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Aim: To determine if the outcomes of patients with ILC co-occurring with LCIS are similar to pure ILC and if the presence of LCIS is a prognostic factor for ILC., Methods: In an observational, population-based investigation using data from the MD Anderson breast cancer prospectively collected electronic database, we analysed patients with a diagnosis of stage I-III ILC. Patients were divided into two groups: those with ILC with co-occurring ipsilateral LCIS (ILC + LCIS) and those with pure ILC without a histologically detected co-occurring ipsilateral LCIS (ILC alone). We obtained data on demographics, pathologic tumour size (pT), pathologic lymph node (pN) involvement, estrogen (ER), progesterone (PR) receptor status, HER2 status, Ki67, treatment received, distant recurrence-free and overall survival (DRFS, OS)., Results: We identified 4217 patients with stage I-III ILC treated at MD Anderson between 1966 and 2021. 45% of cases (n = 1881) had co-existing LCIS. Statistically and numerically, ILC alone tended to associate with pT4 and pN3 stage (P < 0.001), ER/PR negativity (P = 0.0002), HER2 positivity (P = 0.010), higher Ki67 (P = 0.005), non-classical ILC subtype (P = 0.04) and more exposure to neoadjuvant chemotherapy (P = 0.0002) compared to the ILC + LCIS group. The median follow-up time was 6.5 years. Patients with ILC + LCIS had better median DRFS (16.8 versus 10.1 years, Hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.50-0.60, P < 0.0001) and better median OS (18.9 versus 13.7 years, HR 0.62, 95% CI 0.56-0.69; P < 0.0001). Multivariate analysis showed the absence of LCIS to be an independent poor prognostic factor along with a higher pT stage and higher pN stage for DRFS and OS., Conclusion: The findings of this study suggests that the absence of ipsilateral LCIS with ILC is an independent poor prognostic factor and that further studies are warranted to understand this phenomenon., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jason A. Mouabbi: Consulting fees from GE Healthcare, Genentech, BostonGene, and Cardinal Health. Gabriel Hortobagyi: Consultant to AstraZeneca, Blueprint Medicines, Novartis and Seagen. Amy Hassan: Consulting fees for AIM Specialty Health, Oncology Pathways Program. Debasish Tripathy: Research support from Novartis and Pfizer. Consulting fees from Novartis, Pfizer, and AstraZeneca. Rachel M. Layman: Research support from Pfizer, Eli Lilly, Novartis, Pfizer, Puma, Zentalis, and Celcuity. Consulting fees from Pfizer, Eli Lilly, Novartis, and Celcuity. The following authors: Akshara Singareeka Raghavendra, Roland L. Bassett, Jr, Matthias Christgen, Azadeh Nasrazadani, Lavinia Middleton, Mediget Teshome have no conflict of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Importance: Approximately 45% to 60% of hormone receptor (HR)-positive metastatic breast cancer (mBC) shows a low-level expression of ERBB2. Low ERBB2 expression is defined as ERBB2 immunohistochemical expression of 1+ or 2+ with a negative ERBB2 amplification by in situ hybridization. The efficacy of the antibody-drug conjugate trastuzumab deruxtecan in low-ERBB2, HR-positive mBC has been practice changing. However, there are conflicting data on the prognostic value of low ERBB2 expression in HR-positive mBC and whether low ERBB2 expression is a separate entity., Objective: To examine whether outcomes differ by immunohistochemical analysis for patients with HR-positive mBC with low ERBB2 expression vs those without ERBB2 expression when treated with targeted therapy (TT) plus endocrine therapy (ET)., Design, Setting, and Participants: This single-institution cohort study used prospectively collected electronic data from the MD Anderson Cancer Center for patients with a diagnosis of HR-positive mBC treated with ET in combination with a TT (cyclin-dependent kinase 4/6 inhibitors [CDK4/6is], everolimus, or alpelisib) between January 1, 2010, and December 31, 2021., Exposure: HR-positive mBC with either low or no ERBB2 expression., Main Outcome and Measures: The main outcomes were median progression-free survival and overall survival. Data on demographic characteristics, estrogen and progesterone receptor status, ERBB2 status, histologic subtype, menopausal status, treatment duration, and survival status were collected., Results: A total of 1585 women (median [range] age, 51 [24-92] years) were included in the study. Of these women, 1013 (63.9%) had mBC with low ERBB2 expression and 572 (36.1%) had mBC with no ERBB2 expression. A total of 1084 (68.4%) were treated with a CDK4/6i (912 patients were treated in the first line and 172 were treated in the second line); 475 (30.0%) received everolimus and 26 (1.6%) received alpelisib. In the patients who received a first-line CDK4/6i, 618 (67.8%) received an aromatase inhibitor as their ET backbone and 265 (29.1%) received fulvestrant. With a median follow-up time of 17.9 months (range, 1-111 months), progression-free survival and overall survival were not statistically different between the patients with low and no ERBB2 expression treated with TT plus ET., Conclusions and Relevance: In this cohort study of patients with HR-positive mBC treated with TT plus ET, low ERBB2 expression did not have a significant association with prognosis.

Objective: Historically, wire localization was the most widely utilized procedure for preoperative breast lesion localization. Occasionally a portion of the wire is retained in the breast. When recognized intraoperatively, the fragment can be removed immediately, but some cases are identified during post-surgical mammographic follow-up. There is little research detailing long-term stability of retained wire fragments, associated complications, or management options for cases requiring removal. We aimed to determine how often retained wire fragments remained stable, the frequency with which intervention was required, and methods available for fragment removal., Methods: Following IRB approval, we conducted a retrospective review of patients with a retained wire localization fragment identified by EMR search seen at our institution between January 1990 and July 2019. Mammograms, localization images, specimen radiographs, and relevant clinical notes were reviewed. Information collected included breast tissue density, patient age, associated pathology, length of time the fragment was retained, presence and/or absence of fragment migration or other complications, and management of removed fragments., Results: Eighteen eligible patients were identified with 19 retained wire fragments. Fragments ranged in length from 1 mm -33 mm. Twelve wire fragments had mammograms available to evaluate stability. All twelve fragments were stable mammographically for an average of 96.9 months. Seven wire fragments had no follow-up mammograms available. Eight wire fragments were surgically excised. None were excised due to migration., Conclusion: Localization wire fragments retained in the breast are at low risk for clinically significant migration and can be safely followed mammographically rather than undergoing immediate surgical excision or imaging-guided percutaneous removal., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Increased levels of stromal tumor-infiltrating lymphocytes (sTILs) have recently been considered a favorable independent prognostic and predictive biomarker in triple-negative breast cancer (TNBC). The purpose of this study was to determine the relationship between BI-RADS (Breast Imaging Reporting and Data System) ultrasound lexicon descriptors and sTILs in TNBC., Materials and Methods: Patients with stage I-III TNBC were evaluated within a single-institution neoadjuvant clinical trial. Two fellowship-trained breast radiologists used the BI-RADS ultrasound lexicon to assess pretreatment tumor shape, margin, echo pattern, orientation, posterior features, and vascularity. sTILs were defined as low <20 or high ≥20 on the pretreatment biopsy. Fisher's exact tests were used to assess the association between lexicon descriptors and sTIL levels., Results: The 284 patients (mean age 52 years, range 24-79 years) were comprised of 68% (193/284) with low-sTIL tumors and 32% (91/284) with high-sTIL tumors. TNBC tumors with high sTILs were more likely to have the following features: (1) oval/round shape than irregular shape (p = 0.003), (2) circumscribed or microlobulated margins than spiculated, indistinct, or angular margins (p = 0.0005); (3) complex cystic and solid pattern than heterogeneous pattern (p = 0.006); and (4) posterior enhancement than shadowing (p = 0.002). There was no significant association between sTILs and descriptors for orientation and vascularity (p = 0.06 and p = 0.49, respectively)., Conclusion: BI-RADS ultrasound descriptors of the pretreatment appearance of a TNBC tumor can be useful in discriminating between tumors with low and high sTIL levels. Therefore, there is a potential use of ultrasound tumor characteristics to complement sTILs when used as stratification factors in treatment algorithms for TNBC., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Human epidermal growth factor receptor 2 (HER2)-positive classic invasive lobular carcinoma (ILC) is a rare entity, and its specific pathological characteristics and clinical behavior are unclear. Therefore, we retrospectively investigated the clinicopathological features of HER2-positive classic ILC and described HER2-targeted neoadjuvant chemotherapy outcome. Fourteen HER2-positive classic ILC cases were identified, their clinicopathological data were collected, and their clinical management was investigated. In general, HER2 positivity is associated with higher grade carcinoma in ductal lesions; however, our 14 cases had typical morphologic features of classic ILC. We did not identify unique morphologic features in HER2-positive classic ILC with the clinicopathological parameters examined, including age, menopausal status, histological grade, and hormone receptor status. Four of six patients who received HER2-targeted neoadjuvant chemotherapy had a pathological complete or partial response. Based on our findings, clinicopathological features of classic ILC may not predict HER2 overexpression or amplification. HER2-targeted neoadjuvant chemotherapy was effective against some HER2-positive classic ILCs. Taken together, these results demonstrate that HER2 immunohistochemistry and fluorescence in situ hybridization should be considered for all ILC patients regardless of subtype., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: HER2 overexpression and gene amplification are routinely tested by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. In addition, HER2 mRNA expression is also tested by the Oncotype DX assay. Discordance between laboratories among the different assays remains a problem. To improve the routine HER2 reporting, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) updated their guidelines in 2018. Our study will compare concordance of HER2 status by IHC and FISH using ASCO/CAP 2013 and 2018 guidelines with Oncotype DX., Methods: We retrospectively reviewed 657 estrogen receptor positive primary breast cancer cases with available Oncotype DX tests between 2011 and 2018. Medical records were reviewed for HER2 results by IHC, FISH, and Oncotype DX. The HER2 results by different assays and between 2013 and 2018 guidelines were compared., Results: Of the 657 cases, 280 were tested by IHC, FISH, and Oncotype DX. HER2-equivocal cases by IHC 2013 guidelines were all negative (67/67, 100%) by FISH 2018 guidelines and by Oncotype DX. HER2-equivocal cases by FISH 2013 guidelines were all negative (16/16, 100%) by FISH 2018 guidelines, while 15/16 (93.8%) negative and 1/16 (6.2%) equivocal by Oncotype DX. The HER2-equivocal and HER2-negative groups were similar in age, gender, histology, grade, and Ki67 score., Conclusions: HER2 concordance was highest between Oncotype DX (99.6%) and FISH per 2018 guidelines. This suggests that the ASCO/CAP 2018 guidelines improved the accurate stratification of HER2-equivocal cases.

Pseudoangiomatous stromal hyperplasia (PASH), a rare, noncancerous lesion, is often an incidental finding on magnetic resonance imaging (MRI)-guided biopsy analysis of other breast lesions. We sought to describe the characteristics of PASH on MRI and identify the extent to which these characteristics are correlated with the amount of PASH in the pathology specimens. We identified 69 patients who underwent MRI-guided biopsies yielding a final pathological diagnosis of PASH between 2008 and 2015. We analyzed pre-biopsy MRI scans to document the appearance of the lesions of interest. All biopsy samples were classified as having ≤50% PASH or ≥51% PASH present on the pathological specimen. On MRI, 9 lesions (13%) appeared as foci, 19 (28%) appeared as masses with either washout or persistent kinetics, and 41 (59%) appeared as regions of nonmass enhancement. Of this latter group, 33 lesions (80%) showed persistent kinetic features. Masses, foci, and regions of nonmass enhancement did not significantly correlate with the percentage of PASH present in the biopsy specimens (P ≥ .05). Our findings suggest that PASH has a wide-ranging appearance on MRI but most commonly appears as a region of nonmass enhancement with persistent kinetic features. Our finding that most specimens had ≤50% PASH supports the notion that PASH is usually an incidental finding. We did not identify a definitive imaging characteristic that reliably identifies PASH., (© 2021 Wiley Periodicals LLC.)

Abstract: The objective of this study was to describe the diagnostic value of positron emission tomography/computed tomography (PET/CT) and ultrasound (US) for identifying metastatic axillary disease in primary breast cancer. This is a retrospective review of 240 patients with treatment-naive unilateral primary breast cancer of at least stage T2. Eighty-five patients met our inclusion criteria. Initial whole-body PET/CT and axillary US examinations were reviewed and compared with the criterion standard of fine-needle aspiration cytology. Sensitivity, accuracy, and positive predictive value (PPV) for each modality were computed. Because of all positive US cases, specificity and negative predictive value of US were not determined. Sensitivity and accuracy between modalities were compared using McNemar test. The majority of the patients were White women with clinical inflammatory breast cancer and with histologically invasive ductal carcinoma. The most common tumor and nodal stage was T4N3. The tumors were predominantly estrogen receptor positive, progesterone receptor negative, and human epidermal growth factor receptor 2 negative. The sensitivities of PET/CT and US were 96.2% and 100%, respectively. The accuracies for PET/CT and US were 91.8% and 94.1%, respectively. The PPV for PET/CT was 95.1%, and for US, the PPV was 94.1%. No significant difference in sensitivity or accuracy was shown between PET/CT and US for the diagnosis of metastatic axillary nodal disease. Three of 85 cases showed discordance between negative PET/CT and positive US and fine-needle aspiration cytology., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The primary objective was to determine whether mid-treatment ultrasound measurements of index breast tumors and index axillary nodes of different cancer subtypes associate with residual cancer burden (RCB)., Methods: Patients with invasive breast cancer who underwent neoadjuvant chemotherapy and had pre-treatment and mid-treatment breast and axillary ultrasound were included in this single-institution, retrospective cohort study. Linear regression analysis assessed associations between RCB with (a) change in index breast tumor size, (b) change in index node size, and (c) absolute number of abnormal nodes at mid-treatment. Multivariate linear regression was used to calculate best-fit models for RCB., Results: One hundred fifty-nine patients (68 triple negative breast cancer [TNBC], 45 hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]-, and 46 HR-/HER2+) were included. Median age at diagnosis was 50 years, range 30-76. Median tumor size was 3.4 cm, range 0.9-10.4. Pathological complete response/RCB-I rates were 36.8% (25/68) for TNBC patients, 24.4% (11/45) for HR+/HER2- patients, and 71.7% (33/46) for HR-/HER2+ patients. Linear regression analyses demonstrated associations between percent change in tumor ultrasound measurements at mid-treatment with RCB index score in TNBC and HR+/HER2- ( p  < .05) but not in HR-/HER2+ ( p  > .05) tumors and an association between axillary ultrasound assessment of number of abnormal nodes at mid-treatment with RCB index score across all subtypes ( p  < .05)., Conclusion: Performance characteristics of breast ultrasound associated with RCB vary by cancer subtype, whereas the performance characteristics of axillary ultrasound associated with RCB are consistent across cancer subtype. Breast and axillary ultrasound may be valuable in monitoring response to neoadjuvant therapy. The Oncologist 2017;22:394-401 IMPLICATIONS FOR PRACTICE: The differential performance characteristics of breast ultrasound by molecular subtype and the consistent performance characteristics of axillary ultrasound across molecular subtypes can have clinical utility in monitoring response to neoadjuvant therapy., (© AlphaMed Press 2017.)

Purpose: Early-stage breast cancer patients with minimal axillary disease identified by sentinel lymph node dissection (SLND) have low regional recurrence rates when treated with breast-conserving surgery and radiation therapy (XRT) and many avoid a completion axillary lymph node dissection (CLND). As the incidence of total mastectomy (TM) has increased, it has become important to characterize which TM patients with a positive SLN may not benefit from further axillary treatment., Methods: An institutional database was utilized to identify patients treated with a TM for invasive breast cancer and who had a positive SLN from 1994 to 2010. Clinicopathologic factors were analyzed. Regional recurrence rate, recurrence-free survival (RFS), and overall survival (OS) were determined., Results: A total of 525 patients with invasive breast cancer and a positive SLN were treated with TM, including 58 patients who did not have CLND or XRT and 12 patients who did not have CLND but did receive XRT. Median follow-up was 66 months. The incidence of regional recurrence was not significantly different for patients who received no further axillary treatment compared to those who underwent CLND without XRT or those treated with XRT without CLND (10 years rate: 3.8 vs. 1.6 and 0 % respectively). RFS and OS were not significantly different among patients who received no further axillary treatment compared to those who underwent CLND, XRT, or both., Conclusions: In select patients with early-stage breast cancer treated with mastectomy with a positive SLN, CLND may be avoided without adversely affecting recurrence or survival.

Background: Many patients with clinically node-positive breast cancer receive neoadjuvant chemotherapy (NAC). Recent trials suggest the potential for limiting axillary surgery in patients who convert to pathologically node-negative disease. The authors developed a nomogram to predict axillary response to NAC in patients with cN1 disease that can assist clinicians in treatment planning., Methods: Patients with cT1-4N1M0 breast cancer who received NAC and underwent axillary lymph node dissection from 2001 through 2013 were identified (n = 584). Uni- and multivariate logistic regression analyses were performed to determine factors predictive of nodal conversion. A nomogram to predict the likelihood of nodal pathologic complete response (pCR) was constructed based on clinicopathologic variables and validated using an external dataset., Results: Axillary pCR was achieved for 217 patients (37 %). Patients presenting with high nuclear grade [grade 3 vs. 1, odds ratio (OR) 13.4], human epidermal growth factor receptor 2-positive (OR 4.7), estrogen receptor (ER)-negative (OR 3.5), or progesterone receptor-negative (OR 4.3) tumors were more likely to achieve nodal pCR. These factors, together with clinically relevant factors including presence of multifocal/centric disease, clinical T stage, and extent of nodal disease seen on regional nodal ultrasound at diagnosis were used to create nomograms predicting nodal conversion. The discrimination of the nomogram using ER+ status (>1 % staining) versus ER- status [area under the curve (AUC) 78 %] was improved slightly using the percentage of ER staining (AUC 78.7 %). Both nomograms were validated using an external cohort., Conclusion: Nomograms incorporating routine clinicopathologic parameters can predict axillary pCR in node-positive patients receiving NAC and may help to inform treatment decisions.

Background: Oncoplastic reconstruction is an approach that enables patients with locally advanced or adversely located tumors to undergo breast conserving surgery (BCS). The objectives were to identify the use of BCS with oncoplastic reconstruction (BCS + R) and determine the operative and oncologic outcomes compared with other breast surgical procedures for breast cancer., Methods: This retrospective cohort study interrogated a single institution's prospectively maintained databases to identify patients who underwent surgery for breast cancer between 2007 and 2014. Surgeries were categorized as BCS, BCS + R, total mastectomy (TM), or TM with immediate reconstruction (TM + R). Demographic and clinicopathologic characteristics and postoperative complications were analyzed., Results: There were 10,607 operations performed for 9861 patients. Median follow-up was 3.4 years (range, 0-9.1 years). The use of BCS + R had a nearly fourfold increase in the percentage of all breast cancer surgeries during the study period; 75 % of patients who underwent BCS + R had a T1 or T2 tumor. There was no difference in the use of BCS + R compared with BCS for any quadrant of the breast except the lower outer quadrant (11.1 vs. 6.8 %; p < .0001). BCS + R had a lower rate of seroma formation (13.4 vs. 18 %; p = .002) and positive or close margins compared with BCS (5.8 vs. 8.3 %; p = .04). There was no difference in overall survival or recurrence-free survival when comparing BCS and BCS + R., Conclusions: Patients undergoing BCS + R are not disadvantaged in terms of complications and short-term (3-year) outcomes compared with BCS patients or patients who underwent TM.

Objective: The purpose of this study was to determine the diagnostic value of strain elastography (SE) alone and in combination with gray-scale ultrasound in the diagnosis of benign versus metastatic disease for abnormal axillary lymph nodes in breast cancer patients., Subjects and Methods: Patients with breast cancer and axillary lymph nodes suspicious for metastatic disease on conventional ultrasound who underwent SE of the suspicious node before ultrasound-guided fine-needle aspiration biopsy (FNAB) were included in this study. On conventional ultrasound, the long- and short-axis diameters, long-axis-to-short-axis ratio, cortical echogenicity, thickness, and evenness were documented. The nodal vascularity was assessed on power Doppler imaging. Elastograms were evaluated for the percentage of black (hard) areas in the lymph node, and the SE-ultrasound size ratio was calculated. Two readers assessed the images independently and then in consensus in cases of disagreement. ROC AUCs were calculated for conventional ultrasound, SE, and both methods combined. Interreader reliability was assessed using kappa statistics., Results: A total of 101 patients with 104 nodes were examined; 35 nodes were benign, and 69 had metastases. SE alone showed a significantly lower AUC (62%) than did conventional ultrasound (92%) (p<0.001). There was no difference between the AUC of conventional ultrasound and the AUC of the combination of conventional ultrasound and SE (93%) (p=0.16). Interreader reliability was moderate for all variables (κ≥0.60) except the SE-ultrasound size ratio (κ=0.35)., Conclusion: Added SE does not improve the diagnostic ability of conventional ultrasound when evaluating abnormal axillary lymph nodes.

Purpose: Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown., Patients and Methods: We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up., Results: The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively)., Conclusion: Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants.

Background: The management of benign papilloma (BP) without atypia identified on breast core needle biopsy (CNB) is controversial. In this study, we determined the upgrade rate to malignancy for BPs without atypia diagnosed on CNB and whether there are factors associated with upgrade., Methods: Through our pathology database search, we studied 80 BPs without atypia identified on CNB from 80 patients from 1997 to 2010, including 30 lesions that had undergone excision and 50 lesions that had undergone ≥ 2 years of radiologic follow-up. Associations between surgery or upgrade to malignancy and clinical, radiologic, and pathologic features were analyzed., Results: Mass lesions, lesions sampled by ultrasound-guided CNB, and palpable lesions were associated with surgical excision. All 3 upgraded cases were mass lesions sampled by ultrasound-guided CNB. None of the lesions with radiologic follow-up only were upgraded to malignancy. The overall upgrade rate was 3.8%. None of the clinical, radiologic, or histologic features were predictive of upgrade., Conclusion: Because the majority of patients can be safely managed with radiologic surveillance, a selective approach for surgical excision is recommended. Our proposed criteria for excision include pathologic/radiologic discordance or sampling by ultrasound-guided CNB without vacuum assistance when the patient is symptomatic or lesion size is ≥ 1.5 cm., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Context: Whole slide imaging (WSI) is now used for educational purposes, for consultation, and for archiving and quantitation of immunostains. However, it is not routinely used for the primary diagnosis of hematoxylin-eosin-stained tissue sections., Objective: To compare WSI using the Aperio digital pathology system (Aperio Technologies, Inc, Vista, California) with optical microscopy (OM) for the interpretation of hematoxylin-eosin-stained tissue sections of breast lesions., Design: The study was conducted at 3 clinical sites; 3 breast pathologists interpreted 150 hematoxylin-eosin-stained slides at each site, 3 times each by WSI and 3 times each by OM. For WSI, slides were scanned using an Aperio ScanScope and interpreted on a computer monitor using Aperio ImageScope software and Aperio Spectrum data management software. Pathologic interpretations were recorded using the College of American Pathologists breast checklist. WSI diagnoses were compared with OM diagnoses for accuracy, precision (interpathologist variation), and reproducibility (intrapathologist variation). Results were considered accurate only if the interpretation matched exactly between WSI and OM. The proportion of accurate results reported by each pathologist was expressed as a percentage for the comparison of the 2 platforms., Results: The accuracy of WSI for classifying lesions as not carcinoma or as noninvasive (ductal or lobular) or invasive (ductal, lobular, or other) carcinoma was 90.5%. The accuracy of OM was 92.1%. The precision and reproducibility of WSI and OM were determined on the basis of pairwise comparisons (3 comparisons for each slide, resulting in 36 possible comparisons). The overall precision of WSI was 90.5% in comparison with 92.1% for OM; reproducibility of WSI was 91.6% in comparison with 94.5% for OM, respectively., Conclusions: In this study, we demonstrated that WSI and OM have similar accuracy, precision, and reproducibility for interpreting hematoxylin-eosin-stained breast tissue sections. Further clinical studies using routine surgical pathology specimens would be useful to confirm these findings and facilitate the incorporation of WSI into diagnostic practice.

Purpose: The purpose of the study was to evaluate the conspicuity of bone metastases on each of the numerous sequences produced by fast Dixon-based multisequence whole-body (WB) magnetic resonance imaging (MRI) scanning in order to determine the most clinically useful sequences overall and per anatomic region., Materials and Methods: Twenty-seven breast cancer patients with bone metastases were prospectively studied with fast Dixon-based WB MRI including head/neck, chest, abdominal, pelvic, thigh, calf/feet and either cervical, thoracic and lumbar or cervical/thoracic and thoracic/lumbar regions. Sequences included coronal T2, axial T1 without and with intravenous gadolinium (+C), sagittal T1 spine+C, each associated fat-only (FO) and fat-saturated (FS) sequence, axial diffusion-weighted imaging (DWI) and short tau inversion recovery (STIR). Blinded reviewers evaluated lesion conspicuity, a surrogate of clinical utility, on a five-point scale per anatomic region. Sequences were compared using analysis of variance, differences were detected with Tukey's honestly significant difference test, and the four sequences with highest mean conspicuity were compared to the remainder overall and per anatomic region., Results: Overall, a significant lesion conspicuity difference was found (P<.0001), and lesion conspicuity was significantly higher on FS T1+C, FO T1+C, T1+C sagittal and FS T1+C axial sequences (P<.0001). Per-region results were the same in the head/neck. Other sequences overlapped with these and included the following: chest/abdomen - FO T2, DWI; pelvis - DWI, FO T2; thigh - FS T2, FO T2, FO T1+C; calf/feet - FS T2, DWI, FO T2, STIR., Conclusion: Overall, bone lesions were most conspicuous on FS T1+C sagittal, FO T1+C sagittal, T1+C sagittal and FS T1+C axial fast Dixon WB MRI sequences., (Copyright © 2013 Elsevier Inc. All rights reserved.)

BRCA testing of patients with breast cancer considered at high risk for having a germ-line BRCA mutation usually consists of comprehensive mutational analysis of both BRCA1 and BRCA2. A more cost-effective strategy of triaging patients for analysis of a single gene could be adopted if tissue-based predictors indicated a high risk specifically for either BRCA1 or BRCA2. To identify potentially useful tissue-based predictors of BRCA mutation status in breast cancer, we evaluated multiple histopathologic features of invasive breast carcinoma on archival tissue sections from 196 high-risk patients who had undergone BRCA testing, and we analyzed which individual or combination of features was most associated with BRCA mutations. Of the 196 patients with invasive breast carcinoma, there were 44 (22%) with a deleterious BRCA1 mutation and 27 (14%) with a deleterious BRCA2 mutation. For patients with available untreated surgical resection specimens for evaluation (n=172), estrogen receptor-positive phenotype was inversely associated with the presence of a BRCA1 mutation (odds ratio, 0.243; 95% confidence interval, 0.070-0.840; P=.025), and high mitotic activity (≥25 mitotic figures per 10 high-power fields) was directly associated with the presence of a BRCA1 mutation (odds ratio, 4.222; 95% confidence interval, 1.353-13.18; P=.013). The combination of estrogen receptor-negative phenotype and high mitotic rate had high specificity (99%; 95% confidence interval, 95%-100%) but low sensitivity (43%; 95% confidence interval, 26%-61%) for identifying a deleterious BRCA1 mutation. In patients with breast cancer at high risk for carrying a BRCA mutation, those with estrogen receptor-negative phenotype and high mitotic rate could be triaged specifically for BRCA1 testing instead of initially performing mutational analysis for both BRCA1 and BRCA2., (Copyright © 2012 Elsevier Inc. All rights reserved.)

While breast cancer mortality rate has seen a steady decline in the last few decades, advances in better treatment and diagnostic tools remain important as we come into the age of personalized therapy. In this report, we describe our studies of SGK3's role in breast cancer. SGK3 (also known as CISK) is a member of the AGC family of kinases. Our previous work indicates that SGK3 functions downstream of the PI 3-kinase cascade and shares molecular and biochemical similarities with Akt. Here, we show that SGK3 expression is linked to estrogen receptor (ER) both in breast caner cell lines and in primary tumor samples. Our analysis also indicated a positive correlation between SGK3 expression and tumor prognosis. Importantly, our immunochemistry analysis of human tumor samples established a clinical link between SGK3 expression and ER+ tumors. These findings implicate SGK3 as an additional component to a complex and heterogeneous disease, and point to the potential benefits of incorporating SGK3 into the process of breast cancer diagnosis and treatment.

The World Health Organization classification of tumors of the breast includes a rare variant of invasive ductal carcinoma termed pleomorphic carcinoma. This variant has marked nuclear pleomorphism (>6-fold variation in nuclear size by definition, but often>10-fold) and characteristically contains multinucleated tumor giant cells. Approximately one-third of the cases in the initial series contained a focal spindle cell metaplastic component. The tumors are reported to have an aggressive behavior, but because some contain a spindle cell metaplastic component, it is unclear whether the metaplastic component or other clinicopathologic features account for the poor clinical outcome. We identified 37 cases of pleomorphic carcinoma of the breast and evaluated the association between clinical outcome and multiple clinicopathologic features. Patients with invasive pleomorphic lobular carcinoma and those without at least a tissue biopsy before chemotherapy were excluded. Patients ranged in age from 23 to 78 years (median, 49 y). Tumor size was >5 cm in 12 cases and <5 cm in 22. A focal spindle cell component (<25% of the tumor) was present in 14 tumors (38%). Clinical follow-up was available for 36 patients (median, 17 mo). In multivariate analysis, when the 2 stage-IV patients were excluded, the presence of a spindle cell component and tumor size >5 cm were each independently associated with decreased overall survival. The actuarial 5-year overall survival for patients with and without a metaplastic spindle cell component was 38%+/-15% and 89%+/-7%, respectively. Poor clinical outcome, therefore, is associated with the subset of pleomorphic carcinomas with a spindle cell metaplastic component. As the morphologic features of pleomorphic carcinoma can be seen in primary tumors from other sites, it is important to recognize this tumor as a rare variant of invasive breast carcinoma.

Objective: The purpose of this study was in vitro sonographic-pathologic correlation of findings in dissected axillary lymph nodes from breast cancer patients undergoing axillary lymph node dissection and classification of the sonographic appearance of the nodes on the basis of cortical morphologic features to facilitate early recognition of metastatic disease., Materials and Methods: High-resolution sonography was used for in vitro examination of 171 lymph nodes from 19 axillae in 18 patients with unknown nodal status who underwent axillary lymph node dissection for early infiltrating breast cancer. The images were evaluated by two blinded observers, and discordant readings were referred to a third blinded observer. Each lymph node was classified as one of types 1-6 according to cortical morphologic features. Types 1-4 were considered benign, ranging from hyperechoic with no visible cortex to thickened generalized hypoechoic cortical lobulation. Type 5 (focal hypoechoic cortical lobulation) and type 6 (hypoechoic node with absent hilum) nodes were considered metastatic. The reference standard for metastatic disease was histopathologic evaluation of sectioned nodes by a single pathologist blinded to sonographic findings. Largest nodal diameter also was measured., Results: Interobserver agreement was 77% for classification of nodal morphology (types 1-6) and 88% for characterization of a node as benign or malignant. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of cortical shape in prediction of metastatic involvement of axillary nodes were 77%, 80%, 36%, 96%, and 80%. Type 4 nodes had the most false-negative findings (four of 36). Node size ranged from 0.2 to 3.8 cm, and subcentimeter nodes of all types were detected., Conclusion: In breast cancer, axillary lymph nodes can be classified according to cortical morphologic features. Predominantly hyperechoic nodes (types 1-3) can be considered benign. Generalized cortical lobulation (type 4) is uncommonly a false-negative finding, but metastasis, if present, is invariably detected at sentinel node mapping. The presence of asymmetric focal hypoechoic cortical lobulation (type 5) or a completely hypoechoic node (type 6) should serve as a guideline for universal performance of fine-needle aspiration for preoperative staging of breast cancer. This classification, when verified with larger samples, may serve as a useful clinical guideline if proven with results of in vivo studies.