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1.
Eur J Radiol ; 152: 110323, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35576721

RESUMO

PURPOSE: To use mammographic tumour features (imaging biomarkers) to identify and investigate breast cancers originating from the terminal ductal lobular units (TDLUs) of the breast in order to overcome the confusion arising from the current histopathology terminology, which calls cancers arising from the TDLUs either "ductal" or "lobular". METHOD: Prospectively collected data from a randomized controlled mammography screening trial with more than four decades of follow up, and data from the subsequent population-based service screening program in Dalarna County, Sweden, provided the database necessary for studying nonpalpable, primarily screen-detected breast cancer cases in their earliest detectable phases. Large format thick (subgross) and thin section histopathologic images of breast cancers originating from the TDLUs were correlated with their mammographic tumour features (imaging biomarkers) and long-term patient outcome. RESULTS: This systematic correlation indicates that imaging biomarkers can reliably determine the site of origin of breast cancers arising from the terminal ductal lobular units (TDLUs). This breast cancer subgroup has four specific mammographic tumour features: the in situ carcinomas developing from the TDLUs appear as powdery or crushed stone-like calcifications, while the invasive carcinomas appear as stellate/spiculated or circular/oval shaped tumour masses. These features are easily identified with breast imaging, either alone or in combination, unifocal or multifocal. We propose calling breast cancers of TDLU origin acinar adenocarcinoma of the breast (AAB). CONCLUSIONS: The era of early detection necessitates rectifying the current, confusing histopathological nomenclature to one that is based on the anatomical site of origin of breast cancers. Invasive cancers originating from the TDLUs are either stellate/spiculated or circular, irrespective of the complex WHO histopathologic terminology. The mortality reduction accomplished by participation in mammography screening is mostly accomplished by identifying and treating the AABs in their non-palpable, early phase. AABs detected when < 15 mm diameter with no associated carcinoma originating from the major lactiferous ducts (ductal adenocarcinoma of the breast, DAB) have a good to excellent long-term outcome, irrespective of the current terminology, which tends to lead to overtreatment of these early invasive tumours. The conventionally used prognostic factors, including immunohistochemical biomarkers, fail to identify those 1-14 mm invasive AABs tumours that are eventually fatal. This identification can be made preoperatively by including the characteristic mammographic tumour features, imaging biomarkers, in primary diagnosis, treatment planning, and predicting long-term patient outcome. Forthcoming articles will address breast malignancies originating from structures of the breast other than the TDLUs.


Assuntos
Adenocarcinoma , Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Carcinoma , Biomarcadores , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Mamografia
2.
Sci Rep ; 12(1): 5859, 2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35393463

RESUMO

Little is known about the role of diet in the risk of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast, the most common histological subtypes of breast cancer (BC). This is because, the majority of studies on the association of diet and the risk of BC are focused on single food items, and studies considering the overall diet in terms of dietary patterns are limited. Also, the potential heterogeneity in the impact of Western diet (WD) on histological subtypes of BC is not established. This, the age-frequency-matched case-control study included 1009 incident BC cases and 1009 healthy controls. The required data was obtained from the patients' medical files and interviews using a previously validated researcher-designed questionnaire for collecting data on socio-economic and anthropometric statuses and a valid food frequency questionnaire (FFQ) to measure the participants' dietary intake. We used multinomial logistic regression, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A positive and significant association was observed between higher adherence to a WD and risk of IDC (OR comparing highest with the lowest tertile: 2.45, 95% CI 1.88, 3.17; p-trend < 0.001), whereas no significant association was observed between adherence to the WD and the risk of ILC (OR comparing highest with the lowest tertile: 1.63, 95% CI 0.63, 3.25) (p for heterogeneity = 0.03). The results of an analysis stratified by menopausal status suggested a similar pattern. We provided evidence that adherence to a WD raises the risk of IDC, but not ILC, suggesting different etiological mechanisms for IDC and ILC.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Neoplasias da Mama/complicações , Neoplasias da Mama/etiologia , Carcinoma Ductal de Mama/complicações , Carcinoma Ductal de Mama/etiologia , Carcinoma Lobular/epidemiologia , Carcinoma Lobular/etiologia , Carcinoma Lobular/patologia , Estudos de Casos e Controles , Dieta Ocidental , Feminino , Humanos
4.
Oncogene ; 41(21): 2932-2944, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35437308

RESUMO

Invasive lobular breast carcinoma (ILC) is characterized by proliferative indolence and long-term latency relapses. This study aimed to identify how disseminating ILC cells control the balance between quiescence and cell cycle re-entry. In the absence of anchorage, ILC cells undergo a sustained cell cycle arrest in G0/G1 while maintaining viability. From the genes that are upregulated in anchorage independent ILC cells, we selected Inhibitor of DNA binding 2 (Id2), a mediator of cell cycle progression. Using loss-of-function experiments, we demonstrate that Id2 is essential for anchorage independent survival (anoikis resistance) in vitro and lung colonization in mice. Importantly, we find that under anchorage independent conditions, E-cadherin loss promotes expression of Id2 in multiple mouse and (organotypic) human models of ILC, an event that is caused by a direct p120-catenin/Kaiso-dependent transcriptional de-repression of the canonical Kaiso binding sequence TCCTGCNA. Conversely, stable inducible restoration of E-cadherin expression in the ILC cell line SUM44PE inhibits Id2 expression and anoikis resistance. We show evidence that Id2 accumulates in the cytosol, where it induces a sustained and CDK4/6-dependent G0/G1 cell cycle arrest through interaction with hypo-phosphorylated Rb. Finally, we find that Id2 is indeed enriched in ILC when compared to other breast cancers, and confirm cytosolic Id2 protein expression in primary ILC samples. In sum, we have linked mutational inactivation of E-cadherin to direct inhibition of cell cycle progression. Our work indicates that loss of E-cadherin and subsequent expression of Id2 drive indolence and dissemination of ILC. As such, E-cadherin and Id2 are promising candidates to stratify low and intermediate grade invasive breast cancers for the use of clinical cell cycle intervention drugs.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Animais , Neoplasias da Mama/patologia , Caderinas/genética , Caderinas/metabolismo , Carcinoma Lobular/genética , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Ciclo Celular/genética , Feminino , Humanos , Proteína 2 Inibidora de Diferenciação/genética , Camundongos , Invasividade Neoplásica , Recidiva Local de Neoplasia
5.
Mol Cancer Res ; 20(6): 837-840, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35276005

RESUMO

Preclinical model systems are essential research tools that help us understand the biology of invasive lobular carcinoma of the breast (ILC). The number of well-established ILC models is increasing but remain limited. Lower incidence of ILC, underrepresentation of patients with ILC in clinical trials, and intrinsic ILC tumor characteristics all contribute to this challenge. Hence, there is significant need to continually develop better model systems to recapitulate the essential characteristics of ILC biology, genetics, and histology, and empower preclinical therapeutic studies to be translated back into the clinic. In this Perspective, we highlight recent advances in in vivo experimental models, which recapitulate key features of ILC biology and disease progression and potentially reshape the future of ILC translational research. We assert that all existing in vitro and in vivo ILC preclinical models have their strengths and weaknesses, and that it is necessary to bridge key deficiencies in each model context as we move forward with ILC research. Thus, unlocking the mysteries of ILC will be best achieved by choosing the right combination of preclinical model systems.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Biologia , Mama/patologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/genética , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Feminino , Humanos
6.
Breast Cancer Res Treat ; 193(2): 361-379, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35348974

RESUMO

BACKGROUND: Invasive lobular carcinoma (ILC) treatment is similar to invasive ductal carcinoma (IDC; now invasive carcinoma-no special type, IBC-NST), based on its intrinsic subtype. However, further investigation is required for an integrative understanding of differentially perturbed molecular patterns and pathways in these histotypes. METHODS: A dataset of 780 IDC and 201 ILC samples from the TCGA-BRCA project for cross-platform multi-omics was analyzed. We leveraged a consensus approach integrating different bioinformatic algorithms to analyze mutations, CNAs, mRNA, miRNA abundance, methylation, and protein abundance to understand the complex crosstalks that distinguish ILC and IDC samples. A histotype-matched comparison was performed. We performed Cox survival analyses for prognosis based on our identified 53 histotype-specific and four discordant genes. RESULTS: Approximately 90% of ILC cases were of the luminal subtype. Somatic mutations in CDH1 were higher in ILC than in IDC (FDR-adjusted p < 0.01). Fifty-three significant oncogenic or tumor-suppressive DEGs were identified in a single histotype. PPAR signaling and lipolysis regulation in adipocytes were significantly enriched in ILC tumors. CDH1 protein had the highest differential abundance (AUC: 0.85). Moreover, BTG2, GSTA2, GPR37L1, and PGBD5 amplification was associated with poorer OS in ILC compared with no alteration. RIMS2, NACA4P, MYC, ZFPM2, and POU5F1B amplification showed a lower overall survival in patients with IDC. miR-195 showed an IDC-specific downregulation, causing overexpression of CCNE1. Integrative multi-omics supervised analysis identified 296 differentially expressed genes that successfully distinguished IDC and ILC histotypes. CONCLUSIONS: Our findings identify novel molecular candidates that potentially drive and modify the disease differentially among these histotypes.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Proteínas Imediatamente Precoces , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Prognóstico , Receptores Acoplados a Proteínas G , Análise de Sobrevida , Proteínas Supressoras de Tumor
8.
PLoS One ; 17(2): e0263222, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35113931

RESUMO

Breast cancer is a major health problem worldwide. Analysis of breast cancer epidemiology in emerging countries enables assessment of prognostic factors, cancer care quality, and the equity of resource distribution. We aimed to estimate the overall (OS) and cancer-specific survival (SS) of breast cancer patients in the northeastern Brazilian state of Sergipe to identify independent prognostic factors. We analyzed a cohort for the factors age at diagnosis, place of residence, time to treatment, staging, and molecular classification, using the Kaplan-Meier method, log-rank test, Pearson's chi-squared test and Cox regression model. The outcome was the vital status at the end of the study. Our analysis showed an OS probability of 0.72 and an SS probability of 0.75. In multivariate analysis, time to treatment within 60 days, stage IV, and triple-negative classification remained independent prognostic factors for both OS [unadjusted hazard ratio (HRp) 1.50 (1.21; 1.86), HRp 16.56 (8.35; 32.85), and HRp 2.73 (1.73; 4.29), respectively] and SS [HRp 1.43 (1.13; 1.81), HRp 20.53 (9.45; 44.56), and HRp 3.14 (1.88; 5.26), respectively]. Better survival was demonstrated for the following patients: those receiving their first treatment after 60 days, with an OS of 52.5 months (51.2; 53.8) and SS of 53.5 months (52.3; 54.7); stage I patients, with an OS of 58.8 months (57.7; 60.0) and SS of 59.2 months (58.1; 60.3); patients without nodal metastasis, with an OS of 54.2 months (53.0; 55.4) and SS of 55.6 months (54.5; 56.7); and patients with luminal A classification, with an OS of 56.8 months (55.0; 58.5) and SS of 57.8 months (56.2; 59.4). This study identified independent prognostic factors and that OS and SS were lower for patients from Sergipe than for patients in high-income areas. Therefore, determining the profiles of breast cancer patients in this population will inform specific cancer care.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida
9.
Cancer ; 128(9): 1738-1747, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35137951

RESUMO

BACKGROUND: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients. METHODS: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy. RESULTS: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease. CONCLUSIONS: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease. LAY SUMMARY: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/genética , Carcinoma Lobular/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Prognóstico
10.
Eur J Cancer ; 164: 70-79, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35176614

RESUMO

BACKGROUND: The impact of the histological lobular subtype on overall survival (OS) in metastatic breast cancer (MBC) is still under debate, with very few data available. PATIENTS AND METHODS: Using the French national multicentre Epidemiological Strategy and Medico Economics [ESME]) data platform, the primary objective was to compare the OS of patients with invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) MBC, with adjustment on the main prognostic factors using two approaches: multivariable analysis and matching with a propensity score. Secondary objectives were to compare first-line progression-free survival (PFS1) and describe patients and tumour characteristics. RESULTS: Of the 16,703 patients with MBC in the ESME database, 13,111 met all inclusion criteria for the present analysis. One-thousand eight-hundred and four (13.8%) patients had ILC and 11.307 (86.2%) IDC. In the multivariable analysis, patients with ILC had a worse OS [hazard ratio (HR): 1.31; 95%CI 1.20-1.42; p < 0.0001] and a worse PFS1 (HR: 1.15; 95%CI 1.07-1.22; p < 0.0001) as compared with those with IDC, independently of hormone receptor and HER2 status. Interestingly, OS was better (HR 0.79; 95% confidence interval [CI] 0.64-0.98; p = 0.0302), worse (HR: 1.17; 95%CI 1.08-1.27; p = 0.0001) or similar (HR: 0.88; 95%CI 0.67-1.15; p = 0.3455) in patients with ILC with triple-negative, hormone receptor-positive/HER2-negative and HER2-positive MBC, respectively, compared with patients with IDC. CONCLUSION: Lobular histology is an independent adverse prognostic factor among women with MBC. ILC MBC could be considered a specific entity. Dedicated prospective studies are needed to tailor the management of these patients.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
11.
Clin Cancer Res ; 28(10): 2118-2130, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35190802

RESUMO

PURPOSE: We wanted to determine the prognosis and the phenotypic characteristics of hormone receptor-positive advanced breast cancer tumors harboring an ERBB2 mutation in the absence of a HER2 amplification. EXPERIMENTAL DESIGN: We retrospectively collected information from the American Association of Cancer Research-Genomics Evidence Neoplasia Information Exchange registry database from patients with hormone receptor-positive, HER2-negative, ERBB2-mutated advanced breast cancer. Phenotypic and co-mutational features, as well as response to treatment and outcome were compared with matched control cases ERBB2 wild type. RESULTS: A total of 45 ERBB2-mutant cases were identified for 90 matched controls. The presence of an ERBB2 mutation was not associated with worse outcome determined by overall survival (OS) from first metastatic relapse. No significant differences were observed in phenotypic characteristics apart from higher lobular infiltrating subtype in the ERBB2-mutated group. ERBB2 mutation did not seem to have an impact in response to treatment or time-to-progression (TTP) to endocrine therapy compared with ERBB2 wild type. In the co-mutational analyses, CDH1 mutation was more frequent in the ERBB2-mutated group (FDR < 1). Although not significant, fewer co-occurring ESR1 mutations and more KRAS mutations were identified in the ERBB2-mutated group. CONCLUSIONS: ERBB2-activating mutation was not associated with a worse OS from time of first metastatic relapse, or differences in TTP on treatment as compared with a series of matched controls. Although not significant, differences in coexisting mutations (CDH1, ESR1, and KRAS) were noted between the ERBB2-mutated and the control group.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Estudos de Casos e Controles , Feminino , Humanos , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Recidiva , Estudos Retrospectivos
12.
PLoS One ; 17(1): e0262709, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35051228

RESUMO

BACKGROUND: We compared the clinicopathological characteristics and survival outcomes of invasive lobular carcinoma (ILC) cases with those of invasive ductal carcinoma (IDC) cases in various hormone receptor expression subgroups. METHODS: We compared clinicopathological characteristics, overall survival (OS), and breast cancer-specific survival (BCSS) between patients with IDC (n = 95,486) and ILC (n = 3,023). In addition, we analyzed the effects of different hormone receptor expression subgroups on survival. RESULTS: The ILC group had more instances of advanced stage and hormonal receptor positivity than did the IDC group (p < 0.001), but the IDC group had higher histological grade and nuclear grade, as well as higher frequency of human epidermal growth factor receptor 2 and Ki67 expression than did the ILC group (p < 0.001). The OS and BCSS were not significantly different between the IDC and ILC groups. The 5-year OS of the IDC group was 88.8%, while that of the ILC group was 90.6% (p = 0.113). The 5-year BCSS of the IDC group was 94.8%, while that of the ILC group was 95.0% (p = 0.552). When analyzing each hormone receptor expression subgroup, there were no significant differences in survival between the IDC and ILC groups. However, the estrogen receptor (ER) negative/progesterone receptor (PR) negative subgroup showed differences in survival between the IDC and ILC groups. Moreover, the hazard ratio of ILC in the ER negative/PR negative subgroup was 1.345 (95% confidence interval: 1.012-1.788; p = 0.041). CONCLUSIONS: Hormone receptor expression should be considered when determining prognosis and treatment regimen for IDC and ILC. Researchers should further study the ER negative/PR negative population to identify treatment and prognostic models that will facilitate the development of individualized therapy for these patients, which is needed for good outcomes.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , República da Coreia/epidemiologia , Análise de Sobrevida , Taxa de Sobrevida
13.
Women Health ; 62(2): 144-156, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35068353

RESUMO

Invasive lobular carcinoma (ILC) of the breast is known to have typical molecular, clinical, and pathological characteristics that differ from invasive cancer of no special type (NST). In the German mammography screening program (MSP), we evaluated clinical differences between these tumor types at the time of their detection. Clinical features of NSTs (n = 785) and ILCs (n = 141) diagnosed in the MSP between 2009 and 2016 were compared. Compared to NST, ILC was significantly correlated with advanced age (59.1 years versus 60.6 years) and larger tumor size (1.5 cm versus 2.3 cm). ILC was significantly more frequently associated with moderate tumor differentiation (G2), whereas NST was associated with a higher rate of poorly differentiated tumors (p < .001). Furthermore, ILC presented more often as multifocal tumors (36% versus 11%, p < .001), and mastectomies were performed more often in the ILC group (27% versus 12%, p < .001). ILCs and NSTs had different clinical features at the time of detection. The pathological profile of ILC may explain some of these features. Specialists should be aware of the fact that ILC may escape detection by conventional imaging modalities for a long time, and may present later in life as more advanced multifocal disease.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/patologia , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
J Surg Oncol ; 125(4): 577-588, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34779520

RESUMO

BACKGROUND AND OBJECTIVES: Optimal margins for ductal carcinoma in situ (DCIS) remain controversial in breast-conserving surgery (BCS) and mastectomy. We examine the association of positive margins, reoperations, DCIS and age. METHODS: A retrospective study of histopathological reports (4489 patients). Margin positivity was defined as ink on tumor for invasive carcinoma. For DCIS, we applied 2 mm anterior and side margin thresholds, and ink on tumor in the posterior margin. RESULTS: The incidence of positive side margins was 20% in BCS and 5% in mastectomies (p < 0.001). Of these patients, 68% and 14% underwent a reoperation (p < 0.001). After a positive side margin in BCS, the reoperation rates according to age groups were 74% (<49), 69% (50-64), 68% (65-79), and 42% (80+) (p = 0.013). Of BCS patients with invasive carcinoma in the side margin, 73% were reoperated on. A reoperation was performed in 70% of patients with a close (≤1 mm) DCIS side margin, compared to 43% with a wider (1.1-2 mm) margin (p = 0.002). The reoperation rates were 55% in invasive carcinoma with close DCIS, 66% in close extensive intraductal component (EIC), and 83% in close pure DCIS (p < 0.001). CONCLUSIONS: Individual assessment as opposed to rigid adherence to guidelines was used in the decision on reoperation.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/cirurgia , Margens de Excisão , Mastectomia/métodos , Reoperação/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
15.
Arch Pathol Lab Med ; 146(4): 478-484, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34343231

RESUMO

CONTEXT.­: Recurrence score (RS) testing was developed and validated in invasive ductal and rare lobular carcinomas, although it is used for all special types of breast cancers. OBJECTIVE.­: To determine association of histologic type (HT) and RS, specifically high-risk RS. DESIGN.­: We used RSs linked to Surveillance, Epidemiology, and End Results Program registries of invasive breast cancers diagnosed in 2004 through 2015. Multivariable logistic regression was used to evaluate association between HT and high-risk RS. Relationships between HT and low-, intermediate-, and high-risk RS were compared with χ2 test. Kaplan-Meier curves were compared using log-rank test. RESULTS.­: A total of 110 318 patients had RS testing. Of these, 23 220 (21%) had low, 70 822 (64.2%) intermediate, and 16 276 (14.8%) high RS. Histologic types were 80 476 (73%) ductal, 12 713 (11.5%) lobular, 12 449 (11.3%) mixed, 2151 (2%) mucinous, 610 (0.6%) tubular, 382 (0.4%) micropapillary, 365 (0.3%) salivary, 208 (0.2%) papillary, 49 (0.04%) medullary, 26 (0.02%) metaplastic, 26 (0.02%) neuroendocrine, and 863 (0.8%) unknown. The distribution of low-, intermediate-, and high-risk RS was significantly different among HTs. Higher percentages of high-risk RS were identified in patients with ductal, medullary, and metaplastic types (P < .001). The odds of having high-risk RS were lower for some HTs, including micropapillary, after multivariable adjustment (P < .05). The low number of estrogen receptor-positive medullary and metaplastic carcinomas tested had higher odds of having high-risk RS. In T1 and T2 tumors, when ductal, lobular, mixed, and other types combined were compared, the mortality was different. CONCLUSIONS.­: This population-based study of RS in HTs showed high-risk RSs are identified in traditionally good prognostic subtypes. Micropapillary carcinoma has lower odds of high-risk RS even after multivariable adjustment.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Carcinoma Papilar , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/genética , Carcinoma Lobular/patologia , Feminino , Humanos , Prognóstico , Fatores de Risco
16.
AJR Am J Roentgenol ; 218(1): 33-41, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34319162

RESUMO

BACKGROUND. Invasive lobular carcinoma is more subtle on imaging compared with invasive ductal carcinoma; nodal metastases may also differ on imaging between these two. OBJECTIVE. The purpose of this study was to determine whether invasive lobular carcinoma and invasive ductal carcinoma differ in the detection rate by ultrasound (US) of metastatic axillary nodes and in the metastatic nodes' US characteristics. METHODS. This retrospective study included 695 women (median age, 53 years) who had breast cancer in a total of 723 breasts (76 lobular, 586 ductal, 61 mixed ductal and lobular histology) with biopsy-proven axillary nodal metastases and who underwent pretreatment US. A single breast radiologist reviewed US images in patients with suspicious nodes on US and classified number of nodes, size, and morphology. Morphologic assessment used a previously described classification according to the relationship between node cortex and hilum. Nodal findings were compared between lobular and ductal carcinoma. A second radiologist independently classified node morphology in 241 cancers to assess interreader agreement. RESULTS. A total of 99 metastatic axillary nodes (15 lobular, 66 ductal, 18 mixed histology) were not visualized on US and were diagnosed by surgical biopsy. The remaining 624 metastatic nodes (61 lobular, 520 ductal, 43 mixed ductal and lobular histology) were visualized on US and diagnosed by US-guided fine-needle aspiration. US detected the metastatic nodes in 80.3% for lobular carcinoma versus 88.7% for ductal carcinoma (p = .04). Among metastatic nodes detected by US, retrospective review identified three or more abnormal nodes in 50.8% of lobular carcinoma versus 69.2% of ductal carcinoma (p = .003); node size was 2.0 cm or smaller in 65.6% for lobular carcinoma versus 47.3% for ductal carcinoma (p = .03); morphology was type III or IV (diffuse cortical thickening without hilar mass effect) rather than type V or VI (marked cortical thickening with hilar mass effect) in 68.9% for lobular carcinoma versus 28.8% for ductal carcinoma (p < .001). Interreader agreement assessment for morphology exhibited a kappa coefficient of 0.63 (95% CI, 0.54-0.73). CONCLUSION. US detects a lower percentage of nodal metastases in lobular than in ductal carcinoma. Nodal metastases in lobular carcinoma more commonly show diffuse cortical thickening and with less hilar mass effect. CLINICAL IMPACT. A lower threshold may be warranted to recommend biopsy of suspicious axillary nodes detected on US in patients with lobular carcinoma.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Metástase Linfática/diagnóstico por imagem , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Mama/patologia , Diagnóstico Diferencial , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Adulto Jovem
17.
Br J Radiol ; 95(1130): 20210438, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34860574

RESUMO

OBJECTIVES: The aim of this study was to investigate the detection efficacy of deep learning (DL) for automatic breast ultrasound (ABUS) and factors affecting its efficacy. METHODS: Females who underwent ABUS and handheld ultrasound from May 2016 to June 2017 (N = 397) were enrolled and divided into training (n = 163 patients with breast cancer and 33 with benign lesions), test (n = 57) and control (n = 144) groups. A convolutional neural network was optimized to detect lesions in ABUS. The sensitivity and false positives (FPs) were evaluated and compared for different breast tissue compositions, lesion sizes, morphologies and echo patterns. RESULTS: In the training set, with 688 lesion regions (LRs), the network achieved sensitivities of 93.8%, 97.2% and 100%, based on volume, lesion and patient, respectively, with 1.9 FPs per volume. In the test group with 247 LRs, the sensitivities were 92.7%, 94.5% and 96.5%, respectively, with 2.4 FPs per volume. The control group, with 900 volumes, showed 0.24 FPs per volume. The sensitivity was 98% for lesions > 1 cm3, but 87% for those ≤1 cm3 (p < 0.05). Similar sensitivities and FPs were observed for different breast tissue compositions (homogeneous, 97.5%, 2.1; heterogeneous, 93.6%, 2.1), lesion morphologies (mass, 96.3%, 2.1; non-mass, 95.8%, 2.0) and echo patterns (homogeneous, 96.1%, 2.1; heterogeneous 96.8%, 2.1). CONCLUSIONS: DL had high detection sensitivity with a low FP but was affected by lesion size. ADVANCES IN KNOWLEDGE: DL is technically feasible for the automatic detection of lesions in ABUS.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Aprendizado Profundo , Ultrassonografia Mamária/métodos , Adulto , Idoso , Algoritmos , Densidade da Mama , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/patologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
Am J Surg Pathol ; 46(3): 383-391, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34653059

RESUMO

Invasive lobular carcinoma (ILC) of the breast is characterized by the discohesive growth of tumor cells, which is mainly associated with the complete loss of E-cadherin (E-cad) expression. However, some aberrant expression patterns of E-cad protein that are inconsistent with their morphologies have been reported in ILC. We report herein ILC cases expressing a new type of abnormal E-cad protein that lacks the N-terminal domain, but conserves the C-terminal domain on the cell membrane. Immunohistochemical staining of 299 ILC cases using specific antibodies against the N-terminal or C-terminal region of E-cad revealed that 227 (76%) cases showed loss of the membranous expression of both terminuses (N-/C-) and 72 (24%) cases showed expression of only the C-terminus (N-/C+). In all cases, the expression of p120-catenin and ß-catenin coincided with the expression of the C-terminus of E-cad. Clinicopathologic analysis revealed that N-/C+ expression in ILC cells was significantly associated with the histologic subtype (especially mixed-type ILC with another histologic type) and immunohistochemical molecular subtype (especially the triple-negative subtype), but not with prognostic factors (pT or pN). In addition, 12 of 15 cases (80%) with aberrant cytoplasmic localization of the N-terminal of E-cad showed diffuse membranous expression of the C-terminal domain. Additional immunohistochemistry using an antibody recognizing the extracellular juxtamembrane region showed that 28 (39%) of the N-/C+ cases had lost membranous expression, suggesting diversity in the deletion pattern of the N-terminal region. Our findings provide a novel mechanism for the loss of E-cad function because of N-terminal-deficient E-cad protein in ILC.


Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Caderinas/metabolismo , Carcinoma Lobular/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/química , Biomarcadores Tumorais/química , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Caderinas/química , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade Neoplásica
20.
Head Neck Pathol ; 16(1): 314-321, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34115320

RESUMO

Salivary and mammary glands are both exocrine organs sharing multiple tumorigenic processes. To the best of our knowledge, salivary gland tumors mimicking invasive lobular carcinoma of the breast have not yet been described. Herein, we report a case of a 62-year-old male who presented with progressive facial paralysis. Pathologic examination revealed an ill-defined epithelial neoplasm exhibiting discohesive growth set within an extensively fibrotic stroma. Both perineural and intraneural invasion were present. E-cadherin and p120 immunostaining showed aberrant cytoplasmic expression. Targeted next-generation sequencing detected a frameshift mutation of the CTNNA1 gene as the only known pathogenic variant. The patient was treated with surgical resection, immunotherapy, and chemotherapy. Currently, he is alive with disease twenty months after disease onset.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Neoplasias das Glândulas Salivares , Neoplasias da Mama/genética , Caderinas , Carcinoma Lobular/genética , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia
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