Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006).

PURPOSE: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. METHODS: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3-4, 5-6, and 7-8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. RESULTS: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8-96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. CONCLUSION: Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01069211.

Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment.

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from -0.39 at baseline to -0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.

Computer-aided Diagnosis-generated Kinetic Features of Breast Cancer at Preoperative MR Imaging: Association with Disease-free Survival of Patients with Primary Operable Invasive Breast Cancer.

Purpose To retrospectively investigate the relationship between the kinetic features of breast cancer assessed with computer-aided diagnosis (CAD) at preoperative magnetic resonance (MR) imaging and disease-free survival in patients with primary operable invasive breast cancer. Materials and Methods This retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. The authors identified 329 consecutive women (mean age, 52.9 years; age range, 32-88 years) with newly diagnosed invasive breast cancer who had undergone preoperative MR imaging and surgery between January 2012 and February 2013. All MR images were retrospectively reviewed by using a commercially available CAD system, and the following kinetic parameters were noted for each lesion: peak enhancement (highest pixel signal intensity in the first series obtained after administration of contrast material), angio-volume (total volume of the enhancing lesion), and delayed enhancement profiles (the proportions of washout, plateau, and persistently enhancing component within a tumor). Cox proportional hazards modeling was used to identify the relationship between CAD-generated kinetics and disease-free survival after adjusting for clinical-pathologic variables. Results A total of 36 recurrences developed at a median follow-up of 50 months (range, 15-55 months). CAD-measured peak enhancement at preoperative MR imaging enabled differentiation between patients with and patients without recurrence (area under the receiver operating characteristic curve = 0.728; 95% confidence interval [CI]: 0.676, 0.775; P < .001). Multivariate Cox analysis showed that a higher peak enhancement (hazard ratio [HR] = 1.001; 95% CI: 1.000, 1.002; P = .004), a higher washout component (HR = 1.029; 95% CI: 1.005, 1.054; P = .017), and lymphovascular invasion at histopathologic examination (HR = 3.011; 95% CI: 1.302, 6.962; P = .010) were associated with poorer disease-free survival. Conclusion Higher values of CAD-measured peak enhancement and washout component at preoperative MR imaging were significantly associated with poorer disease-free survival of patients with primary operable breast cancer. © RSNA, 2017.

Apparent diffusion coefficient of breast cancer and normal fibroglandular tissue in diffusion-weighted imaging: the effects of menstrual cycle and menopausal status.

The purpose of this study was to investigate prospectively whether the apparent diffusion coefficients (ADCs) of both breast cancer and normal fibroglandular tissue vary with the menstrual cycle and menopausal status. Institutional review board approval was obtained, and informed consent was obtained from each participant. Fifty-seven women (29 premenopausal, 28 postmenopausal) with newly diagnosed breast cancer underwent diffusion-weighted imaging twice (interval 12-20 days) before surgery. Two radiologists independently measured ADC of breast cancer and normal contralateral breast tissue, and we quantified the differences according to the phases of menstrual cycle and menopausal status. With normal fibroglandular tissue, ADC was significantly lower in postmenopausal than in premenopausal women (P = 0.035). In premenopausal women, ADC did not differ significantly between proliferative and secretory phases in either breast cancer or normal fibroglandular tissue (P = 0.969 and P = 0.519, respectively). In postmenopausal women, no significant differences were found between ADCs measured at different time intervals in either breast cancer or normal fibroglandular tissue (P = 0.948 and P = 0.961, respectively). The within-subject variability of the ADC measurements was quantified using the coefficient of variation (CV) and was small: the mean CVs of tumor ADC were 2.90 % (premenopausal) and 3.43 % (postmenopausal), and those of fibroglandular tissue ADC were 4.37 % (premenopausal) and 2.55 % (postmenopausal). Both intra- and interobserver agreements were excellent for ADC measurements, with intraclass correlation coefficients in the range of 0.834-0.974. In conclusion, the measured ADCs of breast cancer and normal fibroglandular tissue were not affected significantly by menstrual cycle, and the measurements were highly reproducible both within and between observers.

Early-stage invasive ductal carcinoma: Association of tumor apparent diffusion coefficient values with axillary lymph node metastasis.

PURPOSE: To evaluate any association between tumor apparent diffusion coefficient (ADC) values and axillary lymph node metastasis (ALNM) in early-stage invasive ductal carcinoma. MATERIALS AND METHODS: Records of 270 invasive ductal carcinoma patients with stages T1 and T2 disease who underwent breast magnetic resonance imaging, including diffusion-weighted imaging with b values of 0 and 1000s/mm(2) were reviewed retrospectively. The tumor ADC values were analyzed for their utility in predicting ALNM using multivariate regression analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 270 patients, 58 (21.5%) experienced ALNM. The mean tumor ADC values were significantly lower in patients with ALNM than in those without metastasis (0.880 × 10(-3) vs. 0.999 × 10(-3)mm(2)/s, P<0.001). A ROC curve demonstrated a tumor ADC value of 0.991 × 10(-3)mm(2)/s to be the optimal cut-off for predicting ALNM. In a multivariate analysis, lower tumor ADC (≤ 0.991 × 10(-3)mm(2)/s; adjusted odds ratio (OR)=5.861, P<0.001), large tumor size (>2 cm; adjusted OR=3.156, P=0.002) and the presence of lymphovascular invasion (adjusted OR=4.125, P<0.001) were independent variables associated with ALNM. When tumor ADC value was added to known risk factors (i.e., tumor size and lymphovascular invasion), a significant improvement in the accuracy of risk prediction for axillary node metastasis was shown (c-statistic=0.758 vs. 0.816, P=0.026). CONCLUSION: In early-stage invasive ductal carcinoma, lower tumor ADC values are associated with the presence of ALNM.

Tumour 18 F-FDG Uptake on preoperative PET/CT may predict axillary lymph node metastasis in ER-positive/HER2-negative and HER2-positive breast cancer subtypes.

OBJECTIVES: To evaluate the association between tumour FDG uptake on preoperative PET/CT and axillary lymph node metastasis (ALNM) according to breast cancer subtype. METHODS: The records of 671 patients with invasive breast cancer who underwent (18) F-FDG PET/CT and surgery were reviewed. Using immunohistochemistry, tumours were divided into three subtypes: oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive, and triple-negative. Tumour FDG uptake, expressed as maximum standardized uptake value (SUVmax), and clinicopathological variables were analysed. RESULTS: ALNM was present in 187 of 461 ER-positive/HER2-negative, 54 of 97 HER2-positive, and 38 of 113 triple-negative tumours. On multivariate analysis, high tumour SUVmax (≥4.25) (P < 0.001), large tumour size (>2 cm) (P = 0.003) and presence of lymphovascular invasion (P < 0.001) were independent variables associated with ALNM. On subset analyses, tumour SUVmax maintained independent significance for predicting ALNM in ER-positive/HER2-negative (adjusted odds ratio: 3.277, P < 0.001) and HER2-positive tumours (adjusted odds ratio: 14.637, P = 0.004). No association was found for triple-negative tumours (P = 0.161). CONCLUSIONS: Tumour SUVmax may be an independent prognostic factor for ALNM in patients with invasive breast cancer, especially in ER-positive/HER2-negative and HER2-positive subtypes, but not in those with triple-negative subtype. KEY POINTS: • Tumour SUVmax could be an imaging biomarker for predicting ALNM • Tumour SUVmax predicting ALNM is effective in ER-positive/HER2-negative and HER2-positive subtypes • Tumour SUVmax predicting ALNM is inaccurate in triple-negative subtypes • Accurate prognostic prediction based on molecular subtype may facilitate individualized management.

The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean Hereditary Breast Cancer study.

The primary aim of this study was to estimate the prevalence of BRCA1/2 mutations among familial breast cancer (BC) patients in Korea. We analyzed 775 familial BC patients who were enrolled in the Korean Hereditary Breast Cancer (KOHBRA) study and treated at 36 institutions between May 2007 and May 2010. Patients with familial BC were defined as BC patients with family histories of BC or ovarian cancer (OC) in any relatives. All probands received genetic counseling and BRCA genetic testing was performed after obtaining informed consent. The mean age of BC diagnosis was 43.6 years. The numbers of probands with family histories of BC only and OC only were 682 and 93, respectively. The overall prevalence of the BRCA mutation among familial BC patients was 21.7 % (BRCA1 9.3 % and BRCA2 12.4 %). Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6 % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and 36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1 %). Most of the subgroups satisfied the 10 % probability criteria to undergo BRCA testing. However, the prevalence of the BRCA mutations among subgroups that had 2 BC patients in a family with both age at diagnosis of more than 50 years old did not reach the 10 % criteria (4.1 %). Korean familial BC patients are good candidates for BRCA testing even when they have family histories of single breast cancers. However, proband age at diagnosis should be carefully considered when selecting patients for testing.

Incidental diffuse thyroid 18F-FDG uptake related to autoimmune thyroiditis may be a favorable prognostic factor in advanced breast cancer.

UNLABELLED: Patients with breast cancer have a relatively high prevalence of diffuse thyroid uptake of (18)F-FDG related to thyroid autoimmunity. It is postulated that the presence of thyroid autoimmunity has prognostic implications for breast cancer. The aim of this study was to evaluate the prognostic value of incidental diffuse thyroid uptake in breast cancer patients. METHODS: This was a retrospective observational cohort study in a tertiary referral hospital. We evaluated a total of 564 patients who had undergone surgery for primary breast cancer between January 2006 and December 2009. Patients were divided into 2 groups according to their diffuse thyroid uptake. The main outcome measure was disease-free survival. RESULTS: Of the 564 patients, 108 (19.1%) showed diffuse thyroid uptake. The median follow-up period was 36.0 mo (range, 1.0-77.0 mo). Both thyroperoxidase and thyroglobulin antibody titers were higher in patients with thyroid uptake than in those without (P < 0.001 for both). Of the 108 patients with thyroid uptake, 5 had a recurrence of breast cancer during the follow-up, whereas 85 without uptake had a recurrence (log-rank statics, 12.28; P < 0.001). The association between diffuse thyroid uptake and tumor recurrence was not significant in multivariate analysis of patients with early-stage breast cancer (hazard ratio, 0.26; 95% confidence interval, 0.06-1.10; P = 0.067). However, the association between diffuse thyroid uptake and breast cancer recurrence was statistically significant in multivariate analysis with adjustment for several prognostic variables (hazard ratio, 0.19; 95% confidence interval, 0.57-0.62; P = 0.006). CONCLUSION: Incidental diffuse thyroid uptake related to autoimmune thyroiditis was an independently favorable prognostic factor in advanced breast cancer. These findings support evidence that thyroid autoimmunity has a beneficial effect on the outcomes of breast cancer patients.

Factors associated with the development of new onset diffuse thyroid F18-fluorodeoxyglucose uptake after treatment of breast cancer in patients without a history of thyroid disease or thyroid dysfunction.

BACKGROUND: Many studies have shown an association between thyroid disorders and breast cancer. Among them, diffusely increased thyroid uptake of F18-fluorodeoxyglucose (F-18 FDG) has been associated with chronic lymphocytic thyroiditis. There is little or no information regarding the relationship between treatment of breast cancer and the development of new diffuse thyroid F-18 FDG uptake. Here, we report the frequency of this occurrence and some of the factors associated with it. METHODS: We performed a retrospective review of the positron emission tomography (PET) computed tomography (CT) database and identified 290 women who had underwent PET-CTs both before and after breast surgery. Of these, 246 were enrolled in this study and 44 were excluded, because before breast surgery they had either a history of prior thyroid disorders including thyroid cancer or abnormal serum free thyroxine and thyroid-stimulating hormone, or other malignancies. Tests for serum antithyroid antibodies were not available before thyroid surgery in all patients. There were 62 patients who did have antithyroid antibody tests before surgery and 27 were positive. They were not excluded from the study. RESULTS: Diffuse thyroidal uptake on PET-CT developed in 23 (9.3%) patients during the follow-up period (median=21.1 months; range=3.1-47.3 months). Age (≥55 years; hazard ratio [HR]=0.15; 95% confidence interval [CI]: 0.03-0.65; p=0.012), bilaterality of breast cancer (HR=3.87; 95% CI: 1.02-14.62; p=0.046), and postsurgical radiotherapy (HR=3.06; 95% CI: 1.03-9.16; p=0.045) showed independent association with new thyroid FDG uptake in multivariate analysis. All patients with thyroid FDG uptake met at least one of some criteria related to chronic thyroditis (positive for antithyroid antibodies or cytology findings or ultrasonography findings of Hashimoto's thyroiditis) and were associated with development of hypothyroidism (52.2% vs. 4.5% in patients without uptake; p<0.001). CONCLUSIONS: Radiotherapy in breast cancer may be an independent predictive factor for the development of new diffuse thyroidal uptake in PET-CT associated with thyroid dysfunction during follow-up. The development of diffuse F-18 FDG uptake is a marker for thyroid abnormalities. Younger women who have radiotherapy after surgery for breast cancer, in particular, are candidates for close follow-up of their thyroid function.

Lateral decubitus positioning stereotactic vacuum-assisted breast biopsy with true lateral mammography.

Stereotactic vacuum-assisted breast biopsy (VAB) has been used to evaluate microcalcifications or non-palpable breast lesions on mammography. Although stereotactic VAB is usually performed in a prone or upright position, an expensive prone table is necessary and vasovagal reactions often occur during the procedure. For these reasons, the lateral decubitus position can be applied for stereotactic VAB, and true lateral mammography can be used to detect the lesion. We report on 15 cases of lateral decubitus positioning for stereotactic VAB with true lateral mammography for non-palpable breast lesions or microcalcifications. The mean procedure time was approximately 30.1 minutes, and no complications occurred during the procedures. Fourteen cases had benign breast lesions and one case had a ductal carcinoma in situ. The lateral decubitus stereotactic VAB with true lateral mammography can be applied for microcalcifications or non-palpable breast lesions and helps to minimize anxiety and vasovagal reactions in patients.

Diagnostic performances of double-phase tc-99m MIBI scintimammography in patients with indeterminate ultrasound findings: visual and quantitative analyses.

The aim of the study was to compare the diagnostic performances of visual and quantitative analyses of double-phase Tc-99m methoxyisobutylisonitrile (MIBI) scintimammography (SMM) in patients with ultrasonographically indeterminate findings. SMM (early: 10min; delayed: 3h) was performed on 78 patients (malignant 66, benign 12). For visual analysis, the five-scoring method was used. For quantitative analysis, ratios of early and delayed lesions to non-lesion (L/Ns) were calculated. When a visual grade of over 3 was used as the cut-off value for the detection of primary breast cancer, the sensitivity and specificity were 86.4%/ and 100%, respectively. The area under the curve (AUC) was 0.972. The optimal L/N ratios were 1.22 for early and 1.1 for delayed images. When early L/N 1.22 was used as the cut-off point, the sensitivity and specificity of SMM were 92.4% and 91.7'%, respectively. The AUC was 0.952. When delayed L/N 1.1 was used as the cut-off value, the sensitivity and specificity were 78.8% and 91.7%, respectively. The AUC was 0.863. Visual interpretation and early L/N were superior to delayed L/N for the detection of breast cancer. This study suggests the possible diagnostic role of visual and quantitative analyses of double-phase SMM for differentiating malignant breast lesions in patients with ultrasonographi-cally indeterminate findings.

Characterization of breast lesion using double phase Tc-99m Tetrofosmin scintimammography: comparison of visual and quantitative analyses.

UNLABELLED: To compare the diagnostic performances of visual and quantitative indices of double phase Tc-99m Tetrofosmin scintimammography (TF-SMM) for the detection of breast cancer. METHODS: Double phase TF-SMM (early, 10 min; delayed, 3h) were performed after injection of 925 MBq of Tc-99m Tetrofosmin in 75 highly suspected breast cancer patients (malignant: 49, benign: 26). For visual analysis, five scoring method was used. For quantitative analysis, early, delayed lesions to non-lesion ratios (L/Ns) and washout rate (%, WR) were calculated. Receiver operating characteristic curve (ROC) analyses were performed to determine the optimal visual grade, to calculate cut-off values of quantitative indices, and to compare visual and quantitative diagnostic performances. RESULTS: When over grade 3 of visual grade was used as cut-off value in the defection of primary breast cancer, the sensitivity and specificity were 75.5 and 80.8%, respectively. The positive and negative predictive values were 88.1 and 63.6%, respectively. The area under curve was 0.824 (95% CI, 0.719-0.902) and standard error (S.E.) was 0.047. The optimal L/N ratios were 3.13 for early and 2.56 for delayed image. When early L/N 3.13 was used as cut-off point, the sensitivity and specificity of TF-SMM were 61.2 and 96.2%, respectively. The positive and negative predictive values were 96.8 and 56.8%, respectively. The AUC was 0.809 (95% CI, 0.702-0.890) and S.E. was 0.049. When delayed L/N 2.56 was used as cut-off value, the sensitivity and specificity were 46.9 and 96.2%, respectively. The positive and negative predictive values were 95.8 and 49%, respectively. The AUC was 0.741 (95% CI, 0.627-0.835) and S.E. was 0.057. No statistical differences between visual assessment and quantitative analysis of early image (difference between area, 0.015; S.E., 0.044; 95% CI, -0.072 to 0.102; p = 0.736) and delayed image (difference between area, 0.083; S.E., 0.054; 95% CI, -0.023 to 0.060; p = 0.189) was noted. However, early L/N was superior to delayed L/N ratio for the detection of breast cancer (difference between area, 0.068; S.E., 0.033; 95% CI, 0.004-0.132; p = 0.038). CONCLUSION: In conclusion, TF-SMM showed a favorable diagnostic accuracy in differentiating benign from malignant breast lesions. The optimal visual interpretation grades for the detection of primary breast cancer of double phase TF-SMM were grade 4 and 5. The optimal quantitative indices for the detection of breast cancer were 3.12 for early L/N and 2.56 for delayed L/N. Visual and quantitative analyses showed similar results. However, early L/N was superior to delayed one for the detection of breast cancer. Therefore, the delayed image should not be routinely performed for the purpose of primary breast cancer detection. These findings deserve further investigation on a larger number of patients to be performed to allow a better validation of the differentiation malignant from benign breast lesions using double phase TF-SMM.

Determination and prediction of P-glycoprotein and multidrug-resistance-related protein expression in breast cancer with double-phase technetium-99m sestamibi scintimammography. Visual and quantitative analyses.

PURPOSE: To determine and predict P-glycoprotein (Pgp) and multidrug-resistance-related protein (MRP) expression in untreated breast cancer patients by visual and quantitative indices of double-phase (99m)Tc MIBI scintimammography (DSMM). PATIENTS AND METHODS: Eighty-two patients with untreated breast cancer received DSMM. Pgp and MRP expression was assessed by immunohistochemical (IHC) staining of surgical specimens. Visual and quantitative analyses were compared with the results of IHC to determine and predict Pgp and MRP. RESULTS: The early and delayed tumor to normal tissue ratio (T/N) of the Pgp-negative and MRP-negative group had significantly higher values than those of the Pgp-positive and MRP-positive group. However, there were no statistically significant differences in washout rate (WR, in %) according to the expression of Pgp and MRP. The optimal T/N ratios were

Inhibitory effects of costunolide on the telomerase activity in human breast carcinoma cells.

Costunolide, a natural sesquiterpene compound, has been known having cytotoxic and chemopreventive effects on various human cancer cells. In the present study, we examined the effects of costunolide on telomerase activity and on the components of telomerase in MCF-7 (wild-type p53) and MDA-MB-231 (mutant p53) cells. We found that costunolide inhibited the growth and telomerase activity of MCF-7 and MDA-MB-231 cells in a concentration- and time-dependent manner. The expression of hTERT mRNA was also inhibited but hTR mRNA was not. In addition, the bindings of transcription factors in hTERT promoters were significantly decreased in both cells by the treatment of costunolide. These results suggest that costunolide inhibited the growth of both MCF-7 and MDA-MB-231 cells and this effect was mediated at least in part by a significant reduction in telomerase activity.

Comparison of quantitative and visual analysis of Tc-99m MIBI scintimammography for detection of primary breast cancer.

UNLABELLED: Tc-99m MIBI scintimammography (SMM) is known to be a useful diagnostic tool for primary breast cancer. We conducted this study to compare the quantitative and visual analysis for detection of primary breast cancer and also investigated the incremental role of quantitative index of SMM. METHODS: 520 highly suspected breast cancer patients (malignant 370: palpable 232, nonpalpable 138; benign 150: palpable 67, nonpalpable 83) were included in this study. The SMM was performed 10 min after the injection of 750 MBq of Tc-99m MIBI. For visual analysis, three-scoring based method was used. The lesions to non-lesion ratios (L/Ns) were calculated. Receiver operating characteristic curve (ROC) analyses were performed to determine the optimal visual grade, to calculate cut-off value of L/N and to investigate whether the L/N could provide incremental value additive to visual analysis. The patients were divided into four groups according to the tumor size (group A: size 5 cm). Also, the patients were divided into two groups according to age (under and over 45 years) to investigate incremental value of quantitative analysis. RESULTS: When visual grade 3 was used as the cut-off grade, the sensitivity and specificity were 82.7 and 78%, respectively. The L/N of malignant breast disease was significantly higher than that of benign (2.00 +/- 1.88 versus 0.60 +/- 0.7, P < 0.01). When L/N of 1.27 was used as the cut-off value, the sensitivity and specificity of SMM were 77.6 and 83.3%, respectively. When the L/N was added to visual grade, the area under curve (AUC) of visual + quantitative (V + Q) analyses was higher than that of visual (V) and quantitative (Q) analyses (AUC 0.874 versus 0.803, P < 0.01). In group A and B, the AUCs of V + Q (0.861, 0.895) were higher than those of V (0.808, 0.781) and Q (0.808, 0.813). In group C, the AUC of V + Q (0.847) was higher than that of Q (0.803, P = 0.041). However, the AUC of V (0.915) was higher than that of V + Q (P = 0.009). In group D, there were no statistical differences between V + Q (0.685) and V (0.570, P = 0.058) and Q (0.620, P = 0.145). The V + Q revealed incremental value in the detection of primary breast cancer in both age groups. Also, in older age patients group (over 45 years), the specificities of Q and V + Q were higher than younger group (under 45 years). For axillary lymph node involvement, the sensitivity, specificity, and accuracy of SMM were 66.9, 70.1, and 68%, respectively. CONCLUSION: From this study, the optimal visual grade for diagnosis of breast cancer was grade 3 and cut-off value of L/N was 1.27. Also, we found that the L/N provides incremental value additive to visual analysis. Especially, when the tumor is small (size

Incremental diagnostic value of quantitative analysis of double phase Tc-99m MIBI scintimammography for the detection of primary breast cancer additive to visual analysis.

UNLABELLED: Tc-99m MIBI scintimammography (SMM) is known to be a useful diagnostic tool for primary breast cancer. We conducted this study to establish optimal visual grades for the detection of primary breast cancer and to investigate whether the quantitative indices of double phase SMM could provide incremental diagnostic value additive to visual analysis. METHODS: Five hundred and twenty highly suspected breast cancer patients (malignant: 370; benign: 150) were included in this study. Double phase Tc-99m MIBI SMM (early: 10 min; delayed: 3 h) was performed after injection of 750 MBq of Tc-99m MIBI. For visual analysis, five scoring method was used. The early and delayed lesion to non-lesion ratios (L/N) and retention index (RI) were calculated. Receiver operating characteristic curve (ROC) analyses was performed to determine the optimal visual grade, to calculate cut-off value of quantitative indices for differentiation malignant and benign diseases and to investigate whether the quantitative indices could provide incremental diagnostic value additive to visual analysis. To investigate the incremental diagnostic value of quantitative index in variable tumor size groups, the patients were subdivided into four groups (group A: size 5 cm). RESULTS: When over visual grade 3 was used as the cut-off grade for the diagnosis of breast cancer, the sensitivity and specificity were 75.5, 86.4%, respectively. Early L/N of malignant breast disease was significantly higher than that of benign (2.00 +/- 1.88 vs. 0.60 +/- 0.7; p < 0.01). However, delayed L/N and RI had no significant difference between malignant and benign breast diseases. When early L/N of 1.27 was used as the cut-off value, the sensitivity and specificity of SMM were 77.6, 83.3%, respectively. When the early L/N was added to visual grade, the area under curve (AUC) of visual + quantitative analysis (V + Q) was higher than that of visual analysis (V) alone (AUC 0.893 vs. 0.803; p < 0.01). In group A, the AUC of V + Q was higher than that of V alone (0.843 vs. 0.808; p = 0.029). In group B, the AUC of V + Q was also higher (0.913 vs. 0.781; p < 0.01). However, in groups C and D, the AUCs of V + Q and V were not different (0.926 vs. 0.915; p = 0.144: 0.663 vs. 0.570; p = 0.093). For axillary lymph node involvement, the sensitivity, specificity, and of SMM were 66.9, 70.1, and 68%, respectively. CONCLUSION: From this study, the optimal visual interpretation grades for diagnosis of breast cancer were grades 4 and 5 and cut-off value of early L/N was 1.27. Also, we found that delayed image was not required for breast cancer detection and quantitative index of early L/N provide incremental diagnostic value additive to visual analysis. Especially, when the tumor is small (size