Conventional Tools for Predicting Satisfactory Response to Neoadjuvant Chemotherapy in HR+/HER2- Breast Cancer Patients.

Aim: The aim of the study was to assess the role of Magee Equation 3 (MagEq3), IHC4 score, and HER2-low status in predicting "satisfactory response (SR)" to neoadjuvant chemotherapy (NAC) in HR+/HER2- breast cancer (BC) patients. Methods: In a retrospective study, female patients of any age with T1-4, N0-2, M0 HR+/HER2- BC who received NAC and underwent adequate locoregional surgical treatment were included. Patients were grouped according to 2 outcomes: (a) overall response to NAC in breast and axilla by using residual cancer burden (RCB) criteria and (b) axillary downstaging after NAC by using N staging. 2 cohorts for overall response were overall SR (RCB 0-1) and no SR (RCB 2-3). On the other hand, for axillary downstaging, 2 cohorts constituted from axillary SR (ypN0 and ypN0i+) and no SR (ypNmic-N3). MagEq3 and IHC4 scores were calculated from their pathological tumor slides in each patient. HER2 status was categorized as either "no" or "low." In addition, patient age, family history, tumor histology, stage at admission, and Ki-67 status were compared between cohorts according to predefined outcomes. Results: In a total of 230 BC patients, 228 patients were included to compare according to their RCB levels. The mean age of patients with overall SR was significantly lower than those without. Patients with high Ki-67 expression, high (>30) MagEq3 score, high ICH4 quartile, and HER2-low status had significantly more overall SR. On the other hand, only patients with high Ki-67 expression had significantly more axillary SR. MagEq3 score levels, ICH4 quartiles, and HER2 status were similar between patients with axillary SR and not. Conclusion: MagEq3 and IHC4 tools seemed to be useful to predict those HR+/HER2- BC patients who are most likely to get benefit from NAC. But, only high Ki-67 expression level significantly predicted satisfactory axillary downstaging in HR+/HER2- BC patients.

Prediction of nipple involvement in breast cancer after neoadjuvant chemotherapy: Should we rely on breast MRI to preserve the nipple?

BACKGROUND: Indications for nipple sparing mastectomy (NSM) is extending to post-neoadjuvant chemotherapy (NAC) setting. Eligibility for NSM with an optimum tumor-nipple distance (TND) after NAC is unclear. We examined predictive factors for nipple tumor involvement in patients undergoing total mastectomy following NAC. METHODS: Clinical and pathological data from prospectively collected medical records of women with invasive breast carcinoma, who were undergone NAC and total mastectomy with sentinel lymph node biopsy and/or axillary lymph node dissection were analyzed. PreNAC and postNAC magnetic resonance imaging (MRI) views were examined and a cut-off TND value for predicting the negative nipple tumor status was determined. RESULTS: Among 180 women, the final mastectomy specimen analysis revealed that 12 (7%) had nipple involvement as invasive carcinoma. Patients with nipple involvement had more postNAC multifocal/multicentric tumors (p: 0.03), larger tumors on preNAC and postNAC images (p: 0.002 and p < 0.001), shorter median TNDs on preNAC and postNAC images (7 mm-IQR 1.5-14, p: 0.005 and 8.5 mm-IQR 3-15.5, p < 0.001, respectively), more nipple retraction on preNAC and postNAC images (p: 0.007 and p: 0.006) and more nipple areola complex skin thickening (> 2mm) on preNAC and postNAC images (p < 0.001 and p: 0.01). The best likelihood ratios (LR) belonged to the postNAC positivity of the < 20 mm TND, with a + LR of 3.40, and - LR of 0.11 for nipple involvement. PreNAC positivity of the < 20 mm TND also had a similar - LR of 0.14. CONCLUSION: A TND-cut-off  ≥ 2 cm on preNAC and postNAC MRI was shown to be highly predictive of negative nipple tumor involvement.

Linear Regression Modeling Based Scoring System to Reduce Benign Breast Biopsies Using Multi-parametric US with Color Doppler and SWE.

RATIONALE AND OBJECTIVES: To develop a simple ultrasound (US) based scoring system to reduce benign breast biopsies. MATERIALS AND METHODS: Women with BI-RADS 4 or 5 breast lesions underwent shear-wave elastography (SWE) imaging before biopsy. Standard US and color Doppler US (CDUS) parameters were recorded, and the size ratio (SzR=longest/shortest diameter) was calculated. Measured/calculated SWE parameters were minimum (SWVMin) and maximum (SWVMax) shear velocity, velocity heterogeneity (SWVH=SWVMax-SWVMin), velocity ratio (SWVR=SWVMin/SWVMax), and normalized SWVR (SWVRn=(SWVMax-SWVMin)/SWVMin). Linear regression analysis was performed by converting continuous parameters into categorical corresponding equivalents using decision tree analyses. Linear regression models were fitted using stepwise regression analysis and optimal coefficients for the predictors in the models were determined. A scoring model was devised from the results and validated using a different data set from another center consisting of 187 cases with BI-RADS 3, 4, and 5 lesions. RESULTS: A total of 418 lesions (238 benign, 180 malignant) were analyzed. US and CDUS parameters exhibited poor (AUC=0.592-0.696), SWE parameters exhibited poor-good (AUC=0.607-0.816) diagnostic performance in benign/malignant discrimination. Linear regression models of US+CDUS and US+SWE parameters revealed an AUC of 0.819 and 0.882, respectively. The developed scoring system could have avoided biopsy in 37.8% of benign lesions while missing 1.1% of malignant lesions. The scoring system was validated with a 100% NPV rate with a specificity of 74.6%. CONCLUSION: The linear regression model using US+SWE parameters performed better than any single parameter alone. The developed scoring method could lead to a significant decrease in benign biopsies.

Breast lesions with myoepithelial phenotype.

Myoepithelial cells (MECs) constitute a continuous layer of cells surrounding the breast glands, localised between the epithelial cells (ECs) and the basal membrane. MECs play important roles in normal mammary gland as they produce basal membrane and stimulate secretion. During neoplastic transformation, MECs act as a barrier preventing stromal invasion. MECs themselves can undergo a great variety of changes, ranging from hyperplastic to metaplastic, to neoplastic, and giving rise to a wide spectrum of morphological pictures sometimes difficult to interpret on routine diagnoses. Several benign and malignant breast tumours can present features of MECs differentiation. As these latter tumours are quite infrequent, the purpose of the present study is to offer a review of the morphological spectrum of MECs lesions, with correlations to prognosis.

Predictive value of 18F-FDG PET/CT indices on extensive residual cancer burden in breast cancer patients treated with neoadjuvant chemotherapy.

AIM: We investigated the correlation between 18F-FDG PET/CT indices and pathological response in breast cancer treated with neoadjuvant chemotherapy (NACT) which was scored with Residual Cancer Burden (RCB) system after surgery. Our aim is to detect extensive residual cancer burden earlier by using PET/CT indices. METHODS: Characteristics of patients were retrieved retrospectively. Baseline maximum Standart Uptake Value (SUVmax), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) indices and reduction rate (RR) between baseline and interim evaluation were calculated with FDG PET/CT scan. All patients were evaluated according to RCB scores after surgery. Pathological responses and PET/CT measurement results were analyzed with demographic and clinical parameters. RESULTS: A total of 95 patients were included in the study. According to pathological responses, the distribution of RCB -0, -1, -2, -3 were 13 (13.7%), 11 (11.6%), 30 (31.6%), 41 (43.2%), respectively. Disease-free survival was significantly lower in the RCB3 group compared to the pathological responder group (p = 0.01). According to multivariate analysis, RR of SUVmax was determined as an independent variable predicting extensive residual cancer burden with an optimal cut-off value of 86% (p < 0.05). CONCLUSIONS: We determined RR of SUVmax as an independent factor for predicting extensive residual tumor burden. We believe that RR of SUVmax is sufficient to predict pathological response in daily practice. In addition, MTV and TLG measurements do not contribute additionally to SUVmax alone and can cause unnecessary labor loss.

Relationship of PPARG overexpression with prognostic parameters in papillary thyroid carcinoma.

Objectives: PAX8/PPARG chromosomal rearrangement is frequently seen in thyroid cancer, and PPARG overexpression has been shown in the follicular variant of papillary thyroid carcinoma, but not in papillary thyroid carcinoma other than the follicular variant. The main aim of this study was to investigate the frequency of PPARG overexpression among papillary thyroid carcinoma and if there were any variants of papillary thyroid carcinoma with PPARG overexpression other than the follicular variant. Methods: Immunohistochemical analysis of PPARG overexpression was performed using a PPARG monoclonal antibody in a series of 111 paraffin-embedded blocks of thyroid tumours. Of the patients in our study, 100 were diagnosed with papillary thyroid carcinoma, 9 with follicular adenoma and 2 with follicular carcinoma. Results: PPARG staining was detected in 19 of the 111 cases. Sixteen patients with PPARG overexpression had papillary thyroid carcinoma and 3 had follicular adenoma. Conclusion: PPARG overexpression was detected mainly in follicular-variant papillary thyroid carcinoma. Vascular invasion, lymphatic invasion, thyroid capsule invasion and lymph node positivity were lower in patients with PPARG overexpression.

The value of MRI contrast enhancement in biopsy decision of suspicious mammographic microcalcifications: a prospective multicenter study.

OBJECTIVES: To investigate the inclusion of breast MRI in radiological assessment of suspicious, isolated microcalcifications detected with mammography. METHODS: In this prospective, multicenter study, cases with isolated microcalcifications in screening mammography were examined with dynamic contrast-enhanced MRI (DCE-MRI) before biopsy, and contrast enhancement of the relevant calcification localization was accepted as a positive finding on MRI. Six experienced breast radiologists evaluated the images and performed the biopsies. Imaging findings and histopathological results were recorded. Sensitivity, specificity, NPV, and PPV of breast MRI were calculated and compared with histopathological findings. RESULTS: Suspicious microcalcifications, which were detected by screening mammograms of 444 women, were evaluated. Of these, 276 (62.2%) were diagnosed as benign and 168 (37.8%) as malignant. Contrast enhancement was present in microcalcification localization in 325 (73.2%) of the cases. DCE-MRI was positive in all 102 invasive carcinomas and in 58 (87.9%) of 66 DCIS cases. MRI resulted in false negatives in eight DCIS cases; one was high grade and the other seven were low-to-medium grade. The false-negative rate of DCE-MRI was 4.76%. The sensitivity, specificity, PPV, and NPV for DCE-MRI for mammography-detected suspicious microcalcifications were 95.2%, 40.2%, 49.2%, and 93.3%, respectively. CONCLUSIONS: In this study, all invasive cancers and all DCIS except eight cases (12.1%) were detected with DCE-MRI. DCE-MRI can be used in the decision-making algorithm to decrease the number of biopsies in mammography-detected suspicious calcifications, with a tradeoff for overlooking a small number of DCIS cases that are of low-to-medium grade. KEY POINTS: • All invasive cancer cases and 87.8% of all in situ cancer cases were detected with MRI, showing a low false-negative rate of 4.7%. • Dynamic contrast-enhanced MRI can be used in the decision-making algorithm to decrease the number of biopsies in mammography-detected suspicious calcifications, with a tradeoff for overlooking a small number of DCIS cases that are predominantly low-to-medium grade. • If a decision for biopsy were made based on MRI findings in mammography-detected microcalcifications in this study, biopsy would not be performed to 119 cases (26.8%).

Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?

PURPOSE: Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment. METHODS: Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin × fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. RESULTS: Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7-17.2), p = 0.01]. CONCLUSION: Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.

Prognostic Role of Immune Markers in Triple Negative Breast Carcinoma.

Tumor immune microenvironment (TIME) is a significant prognostic parameter for triple negative breast carcinomas (TNBC) due to being a target for immunotherapeutic agents and its essential role during the cancer immunoediting process. In this study, CD8, FOXP3, CD163, PD-L1/SP142 and PD-L1/SP263 antibodies were examined in a sample of 51 TNBC cases. Patients who received neoadjuvant therapy were excluded. CD8, FOXP3 and CD163 antibodies were evaluated separately in intratumoral area (ITA) and tumor stroma (TS). PD-L1 status was also examined in tumor cells (TC) and immune cells (IC) using both SP142 and SP263 antibodies. In multivariate Cox regressions, the only antibody that was found to be significantly associated with survival was SP142. SP142-positivity in TC and IC was related to increased overall survival. Higher CD163 expression in ITA and SP263-positivity in IC were associated with younger age. Lymphatic/angioinvasion was more frequent in cases with negative/low CD8 and FOXP3 expressions. Moreover, metastatic axillary lymph node(s) was associated with negative/low FOXP3 expression in TS. CD8, FOXP3, CD163, SP142 and SP263 expressions were positively correlated with each other, except a mild discordance caused by CD163 in ITA. Although PD-L1 status with both SP142 and SP263 antibodies were concordant in the majority of cases, 33.3% and 13.7% of the cases showed SP142-negative/SP263-positive pattern in TC and IC respectively. In conclusion, we suggest that composition, density and localization of the immune cells and the check point molecules are important prognostic parameters in TNBC. Immunohistochemistry can be used as an accessible and less expensive tool to demonstrate TIME.

Pre-operative management of Pleomorphic and florid lobular carcinoma in situ of the breast: Report of a large multi-institutional series and review of the literature.

BACKGROUND: Pleomorphic and Florid Lobular carcinoma in situ (P/F LCIS) are rare variants of LCIS, the exact nature of which is still debated. AIM: To collect a large series of P/F LCIS diagnosed on preoperative biopsies and evaluate their association with invasive carcinoma and high grade duct carcinoma in situ (DCIS). Data obtained were compared with those reported in the literature. METHODS: A multi-institutional series of P/F LCIS was retrieved. All cases were diagnosed on pre-operative biopsies, which was followed by an open surgical excision. Data on post-operative histopathology were available. A literature review was performed. RESULTS: A total of 117 cases were collected; invasive carcinoma and/or DCIS was present in 78/117 cases (66.7%). Seventy cases of P/F LCIS were pure on biopsy and 31 of these showed pathological upgrade in post-surgical specimens. Pre-operative biopsy accuracy was 47/78 (60.3%); pre-operative biopsy underestimation of cancer was 31/78 (39,7.%). In the literature review papers, invasive carcinoma or DCIS was associated with 274 of 418 (65.5%) cases of P/F LCIS. Pre-operative biopsy accuracy was 66% (181/274) whereas pre-operative biopsy underestimation of cancer was 33.9% (93/274). CONCLUSIONS: The data presented here indicate that P/F LCIS is frequently associated with invasive carcinoma or high grade DCIS and that pre-operative biopsy is associated with an underestimation of malignancy. Open surgery is indicated when P/F LCIS is diagnosed pre-operatively.

Anti-metastatic effect of ranolazine in an in vivo rat model of prostate cancer, and expression of voltage-gated sodium channel protein in human prostate.

BACKGROUND: Voltage-gated Na+ channels (VGSCs) are functionally upregulated in rat and human prostate cancer (PCa) where channel activity promotes cellular invasiveness in vitro and metastasis in vivo. Ranolazine is a clinically used VGSC inhibitor/anti-anginal drug, which has been shown previously to inhibit breast cancer metastasis in vivo. METHODS: Using the Dunning model of rat PCa, the effect of ranolazine applied systemically (by gavage) was tested on the development of primary tumours and metastases following subcutaneous inoculation of Mat-LyLu cells into Copenhagen rats. In addition, human prostate tissue microarrays were used to determine VGSC protein expression in cancerous versus non-cancerous tissue. Several public databases were searched to compare Nav1.7/ SCN9A expression levels in 'normal' vs. PCa tissues. RESULTS: Ranolazine (2.5 and 5 µM) decreased the number of lung metastases by up to 63%. In contrast, primary tumourigenesis was not affected. Ranolazine also reduced the percentage of cells in the metastases expressing Nav1.7, the main VGSC subtype expressed in PCa, but the expression level was higher. In prostate tissue microarrays, VGSC protein expression was significantly higher in cancerous versus non-cancerous tissue. There was no correlation between the VGSC expression and either prostate-specific antigen or Gleason score. In public databases, little information could be found on Nav1.7 protein expression in PCa. In addition, the database information on Nav1.7 mRNA (SCN9A) expression levels did not correlate with previously reported upregulation in PCa cells and tissues. CONCLUSIONS: The main conclusions were (i) ranolazine inhibited metastasis and (ii) it was a subpopulation of cells with particularly high levels of Nav1.7 protein that reached the metastatic sites. These data extend earlier studies and suggest that Nav1.7 expression could serve as a functional biomarker of metastatic PCa and that VGSC blockers may be useful as anti-metastatic agents.

BRAFV600E Immunohistochemistry in Papillary Thyroid Carcinomas: Relationship Between Clinical and Morphological Parameters.

OBJECTIVE: To investigate the association of the BRAFV600E mutation with papillary thyroid carcinoma using clinical, morphological and prognostic parameters. We also intend to assess the utility of the BRAFV600E immunohistochemistry and compare it with BRAF polymerase chain reaction (RT-PCR). MATERIAL AND METHOD: We applied BRAFV600E immunohistochemistry in a cohort of 107 papillary carcinomas, 19 adenomas and 13 normal thyroid tissues that was chosen retrospectively between 2011 and 2015. Statistical analysis was based on semiquantitative immunohistochemistry findings. We also applied BRAF RT-PCR in a subgroup of 14 papillary carcinomas, 13 metastatic lymph nodes and 4 adenomas that was chosen randomly. RESULTS: In regard to the comparison of BRAFV600E immunohistochemistry and BRAF RT-PCR, a 3+ nuclear and cytoplasmic immunoexpression was considered 'positive'. The BRAFV600E mutation was most frequently observed in classic variant cases. No mutation was detected in follicular variant cases. The mutational status of the primary tumour and the lymph node metastasis was consistent. A significant relationship of the BRAFV600E mutation was found with prognostic factors such as higher pT stage, classic variant, lymphatic invasion, perineural invasion, lower mitotic index, lack of tumour capsule, intrathyroidal spread and extrathyroidal extension. CONCLUSION: Immunohistochemistry, using the VE1 clone, is a reliable technique for detection of the BRAFV600E mutation. Our results with immunohistochemistry are consistent with a previous effort. In our study, despite the correlation between some pathological prognostic parameters and the BRAFV600E mutation; poor prognosis was found to be irrelevant overall. Morphological parameters seem to be keener than the BRAFV600E mutation. Nevertheless, different series display different results, possibly due to environmental factors. Considering this and the proven success of targeted therapies against the BRAFV600E mutation a thorough assessment would be important.

A case of primary squamous cell carcinoma of the breast with pathologic complete response after neoadjuvant chemotherapy.

BACKGROUND: Primary squamous cell carcinoma (SCC) of the breast is a metaplastic carcinoma subtype which includes fibromatosis-like and sarcomatoid features. This is a very aggressive tumor with poor prognosis. Other sites of primary SCC should be ruled out first to classify these tumors as primary SCC of the breast. Here we present a case of locally advanced primary SCC of the breast. CASE REPORT: A 72 years old woman presented with a right axillary lump. Trucut biopsy was performed, it showed squamous cell carcinoma. Estrogen receptor had poor immunoreactivity, negative for both progesteron receptor and HER 2 in immunohistochemistry staining. PETCT imaging were conducted to showing only 6 × 6.5 cm mass in right breast adjacent to axilla, multiple lymphadenomegaly in right axillary. We planned neoadjuvant chemotherapy consisting of weekly paclitaxel followed by epirubicin and cyclophosphamide combination. Postoperative pathology revealed wide necrosis, no viable tumor cell. We started adjuvant anastrozole treatment of 1 mg/day. No evidence of disease was detected after 1 year follow up. CONCLUSION: Primary squamous cell carcinoma of the breast is a very rare disease with no standard treatment approach. Our case achieved pathologic complete response after neoadjuvant chemotherapy.

Is Regression after Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer Different in Sentinel and Non-sentinel Nodes?

Tumor draining sentinel lymph nodes (SLNs) are the sites of selective changes as compared to non-SLNs. They show features of tumor-reactive lymphadenopathy, including increased total number of functional blood vessels, but a relative immunosuppressed status has also been described in them. We explored the hypothesis of a selective regression or non-regression in SLNs versus non-SLNs in 142 patients with 110 estrogen receptor-positive and 32 estrogen receptor-negative tumors undergoing both SLN biopsy and axillary lymph node dissection after neoadjuvant therapy by assessing the tumoral (metastatic) and regression statuses of SLNs and non-SLNs separately. Of the 89 cases with signs of nodal regression, 22 cases (25%) were in favor of a selective non-regression in SLNs, 18 cases (20%) were supportive of a selective and more pronounced regression in the SLNs and the remaining showed equal degrees of regression or non-regression in SLNs and non-SLNs. The results indicate that there is no obvious difference in the degree of regressive histological changes shown by SLNs and NSLNs. Therefore, this phenomenon may not be a major contributor to the higher false negative rate of SLN biopsy after neoadjuvant treatment.

Changes in 18F-FDG-PET/CT tumor metabolism are not consistent with pathologic complete response in hormone-positive breast cancer.

PURPOSE: Current evaluation of response to neoadjuvant chemotherapy (NAC) shows that it could achieve pathological complete response (pCR). The purpose of this study was to assess the consistency of maximum uptake values (SUVmax) changes and pCR in hormone-positive locally advanced breast cancer (LABC). METHODS: Ninety hormone-positive LABC patients treated at Marmara University Medical Oncology Clinic, Istanbul, Turkey, between 2009 and 2015 were retrospectively studied. All eligible patients (n=5) received NAC (4-8 cycles) and were evaluated for pCR. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG- PET/CT) scan was performed before and after the completion of NAC. The relative changes of SUVmax both in the primary tumor and the axilla were assessed for consistency with pCR. RESULTS: The patient median age was 46 years (range 26- 76). The patients 13.7% achieved pCR. Values of >50% (n=40) and <50% (n=11) SUVmax changes were not associated with pCR (15% and 18% respectively) (p=1.00). Patients with >75% SUVmax changes could achieve pCR of 20%. Interestingly, most patients with complete metabolic response did not achieve pCR (81%). The difference of the Ki67 levels before and after NAC, tumor localization, HER- 2 positivity, menopausal status, grade of differentiation, lymphovascular and perineural invasion were not associated with pCR. CONCLUSION: SUVmax changes in later cycles of NAC as commonly practised in oncology clinics were not consistent with pCR (p=1.0). Complete metabolic response may not be associated with pCR in hormone-positive LABC. However, almost 80% of patients had >50% decrease in SUVmax and may still have a chance for conservative surgery and less postoperative morbidity. Therefore, 18F-FDG-PET/CT may still have a role to evaluate the tumor response with a need of larger studies and analysis for cost-effectiveness.

Neonatal Nav1.5 protein expression in normal adult human tissues and breast cancer.

Expression of the neonatal splice variant of the voltage-gated sodium channel α-subunit (VGSC) subtype Nav1.5 (nNav1.5), encoded by the gene SCN5A, was shown earlier to be upregulated in human breast cancer (BCa), both in vitro and in vivo. Channel activity promoted BCa invasion of Matrigel®in vitro and metastasis in vivo. Consequently, expression of nNav1.5 has been proposed as a functional biomarker of BCa cells with metastatic potential. Here, we have determined immunohistochemically both nNav1.5 and total VGSC (tVGSC) protein expression in a range of adult human tissues. Some VGSC protein was expressed in normal colon, small intestine, stomach, prostate, bladder and breast. As expected, high levels of VGSC protein were expressed in brain, skeletal muscle and cardiac muscle. On the other hand, nNav1.5 protein was not expressed in any of the normal tissues tested except breast where a low-level of protein was present. In comparison to normal breast, nNav1.5 protein expression in BCa was consistently widespread and occurred at a significantly higher level. We also questioned whether there was any relationship between the nNav1.5 protein expression and the estrogen receptor (ERα) status of BCa and obtained the following results. First, all cases lacking nNav1.5 were positive for ERα. Second, in all ERα-negative tissues, nNav1.5 protein was expressed in plasma membrane. Third, however, in ERα-positive cases, nNav1.5 protein expression was observed in both plasma membrane and cytoplasm. In conclusion, nNav1.5 protein has a restricted expression pattern among human tissues. High level expression occurs in BCa and associates with ERα status. These results further support the proposition that nNav1.5 is a novel biomarker of metastatic BCa.

Volume Navigation Technique for Ultrasound-Guided Biopsy of Breast Lesions Detected Only at MRI.

OBJECTIVE: The purpose of this study is to assess the utility of a volume navigation technique (VNT) for ultrasound-guided biopsy of MRI-detected, but sonographically ambiguous or occult, breast lesions. SUBJECTS AND METHODS: Within a recruitment period of 13 months (January 1, 2014, through February 1, 2015), 22 patients with 26 BI-RADS category 4 or 5 lesions that were detected at MRI but missed at second-look ultrasound were reimaged using a rapid sequence and a flexible body coil in a 3-T MRI scanner. Patients were supine, with three skin markers placed on the breasts. MRI volume data were coregistered to real-time ultrasound in a dedicated platform, and MRI-detected lesions (six masses, 11 nonmass enhancements, eight foci, and one architectural distortion) were sought using VNT-guided ultrasound. Five needle biopsy specimens were obtained either from each sonographically detected lesion (n = 11) or from VNT-guided sonographically localized breast volume corresponding to the MRI-detected, but still ultrasound-occult, lesions (n = 15). RESULTS: Histopathologic analysis revealed 18 benign and six malignant lesions. The remaining two lesions, both of which appeared as masses at MRI, were high risk and were upgraded to carcinoma after excisional biopsy. All malignant lesions underwent curative surgery; the final histopathologic diagnoses remained unchanged. Of the six malignant lesions, one was a mass, three were nonmass enhancements, and two were enhancing foci at MRI. Three malignant lesions were occult at ultrasound, and three were discerned as subtle hypoechoic changes. No benign lesion was sonographically visualized as a mass, and none progressed, with 56% disappearing at MRI performed during the follow-up period (mean, 14 months). CONCLUSION: Coregistration of MRI and real-time ultrasound enables sonographic localization of breast lesions detected at MRI only. VNT is a feasible alternative to MRI-guided biopsy of ultrasound-occult breast lesions.

Ultrasound Guided Therapeutic Excisional Vacuum Assisted Biopsy in Breast Fibroadenomas.

OBJECTIVE: The aim of this study was to evaluate the performance of ultrasound (US) guided Vacuum Assisted Biopsy (VAB) in the therapeutic excision of breast fibroadenomas. MATERIALS AND METHODS: Patients who underwent excisional US guided VAB of their fibroadenomas between December 1999-May 2001 were retrospectively evaluated. Seventy-eight patients with BI-RADS category 3 and 4a lesions (one lesion per patient) with a maximum diameter smaller than 3 cm were enrolled in the study. Fifty-one of those were diagnosed with fibroadenoma. Biopsies were performed with a 11G needle using the Mammotome (Johnson & Johnson, New Jersey, USA) vacuum biopsy device. Patients were followed up with US for three years. Follow-ups were done semiannually in the first year and annually afterwards. RESULTS: Ten patients (19%) were found to have residual lesions in the first week after the biopsy. Additional eight patients (15%) were found to have residual-recurrent lesions in their annual follow up. However, none of these eight lesions demonstrated growth during the three year follow-up. The initial size of the FA was not found to be significantly different between the lesions which were completely excised with no residue or recurrence and those which were not (p>0.05). CONCLUSION: The VAB method for the therapeutic excision of small FAs or other benign lesions is practical and easily tolerated by patients. Lesions smaller than 3 cm should be preferred for VAB. A multidisciplinary clinical environment is necessary for each step of the treatment.

Concordance of immunohistochemistry between core needle biopsy and surgical resection of breast cancer

Background/aim: The purpose of this study was to evaluate the concordance of immunohistochemical (IHC) parameters of breast lesions between the core needle biopsy (CNB) and the surgical resection specimen. Materials and methods: CNB and resection specimens of female patients were retrospectively analyzed. ER, PR, HER-2, and Ki-67 parameters were compared for each patient. A total of 284 cases were assessed. Forty-one and 48 cases were excluded from the HER-2 and Ki-67 examinations, respectively, because the CNBs did not allow for IHC. Results: Concordance rates were 93.3% for ER, 89.4% for PR, 90.1% for HER-2, and 80.9% for Ki-67.Conclusion: CNB is accurate for the evaluation of the surrogate molecular profile of invasive breast cancer despite the heterogeneity of tumors.