Percutaneous ultrasound-guided cryoablation for early-stage primary breast cancer: a follow-up study in Japan.

BACKGROUND: Ultrasound-guided percutaneous cryoablation (PCA) for early-stage breast cancer (ESBC) can be performed under local anesthesia in an outpatient clinic. This study continues a pilot stage to examine local control, safety, patient quality of life (QoL), satisfaction and cosmetic outcomes of cryoablation for ESBC. METHODS: PCA was performed under local anesthesia for patients with primary ESBC, followed by radiation and endocrine therapies. Oncologic outcomes were examined by imaging (mammography, ultrasound, MRI) at baseline and 1, 6, 12, 24, 36, and 60 months post-cryoablation. EQ-VAS, EQ-5D-5L, subjective satisfaction and Moiré topography were used to measure health-related QoL outcomes. RESULTS: Eighteen patients, mean aged 59.0 ± 9.0 years, mean tumor size 9.8 ± 2.3 mm, ER + , PR + (17/18), HER2-, Ki67 < 20% (15/18), underwent PCA and were followed for a mean of 44.3 months. No serious adverse events were reported, and no patients had local recurrence or distant metastasis in the 5-year follow-up. Cosmetic outcomes, satisfaction level, and QoL all improved post-cryoablation. Five-year average reduction rates of the cryolesion long, short, and depth diameters, on US, were 61.3%, 42.3%, and 22.8%, respectively, compared to the 86.2% volume reduction rate on MRI. The correlation coefficient between MRI and US measurement criteria was highest for the long diameter. During follow-up, calcification of the treated area was observed in 13/18 cases. CONCLUSION: Cryoablation for ESBC is an effective and safe procedure with excellent cosmetic outcomes and improved QoL. This study contributes to the growing evidence supporting cryoablation as a potential standard treatment for ESBC, given compliance to pre-defined patient selection criteria.

Inter- and intra-observer variability of qualitative visual breast-composition assessment in mammography among Japanese physicians: a first multi-institutional observer performance study in Japan.

BACKGROUND: Visual assessment of mammographic breast composition remains the most common worldwide, although subjective variability limits its reproducibility. This study aimed to investigate the inter- and intra-observer variability in qualitative visual assessment of mammographic breast composition through a multi-institutional observer performance study for the first time in Japan. METHODS: This study enrolled 10 Japanese physicians from five different institutions. They used the new Japanese breast-composition classification system 4th edition to subjectively evaluate the breast composition in 200 pairs of right and left normal mediolateral oblique mammograms (number determined using precise sample size calculations) twice, with a 1-month interval (median patient age: 59 years [range 40-69 years]). The primary endpoint of this study was the inter-observer variability using kappa (κ) value. RESULTS: Inter-observer variability for the four and two classes of breast-composition assessment revealed moderate agreement (Fleiss' κ: first and second reading = 0.553 and 0.587, respectively) and substantial agreement (Fleiss' κ: first and second reading = 0.689 and 0.70, respectively). Intra-observer variability for the four and two classes of breast-composition assessment demonstrated substantial agreement (Cohen's κ, median = 0.758) and almost perfect agreement (Cohen's κ, median = 0.813). Assessments of consensus between the 10 physicians and the automated software Volpara® revealed slight agreement (Cohen's κ; first and second reading: 0.104 and 0.075, respectively). CONCLUSIONS: Qualitative visual assessment of mammographic breast composition using the new Japanese classification revealed excellent intra-observer reproducibility. However, persistent inter-observer variability, presenting a challenge in establishing it as the gold standard in Japan.

Use of machine learning with two-dimensional synthetic mammography for axillary lymph node metastasis prediction in breast cancer: a preliminary study.

Background: As of 2020, breast cancer is the most common type of cancer and the fifth most common cause of cancer-related deaths worldwide. The non-invasive prediction of axillary lymph node (ALN) metastasis using two-dimensional synthetic mammography (SM) generated from digital breast tomosynthesis (DBT) could help mitigate complications related to sentinel lymph node biopsy or dissection. Thus, this study aimed to investigate the possibility of predicting ALN metastasis using radiomic analysis of SM images. Methods: Seventy-seven patients diagnosed with breast cancer using full-field digital mammography (FFDM) and DBT were included in the study. Radiomic features were calculated using segmented mass lesions. The ALN prediction models were constructed based on a logistic regression model. Parameters such as the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: The FFDM model yielded an AUC value of 0.738 [95% confidence interval (CI): 0.608-0.867], with sensitivity, specificity, PPV, and NPV of 0.826, 0.630, 0.488, and 0.894, respectively. The SM model yielded an AUC value of 0.742 (95% CI: 0.613-0.871), with sensitivity, specificity, PPV, and NPV of 0.783, 0.630, 0.474, and 0.871, respectively. No significant differences were observed between the two models. Conclusions: The ALN prediction model using radiomic features extracted from SM images demonstrated the possibility of enhancing the accuracy of diagnostic imaging when utilised together with traditional imaging techniques.

Radiomics model of diffusion-weighted whole-body imaging with background signal suppression (DWIBS) for predicting axillary lymph node status in breast cancer.

BACKGROUND: In breast cancer diagnosis and treatment, non-invasive prediction of axillary lymph node (ALN) metastasis can help avoid complications related to sentinel lymph node biopsy. OBJECTIVE: This study aims to develop and evaluate machine learning models using radiomics features extracted from diffusion-weighted whole-body imaging with background signal suppression (DWIBS) examination for predicting the ALN status. METHODS: A total of 100 patients with histologically proven, invasive, clinically N0 breast cancer who underwent DWIBS examination consisting of short tau inversion recovery (STIR) and DWIBS sequences before surgery were enrolled. Radiomic features were calculated using segmented primary lesions in DWIBS and STIR sequences and were divided into training (n = 75) and test (n = 25) datasets based on the examination date. Using the training dataset, optimal feature selection was performed using the least absolute shrinkage and selection operator algorithm, and the logistic regression model and support vector machine (SVM) classifier model were constructed with DWIBS, STIR, or a combination of DWIBS and STIR sequences to predict ALN status. Receiver operating characteristic curves were used to assess the prediction performance of radiomics models. RESULTS: For the test dataset, the logistic regression model using DWIBS, STIR, and a combination of both sequences yielded an area under the curve (AUC) of 0.765 (95% confidence interval: 0.548-0.982), 0.801 (0.597-1.000), and 0.779 (0.567-0.992), respectively, whereas the SVM classifier model using DWIBS, STIR, and a combination of both sequences yielded an AUC of 0.765 (0.548-0.982), 0.757 (0.538-0.977), and 0.779 (0.567-0.992), respectively. CONCLUSIONS: Use of machine learning models incorporating with the quantitative radiomic features derived from the DWIBS and STIR sequences can potentially predict ALN status.

Evaluation of imaging findings and prognostic factors after whole-brain radiotherapy for carcinomatous meningitis from breast cancer: A retrospective analysis.

This study aimed to evaluate the imaging findings and prognostic factors after whole-brain radiotherapy in patients with carcinomatous meningitis from breast cancer.A retrospective analysis of imaging data and prognostic factors was performed in patients treated with whole-brain radiotherapy or whole-brain/spine radiotherapy immediately after the first diagnosis of carcinomatous meningitis from breast cancer at our hospital from January 1, 2010 to December 31, 2018. Statistical significance was set at P < .05 (two-tailed).All patients (n = 31) were females with the mean age of 58.0 ±â€Š11.0 years. The breast cancer subtypes were luminal (n = 14, 45.1%), human epidermal growth factor receptor 2 (HER2)-positive (n = 9, 29.0%), and triple-negative (n = 8, 26.0%) breast cancer. Brain metastasis and abnormal contrast enhancement in the sulci were observed in 21 (67.7%) and 24 (80.6%) patients, respectively. The median survival time after cancerous meningitis diagnosis was 62 (range, 6-657) days. Log-rank test showed significant differences in median survival time after cancerous meningitis diagnosis: 18.0 days for subjects treated with 30 Gy in < 10 fractions (n = 7) vs 78.5 days for subjects treated with 30 Gy in ≥10 fractions (n = 24) (P < .01) and 23.0 days for the triple-negative subtype vs 78.5 days for the other subtype (P < .01) groups. Univariate analysis using the Cox regression model showed significant differences in median survival time after cancerous meningitis diagnosis between the group treated with 30 Gy in <10 fractions and the group treated in ≥10 fractions (hazard ratio [HR] 0.08, 95% confidence interval [CI], 0.03-0.26; P < .01), and between the triple-negative subtype and the other subtypes (HR = 5.48; 95% CI, 1.88-16.0; P < .01) groups.Discontinuation of whole-brain radiotherapy and the presence of triple-negative breast cancer were indicators of poor prognosis.

Survival time and prognostic factors after whole-brain radiotherapy of brain metastases from of breast cancer.

BACKGROUND: Breast cancer has a poor prognosis due to the high risk of distant metastasis. PURPOSE: To identify the prognosticators of brain metastasis from breast cancer treated by whole-brain radiotherapy. MATERIAL AND METHODS: We evaluated patients diagnosed with primary brain metastasis without carcinomatous meningitis from breast cancer and had undergone whole-brain radiotherapy as initial treatment between 1 January 2010 and 30 September 2019. We investigated associations between overall survival time from diagnosis using cranial contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) and the following parameters: (i) age; (ii) sex; (iii) time to appearance of brain metastasis; (iv) other metastasis at appearance of brain metastasis; (v) blood test; (vi) symptoms at time of brain metastasis; (vii) whole-brain radiotherapy dose; (viii) whether whole-brain radiotherapy was completed; (ix) course of chemo- or radiotherapy; (x) subtype; (xi) additional irradiation after whole-brain radiotherapy; (xii) pathology; and (xiii) imaging findings. RESULTS: We evaluated 29 consecutive female patients (mean age 55.2 ± 12.1 years). Median overall survival time after diagnosis on cranial contrast-enhanced MRI/CT was 135 days (range 16-2112 days). Multivariate stepwise analysis of the three parameters of lactate dehydrogenase, dose, and subtype identified the following significant differences: Hazard Ratio (HR) for dose (discontinued, 30 Gy/10 fractions, 31.5 Gy/11 fractions, 32.5 Gy/11 fractions, 37.5 Gy/15 fractions) was 0.08 (95% confidence interval [CI] 0.02-0.30, P < 0.01), and HR for subtype (luminal, HER2, triple-negative) was 2.70 (95% CI 1.16-6.243, P < 0.01). CONCLUSION: HER2-type and 37.5 Gy/15 fractions are good prognostic factor after whole-brain radiotherapy in breast cancer with brain metastases.

Trastuzumab Emtansine (T-DM1) Plus S-1 in Patients with Trastuzumab-Pretreated HER2-Positive Advanced or Metastatic Breast Cancer: A Phase Ib Study.

BACKGROUND: In treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, the efficacy of capecitabine combined with HER2-directed agents such as trastuzumab and lapatinib is supported by some evidence. The combination of T-DM1 and S-1, another oral 5-FU, may be a safe alternative treatment for metastatic breast cancer. OBJECTIVES: The optimal dose of S-1 was evaluated in combination with T-DM1 for patients with HER2-positive advanced or metastatic breast cancer. The safety and clinical response of this combination treatment were also assessed. METHODS: This 3 + 3 dose-escalation study of S-1 given for the first 2 of 3 weeks, in combination with T-DM1 (3.6 mg/kg given every 3 weeks) to patients with trastuzumab-pretreated HER2-positive advanced or metastatic breast cancer was designed to evaluate the dose-limiting toxicity (DLT) occurrence in the first cycle. We also evaluated the safety and clinical activity of this combination treatment in multiple cycles. Two different dose levels of S-1 (65 and 80 mg/m2/day) were planned, although the capecitabine arm was abandoned because of slow recruitment. RESULTS: Twelve out of the 13 patients enrolled were evaluable for DLT. One DLT (grade ≥3 non-hematological adverse events) occurred at dose level 0, leading to the expansion of this cohort to 6 patients, with an additional DLT (≥7 days discontinuation of medication), while no DLT occurred at dose level 1. As a result, the maximum tolerable dose of S-1 was determined to be 80 mg/m2/day for 14 days with T-DM1 3.6 mg/kg, repeated every 3 weeks. Two patients had grade 3 thrombocytopenia at dose level 0, and 1 patient at dose level 1. CONCLUSIONS: S-1 can be safely combined with the clinically relevant dose of T-DM1 in patients with HER2-positive advanced or metastatic breast cancer. Further evaluation with a larger sample size is required for efficacy assessment.

Effects of menstrual cycle on background parenchymal enhancement and detectability of breast cancer on dynamic contrast-enhanced breast MRI: A multicenter study of an Asian population.

PURPOSE: To evaluate the effect of the menstrual cycle on BPE and cancer detectability in an Asian population. MATERIAL AND METHODS: 266 premenopausal patients with regular menstrual cycles from 24 centers were included, and 176 of them were diagnosed by pathology as having breast cancer. Thirty-five patients were examined in the menstrual phase (days 1-4), 105 in the proliferative phase (days 5-14), and 126 in the secretory phase (days 15-30). Measurement of the following signal intensities (SIs) were obtained: breast tissue on the unaffected side on a pre-contrast image (SI1) and an early-phase image (SI2); the SIs of breast tissue on the affected side on a pre-contrast image (SI3) and an early-phase image (SI4); and the SIs of breast cancer on a pre-contrast image (SI5) and an early-phase image (SI6). We calculated the BPE ratio, i.e., (SI2- SI1)/SI1 and the cancer/background enhancement ratio (C/B) ratio, i.e., (SI6- SI5) / (SI4- SI3). The BPE was classified as minimal, mild, moderate, or marked, and the cancer detectability was classified as excellent, good, or poor independently by two radiologists. RESULTS: The average C/B ratio was 20.1, 15.7, and 9.1 at the menstrual, proliferative, and secretory phases (p < 0.001). BPE was determined as moderate or marked in 0% and 5.4% at the menstrual phase, 10.3% and 11.0% at the proliferative phase, and 17.5% and 21.7% at the secretory phase by the two observers, respectively (p = 0.01, p = 0.01). The detectability of breast cancer was classified as poor in 0% and 0%, 1.4% and 13.0%, and 8.0% and 22.1% at the menstrual, proliferative, and secretory phases by the two observers, respectively (p = 0.07, p = 0.02). CONCLUSION: The menstrual phase and the proliferative phase seem to be suitable for breast MRI of Asian women.

Use of immunohistochemical analysis of CK5/6, CK14, and CK34betaE12 in the differential diagnosis of solid papillary carcinoma in situ from intraductal papilloma with usual ductal hyperplasia of the breast.

OBJECTIVES: The aim of this study was to use immunohistochemistry to differentiate solid papillary carcinoma in situ from intraductal papilloma with usual ductal hyperplasia (IPUDH). Three types of high-molecular-weight cytokeratins (CKs) - CK5/6, CK14, and CK34betaE12 - were targeted. METHODS: We studied 17 patients with solid papillary carcinoma in situ and 18 patients with IPUDH diagnosed by at least two pathologists. Immunohistochemical analyses used antibodies to CK5/6, CK14, and CK34betaE12 to make the differential diagnosis of solid papillary carcinoma in situ versus IPUDH. Immunohistochemical staining was scored as 0-5 using Allred score. RESULTS: Immunohistochemistry with CK5/6 and CK14 antibodies produced scores of 0-3 in all patients with solid papillary carcinoma in situ and 2-5 in all patients with IPUDH. Immunohistochemical staining with CK34betaE12 antibody produced scores of 1-3 in all patients with solid papillary carcinoma and 3-5 in all patients with IPUDH. In tissues from patients with IPUDH, significantly more cells were stained with CK34betaE12 than CK5/6 (p < 0.05) or CK14 (p < 0.05). CONCLUSION: The immunoreactivity of CK5/6, CK14, and CK34betaE12 antibodies was useful to differentiate solid papillary carcinoma in situ from IPUDH. CK34betaE12 is especially useful for distinguishing solid papillary carcinoma from IPUDH.

Comparison of detectability of breast cancer by abbreviated breast MRI based on diffusion-weighted images and postcontrast MRI.

PURPOSE: To compare the detectability of unenhanced abbreviated magnetic resonance imaging (MRI) based on diffusion-weighted imaging (DWI) and abbreviated postcontrast MRI for breast cancer. METHODS: The study population consisted of 87 patients undergoing breast MRI between December 2016 and March 2017 in a clinical setting. All breast MRIs were performed using a 1.5-T MRI scanner with a 16-channel breast radiofrequency coil. The abbreviated protocols based on DWI (AP1) and postcontrast MRI (AP2) were assessed independently by two radiologists. Sensitivity and specificity were calculated. Receiver operating characteristic analysis was performed and the areas under the curves (AUCs) were compared between AP1 and AP2. RESULTS: The study included 87 patients with 89 breast cancer lesions ≤ 2 cm in diameter. The sensitivity/specificity for AP1 and AP2 for reader 1 was 89.9/97.6% and 95.5/90.6%, respectively, and those for reader 2 was 95.5/94.1% and 98.9/94.1%, respectively. The AUCs for AP1 and AP2 for reader 1 were 0.9629 and 0.9640 (p = 0.95), respectively, and those for reader 2 were 0.9755 and 0.9843 (p = 0.46), respectively. CONCLUSIONS: The detectability of the unenhanced abbreviated protocol based on DWI would be comparable to that of abbreviated postcontrast MRI for breast cancer.

Grading System to Categorize Breast MRI in BI-RADS 5th Edition: A Multivariate Study of Breast Mass Descriptors in Terms of Probability of Malignancy.

OBJECTIVE: The purpose of this study is to analyze the association between the probability of malignancy and breast mass descriptors in the BI-RADS 5th edition and to devise criteria for grading mass lesions, including subcategorization of category 4 lesions with or without apparent diffusion coefficient (ADC) values. MATERIALS AND METHODS: A total of 519 breast masses in 499 patients were selected. Breast MRI was performed with a 1.5-T MRI scanner using a 16-channel dedicated breast radiofrequency coil. Two radiologists determined the morphologic and kinetic features of the breast masses. Mean ADC values were measured on ADC maps by placing round ROIs that encircled the largest possible solid mass portions. An optimal ADC threshold was chosen to maximize the Youden index. Corresponding pathologic diagnoses were obtained by either biopsy or surgery. RESULTS: A total of 472 masses were malignant. Multivariate model analysis showed that shape (irregular, p < 0.001), margin type (not circumscribed, p < 0.001), internal enhancement (rim enhancement and heterogeneous enhancement, p = 0.0001), and delayed phase (washout, p = 0.0003) were the significant explanatory variables. The 3-point scoring system for findings suspicious for malignancy and the proposed classification system for breast mass descriptors (with points for category designation ranging from 0 to > 4) were significant with respect to malignancy (p < 0.01). The inclusion of ADC values improved the positive predictive values for categories 3, 4A, and 4B. CONCLUSION: The 3-point scoring system for findings suspicious for malignancy and the proposed classification system for breast mass descriptors would be valid as a categorization system. ADC values may be used to downgrade benign lesions in categories 3, 4A, and 4B.

Grading system to categorize breast MRI using BI-RADS 5th edition: a statistical study of non-mass enhancement descriptors in terms of probability of malignancy.

PURPOSE: To analyze the association of breast non-mass enhancement descriptors in the BI-RADS 5th edition with malignancy, and to establish a grading system and categorization of descriptors. MATERIALS AND METHODS: This study was approved by our institutional review board. A total of 213 patients were enrolled. Breast MRI was performed with a 1.5-T MRI scanner using a 16-channel breast radiofrequency coil. Two radiologists determined internal enhancement and distribution of non-mass enhancement by consensus. Corresponding pathologic diagnoses were obtained by either biopsy or surgery. The probability of malignancy by descriptor was analyzed using Fisher's exact test and multivariate logistic regression analysis. The probability of malignancy by category was analyzed using Fisher's exact and multi-group comparison tests. RESULTS: One hundred seventy-eight lesions were malignant. Multivariate model analysis showed that internal enhancement (homogeneous vs others, p < 0.001, heterogeneous and clumped vs clustered ring, p = 0.003) and distribution (focal and linear vs segmental, p < 0.001) were the significant explanatory variables. The descriptors were classified into three grades of suspicion, and the categorization (3, 4A, 4B, 4C, and 5) by sum-up grades showed an incremental increase in the probability of malignancy (p < 0.0001). CONCLUSION: The three-grade criteria and categorization by sum-up grades of descriptors appear valid for non-mass enhancement.

Effectiveness of computer-aided diagnosis (CADx) of breast pathology using immunohistochemistry results of core needle biopsy samples for synaptophysin, oestrogen receptor and CK14/p63 for classification of epithelial proliferative lesions of the breast.

AIMS: The aim of this study was to develop a computer-aided diagnosis (CADx) system for identifying breast pathology. METHODS: Two sets of 100 consecutive core needle biopsy (CNB) specimens were collected for test and validation studies. All 200 CNB specimens were stained with antibodies targeting oestrogen receptor (ER), synaptophysin and CK14/p63. All stained slides were scanned in a whole-slide imaging system and photographed. The photographs were analysed using software to identify the proportions of tumour cells that were positive and negative for each marker. In the test study, the cut-off values for synaptophysin (negative and positive) and CK14/p63 (negative and positive) were decided using receiver operating characteristic (ROC) analysis. For ER analysis, samples were divided into groups with <10% positive or >10% positive cells and decided using receiver operating characteristic (ROC) analysis. Finally, these two groups categorised as ER-low, ER-intermediate (non-low and non-high) and ER-high groups. In the validation study, the second set of immunohistochemical slides were analysed using these cut-off values. RESULTS: The cut-off values for synaptophysin, <10% ER positive, >10% ER positive and CK14/p63 were 0.14%, 2.17%, 77.93% and 18.66%, respectively. The positive predictive value for malignancy (PPV) was 100% for synaptophysin-positive/ER-high/(CK14/p63)-any or synaptophysin-positive/ER-low/(CK14/p63)-any. The PPV was 25% for synaptophysin-positive/ER-intermediate/(CK14/p63)-positive. For synaptophysin-negative/(CK14/p63)-negative, the PPVs for ER-low, ER-intermediate and ER-high were 100%, 80.0% and 95.8%, respectively. The PPV was 4.5% for synaptophysin-negative/ER-intermediate/(CK14/p63)-positive. CONCLUSION: The CADx system was able to analyse sufficient data for all types of epithelial proliferative lesions of the breast including invasive breast cancer. This system may be useful for pathological diagnosis of breast CNB in routine investigations.

Feasibility and potential limitations of abbreviated breast MRI: an observer study using an enriched cohort.

BACKGROUND: Breast cancer screening using magnetic resonance imaging (MRI) has been introduced in Western countries primarily for populations with an elevated risk of breast cancer. We conducted an observer study involving an experimental abbreviated MRI interpretation by Japanese radiologists, using an enriched cohort, to evaluate its feasibility in a screening setting. METHODS: Eighty-eight breast MRI examinations including 28 cases with breast cancer were enrolled as study subjects. Two radiologists independently reviewed the MR images, first with only two sequences (abbreviated series), and then with all of the images provided for clinical care (full diagnostic series). The difference in sensitivity and specificity was evaluated using McNemar's test. Interobserver agreement was assessed by calculating κ values. RESULTS: A total of 176 breasts including 31 cancers (3 cases with bilateral disease) were included. No significant difference in sensitivity or specificity for either observer was observed between the abbreviated series and the full diagnostic series (observer 1: sensitivity 87.1 vs 87.1 %, p = 1.00, specificity 91.7 vs 90.3 %, p = 0.791; observer 2: sensitivity 93.5 vs 96.8 %, p = 1.00, specificity 83.4 vs 89.7 %, p = 0.064). Moderate interobserver agreement (κ = 0.56) was observed for the abbreviated series, whereas substantial agreement (κ = 0.69) was observed for the full diagnostic series. CONCLUSIONS: The diagnostic accuracy of the abbreviated breast MRI was not inferior to that of the conventional full diagnostic interpretation, although a slight decline in interobserver agreement was observed.

Can synaptophysin be used as a marker of breast cancer diagnosed by core-needle biopsy in epithelial proliferative diseases of the breast?

The differential diagnosis of epithelial proliferative disease using core needle biopsy (CNB) is problematic because it is difficult to differentiate between intraductal papilloma, ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Many studies have reported that breast cancer lesions are positive for neuroendocrine (NE) markers, whereas only a small number of studies have reported immunopositivity for NE markers in normal mammary tissues or benign lesions. We asked whether NE factors could be used as markers of breast cancer. We determined the immunopositivity rate of synaptophysin, an NE marker, in 204 lesions excised from the breast using CNB in patients who visited a university-affiliated comprehensive medical facility and examined whether synaptophysin is a marker of breast cancer. The specimens were classified as synaptophysin-negative cases (56 benign, 99 malignant); equivocal cases (<1 %: 2 benign, 15 malignant); and synaptophysin-positive cases (1 benign, 31 malignant). The sensitivity, specificity, positive predictive value, and negative predictive value for malignancy of the lesions classified as synaptophysin positive were 23.3 %, 98.2 %, 96.9 %, and 36.1 %, respectively. The respective values for lesions classified as equivocal were 11.6 %, 96.6 %, 88.2 %, and 36.1 %. Synaptophysin may provide a marker of breast cancer diagnosed by CNB.

Magnetic resonance examination to predict pathological complete response following neoadjuvant chemotherapy: when is it appropriate for HER2-positive and triple-negative breast cancers?

BACKGROUND: To clarify appropriate timing for magnetic resonance examination to predict pathological complete response to neoadjuvant chemotherapy for patients with human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers in terms of tumor volume change. METHODS: Between September 2009 and December 2014, 113 women with HER2-positive (n = 51) and triple-negative (n = 62) invasive breast cancers undergoing neoadjuvant chemotherapy were enrolled. Patients with HER2-positive tumors underwent neoadjuvant chemotherapy with an anthracycline-based regimen followed by docetaxel with trastuzumab. Patients with triple-negative tumors underwent neoadjuvant chemotherapy with anthracycline-based (first in most cases) and taxane-based regimens. Magnetic resonance imaging was performed before neoadjuvant chemotherapy, between the regimens (midpoint examination), and after neoadjuvant chemotherapy (final examination). Response ratio of tumor volume was calculated and receiver-operating characteristic analyses for them for both subtypes were performed at the midpoint and final examinations. RESULTS: Twenty-eight women with HER2-positive tumors (54.9 %) and 29 women with triple-negative tumors (46.8 %) had pathological complete response. The response ratios were better in cases with pathological complete response than in those without (p = 0.0341, p < 0.0001). The area under the curve at the final examination was higher than that at the midpoint examination for HER2-positive tumors (p = 0.039); whereas for the triple-negative tumors, no significant difference between the two examinations was shown (p = 0.5218). CONCLUSIONS: Magnetic resonance examination to predict pathological complete response would be feasible after completion of a regimen including trastuzumab for HER2-positive tumors and at the midpoint of neoadjuvant chemotherapy for triple-negative tumors.

Oncologic outcomes and technical considerations of nipple-sparing mastectomies in breast cancer: experience of 425 cases from a single institution.

BACKGROUND: Nipple-sparing mastectomy (NSM) is an advantageous treatment option, providing a complete cure and good cosmetic results. We tested whether NSM is a surgically and oncologically safe technique. METHODS: We evaluated the oncological outcome of 425 breasts in 413 patients who underwent NSM between January 2000 and March 2013. We retrospectively reviewed patient data and analyzed all patient characteristics as potential risk factors of recurrence at the nipple-areola complex (NAC). To confirm the oncological safety of NSM, we compared outcomes of NSM and conventional total mastectomy. RESULTS: The median follow-up time after surgery was 46.8 months (range 6-158 months). Nipple necrosis was observed in 6 cases (1.4 %). The cumulative local recurrence rate after NSM was 5.8 % (25/425 cases), similar to that of conventional total mastectomy in the same period (5.6 %, 49/878 cases). Furthermore, the cumulative local recurrence rate at the NAC was 2.3 % (10 cases). HER2-enriched tumors and young age (<40 years) were significant risk factors for recurrence at the NAC. In patients with recurrence, the site of recurrence was easily excised, and good cosmetic results were achieved in breast reconstruction cases. CONCLUSION: NSM is safe with a low complication rate. No significant difference was observed in cumulative local recurrence rate, cumulative distant disease recurrence rate, and overall survival between patients who underwent NSM or conventional total mastectomy, confirming that NSM was surgically and oncologically safe.

Positive predictive value for malignancy of pure flat epithelial atypia diagnosis by percutaneous needle biopsy of the breast: management of FEA in ultrasonography.

BACKGROUND: Some reports suggest that the rate of definitive diagnosis of malignant tumors, namely, the final diagnosis being revised to a higher stage, in patients diagnosed as having flat epithelial atypia (FEA) by percutaneous needle biopsy of the breast (PNB) is as low as 0-3 %. However, other reports suggest that the rate is as high as 10 % or more, bringing confusion on this issue. We examined the positive predictive value for malignancy in the patients diagnosed as having pure FEA and the patients' radiolopathological characteristics observed in our hospital. METHODS: Of the patients who underwent PNB in our facility, those who were diagnosed as having pure FEA were recruited as the subjects of this study. RESULTS: Of the 4,197 consecutive patients who underwent PNB, 44 (1.0 %) were diagnosed as having pure FEA following a re-examination. Among 44 cases, 39 cases were selected as the subjects of this study. Among the 39 patients, six patients were diagnosed as having malignant lesions, two of whom had invasive carcinoma of no special type (papillotubular type), one had tubular carcinoma, one had ductal carcinoma in situ (DCIS) of high nuclear grade, one had DCIS of intermediate nuclear grade, and one had DCIS of low nuclear grade. The diameters of 6 malignant lesions were 10-30 mm at ultrasonography (US) examination. Five of the 39 patients had contralateral breast cancer. CONCLUSION: The positive predictive value for malignancy of pure FEA was 15.7 %. The patients with pure FEA may make a follow up without an excisional biopsy when the lesion sizes less than 10 mm on US examination.

Positron emission mammography (PEM): reviewing standardized semiquantitative method.

PURPOSE: To validate semiquantitative analysis of positron emission mammography (PEM). METHODS: Fifty women with histologically confirmed breast lesions were retrospectively enrolled. Semiquantitative uptake values (4 methods), the maximum PEM uptake value (PUVmax), and the lesion-to-background (LTB) value (3 methods) were measured. LTB is a ratio of the lesion's PUVmax to the mean background; LTB1, LTB2, and LTB3 (which were calculated on different background) were used to designate the three values measured. Interobserver reliability between two readers for PUVmax and the LTBs was tested using the interobserver correlation coefficient (ICC). The likelihood ratio test was used to evaluate the relationship between ICCs. Receiver operating characteristic (ROC) curves were calculated for all methods. Diagnostic accuracy in differentiating benign tissue from malignant tissue was compared between PUVmax and LTB1. RESULTS: The ICC rate was 0.971 [95 % confidence interval (CI) 0.943-0.986] for PUVmax, 0.873 (95 % CI 0.758-0.935) for LTB1, 0.965 (95 % CI 0.925-0.983) for LTB2, and 0.895 (95 % CI 0.799-0.946) for LTB3. However, there were some technical difficulties in the practical use of LTB2 and LTB3. The likelihood ratio test between PUVmax and LTB1 was statistically significant (p < 0.001). ROC curves of the 4 methods had similar characteristics. The median PUVmax was 1.39 for benign lesions and 3.70 for malignant lesions. LTB1 was 1.92 for benign lesions and 4.78 for malignant lesions. Significant differences (p < 0.001) in both PUVmax and LTB1 were observed between groups. CONCLUSION: Due to its simplicity and reproducibility, PUVmax is superior to LTB as an indicator for PEM in semiquantitative analysis.