity for larger tumor size, lymph node metastasis, distant metastasis, higher nuclear grade, and higher histologic grade. CONCLUSION In conjunction with the standard BI-RADS MRI lexicon, the adjacent vessel sign and increased ipsilateral whole-breast vascularity may serve as additional predictors of a poor prognosis.

Contralateral Enhancing Lesions on Magnetic Resonance Imaging in Patients With Breast Cancer Role of Second-Look Sonography and Imaging Findings of Synchronous Contralateral Cancer

The purposes of this study were to assess the clinical utility of sonography for evaluation of contralateral suspicious lesions detected on magnetic resonance imaging (MRI) in patients with breast cancer and to compare imaging findings of the index and synchronous contralateral cancers.

Utility of MRI and PET/CT after neoadjuvant chemotherapy in breast cancer patients: correlation with pathological response grading system based on tumor cellularity.

Background MRI and PET/CT are useful for assessing breast cancer patients after neoadjuvant chemotherapy (NAC). Purpose To investigate the utility of MRI and PET/CT in the prediction of pathologic response to neoadjuvant chemotherapy using Miller-Payne grading system in patients with breast cancer. Material and Methods From January 2008 to December 2010, 59 consecutive patients with pathologically proven breast cancer, who underwent neoadjuvant chemotherapy followed by surgery were retrospectively enrolled. The maximal diameter decrease rate and volume reduction rate by three-dimensional (3D) MRI and standardized uptake value (SUV) reduction rate by PET/CT were calculated and correlated with the Miller-Payne grading system using the Spearman rank correlation test. Patients with Miller-Payne grades 1 or 2 were classified into the non-responder group and patients with grades 3, 4, and 5 were in the responder group. To differentiate between responders and non-responders, receiver-operating characteristic (ROC) analysis was performed. Results The volume reduction rate was 64.87 ± 46.95, diameter decrease rate was 48.09 ± 35.02, and SUV decrease rate was 62.10 ± 32.17. Among three parameters, the volume reduction rate was most correlated with histopathologic grades of regression (ρ = 0.755, P <0.0001) followed by diameter decrease rate (ρ = 0.660, P < 0.0001), and SUV decrease rate of primary breast mass (ρ = 0.561, P = 0.0002). The area under the ROC curve (Az) value was largest in the volume reduction rate (Az = 0.9), followed by SUV decrease rate (Az = 0.875), and diameter decrease rate (Az = 0.849). The best cut-offs for differentiating responders from non-responders in the ROC curve analysis were a 50% decrease in diameter, 68.9% decrease in volume, and 60.1% decrease in SUV after NAC. Conclusion Volumetric measurement using 3D MRI combined with conventional diameter measurement may be more accurate to evaluate pathologic response after NAC.