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2.
Am J Surg Pathol ; 44(9): 1161-1172, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32804453

RESUMO

Given the high incidence and excellent prognosis of many papillary thyroid microcarcinomas, the Porto proposal uses the designation papillary microtumor (PMT) for papillary microcarcinomas (PMCs) without risk factors to minimize overtreatment and patients' stress. To validate Porto proposal criteria, we examined a series of 190 PMC series, also studying sex hormone receptors and BRAF mutation. Our updated Porto proposal (uPp) reclassifies as PMT incidental PMCs found at thyroidectomy lacking the following criteria: (a) detected under the age of 19 years; (b) with multiple tumors measuring >1 cm adding up all diameters; and (c) with aggressive morphologic features (extrathyroidal extension, angioinvasion, tall, and/or hobnail cells). PMCs not fulfilling uPp criteria were considered "true" PMCs. A total of 102 PMCs were subclassified as PMT, 88 as PMC, with no age or sex differences between subgroups. Total thyroidectomy and iodine-131 therapy were significantly more common in PMC. After a median follow-up of 9.6 years, lymph node metastases, distant metastases, and mortality were only found in the PMC subgroup. No subgroup differences were found in calcifications or desmoplasia. Expression of estrogen receptor-α and estrogen receptor-ß, progesterone receptor, and androgen receptor was higher in PMC than in nontumorous thyroid tissue. BRAF mutations were detected in 44.7% of PMC, with no differences between subgroups. In surgical specimens, the uPp is a safe pathology tool to identify those PMC with extremely low malignant potential. This terminology could reduce psychological stress associated with cancer diagnosis, avoid overtreatment, and be incorporated into daily pathologic practice.


Assuntos
Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Papilar/química , Carcinoma Papilar/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Receptores de Esteroides/análise , Neoplasias da Glândula Tireoide/química , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Análise Mutacional de DNA , Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Radioterapia Adjuvante , Receptores Androgênicos/análise , Receptores de Progesterona/análise , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Resultado do Tratamento , Adulto Jovem
3.
Eur J Epidemiol ; 35(9): 807-819, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32728914

RESUMO

Identifying the susceptible period when environmental factors affect disease risk is essential for understanding disease etiology. Most existing epidemiologic studies use oversimplified summaries of time-dependent exposures such as baseline or most current exposure, or the cumulative average of exposure over available follow-up periods. In this paper, we introduce a damped exponential weighting model for estimating optimal exposure weights for different time intervals. This model can accommodate flexible patterns of weights and can be fit using standard software. We applied the model to assess the latency of BMI and alcohol for post-menopausal breast cancer based on 30-year exposure history in the Nurses' Health Study. We have also performed a simulation study to assess the validity of the proposed hypothesis testing and estimation procedures in realistic conditions. We found that the type I error is close to 0.05; the bias in our parameter estimates is low and the coverage probability of interval estimates is close to 0.95. For ER+/PR+ breast cancer we found that recent BMI was a more important predictor of risk than more distant BMI; for ER-/PR- breast cancer, no latency was found and risk was characterized by cumulative high levels of BMI over a long period of time. For alcohol intake, we saw a strong positive association with cumulative intake for ER+/PR+ breast cancer; no significant association was found for cumulative intake or for any latency measure of risk for ER-/PR- breast cancer. Our results underscore the value of an easy-to-implement approach to latency analysis of exposure profiles for chronic disease.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias da Mama/etiologia , Doença Crônica/epidemiologia , Suscetibilidade a Doenças/complicações , Exposição Ambiental , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Adulto , Índice de Massa Corporal , Neoplasias da Mama/química , Neoplasias da Mama/epidemiologia , Estudos Epidemiológicos , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Modelos de Riscos Proporcionais , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Fatores de Tempo
4.
Virchows Arch ; 477(4): 545-555, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32383007

RESUMO

Reliable determination of Ki67 labeling index (Ki67-LI) on core needle biopsy (CNB) is essential for determining breast cancer molecular subtype for therapy planning. However, studies on agreement between molecular subtype and Ki67-LI between CNB and surgical resection (SR) specimens are conflicting. The present study analyzed the influence of clinicopathological and sampling-associated factors on agreement. Molecular subtype was determined visually by Ki67-LI in 484 pairs of CNB and SR specimens of invasive estrogen receptor (ER)-positive, human epidermal growth factor (HER2)-negative breast cancer. Luminal B disease was defined by Ki67-LI > 20% in SR. Correlation of molecular subtype agreement with age, menopausal status, CNB method, Breast Imaging Reporting and Data System imaging category, time between biopsies, type of surgery, and pathological tumor parameters was analyzed. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. CNB had a sensitivity of 77.95% and a specificity of 80.97% for identifying luminal B tumors in CNB, compared with the final molecular subtype determination after surgery. The correlation of Ki67-LI between CNB and SR was moderate (ROC-AUC 0.8333). Specificity and sensitivity for CNB to correctly define molecular subtype of tumors according to SR were significantly associated with tumor grade, immunohistochemical progesterone receptor (PR) and p53 expression (p < 0.05). Agreement of molecular subtype did not significantly impact RFS and OS (p = 0.22 for both). The identified factors likely mirror intratumoral heterogeneity that might compromise obtaining a representative CNB. Our results challenge the robustness of a single CNB-driven measurement of Ki67-LI to identify luminal B breast cancer of low (G1) or intermediate (G2) grade.


Assuntos
Neoplasias da Mama/química , Antígeno Ki-67/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Proteína Supressora de Tumor p53/análise
5.
Am J Surg Pathol ; 44(8): 1092-1103, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32317606

RESUMO

To date, the apocrine variant of lobular carcinoma in situ (AP-LCIS) has been cursorily described as a subtype of lobular carcinoma in situ (LCIS). We retrospectively reviewed 34 cases of AP-LCIS (including 23 associated with invasive lobular carcinoma) to fully characterize it. AP-LCIS typically presented with screen-detected calcifications in older women (mean age: 65 y) and was characterized by distended terminal duct lobular units with relatively large "pleomorphic" cells, central necrosis, and calcifications. AP-LCIS cells exhibited abundant eosinophilic occasionally granular cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Synchronous classic and/or florid LCIS was identified in 24/34 (70%) AP-LCIS, and in 9/11 (82%) pure AP-LCIS. Most (68%) cases of AP-LCIS were estrogen receptor-positive (50% strongly), 35% were progesterone receptor-positive, 26% were human epidermal growth factor 2-positive, 18% demonstrated high-proliferation rate (Ki67: >15%), and 90% were androgen receptor-positive. Aurora kinase A, immunoreactive in 38% of AP-LCIS cases, was not significantly associated with recurrence, development of invasion, or nodal positivity (P>0.05). Compared with conventional (nonapocrine) pleomorphic lobular carcinoma in situ (P-LCIS), aurora kinase A was expressed in a significantly greater proportion of P-LCIS (100%). AP-LCIS and P-LCIS did not otherwise differ in clinicopathologic features. Next-generation sequencing utilizing the Oncomine Comprehensive Panel v2, performed on 27 AP-LCIS cases, showed no specific molecular findings. In a mean follow-up of 57 months, 2 (of 11, 18%) pure AP-LCIS cases recurred (2 both in situ and invasive) and none metastasized or proved fatal. AP-LCIS should be regarded as another high-grade LCIS similar to P-LCIS in many respects, and pending additional studies should be managed similarly.


Assuntos
Glândulas Apócrinas , Carcinoma de Mama in situ/classificação , Neoplasias da Mama/classificação , Idoso , Glândulas Apócrinas/química , Glândulas Apócrinas/patologia , Aurora Quinase A/análise , Carcinoma de Mama in situ/química , Carcinoma de Mama in situ/genética , Carcinoma de Mama in situ/patologia , Neoplasias da Mama/química , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Calcinose , Proliferação de Células , Bases de Dados Factuais , Fator de Crescimento Epidérmico/análise , Feminino , Humanos , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Necrose , Recidiva Local de Neoplasia , Prognóstico , Receptores Androgênicos/análise , Receptores de Progesterona/análise , Estudos Retrospectivos
6.
Eur J Cancer ; 129: 60-70, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32135312

RESUMO

AIM: Real-world data inform the outcome comparisons and help the development of new therapeutic strategies. To this end, we aimed to describe the full characteristics and outcomes in the Epidemiological Strategy and Medical Economics (ESME) cohort, a large national contemporary observational database of patients with metastatic breast cancer (MBC). METHODS: Women aged ≥18 years with newly diagnosed MBC and who initiated MBC treatment between January 2008 and December 2016 in one of the 18 French Comprehensive Cancer Centers (N = 22,109) were included. We assessed the full patients' characteristics, first-line treatments, overall survival (OS) and first-line progression-free survival, as well as updated prognostic factors in the whole cohort and among the 3 major subtypes: hormone receptor positive and HER2-negative (HR+/HER2-, n = 13,656), HER2-positive (HER2+, n = 4017) and triple-negative (n = 2963) tumours. RESULTS: The median OS of the whole cohort was 39.5 months (95% confidence interval [CI], 38.7-40.3). Five-year OS was 33.8%. OS differed significantly between the 3 subtypes (p < 0.0001) with a median OS of 43.3 (95% CI, 42.5-44.5) in HR+/HER2-; 50.1 (95% CI, 47.6-53.1) in HER2+; and 14.8 months (95% CI, 14.1-15.5) in triple-negative subgroups, respectively. Beyond performance status, the following variables had a constant significant negative prognostic impact on OS in the whole cohort and among subtypes: older age at diagnosis of metastases (except for the triple-negative subtype), metastasis-free interval between 6 and 24 months, presence of visceral metastases and number of metastatic sites ≥ 3. CONCLUSIONS: The ESME program represents a unique large-scale real-life cohort on MBC. This study highlights important situations of high medical need within MBC patients. DATABASE REGISTRATION: clinicaltrials.gov Identifier NCT032753.


Assuntos
Neoplasias Abdominais/mortalidade , Neoplasias Ósseas/mortalidade , Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/mortalidade , Metástase Linfática , Neoplasias Cutâneas/mortalidade , Neoplasias Abdominais/prevenção & controle , Neoplasias Abdominais/secundário , Adolescente , Adulto , Fatores Etários , Idoso , Neoplasias Ósseas/prevenção & controle , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Mama/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Intervalo Livre de Doença , Feminino , França/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/análise , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/secundário , Adulto Jovem
7.
Arch Pathol Lab Med ; 144(5): 545-563, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31928354

RESUMO

PURPOSE.­: To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer guideline. METHODS.­: A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature. RECOMMENDATIONS.­: The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines .


Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Estrogênios/análise , Receptores de Progesterona/análise , American Medical Association , Neoplasias da Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Oncologia , Patologistas , Patologia Clínica , Prognóstico , Estados Unidos
8.
Am J Clin Pathol ; 153(1): 58-65, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415692

RESUMO

OBJECTIVES: Vacuum-assisted biopsy (VAB) of the breast seems unsuitable for rapid processing due to large size. We tested microwave-based acceleration. METHODS: As a proof-of-principle study, 9-gauge VAB specimens were taken from eight mastectomy specimens. Forty-two biopsy specimens were processed. Quality of H&E was evaluated in 84 slides, and estrogen receptor (ER), progesterone receptor (PR), E-cadherin, and human epidermal growth factor receptor 2 (HER2) stains were evaluated in six slides. Preoperative biopsy specimens were used as a control. RESULTS: Diagnostic quality of H&E slides was good in 87%, reasonable in 12%, and low in 1%. Quality of E-cadherin was good in 75% and reasonable in 25%. Quality of ER was good in 83% and reasonable in 17%. PR and both HER2 immunohistochemistry and fluorescence in situ hybridization were good in all slides. Quality of experimental slides was similar to control slides. CONCLUSIONS: Nine-gauge VAB specimens can be processed within 4 hours. Slides are suitable for all routine pathologic stains. This enables a same-day diagnosis.


Assuntos
Antígenos CD/metabolismo , Neoplasias da Mama/patologia , Caderinas/metabolismo , Receptor ErbB-2/metabolismo , Biópsia por Agulha , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Mastectomia , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Vácuo
9.
J Surg Res ; 247: 211-219, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31706539

RESUMO

BACKGROUND: The eighth edition of the American Cancer Joint Committee on Cancer (AJCC) staging system for breast cancer put forward the prognostic stage groups for the first time based on the traditional anatomic tumor-node-metastasis staging system. Our study intends to validate the predictive significance of the eighth edition staging system in triple-negative breast cancer (TNBC) patients. MATERIALS AND METHODS: We collected and accessed 26,589 eligible cases of TNBC from the Surveillance, Epidemiology, and End Results database (2010-2015) and reclassified the patient cohort according to the eighth edition of the AJCC staging system into anatomic and prognostic stages. RESULTS: The results showed that more than half of the patients upstaged in the prognostic stage when compared with the anatomic stage. By comparing with the anatomic stage, the prognostic stage had a higher likelihood ratio and linear trend χ2 values. The prognostic stage group also had higher Akaike information criterion and Bayesian information criterion values than the anatomic stage group. CONCLUSIONS: The prognostic staging system in TNBC patients performs more optimistic prognostic stratification and predictability than the anatomic staging system. Moreover, the latest AJCC staging system has a milestone importance to the history of breast cancer staging system.


Assuntos
Biomarcadores Tumorais/análise , Mama/patologia , Metástase Linfática/patologia , Neoplasias de Mama Triplo Negativas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Receptor ErbB-2/análise , Receptor ErbB-2/genética , Receptores Estrogênicos/análise , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Programa de SEER/estatística & dados numéricos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Estados Unidos , Adulto Jovem
10.
Turk Patoloji Derg ; 36(1): 23-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31769499

RESUMO

OBJECTIVE: To evaluate the pathological and radiological features, hormone profiles, surgery and treatment methods of metaplastic breast carcinoma cases diagnosed at our center in the light of current literature. MATERIAL AND METHOD: A total of 38 metaplastic breast cancer cases diagnosed between 2006-2018 at our center were included in the study. The patients were evaluated in terms of age, tumor size, localization, histological grade, hormone profiles (ER, PR, Her2-neu), American Joint Committee on Cancer (AJCC) Tumor, Lymph node status, Metastases (TNM) stage, progression, survival, radiological features, types of surgery and therapy modalities (chemotherapy and / or radiotherapy). RESULTS: The age of the patients ranged between 32 and 95 years. Pathological evaluation of cases showed that 14 were pure epithelial (IC-NST + squamous cell carcinoma) and 24 were metaplastic carcinomas with mesenchymal differentiation. Ductal carcinoma in situ (DCIS) was accompanying an invasive component in twenty cases. Seventeen patients had lymph node metastasis. Twelve patients developed distant metastasis. Thirty patients were triple negative for hormone receptors. The mean follow-up period of the patients was 34 months. The estimated life expectancy was 116 months. All of the patients received chemotherapy and 28 patients received adjuvant radiotherapy. There was no correlation between tumor size and lymph node or distant metastasis in our series. Our findings are consistent with the literature. CONCLUSION: Metaplastic breast carcinoma is a rare entity among breast carcinomas. Metaplastic carcinomas of the breast draw attention with the differences in their clinical course and the radiological and pathological heterogeneity.


Assuntos
Neoplasias da Mama/patologia , Carcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma/química , Carcinoma/mortalidade , Carcinoma/terapia , Feminino , Humanos , Metástase Linfática , Metaplasia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Resultado do Tratamento , Carga Tumoral , Turquia
11.
Lancet Oncol ; 21(2): 250-260, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31859246

RESUMO

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDKIs) are indicated with endocrine therapy as first-line or second-line treatment for hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer. We aimed to investigate the benefit of adding CDKIs to endocrine therapy in patients whose tumours might have differing degrees of endocrine sensitivity. METHODS: We pooled individual patient data from all phase 3 randomised breast cancer trials of CDKIs plus endocrine therapy submitted to the US Food and Drug Administration before Jan 1, 2019, in support of marketing applications. Our pooled analysis included all randomly assigned patients in these trials who received at least one dose of CDKI or placebo with endocrine therapy (an aromatase inhibitor [letrozole or anastrazole] or fulvestrant). We did prespecified subgroup analyses in patients with progesterone receptor-negative disease; patients with a disease-free interval of 12 months or less; patients with de-novo metastases, lobular histology, and bone-only disease; patients with visceral metastases; and patients aged up to 40 years. Patients who were not treated, who received tamoxifen as endocrine therapy, or who were treated with an aromatase inhibitor but who had received previous chemotherapy in the metastatic setting (not first-line) were excluded from our pooled analyses. All studies had a primary endpoint of investigator-assessed progression-free survival, defined as time from date of randomisation to the initial date of documented cancer progression or death, whichever occurred first. Median progression-free survival was estimated with Kaplan-Meier methods. Hazard ratios (HR) with 95% CIs for progression-free survival were estimated by means of Cox regression models. FINDINGS: The seven studies meeting this study's inclusion criteria were done between Feb 22, 2013, and Nov 3, 2017, with a median duration of follow-up of 19·7 months (IQR 15·9-25·9). 4200 patients were included in the pooled analysis, of whom 1320 received an aromatase inhibitor plus a CDKI, 932 received placebo plus an aromatase inhibitor, 1296 received fulvestrant plus a CDKI, and 652 received fulvestrant plus placebo. Across all seven pooled trials, the difference in estimated median progression-free survival was 8·8 months in favour of CDKI plus endocrine therapy over placebo plus endocrine therapy (range across the trials 6·8-13·3 months; HR 0·59, 95% CI 0·54-0·64). Progression-free survival results favoured the CDKI group in all prespecified clinicopathological subgroups analysed, with similar HRs to that for the broader intended-use population. In first-line aromatase inhibitor-treated patients (n=2252), the median progression-free survival in the CDKI plus aromatase inhibitor group was 28·0 months (95% CI 25·3-29·1) versus 14·9 months (14·0-16·7) in the placebo plus aromatase inhibitor group (difference 13·1 months; range across the trials 13·0-13·3 months; HR 0·55, 95% CI 0·49-0·62). In first-line fulvestrant-treated patients (n=396), the median progression-free survival was 18·6 months (95% CI 14·8-23·5) in the placebo plus fulvestrant group and not estimable (22·4 to not estimable) in the CDKI plus fulvestrant group (difference not estimable; HR 0·58, 95% CI 0·42-0·80). In the patients treated with fulvestrant in the second-line setting and beyond (n=1552), the difference in estimated median progression-free survival between the CDKI plus fulvestrant group and the placebo plus fulvestrant group was 6·9 months in favour of the CDKI group (range across the trials 5·5-7·3 months; HR 0·56, 95% CI 0·49-0·64). INTERPRETATION: Since the addition of CDKI to endocrine therapy seemed to benefit all clinicopathological subgroups of interest in this pooled analysis, further research is needed to identify patient subgroups for whom endocrine therapy alone might be appropriate for first-line or second-line treatment of hormone receptor-positive, HER2-negative metastatic breast cancer. FUNDING: None.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/administração & dosagem , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Ensaios Clínicos Fase III como Assunto , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Aprovação de Drogas , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Transdução de Sinais , Fatores de Tempo , Estados Unidos , United States Food and Drug Administration
12.
Cancer Cytopathol ; 128(2): 133-145, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31883437

RESUMO

BACKGROUND: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) guide the clinical management of breast cancer metastases. Decalcification of bone core needle biopsies (CNBs) can affect IHC. In the current study, the authors sought to define whether fine-needle aspiration (FNA) would be a better alternative to CNB for reliable IHC. METHODS: Patients with breast cancer metastases to bone that were sampled by both CNB and FNA were selected. ER, PR, and HER2 were performed in FNA cell blocks (FNA-CBs) and concurrent decalcified CNBs. Discrepancies were classified as minor when there was a difference of up to 30% nuclear staining in IHC for ER and PR between paired samples and as major when a clinically relevant change was observed (ie, positive vs negative). Quantitative reverse transcriptase-polymerase chain reaction of ESR1 messenger RNA levels was performed on FNA/CNB pairs with discrepancies for ER IHC. IHC status of the primary breast carcinoma was recorded. RESULTS: Concordance rates for ER, PR, and HER2 were 89%, 67%, and 93%, respectively, between FNA-CB and CNB pairs from 27 patients. Major discrepancies were noted in approximately 11% of FNA/CNB pairs for ER IHC and in 33% of FNA/CNB pairs for PR. ESR1 messenger RNA levels of FNA/CNB matched samples were similar and did not explain the differences in ER IHC expression in the majority of cases. Two of 27 FNA/CNB pairs had different results for HER2 IHC that changed from negative on CNB to equivocal (2+) on FNA-CB. Both cases had prior HER2 amplification by fluorescence in situ hybridization. CONCLUSIONS: FNA-CB and CNB appear to constitute acceptable methods for the assessment of ER, PR, and HER2 for clinical decision making.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Ósseas/diagnóstico , Osso e Ossos/patologia , Neoplasias da Mama/patologia , Carcinoma/diagnóstico , Técnicas de Preparação Histocitológica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina/métodos , Biópsia com Agulha de Grande Calibre/métodos , Neoplasias Ósseas/secundário , Carcinoma/secundário , Tomada de Decisão Clínica/métodos , Estudos de Coortes , Feminino , Humanos , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/análise , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo
13.
Environ Sci Pollut Res Int ; 27(2): 1991-2000, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31768959

RESUMO

The aim was to assess the association of histological tumor grade with other clinical features and epidemiological factors of women with invasive breast carcinoma. A retrospective study of 103 Mizo breast cancer patients visiting hospitals was made in Aizawl, Mizoram, Northeast India. With a prior consent, information on epidemiological factors and family history in relation to cancer was obtained. Clinical reports were obtained from their medical records. The frequency of distribution was calculated for age at diagnosis and tumor characteristics. Statistical analysis for different variables was done using a chi-square test. p < 0.05 was considered significant. The histological tumor grades in our studies were found to be associated with lymph node invasion (p < 0.021), different subtype of hormone receptor such as ER status (p < 0.004), ER/PR status (p < 0.007), HER2/neu status (p < 0.014), and ER/PR/HER2 status (p < 0.025). A patient with a family history of breast cancer in their 1st degree relative is also seen to have association in determining the tumor grade (p < 0.003). Reproductive history, lifestyle and dietary habits, tobacco, and alcohol consumption were found to have no influence on breast cancer tumor grade. Our results showing significant correlation between status of lymph node, ER, PR, and HER2/neu oncoprotein and family history with 1st degree relative breast cancer are the first time report to target and focus on the possible role of biomarkers for diagnosis among the Mizo tribal breast cancer patients.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Saúde da Família , Feminino , Humanos , Índia/epidemiologia , Gradação de Tumores , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Estudos Retrospectivos
14.
Reprod Biol Endocrinol ; 17(1): 111, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31878927

RESUMO

BACKGROUND: Previous studies of expression profiles of major endometrial effectors of steroid physiology in endometriosis have yielded markedly conflicting conclusions, presumably because the relative effects of type of endometriosis, fertility history and menstrual cycle phases on the measured variables were not considered. In the present study, endometrial mRNA and protein levels of several effectors of steroid biosynthesis and action in patients with stage III-IV ovarian endometriosis (OE) with known fertility and menstrual cycle histories were compared with the levels in control endometrium to test this concept. METHODS: Endometrial samples were collected from patients without endometriosis (n = 32) or OE stages III-IV (n = 52) with known fertility and cycle histories. qRT-PCR and immunoblotting experiments were performed to measure levels of NR5A1, STAR, CYP19A1, HSD17Bs, ESRs and PGR transcripts and proteins, respectively. Tissue concentrations of steroids (P4, T, E1 and E2) were measured using ELISAs. RESULTS: The levels of expression of aromatase and ERß were lower (P < 0.0001) and 17ß-HSD1 (P < 0.0001) and PRA (P < 0.01) were higher in OE endometrium. Lower aromatase levels and higher 17ß-HSD1 levels were detected in fertile (aromatase: P < 0.05; 17ß-HSD1: P < 0.0001) and infertile (aromatase: P < 0.0001; 17ß-HSD1: P < 0.0001) OE endometrium than in the matched control tissues. Both proliferative (PP) and secretory (SP) phase OE samples expressed aromatase (P < 0.0001) and ERß (PP: P < 0.001; SP: P < 0.01) at lower levels and 17ß-HSD1 (P < 0.0001) and PRA (PP: P < 0.01; SP: P < 0.0001) at higher levels than matched controls. Higher 17ß-HSD1 (P < 0.01) and E2 (P < 0.05) levels and a lower (P < 0.01) PRB/PRA ratio was observed in infertile secretory phase OE endometrium than in control. CONCLUSIONS: We report that dysregulated expression of 17ß-HSD1 and PGR resulting in hyperestrogenism and progesterone resistance during the secretory phase of the menstrual cycle, rather than an anomaly in aromatase expression, was the hallmark of eutopic endometrium from infertile OE patients. Furthermore, the results provide proof of concept that the fertility and menstrual cycle histories exerted relatively different effects on steroid physiology in the endometrium from OE patients compared with the control subjects.


Assuntos
Endometriose/metabolismo , Endométrio/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Doenças Ovarianas/metabolismo , Receptores de Esteroides/metabolismo , 17-Hidroxiesteroide Desidrogenases/análise , 17-Hidroxiesteroide Desidrogenases/genética , Adolescente , Adulto , Aromatase/análise , Aromatase/genética , Endométrio/química , Estradiol/análise , Feminino , Expressão Gênica , Humanos , Infertilidade Feminina/metabolismo , Ciclo Menstrual , Progesterona/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Receptores de Esteroides/genética , Adulto Jovem
15.
Medicine (Baltimore) ; 98(44): e17854, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689877

RESUMO

Breast cancer is the most common diagnosed malignancy in women. This study genotyped blood samples from 236 Han Chinese women with breast cancer and 128 healthy controls for single nucleotide polymorphisms (SNPs) rs2977537, rs2929970, rs2929973, rs2977530, and rs62514004, to determine whether these WNT1-inducible signaling pathway protein 1 (WISP-1) genetic polymorphisms increase the risk of developing breast cancer. Compared with wild-type (AA) carriers, those carrying the WISP1 rs62514004 AG or AG + GG genetic variants had a greater risk of developing breast cancer. In an evaluation of the association between clinicopathological aspects and the WISP1 SNP rs62514004 in the breast cancer cohort, patients with the GG genotype were less likely than those with the AA genotype to develop stage III/IV disease. Patients carrying the WISP1 rs2929973 GG + TT variant were almost twice as likely as those carrying the GT genotype to have estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors, while those with the WISP1 rs62514004 AG + GG genetic variants were around twice as likely as those with the AA genotype to have HER2-positive tumors. This study details risk associations between WISP1 SNPs and breast cancer susceptibility in women of Han Chinese ethnicity.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Proteínas de Sinalização Intercelular CCN/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Fatores de Risco , Transdução de Sinais
16.
Medicine (Baltimore) ; 98(47): e17818, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764773

RESUMO

To investigate preoperative platelet morphology parameters and other whole blood cells in patients of malignant endometrial carcinoma compared with benign disease.Retrospective analysis was performed through collecting patients' hematological parameters before performing total abdominal/vaginal hysterectomy and standard radical surgery due to benign and malignant endometrial disease between 2006 and 2017. Parameters required included white blood cell (WBC), hemoglobin, platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and platelet thrombocytocrit (PCT). And neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated. For malignant carcinoma, Ki-67 percentage and progesterone receptor (PR) status were further collected.A total of 288 patients were included with 145 benign cases and 143 malignant cases. Patients of confirmed endometrial carcinoma showed a significant lower value of PDW (55.21 ±â€Š4.72 vs 49.54 ±â€Š5.89, P < .001), meanwhile significant higher values of MPV (7.12 ±â€Š1.56 vs 8.89 ±â€Š1.67, P < .001) and PCT (24.18 ±â€Š6.89 vs 27.93 ±â€Š8.93, P = .003). Further analysis of endometrial carcinoma patients showed that no significant difference in platelet parameters was found between patients with stage I to II and stage III to IV (P > .05), while increased value in PDW and reduced value in MPV was found in PR negative compared with positive patients.Preoperative platelet morphology parameters seemed to be used as one kind of predictive factors to discriminate malignant and benign endometrial disease. Limited by present study design, further prospective studies are required to support this finding.


Assuntos
Plaquetas , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/patologia , Histerectomia , Receptores de Progesterona/análise , Neoplasias do Endométrio/química , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Testes de Função Plaquetária , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
18.
Gac Med Mex ; 155(Suppl 1): S39-S43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31638609

RESUMO

Background: Breast cancer subtype classification according to hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) using immunohistochemistry is the standard practice for therapeutic decision making. Objective: To design future studies information on characteristics and survival of each subtype is essential. Method: We conducted a retrospective study to analyze clinical and pathologic features as well as survival data according to breast cancer immunohistochemistry subtype. Results: There were 211 women with a RH(+)/HER2(-) breast cancer subtype, 53 HR(+)/HER2(+), 16 HER2(+) and 23 HR(-)/HER2(-), with a median overall survival in months of 39 (20.5-62.7), 42 (25.5-65), 42 (13.7-67.7) and 26 (11-78), respectively, for a 3.7 hazard ratio of death (95% Confidence Interval [CI]: 1.3-10.3) for the triple negative group as compared to the HR(+)/HER2(-) group (p = 0.01). Conclusions: HR positive subtypes by immunohistochemistry where most frequent and showed a greater overall survival compared to the triple negative subtype.


Assuntos
Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Receptores ErbB/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Adulto , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Arch Pathol Lab Med ; 143(12): 1444-1449, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31373514

RESUMO

CONTEXT.­: Evaluation of estrogen receptor (ER), progesterone receptor (PR), and HER2/neu (HER2) biomarkers is standard of care for all cases of newly diagnosed invasive, recurrent, and metastatic breast cancer. Repeat analysis is also performed in select cases per College of American Pathologists/American Society of Clinical Oncology guidelines and other clinical indications. However, in specific scenarios, preanalytic and analytic variables may pose distinct challenges to testing. OBJECTIVE.­: To provide a review of select challenges in the testing of commonly performed breast cancer biomarkers ER, PR, and HER2 and outline best practices for overcoming these challenges. DATA SOURCES.­: Review of College of American Pathologists/American Society of Clinical Oncology recommendations, current literature, and personal experience of the author. CONCLUSIONS.­: Attention must be given to specimen handling to ensure accurate ER, PR, and HER2 biomarker assessment and appropriate management of breast cancer patients.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Feminino , Humanos
20.
Eur J Cancer ; 118: 131-141, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31330488

RESUMO

BACKGROUND: For luminal metastatic breast cancer (MBC), endocrine therapy (ET) is the recommended initial treatment before chemotherapy. Our objective was to evaluate the efficacy of multiple ET lines in a real-life study. METHODS: The Breast Cancer Epidemiological Strategy and Medical Economics (ESME) project analysed data from all patients with systemic treatment for MBC initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. The primary end-point was the successive progression-free survival (PFS) evaluation. RESULTS: The ESME research programme included 9921 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2) negative (HER2-) MBC. Before any chemotherapy, 4195 (43.4%), 1252 (29.8%) and 279 (6.6%) patients received one, two or three ET ± targeted therapy, respectively. The median PFS for first-, second- and third-line ET ± targeted therapy was 11.5 (95% confidence interval [CI], 10.8-12.1), 5.8 (95% CI, 5.3-6.1) and 5.5 (95% CI, 4.6-6.3) months, respectively. In a multivariate analysis, time from diagnosis to metastatic recurrence (P < 0.0001), presence of symptoms at metastatic relapse (P = 0.01), number of metastatic sites (P = 0.0003) and their localisation (P < 0.0001) were prognostic factors for PFS1. Duration of previous PFS was the only prognostic factor for subsequent PFS (10% threshold). Ten percent of the patients showed long-term response to ET, with a total treatment duration before chemotherapy ≥43.6 months. CONCLUSIONS: Median PFS in our HR+/HER2- real-life cohort is similar to median first-line PFS reported in clinical trials, regardless of ET used as second- and third-line treatment. Despite the international consensus on early initiation of ET, the latter is not prescribed in most of the cases. Patients with a low tumour burden may achieve prolonged response on ET.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/enzimologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , França , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
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