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1.
Theranostics ; 10(4): 1746-1757, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042334

RESUMO

Rationale: The overwhelming majority of radioimmunoconjugates are produced via random conjugation methods predicated on attaching bifunctional chelators to the lysines of antibodies. However, this approach inevitably produces poorly defined and heterogeneous immunoconjugates because antibodies have several lysines distributed throughout their structure. To circumvent this issue, we have previously developed a chemoenzymatic bioconjugation strategy that site-specifically appends cargoes to the biantennary heavy chain glycans attached to CH2 domains of the immunoglobulin's Fc region. In the study at hand, we explore the effects of this approach to site-specific bioconjugation on the Fc receptor binding and in vivo behavior of radioimmunoconjugates. Methods: We synthesized three desferrioxamine (DFO)-labeled immunoconjugates based on the HER2-targeting antibody pertuzumab: one using random bioconjugation methods (DFO-nsspertuzumab) and two using variants of our chemoenzymatic protocol (DFO-sspertuzumab-EndoS and DFO-sspertuzumab-ßGal). Subsequently, we characterized these constructs and evaluated their ability to bind HER2, human FcγRI (huFcγRI), and mouse FcγRI (muFcγRI). After radiolabeling the immunoconjugates with zirconium-89, we conducted PET imaging and biodistribution studies in two different mouse models of HER2-expressing breast cancer. Results: MALDI-ToF and SDS-PAGE analysis confirmed the site-specific nature of the bioconjugation, and flow cytometry and surface plasmon resonance (SPR) revealed that all three immunoconjugates bind HER2 as effectively as native pertuzumab. Critically, however, SPR experiments also illuminated that DFO-sspertuzumab-EndoS possesses an attenuated binding affinity for huFcγRI (17.4 ± 0.3 nM) compared to native pertuzumab (4.7 ± 0.2 nM), DFO-nsspertuzumab (4.1 ± 0.1 nM), and DFO-sspertuzumab-ßGal (4.7 ± 0.2 nM). ImmunoPET and biodistribution experiments in athymic nude mice bearing HER2-expressing BT474 human breast cancer xenografts yielded no significant differences in the in vivo behavior of the radioimmunoconjugates. Yet experiments in tumor-bearing humanized NSG mice revealed that 89Zr-DFO-sspertuzumab-EndoS produces higher activity concentrations in the tumor (111.8 ± 39.9 %ID/g) and lower activity concentrations in the liver and spleen (4.7 ± 0.8 %ID/g and 13.1 ± 4.0 %ID/g, respectively) than its non-site-specifically labeled cousin, a phenomenon we believe stems from the altered binding of the former to huFcγRI. Conclusion: These data underscore that this approach to site-specific bioconjugation not only produces more homogeneous and well-defined radioimmunoconjugates than traditional methods but may also improve their in vivo performance in mouse models by reducing binding to FcγRI.

2.
Radiology ; : 192409, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910074
3.
Cancer Discov ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31806627

RESUMO

HER2 mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with HER2-mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration of response appeared longer in ER+ patients receiving combination therapy, although the study was not designed for direct comparison. Preexistent concurrent activating HER2 or HER3 alterations were associated with poor treatment outcome. Similarly, acquisition of multiple HER2-activating events, as well as gatekeeper alterations, were observed at disease progression in a high proportion of patients deriving clinical benefit from neratinib. Collectively, these data define HER2 mutations as a therapeutic target in breast cancer and suggest that coexistence of additional HER signaling alterations may promote both de novo and acquired resistance to neratinib. SIGNIFICANCE: HER2 mutations define a targetable breast cancer subset, although sensitivity to irreversible HER kinase inhibition appears to be modified by the presence of concurrent activating genomic events in the pathway. These findings have implications for potential future combinatorial approaches and broader therapeutic development for this genomically defined subset of breast cancer.

4.
JAMA Netw Open ; 2(11): e1916211, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774522

RESUMO

Importance: Taxanes with trastuzumab and pertuzumab for initial treatment of human epidermal growth factor receptor 2 (ERBB2, formerly HER2)-positive metastatic breast cancer is associated with improved progression-free survival (PFS) and overall survival. While continued use of trastuzumab in therapeutic combinations after disease progression is standard, the efficacy of continuing pertuzumab is unknown. Objective: To evaluate the efficacy and safety of pertuzumab in combination with gemcitabine and trastuzumab after prior treatment with pertuzumab for ERBB2-positive metastatic breast cancer. Design, Setting, and Participants: This is a phase 2 single-arm clinical trial of dual anti-ERBB2 therapy after prior treatment with pertuzumab. The study took place at a single academic center from March 2015 to April 2017 among women with ERBB2-positive metastatic breast cancer, prior pertuzumab-based treatment, and 3 or fewer prior chemotherapy regimens. Data were analyzed between January 2019 and March 2019. Intervention: Treatment consisted of gemcitabine, 1200 mg/m2 (later amended to 1000 mg/m2) on days 1 and 8 every 3 weeks, plus trastuzumab (8-mg/kg loading dose, then 6 mg/kg) and pertuzumab (840-mg loading dose, then 420 mg) once every 3 weeks. Main Outcomes and Measures: The primary end point was 3-month PFS. Based on prior trials, a target rate of 70% or higher was selected as the promising progression-free rate at 3 months. Secondary outcomes included safety, tolerability, and overall survival. Results: A total of 45 patients (median [range] age, 57.1 [31.7-77.2] years) were enrolled; 22 (49%) were treated in the second-line setting, and 23 (51%) were treated in the third-line setting or beyond. Of these, 22 (49%) received prior trastuzumab emtansine (T-DM1). At a median (range) follow-up of 27.6 (8.3-36.0) months, 3-month PFS was 73.3% (95% CI, 61.5%-87.5%). Overall, median PFS was 5.5 months (95% CI, 5.4-8.2 months). Treatment was well tolerated, with no occurrences of febrile neutropenia or symptomatic left ventricular systolic dysfunction. Conclusions and Relevance: In this phase 2 trial, treatment with gemcitabine, trastuzumab, and pertuzumab after prior pertuzumab-based therapy for ERBB2-positive metastatic breast cancer was associated with a 3-month PFS rate of 73.3% and was well tolerated. Continuation of pertuzumab beyond progression was associated with apparent clinical benefit. Trial Registration: ClinicalTrials.gov identifier: NCT02252887.

5.
Nat Med ; 25(12): 1839-1842, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31768065

RESUMO

Histiocytoses are clonal hematopoietic disorders frequently driven by mutations mapping to the BRAF and MEK1 and MEK2 kinases. Currently, however, the developmental origins of histiocytoses in patients are not well understood, and clinically meaningful therapeutic targets outside of BRAF and MEK are undefined. In this study, we uncovered activating mutations in CSF1R and rearrangements in RET and ALK that conferred dramatic responses to selective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis.


Assuntos
Quinase do Linfoma Anaplásico/genética , Histiocitose/genética , Proteínas Proto-Oncogênicas c-ret/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Adolescente , Adulto , Aminopiridinas/farmacologia , Benzotiazóis/farmacologia , Criança , Pré-Escolar , Feminino , Genoma Humano , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Histiocitose/tratamento farmacológico , Histiocitose/patologia , Humanos , Lactente , Masculino , Mutação , Ácidos Picolínicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Piridinas/farmacologia , Pirróis/farmacologia , Receptores Proteína Tirosina Quinases/genética , Gêmeos Monozigóticos , Sequenciamento Completo do Exoma , Adulto Jovem
6.
J Am Coll Radiol ; 16(11S): S428-S439, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31685110

RESUMO

As the proportion of women diagnosed with early stage breast cancer increases, the role of imaging for staging and surveillance purposes is considered. National and international guidelines discourage the use of staging imaging for asymptomatic patients newly diagnosed with stage 0 to II breast cancer, even if there is nodal involvement, as unnecessary imaging can delay care and affect outcomes. In asymptomatic patients with a history of stage I breast cancer that received treatment for curative intent, there is no role for imaging to screen for distant recurrences. However, routine surveillance with an annual mammogram is the only imaging test that should be performed to detect an in-breast recurrence or a new primary breast cancer in women with a history of stage I breast cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

7.
Clin Nucl Med ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31693614

RESUMO

A 70-year-old woman with breast cancer underwent F-FDG PET/CT for restaging. An FDG-avid focus corresponding to a rib on CT images was identified and interpreted as suggestive of an osseous metastasis. A PET/CT-guided biopsy was planned with the patient in prone position. Prone images demonstrated the FDG focus "moved" to the anterior chest and corresponding to pleural fluid. The diagnosis was altered from osseous metastases to pleural malignancy, and the bone biopsy was not performed. This case not only emphasizes the sensitivity of PET in the detection of malignancy, but also highlights the difficulty localizing small, mobile, FDG-avid foci.

8.
Clin Nucl Med ; 44(12): 969-970, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31689279

RESUMO

A 70-year-old woman with breast cancer underwent F-FDG PET/CT for restaging. An FDG-avid focus corresponding to a rib on CT images was identified and interpreted as suggestive of an osseous metastasis. A PET/CT-guided biopsy was planned with the patient in prone position. Prone images demonstrated the FDG focus "moved" to the anterior chest and corresponding to pleural fluid. The diagnosis was altered from osseous metastases to pleural malignancy, and the bone biopsy was not performed. This case not only emphasizes the sensitivity of PET in the detection of malignancy, but also highlights the difficulty localizing small, mobile, FDG-avid foci.


Assuntos
Neoplasias Ósseas/secundário , Fluordesoxiglucose F18 , Posicionamento do Paciente , Derrame Pleural Maligno/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Humanos
9.
Clin Cancer Res ; 25(24): 7381-7387, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31548342

RESUMO

PURPOSE: To determine whether FDG PET can expand eligibility in biomarker-selected clinical trials by providing a means to quantitate response in patients with non-assessable disease by RECIST. EXPERIMENTAL DESIGN: SUMMIT (NCT01953926) is a multicenter phase II "basket" trial of the Pan-HER kinase inhibitor, neratinib. Patients had advanced ERBB2 (HER2)-mutant solid tumors, ≥1 measurable lesion, preferably defined unidimensionally by RECIST v1.1, or alternatively metabolically by PET Response Criteria (PRC). The primary aim was to determine the proportion of additional breast cancer patients accrued using PRC who would have otherwise been ineligible based on RECIST criteria alone. The secondary aim was to determine the concordance of response versus non-response between RECIST and PRC. RESULTS: Eighty-one patients with HER2-mutant metastatic breast cancer were accrued; 77 were evaluable for response by RECIST and/or PRC. 63 (82%) were RECIST-evaluable and 14 (18%) were accrued using PRC alone. Bone-only disease (n = 11; 79%) was the most common reason for classification as non-measurable by RECIST. Twenty-nine patients were accrued and followed using both criteria, of which 25 (86%; 95% confidence interval, 68%-96%) were concordant for response versus non-response as defined by RECIST and PRC. CONCLUSIONS: PRC allowed patients with non-RECIST measurable disease access to therapy and facilitated more rapid accrual of patients to this trial of a rare biomarker. PRC and RECIST both provided methods of response assessment and were generally concordant. Thus, PRC was useful as a supplement to RECIST criteria. This provides a rationale for including FDG PET measurements in future clinical trials involving rare tumors or rare genomically defined subpopulations of more common cancers.

10.
Clin Nucl Med ; 44(10): 836-837, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31283599

RESUMO

A 46-year-old man with metastatic lung adenocarcinoma was treated with pembrolizumab. FDG PET/CT was performed after 3 cycles of treatment and revealed a focal region of pancreatic tail enlargement with an SUVmax value of 7. Following treatment with corticosteroids and discontinuation of pembrolizumab, radiological resolution was observed, and a diagnosis of focal immunotherapy-induced pancreatitis was made. A unique spectrum of FDG-avid adverse events can develop in patients treated with immune-checkpoint inhibitors that may mimic metastatic disease. Knowledge of the radiologic features of these potential imaging pitfalls is crucial among those interpreting FDG PET/CT to allow prompt and decisive treatment.


Assuntos
Fluordesoxiglucose F18 , Imunoterapia/efeitos adversos , Pancreatite/diagnóstico por imagem , Pancreatite/etiologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade
11.
AJR Am J Roentgenol ; 213(2): 254-265, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31063423

RESUMO

OBJECTIVE. FDG PET/CT affects the management of patients with breast cancer in multiple settings, including initial staging, treatment response assessment, and evaluation of suspected recurrence. This article reviews the strengths and weaknesses of FDG PET/CT for the staging of the primary breast lesion, axillary and extraaxillary nodal metastases, and distant metastases. The utility of FDG PET/CT for measuring breast cancer treatment response is appraised and compared with other imaging modalities. The role that tumor histologic type may have on PET/CT interpretation is also discussed. CONCLUSION. Although FDG PET/CT is currently the PET modality with the greatest effect on clinical management of patients with breast cancer, novel radiotracers and imaging systems continue to broaden the application of PET for patients with breast cancer. National Comprehensive Cancer Network guidelines for FDG PET/CT for patients with breast cancer are reviewed. Emphasis is given where FDG PET/CT has shown clinical effect.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Axila/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Estadiamento de Neoplasias
12.
Nature ; 567(7749): 521-524, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30867592

RESUMO

Histiocytic neoplasms are a heterogeneous group of clonal haematopoietic disorders that are marked by diverse mutations in the mitogen-activated protein kinase (MAPK) pathway1,2. For the 50% of patients with histiocytosis who have BRAFV600 mutations3-5, RAF inhibition is highly efficacious and has markedly altered the natural history of the disease6,7. However, no standard therapy exists for the remaining 50% of patients who lack BRAFV600 mutations. Although ERK dependence has been hypothesized to be a consistent feature across histiocytic neoplasms, this remains clinically unproven and many of the kinase mutations that are found in patients who lack BRAFV600 mutations have not previously been biologically characterized. Here we show ERK dependency in histiocytoses through a proof-of-concept clinical trial of cobimetinib, an oral inhibitor of MEK1 and MEK2, in patients with histiocytoses. Patients were enrolled regardless of their tumour genotype. In parallel, MAPK alterations that were identified in treated patients were characterized for their ability to activate ERK. In the 18 patients that we treated, the overall response rate was 89% (90% confidence interval of 73-100). Responses were durable, with no acquired resistance to date. At one year, 100% of responses were ongoing and 94% of patients remained progression-free. Cobimetinib treatment was efficacious regardless of genotype, and responses were observed in patients with ARAF, BRAF, RAF1, NRAS, KRAS, MEK1 (also known as MAP2K1) and MEK2 (also known as MAP2K2) mutations. Consistent with the observed responses, the characterization of the mutations that we identified in these patients confirmed that the MAPK-pathway mutations were activating. Collectively, these data demonstrate that histiocytic neoplasms are characterized by a notable dependence on MAPK signalling-and that they are consequently responsive to MEK inhibition. These results extend the benefits of molecularly targeted therapy to the entire spectrum of patients with histiocytosis.


Assuntos
Azetidinas/uso terapêutico , Transtornos Histiocíticos Malignos/tratamento farmacológico , Transtornos Histiocíticos Malignos/enzimologia , Histiocitose/tratamento farmacológico , Histiocitose/enzimologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Piperidinas/uso terapêutico , Azetidinas/farmacologia , Transtornos Histiocíticos Malignos/genética , Transtornos Histiocíticos Malignos/patologia , Histiocitose/genética , Histiocitose/patologia , Humanos , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 2/antagonistas & inibidores , MAP Quinase Quinase 2/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mutação , Piperidinas/farmacologia , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-raf/genética
15.
Clin Nucl Med ; 44(4): 330-331, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30688738

RESUMO

Ga-DOTATATE is a radiolabeled somatostatin analog used for the detection and characterization of somatostatin receptor (SSR)-overexpressing tumors, particularly well-differentiated neuroendocrine tumors. We present a case of a 65-year-old man with well-differentiated pancreatic neuroendocrine tumor post-Whipple surgery and a new liver lesion on CT. Ga-DOTATATE PET/CT was performed for SSR characterization and restaging, which demonstrated the lesion to be intensely SSR positive and interpreted as a neuroendocrine metastasis. However, subsequent pathology proved the lesion to be a hepatocellular carcinoma. This case adds hepatocellular carcinoma as a potentially DOTATATE-avid malignancy to be considered in the differential diagnoses of SSR-positive liver lesions.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Compostos Organometálicos , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Metástase Neoplásica , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Receptores de Somatostatina/metabolismo
16.
J Nucl Med ; 60(4): 472-477, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30237211

RESUMO

18F-FDG PET/CT has demonstrated substantial value in systemic staging of newly diagnosed breast cancer in women. However, it is not known whether breast cancer in male patients benefits similarly. This study assesses 18F-FDG PET/CT systemic staging in patients with newly diagnosed male breast cancer and determines detection rates for unsuspected distant metastases stratified by pre-PET/CT stage. Methods: In this Institutional Review Board-approved retrospective study, our Health Care Information System was screened for stage I-III male patients with breast cancer who underwent 18F-FDG PET/CT before systemic or radiation therapy from 2004 to 2017. Initial stage was determined by mammography, ultrasound, or surgery. 18F-FDG PET/CT was evaluated to identify unsuspected extraaxillary regional nodal and distant metastases, and a post-PET/CT stage was determined. Rates of upstaging to stage IV were determined for each initial stage. Results: During the 14-y period, 10,124 unique patients underwent 18F-FDG PET/CT for breast cancer at our institution. Of these, 106 patients were men, and 39 of these patients were imaged at initial staging and met the inclusion criteria. Median age was 62 y (range, 31-90 y), most had ductal carcinoma (95%), and most were estrogen receptor-positive (97%). In 7 of 39 patients (18%), 18F-FDG PET/CT identified previously unsuspected distant metastases, which increased patient stage to IV. This included 3 of 19 (16%) initial stage IIB patients and 4 of 12 (33%) initial stage III patients. 18F-FDG PET/CT also detected an unsuspected synchronous lymphoma in 1 patient. Conclusion: 18F-FDG PET/CT revealed previously unsuspected distant metastases in 16% of male patients with pre-PET/CT stage IIB breast cancer and 33% of those with stage III breast cancer. These rates are comparable to previously published upstaging rates in female patients. 18F-FDG PET/CT demonstrates value for systemic staging of male patients with breast cancer and should be considered for use in newly diagnosed patients, particularly those with stage IIB and III disease.

17.
Abdom Radiol (NY) ; 44(2): 586-592, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30251132

RESUMO

PURPOSE: To investigate the value of second-opinion interpretation of cross-sectional images by subspecialized radiologists to diagnose recurrent pancreatic cancer after surgery. METHODS: The IRB approved and issued a waiver of informed consent for this retrospective study. Initial and second-opinion interpretations of 69 consecutive submitted MRI or CT follow-up after pancreatic cancer resection between January 1, 2009 and December 31, 2013 were evaluated by one oncologic imaging radiologist, who was blinded to patient's clinical details and histopathologic data. The reviewer was asked to classify each interpretation in reference of the diagnosis of PDAC recurrence. It was also recorded if the radiologic interpretation recommended additional imaging studies to confirm recurrence. The diagnosis of recurrence was determined by pathology when available, otherwise by imaging follow-up, clinical, or laboratory assessments. Cohen's kappa statistic was used to assess agreement between initial and second-opinion interpretations. The differences between the initial and second-opinion interpretations were examined using McNemar test or Bowker's test of symmetry. RESULTS: Disagreement on recurrence between the initial report and the second-opinion interpretation was observed in 32% of cases (22/69; k = 0.44). Second-opinion interpretations had a higher sensitivity and a higher specificity on recurrence compared to the initial interpretations (0.93 vs. 0.75 and 0.90 vs. 0.68, respectively), and the difference in specificity was significant (p = 0.016). Additional imaging studies were recommended more frequently in the initial interpretation (22% vs. 6%, p = 0.006). CONCLUSIONS: Our study shows the second-opinion interpretation by subspecialized radiologists improves the detection of pancreatic cancer recurrence after surgical resection.

18.
J Am Coll Radiol ; 15(11S): S313-S320, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30392600

RESUMO

Although the majority of male breast problems are benign with gynecomastia as the most common etiology, men with breast symptoms and their referring providers are typically concerned about whether or not it is due to breast cancer. If the differentiation between benign disease and breast cancer cannot be made on the basis of clinical findings, or if the clinical presentation is suspicious, imaging is indicated. The panel recommends the following approach to breast imaging in symptomatic men. In men with clinical findings consistent with gynecomastia or pseudogynecomastia, no imaging is routinely recommended. If an indeterminate breast mass is identified, the initial recommended imaging study is ultrasound in men younger than age 25, and mammography or digital breast tomosynthesis in men age 25 and older. If physical examination is suspicious for a male breast cancer, mammography or digital breast tomosynthesis is recommended irrespective of patient age. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Assuntos
Doenças Mamárias/diagnóstico por imagem , Neoplasias da Mama Masculina/diagnóstico por imagem , Diagnóstico Diferencial , Medicina Baseada em Evidências , Ginecomastia/diagnóstico por imagem , Humanos , Masculino , Sociedades Médicas , Estados Unidos
19.
PET Clin ; 13(3): 325-338, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30100073

RESUMO

Breast cancer is a heterogeneous disease, observed traditionally by morphology and protein expression but, more recently with the advent of modern molecular technologies, at the genomic and transcriptomic level. This review describes the association between the different molecular subtypes with the histologic subtypes of breast cancer alongside some of their major genomic characteristics and illustrates how these subtypes may affect the appearance of tumors on imaging studies. The authors aim to show how molecular stratification can be used to augment traditional methods to improve our understanding of breast cancers and their clinical management.


Assuntos
Neoplasias da Mama/genética , Genômica/métodos , Neoplasias da Mama/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Feminino , Humanos
20.
PET Clin ; 13(3): 355-361, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30100075

RESUMO

Histologic subtype, receptor status, and other biologic factors greatly affect the avidity of breast malignancy on fluorodeoxyglucose (FDG) PET. FDG PET/computed tomography (CT) has demonstrated excellent value in the evaluation of extra-axillary nodal and distant metastases. Patients with early-stage breast cancers do not benefit from FDG PET/CT; however, unsuspected distant metastases may be revealed by systemic staging of locally advanced breast cancers by FDG PET/CT, and this has substantial impact on patient management. FDG PET/CT has demonstrated value in the evaluation of treatment response and in detection of disease recurrence.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Mama/diagnóstico por imagem , Feminino , Humanos
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