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1.
Oncology ; 99(5): 280-291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33652435

RESUMO

INTRODUCTION: The aim of this study was to assess for clinicopathologic and socioeconomic features that predict improved survival for patients with advanced breast cancer with synchronous brain metastases at diagnosis. METHODS: We utilized the National Cancer Database (NCDB) to identify all patients with brain metastases present at diagnosis, with adequate information on receptor status (ER, PR, Her2), clinical T stage of cT1-4, clinical M1, with 3,943 patients available for analysis. The association between brain metastases patterns and patient/disease variables was examined by robust Poisson regression model. Cox proportional hazards model was used to quantify the associations between overall survival (OS) and these variables. RESULTS: In univariable analysis, OS was significantly associated with the number of sites of metastases (p < 0.0001). Patients with 2 or more additional extracranial sites of metastases had significantly worse OS (median 8.8 months, 95% confidence interval [CI] 7.8, 9.9) than patients with brain metastases only (median OS 10.6 months, 95% CI 9.4, 12.9) or brain metastases plus one other extracranial site of metastases (median OS 13.1 months, 95% CI 11.8, 14.4). Risk factors which predicted poor prognosis included triple-negative disease, high comorbidity score, poorly differentiated tumors, invasive lobular histology, multi-organ involvement of metastases, and government or lack of insurance. Factors which improve survival include younger age and Hispanic race. DISCUSSION/CONCLUSION: Using a large NCDB, we identified various factors associated with prognosis for patients with brain metastases at the time of breast cancer diagnosis. Insurance status and related socioeconomic challenges provide potential areas for improvement in care for these patients. This information may help stratify patients into prognostic categories at the time of diagnosis to improve treatment plans.


Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Bases de Dados Factuais , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
2.
BMC Cancer ; 21(1): 238, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676449

RESUMO

BACKGROUND: Liver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM). METHODS: Data on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients. RESULTS: Young age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88-3.66; P < 0.001) and HR-/HER2+ (HR = 3.43; 95% CI = 2.28-5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58-0.95; P < 0.001). CONCLUSIONS: Breast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/terapia , Quimiorradioterapia Adjuvante/métodos , Conjuntos de Dados como Assunto , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Prognóstico , Receptor ErbB-2/análise , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/análise , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/terapia , Adulto Jovem
3.
BMC Cancer ; 21(1): 212, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648460

RESUMO

BACKGROUND: Information regarding response to past treatments may provide clues concerning the classes of drugs most or least likely to work for a particular metastatic or neoadjuvant early stage breast cancer patient. However, currently there is no systematized knowledge base that would support clinical treatment decision-making that takes response history into account. METHODS: To model history-dependent response data we leveraged a published in vitro breast cancer viability dataset (84 cell lines, 90 therapeutic compounds) to calculate the odds ratios (log (OR)) of responding to each drug given knowledge of (intrinsic/prior) response to all other agents. This OR matrix assumes (1) response is based on intrinsic rather than acquired characteristics, and (2) intrinsic sensitivity remains unchanged at the time of the next decision point. Fisher's exact test is used to identify predictive pairs and groups of agents (BH p < 0.05). Recommendation systems are used to make further drug recommendations based on past 'history' of response. RESULTS: Of the 90 compounds, 57 have sensitivity profiles significantly associated with those of at least one other agent, mostly targeted drugs. Nearly all associations are positive, with (intrinsic/prior) sensitivity to one agent predicting sensitivity to others in the same or a related class (OR > 1). In vitro conditional response patterns clustered compounds into five predictive classes: (1) DNA damaging agents, (2) Aurora A kinase and cell cycle checkpoint inhibitors; (3) microtubule poisons; (4) HER2/EGFR inhibitors; and (5) PIK3C catalytic subunit inhibitors. The apriori algorithm implementation made further predictions including a directional association between resistance to HER2 inhibition and sensitivity to proteasome inhibitors. CONCLUSIONS: Investigating drug sensitivity conditioned on observed sensitivity or resistance to prior drugs may be pivotal in informing clinicians deciding on the next line of breast cancer treatments for patients who have progressed on their current treatment. This study supports a strategy of treating patients with different agents in the same class where an associated sensitivity was observed, likely after one or more intervening treatments.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Resistencia a Medicamentos Antineoplásicos , Terapia de Salvação/métodos , Algoritmos , Antineoplásicos/classificação , Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Linhagem Celular Tumoral , Tomada de Decisão Clínica , Análise por Conglomerados , Terapia Combinada , Mineração de Dados/métodos , Conjuntos de Dados como Assunto , Gerenciamento Clínico , Ensaios de Seleção de Medicamentos Antitumorais , Substituição de Medicamentos , Feminino , Humanos , Internet , Terapia Neoadjuvante , Intervalo Livre de Progressão , Qualidade de Vida , Design de Software , Resultado do Tratamento
4.
Am J Case Rep ; 22: e928012, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544698

RESUMO

BACKGROUND Invasive lobular carcinoma is special subtype of breast cancer that has clinical behavior and morphology distinct from other breast cancer subtypes. It accounts for 5-15% of breast cancer. Overall, HER-2 gene amplification occurs at a significantly lower rate in ILC, but also has been linked to adverse outcomes. Most cases of ILCs with HER-2 overexpression and or amplification generally have the pleomorphic variant. We report the first series of cases from Saudi Arabia for this rare cancer in an Arab population. CASE REPORT Nine patients retrospectively were evaluated with HER-2/neu-positive ILC of the breast that were diagnosed and managed from 2003 to 2020. Four patients were diagnosed as early breast cancer, 3 had metastatic disease and 2 were locally advanced at their initial presentation. The mean age was 58 years; 30% were classic ILC and another 60% were of mixed non-classic variants (histologic pattern represented by nuclear pleomorphism). Management of patients with HER-2-positive ILC was performed according to standard multimodality breast cancer guidelines, consisting of surgery, chemotherapy with anti-HER-2/neu blockade, radiation, and endocrine therapy, based on stage and hormone status. CONCLUSIONS In conclusion, HER-2-positive invasive lobular carcinoma of the breast is uncommon in the Arab population, which has not been previously reported in the literature. Further studies are warranted to explore the biology, molecular characteristics, and clinical course in this group of patients.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Árabes , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/terapia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Arábia Saudita/epidemiologia
5.
BMJ Case Rep ; 13(12)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33370954

RESUMO

Type 1 multiple endocrine neoplasia (MEN-1) syndrome is an autosomal dominant disease, associated with germline mutations in the MEN-1 tumour suppressor gene (encoding the menin protein). Recent studies, through a better characterisation of the functions of the menin protein, have started to demonstrate how changes in this protein may be related to breast cancer. We present the case of a patient whose diagnosis of MEN-1 syndrome was made during treatment for a breast tumour-this diagnosis was obtained after finding multiple neoplastic lesions that fitted the MEN-1 syndrome spectrum, during the initial staging and subsequent follow-up of a breast tumour. In line with the growing evidence that links MEN-1 syndrome to breast cancer tumorigenesis, this case report highlights the following question: should we start screening this subset of patients earlier for breast cancer?


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Proteínas Proto-Oncogênicas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Tumor Carcinoide/sangue , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/genética , Tumor Carcinoide/terapia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Feminino , Aconselhamento Genético , Mutação em Linhagem Germinativa , Humanos , Achados Incidentais , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Imagem por Ressonância Magnética , Mamografia , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/terapia , Mutação , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Glândulas Paratireoides/diagnóstico por imagem , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/sangue , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/genética , Neoplasias das Paratireoides/terapia , Paratireoidectomia , Pneumonectomia , Radioterapia Adjuvante , Tomografia Computadorizada por Raios X , Ultrassonografia Mamária
6.
J Cancer Res Ther ; 16(3): 672-674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719289

RESUMO

Metastases to the parotid gland are very rare. We report the second case of bilateral metastases to the parotid gland from a breast invasive ductal carcinoma. A 50-year-old female was treated for an early left breast cancer in 2007. A pulmonary metastatic relapse was diagnosed in 2013. A metastatic skin extension required several lines of treatment from June 2014 to July 2016. Bilateral parotid gland metastases from a breast invasive ductal carcinoma were confirmed in December 2016. The patient died on May 2017 from cerebral metastases. Only 16 cases of metastasis to the parotid gland from breast cancer have been reported in the literature. Only one case had a bilateral involvement. Prognosis is poor, and there are no specific guidelines for the treatment.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Parotídeas/secundário , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Terapia Combinada , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Cuidados Paliativos , Neoplasias Parotídeas/terapia
7.
Breast Cancer Res ; 22(1): 76, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32665033

RESUMO

BACKGROUND: Early luminal breast cancer (BC) represents 70% of newly diagnosed BC cases. Among them, small (under 2 cm) BC without lymph node metastasis (classified as T1N0) have been rarely studied, as their prognosis is generally favorable. Nevertheless, up to 5% of luminal T1N0 BC patients relapse with distant metastases that ultimately prove fatal. The aim of our work was to identify the mechanisms involved in metastatic recurrence in these patients. METHODS: Our study addresses the role that autonomous and non-autonomous tumor cell features play with regard to distant recurrence in early luminal BC patients. We created a cohort of T1N0 luminal BC patients (tumors between 0.5-2 cm without lymph node metastasis) with metastatic recurrence ("cases") and corresponding "controls" (without relapse) matched 1:1 on main prognostic factors: age, grade, and proliferation. We deciphered different characteristics of cancer cells and their tumor micro-environment (TME) by deep analyses using immunohistochemistry. We performed in vitro functional assays and highlighted a new mechanism of cooperation between cancer cells and one particular subset of cancer-associated fibroblasts (CAF). RESULTS: We found that specific TME features are indicative of relapse in early luminal BC. Indeed, quantitative histological analyses reveal that "cases" are characterized by significant accumulation of a particular CAF subset (CAF-S1) and decrease in CD4+ T lymphocytes, without any other association with immune cells. In multivariate analysis, TME features, in particular CAF-S1 enrichment, remain significantly associated with recurrence, thereby demonstrating their clinical relevance. Finally, by performing functional analyses, we demonstrated that CAF-S1 pro-metastatic activity is mediated by the CDH11/osteoblast cadherin, consistent with bones being a major site of metastases in luminal BC patients. CONCLUSIONS: This study shows that distant recurrence in T1N0 BC is strongly associated with the presence of CAF-S1 fibroblasts. Moreover, we identify CDH11 as a key player in CAF-S1-mediated pro-metastatic activity. This is independent of tumor cells and represents a new prognostic factor. These results could assist clinicians in identifying luminal BC patients with high risk of relapse. Targeted therapies against CAF-S1 using anti-FAP antibody or CDH11-targeting compounds might help in preventing relapse for such patients with activated stroma.


Assuntos
Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Fibroblastos Associados a Câncer/imunologia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/imunologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Microambiente Tumoral/imunologia
8.
Breast Cancer Res ; 22(1): 69, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576238

RESUMO

BACKGROUND: In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant. METHODS: Using FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors. RESULTS: In the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups. CONCLUSIONS: Our findings indicate that the three scoring methods with a 1% cutoff are different in their sensitivity for PD-L1 expression and their associations with clinicopathologic factors. Scoring by TCIC is the most sensitive way to identify PD-L1-positive breast cancer by immunohistochemistry. As a prognostic marker, our study suggests that PD-L1 is associated with worse clinical outcome, most often shown by the IC score; however, the other scores may also have clinical implications in some subgroups. Large clinical trials are needed to test the similarities and differences of these scoring methods for their predictive values in anti-PD-1/PD-L1 therapy.


Assuntos
Antígeno B7-H1/biossíntese , Neoplasias da Mama/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/imunologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Terapia Combinada , Aprovação de Drogas , Feminino , Seguimentos , Humanos , Imuno-Histoquímica/métodos , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos , United States Food and Drug Administration
10.
J Surg Res ; 254: 378-383, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32535256

RESUMO

BACKGROUND: The present literature is conflicting regarding the management of microinvasive ductal carcinoma in situ (miDCIS) as to following recommendations for DCIS (margin status, surgical axillary staging, and possible observation) versus invasive breast cancer. We hypothesize that miDCIS represents more aggressive disease than pure DCIS. METHODS: We performed a retrospective review of female miDCIS patients compared with age-matched cohorts of DCIS and T1b/c patients with invasive breast cancer. We collected demographic, clinicopathologic, treatment, and outcome information. Analysis of variance or Kruskal-Wallis tests were used to analyze continuous variables and chi-square or Fisher's exact tests for categorical variables. Survival outcomes were analyzed using Kaplan-Meier curves. RESULTS: We included 375 patients (125 in each group) with median age 59 y (range 33-91 y). miDCIS tumors were more likely to be hormone receptor negative and human epidermal growth factor receptor 2 positive compared with DCIS or invasive ductal carcinoma (IDC; all P < 0.001). Subgroup analysis by miDCIS focality demonstrated no significant differences. The number of involved lymph nodes was not significantly different from DCIS patients but was significantly fewer than invasive cancer patients. Of 115 miDCIS patients (88%) staged with sentinel lymph node biopsy, eight (7%) had nodal metastases. Six miDCIS patients (5%) were treated with adjuvant chemotherapy. Over a median follow-up of 23.3 mo, there were no significant differences in local or distant recurrence. CONCLUSIONS: Based on our results, miDCIS has more aggressive pathologic features compared with DCIS and warrants surgical treatment and nodal staging similar to the management of IDC. In addition, similar to IDC, nodal and receptor status may influence medical management.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Carcinoma Ductal de Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Breast Cancer Res ; 22(1): 58, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32466799

RESUMO

BACKGROUND: Ultrafast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived kinetic parameters have demonstrated at least equivalent accuracy to standard DCE-MRI in differentiating malignant from benign breast lesions. However, it is unclear if they have any efficacy as prognostic imaging markers. The aim of this study was to investigate the relationship between ultrafast DCE-MRI-derived kinetic parameters and breast cancer characteristics. METHODS: Consecutive breast MRI examinations between February 2017 and January 2018 were retrospectively reviewed to determine those examinations that meet the following inclusion criteria: (1) BI-RADS 4-6 MRI performed on a 3T scanner with a 16-channel breast coil and (2) a hybrid clinical protocol with 15 phases of ultrafast DCE-MRI (temporal resolution of 2.7-4.6 s) followed by early and delayed phases of standard DCE-MRI. The study included 125 examinations with 142 biopsy-proven breast cancer lesions. Ultrafast DCE-MRI-derived kinetic parameters (maximum slope [MS] and bolus arrival time [BAT]) were calculated for the entire volume of each lesion. Comparisons of these parameters between different cancer characteristics were made using generalized estimating equations, accounting for the presence of multiple lesions per patient. All comparisons were exploratory and adjustment for multiple comparisons was not performed; P values < 0.05 were considered statistically significant. RESULTS: Significantly larger MS and shorter BAT were observed for invasive carcinoma than ductal carcinoma in situ (DCIS) (P < 0.001 and P = 0.008, respectively). Significantly shorter BAT was observed for invasive carcinomas with more aggressive characteristics than those with less aggressive characteristics: grade 3 vs. grades 1-2 (P = 0.025), invasive ductal carcinoma vs. invasive lobular carcinoma (P = 0.002), and triple negative or HER2 type vs. luminal type (P < 0.001). CONCLUSIONS: Ultrafast DCE-MRI-derived parameters showed a strong relationship with some breast cancer characteristics, especially histopathology and molecular subtype.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Meios de Contraste , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
13.
Isr Med Assoc J ; 22(3): 160-163, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32147980

RESUMO

BACKGROUND: Male breast cancer (MBC) is a rare disease that is poorly understood. Treatment protocols are widely extrapolated from breast cancer in women. OBJECTIVES: To review the experience with MBC of a single center in Israel over a period of 22 years. METHODS: This single center retrospective study evaluated all patients diagnosed with MBC over a period of 22 years (1993-2015). Data were extracted from patient medical charts and included demographics, clinical, surgical, and oncological outcomes. RESULTS: The study comprised 49 patients. Mean age at diagnosis was 64.1 ± 13.5 years. The majority were diagnosed at early stages (1A-2A) (54.4%), 30.6% were stage 3B mostly due to direct skin and nipple involvement, and 59.2% of the patients had node negative disease. All of the patients were diagnosed with invasive ductal carcinoma and 30.6% had concomitant ductal carcinoma in situ. Estrogen receptor (ER) status was predominantly positive and luminal B (HER2-) was the most common subtype. Of the patients, 18.4% were BRCA carriers. The majority of patients underwent mastectomy. Radiotherapy was delivered to 46.9% and hormonal therapy to 89.8%. Chemotherapy was administered to 42.9%. Overall survival was 79.6% with a median survival of 60.1 (2-178) months; 5- and 10-year survival was 93.9% and 79.6%, respectively. Progesterone receptor (PR)-negative patients had a significantly improved overall survival. CONCLUSIONS: MBC has increasing incidence. PR-negative status was associated with better overall survival and disease-free interval. Indications to radiotherapy and hormonal therapy need standardization and will benefit from prospective randomized control trials.


Assuntos
Neoplasias da Mama Masculina/epidemiologia , Neoplasias da Mama Masculina/terapia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/terapia , Intervalo Livre de Doença , Humanos , Israel/epidemiologia , Masculino , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
World J Surg Oncol ; 18(1): 11, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937323

RESUMO

BACKGROUND: Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear. METHODS: We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples. RESULTS: Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1-19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02). CONCLUSIONS: Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.


Assuntos
Antígeno B7-H1/imunologia , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Metaplasia/patologia , Metaplasia/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/patologia
16.
Breast ; 49: 93-100, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31783315

RESUMO

BACKGROUND: Metastatic regional lymph nodes (LN) is a strong predictor of worse long-term outcome. Therefore, different LN staging systems have been proposed in recent years. In this study, we proposed a modified lymph node ratio (mLNR) as a new lymph node staging system and then compared the prognostic performance of mLNR with American Joint Committee on Cancer N stage, lymph node ratio (LNR) and log odds of metastatic lymph nodes in breast cancer patients. METHODS: Breast cancer patients who underwent surgery between 2004 and 2012 were identified from the Surveillance, Epidemiology, and End Results database. Restricted cubic spline functions were calculated to characterize the association between variables and the risk of death. The Cox proportional hazards models were constructed to assess the predictive ability of different lymph node staging systems using the Akaike's Information Criterion (AIC) and Harrell's concordance index (C-index). RESULTS: A total of 264,096 breast cancer patients were enrolled and 187,785 (71.1%) patients had a limited number of LNs harvested. In the limited LN harvest cohort, the prognostic performance of LNR decreased and mLNR could greatly solve this problem. In addition, among the entire cohort, mLNR modeled as a continuous value had the best predictive ability (AIC: 922021.9 and C-index: 0.727) than other lymph node staging systems. CONCLUSIONS: The predictive ability of LNR is restricted by a limited LN harvest. However, mLNR shows superiority to LNR and other lymph node staging systems especially in a limited LN harvest cohort, making mLNR the most powerful lymph node staging systems.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Razão entre Linfonodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/mortalidade , Carcinoma Lobular/terapia , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Programa de SEER , Análise de Sobrevida , Adulto Jovem
17.
Cancer ; 126(6): 1193-1201, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31860136

RESUMO

BACKGROUND: Despite data demonstrating the safety of omitting axillary surgery in older women with early-stage breast cancer, the incidence of axillary surgery remains high. It was hypothesized that the prevalence of nodal positivity would decrease with advancing age. METHODS: The National Cancer Data Base was used to construct a cohort of adult women with early-stage, clinically node-negative, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative breast cancer treated between 2013 and 2015. Multivariable logistic regression was used to assess the relationship between age and nodal positivity, and this was stratified by the axillary surgery category. Modified Poisson regression was used to estimate the proportion of women receiving adjuvant therapy according to age and nodal status. RESULTS: The incidence of axillary surgery among women aged 70 and older (n = 51,917) remained high nationwide (86%). There was a significant decrease in nodal positivity with advancing age in women with early-stage, ER+, clinically node-negative breast cancer from the youngest cohort up to patients aged 70 to 89 years, and this was independent of histologic subtype (ductal vs lobular), race, comorbidities, and socioeconomic factors. Overall, less than 10% of women aged 70 or older who underwent surgery had node-positive disease, regardless of axillary surgery type, and almost 95% of node-positive patients aged 70 or older were at pathological stage N1mi or N1. CONCLUSIONS: Axillary surgery may be safely omitted for many older women with ER+, clinically node-negative, early-stage breast cancer. Nodal positivity declines with advancing age, and this suggests varied biology in older patients versus younger patients.


Assuntos
Fatores Etários , Neoplasias da Mama/cirurgia , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/química , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Carcinoma Lobular/terapia , Quimioterapia Adjuvante , Estudos de Coortes , Comorbidade , Feminino , Humanos , Linfonodos/patologia , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Distribuição de Poisson , Radioterapia Adjuvante , Receptor ErbB-2 , Receptores Estrogênicos , Análise de Regressão , Fatores Socioeconômicos , Adulto Jovem
18.
Eur J Obstet Gynecol Reprod Biol ; 244: 66-70, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31760264

RESUMO

PURPOSE: In the present study, we present a large institutional study to determine the influence of age≥ 80 years on breast cancer presentation and prognosis. METHODS: The study is a retrospective analysis of our prospectively maintained breast cancer database study using data from of women managed from January 2007 through December 2013. Clinicopathologic characteristics were correlated with outcomes according to age (<80 years and ≥ 80 years). RESULTS: During the study period, 2083 women with invasive breast cancer were included of which 160 women aged ≥ 80 years (7.7 %). Overall survival was lower in the oldest old than in younger counterparts (p < 0.0001) as was distant metastasis free survival (p = 0.004). Differences in management included more radical surgeries and less chemotherapy and radiotherapy in case of age≥ 80 years. By multivariate analysis, age ≥ 80 years was an independent predictive factor of poor overall survival. CONCLUSION: In the present study, age ≥ 80 years was an independent predictive factor of poor overall survival.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/terapia , França/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
19.
Am J Surg Pathol ; 44(2): 182-190, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31609784

RESUMO

Flat epithelial atypia (FEA) is an alteration of terminal duct lobular units by a proliferation of ductal epithelium with low-grade atypia. No consensus exists on whether the diagnosis of FEA in core needle biopsy (CNB) requires excision (EXC). We retrospectively identified all in-house CNBs obtained between January 2012 and July 2018 with FEA. We reviewed all CNB slides and assessed radiologic-pathologic concordance. An upgrade was defined as invasive carcinoma (IC) and/or ductal carcinoma in situ in the EXC. The EXC slides of all upgraded cases were rereviewed. Out of ∼15,700 consecutive CNBs in the study period, 106 CNBs from 106 patients yielded FEA alone or with classic lobular neoplasia (LN). We excluded 52 CNBs (40 patients with prior/concurrent carcinoma and 12 without EXC). After rereview, we reclassified 14 cases (2 marked nuclear atypia, 10 focal atypical ductal hyperplasia, 2 benign). The final FEA study cohort consisted of 40 CNBs from 40 women. The CNB targeted mammographic calcifications in 36 (90%) cases, magnetic resonance imaging nonmass enhancement in 3 (8%), and 1 (2%) sonographic mass. All CNBs were deemed radiologic-pathologic concordant. FEA was present alone in 34 CNBs and with LN in 6. EXC yielded 2 low-grade IC, each spanning <2 mm, identified in tissue sections without biopsy site changes. The remaining 38 cases had no upgrade. Classic LN did not affect the upgrade. The upgrade rate of FEA was 5%; both minute, low-grade "incidental" IC. We conclude that nonsurgical management may be considered in patients without prior/concurrent carcinoma and radiologic-pathologic concordant CNB diagnosis of FEA.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Biópsia com Agulha de Grande Calibre , Mama/diagnóstico por imagem , Mama/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/terapia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/terapia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/terapia , Tratamento Conservador , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Mamografia , Mastectomia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico por imagem , Lesões Pré-Cancerosas/terapia , Estudos Retrospectivos , Medição de Risco , Ultrassonografia Mamária
20.
Breast ; 49: 8-16, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31675684

RESUMO

PURPOSE: Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC. METHODS: The National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS. RESULTS: Altogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p < 0.001). The greater observed OS for patients with TNBC persisted when controlling for stage and when comparing propensity score matched cohorts. On Cox regression, lower age, T1 status, N0 status, chemotherapy, TNBC disease, and radiation therapy (RT) were associated with improved OS. CONCLUSIONS: MBC had an association with poorer OS compared to TNBC, while RT and chemotherapy receipt were associated with improved OS for patients regardless of stage. Further studies are needed to corroborate the conclusions herein.


Assuntos
Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/mortalidade , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Estudos de Casos e Controles , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia , Estados Unidos/epidemiologia
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