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1.
Rev. venez. oncol ; 33(1): 46-59, mar. 2021. tab
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1147479

RESUMO

El cáncer de mama Triple Negativo es un subtipo molecular que se caracteriza por ausencia de expresión de receptores de estrógeno, progesterona y proteína HER2. Representa el 10 % a 15 % de todos los subtipos de cáncer de mama con impacto en el pronóstico y en las líneas de tratamiento; siendo negativo para receptores hormonales y HER2, la terapéutica hormonal y anti-HER2 no cuentan para su manejo. Aún no se dispone de productos dirigidos a blancos específicos para esta categoría.(AU)


The Triple Negative breast cancer is a molecular subtype characterized by no expression of the estrogen, the progesterone and the HER2 protein receptors. They represents 10 % to 15 % of all the breast cancer subtypes with an impact on the prognosis and in the treatment lines; is negative for the hormone receptors and for the HER2, hormonal and the anti-HER2 therapeutics do not count for the management of them. The products targeting specific to this category are not yet available(AU)


Assuntos
Humanos , Feminino , Biomarcadores Tumorais , Antraciclinas/uso terapêutico , Taxoides/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/epidemiologia , Mamografia , Tratamento Farmacológico , Oncologia
2.
Crit Rev Oncol Hematol ; 155: 103094, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33027724

RESUMO

Triple-negative breast cancer (TNBC) is a heterogeneous and complex disease characterized by the absence of immunohistochemical expression of estrogen receptor, progesterone receptor and HER2. These breast tumors present an aggressive biology and offer few opportunities to be treated with targeted therapy resulting in bad disease outcomes. The epidemiology of TNBC is intriguing where the understanding of its biology has progressed quickly. One of the peculiarities of this type of cancer is a high prevalence in Afrodescendants and Hispanic patients compared to Caucasian women. In this review we describe some features of TNBC, focusing in the Hispanic population, such as epidemiological, clinicopathological features and molecular features and the correlation between TNBC prevalence and the human development index.


Assuntos
Neoplasias de Mama Triplo Negativas , Feminino , Hispano-Americanos , Humanos , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Neoplasias de Mama Triplo Negativas/epidemiologia
3.
PLoS One ; 15(8): e0237811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833983

RESUMO

BACKGROUND: Epidemiological studies commonly identify the clinical characteristics and survival outcomes of patients with breast cancer at five years. Our study aims to describe the sociodemographic, clinicopathological characteristics and determine the long-term event-free survival (EFS) and overall survival (OS) of a Peruvian population with triple-negative breast cancer. METHODS: We reviewed the medical records of new cases treated at a single institution in the period 2000-2014. The survival analysis included patients with stages I-IV. Survival estimates at 10 years were calculated with the Kaplan-Meier method and compared with the Log-rank test. We further used multivariate Cox regression analysis to calculate prognostic factors of recurrence and mortality. RESULTS: Among the 2007 patients included, the median age at diagnosis was 49 years (19-95 years). Most patients presented histologic grade III (68.7%), tumor stage II (34.2%), and III (51.0%) at diagnosis. Local and distant relapse was present in 31.9 and 51.4% of the patients, respectively. The most frequent sites of metastasis were the lungs (14.5%), followed by bone (9.7%), brain (9.6%), and liver (7.9%). The median follow-up was 153 months. At 3, 5, and 10 years, the EFS of the population was 55%, 49%, and 41%, respectively, while the OS was 64%, 56%, and 47%, respectively. Moreover, an N3 lymph node status was the most important prognostic factor for both disease relapse (HR: 2.54, 95% CI: 2.05-3.15) and mortality (HR: 2.51, 95% CI: 2.01-3.14) at ten years. An older age and higher T staging were associated with a worse OS, while patients who received radiotherapy and adjuvant chemotherapy had better survival rates. CONCLUSION: The sociodemographic features of Peruvian patients with TNBC are similar to those of other populations. However, our population was diagnosed at more advanced clinical stages, and thus, EFS and OS were lower than international reports while prognostic factors were similar to previous studies.


Assuntos
Neoplasias de Mama Triplo Negativas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica , Peru/epidemiologia , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/cirurgia , Adulto Jovem
5.
Acta Clin Croat ; 59(1): 97-108, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32724280

RESUMO

Triple-negative breast cancer (TNBC) occurs in around one-sixth of all breast cancer (BC) patients, with the most aggressive behavior and worst prognosis of all BC subtypes. It is a heterogeneous disease, with specific molecular characteristics and natural dynamics of early recurrence and fast progression. Due to the lack of biomarkers or any valid treatment targets, it can only be treated with classic cytotoxic chemotherapy. We analyzed a cohort of 152 patients, median age 58 years, diagnosed with and treated for early stage TNBC at the University Hospital for Tumors, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia, during the 2009-2012 period. Patients were treated with primary surgical approach, adjuvant chemotherapy and adjuvant irradiation. We observed a relatively large proportion of locally advanced TNBC at diagnosis, with large tumor size and nodal involvement, with high grade and high proliferation index Ki67. Patient age, tumor size and lymph node involvement, as expected, were significant and clinically most important prognostic factors for 5-year disease-free survival (67%; 95% CI 60%-75%) and overall absolute survival rate (74%; 95% CI 66%-81%).


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Croácia/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/terapia
7.
Oncol Res Treat ; 43(5): 204-210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203954

RESUMO

OBJECTIVE: We evaluated the risk factors of inflammatory breast cancer (IBC) compared to non-IBC and according to histological subtype. METHODS: Cases of IBC (n = 160) and controls of non-IBC (n = 580) were collected from the cohort of breast cancer patients treated in two oncology centers matched based on age at cohort entry. Data about breast cancer risk factors were collected. We evaluated correlation and ORs using conditional logistic regression analysis for each case group versus the control group. We also evaluated those factors in three further subgroups: luminal (HR+, HER2-), HER2-overexpressing (HER2+, HR-), and triple-negative (TN) patients. RESULTS: Long duration of breastfeeding of ≥12 months (OR = 4.64, 95% CI 2.97-7.26), body mass index ≤25 (OR = 2.48, 95% CI 1.71-3.58), and use of oral contraceptives (OR = 2.48, 95% CI 1.62-3.84) were the most significant risk factors in favor of IBC compared to non-IBC. There was no impact of contraceptives use in the luminal subgroup and no impact of long duration of breastfeeding in the TN subgroup. The role of socioeconomic and educational levels was unclear. Age at menarche, age at first pregnancy, and age at menopause were nonsignificant risk factors of IBC. CONCLUSION: Reproductive risk factors were distinct in IBC patients reflecting the clinical entity of IBC.


Assuntos
Neoplasias Inflamatórias Mamárias/epidemiologia , Receptor ErbB-2/metabolismo , Neoplasias de Mama Triplo Negativas/epidemiologia , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Aleitamento Materno , Estudos de Casos e Controles , Anticoncepcionais Orais/uso terapêutico , Escolaridade , Feminino , Humanos , Menarca , Pessoa de Meia-Idade , Gravidez , Receptores Estrogênicos/metabolismo , Fenômenos Reprodutivos Fisiológicos , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
8.
Sci Rep ; 10(1): 2976, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076078

RESUMO

This paper evaluated 3-dimensional radiomics features of breast magnetic resonance imaging (MRI) as prognostic factors for predicting systemic recurrence in triple-negative breast cancer (TNBC) and validated the results with a different MRI scanner. The Rad score was generated from 3-dimensional radiomic features of MRI for 231 TNBCs (training set (GE scanner), n = 182; validation set (Philips scanner), n = 49). The Clinical and Rad models to predict systemic recurrence were built up and the models were externally validated. In the training set, the Rad score was significantly higher in the group with systemic recurrence (median, -8.430) than the group without (median, -9.873, P < 0.001). The C-index of the Rad model to predict systemic recurrence in the training set was 0.97, which was significantly higher than in the Clinical model (0.879; P = 0.009). When the models were externally validated, the C-index of the Rad model was 0.848, lower than the 0.939 of the Clinical model, although the difference was not statistically significant (P = 0.100). The Rad model for predicting systemic recurrence in TNBC showed a significantly higher C-index than the Clinical model. However, external validation with a different MRI scanner did not show the Rad model to be superior over the Clinical model.


Assuntos
Imageamento Tridimensional , Imagem por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico , Nomogramas , Neoplasias de Mama Triplo Negativas/diagnóstico , Adulto , Mama/diagnóstico por imagem , Mama/patologia , Mama/cirurgia , Quimioterapia Adjuvante/estatística & dados numéricos , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
9.
Acad Radiol ; 27(12): e282-e291, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32035756

RESUMO

RATIONALE AND OBJECTIVES: To evaluate a Bayesian network (BN) model learned from epidemiological and clinical information, and various MRI parameters for predicting the risk of triple-negative breast cancer (TNBC). MATERIALS AND METHODS: For this retrospective study, 214 women (mean age ± standard deviation, 50.5±10.6 years) with breast cancer were included between April 2016 and April 2018. All patients underwent MRI, including dynamic contrast-enhanced (DCE)-MRI. The morphologic MRI features, the pattern of the time-signal intensity curve (TIC) and the kinetic parameters were obtained for each lesion. The epidemiological and clinical parameters and those imaging parameters were used to construct BN model to estimate TNBC risk. ROC curves upon probability estimates were used to determine the performance of the BN using area under the ROC curves (Az), sensitivity, specificity, and accuracy. RESULTS: A BN model consisted of 16 epidemiological and clinical characteristics, morphologic MRI features, and quantitative DCE-MRI parameters were established. The posttest probability table showed that patients with age <35 years, mass-like lesions, type I TIC, and MaxCon ≥ 0.186 were at the highest risk of TNBC. The constructed BN model had an Az of 0.663 (95% confidence interval [CI]: 0.654, 0.672), sensitivity of 0.660 (95% CI: 0.644, 0.675), specificity of 0.740 (95% CI: 0.726, 0.753) and accuracy of 0.724 (95% CI: 0.714, 0.733) in classifying TNBC. CONCLUSION: The BN model integrating epidemiological and clinical characteristics, morphologic and kinetic MRI parameters provide a noninvasive analytical approach for preoperative prediction of the risk of TNBC.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Adulto , Teorema de Bayes , Meios de Contraste , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/epidemiologia
10.
Cancer Sci ; 111(4): 1375-1384, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31958182

RESUMO

BRCAness is considered a predictive biomarker to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors. However, recent trials showed that its predictive value was limited in triple-negative breast cancer (TNBC) treated with platinum. Moreover, tumors with mutations of DNA damage response (DDR) genes, such as homologous recombination (HR) genes, could be sensitive to platinum and PARP inhibitors. Thus, we aim to explore the relationship between mutation status of DDR genes and BRCAness in TNBC. We sequenced 56 DDR genes in 120 TNBC and identified BRCAness by array comparative genomic hybridization. The sequencing results showed that 13, 14, and 14 patients had BRCA, non-BRCA HR, and non-HR DDR gene mutations, respectively. Array comparative genomic hybridization revealed that BRCA-mutated and HR gene-mutated TNBC shared similar BRCAness features, both having higher numbers and longer length of large-scale structural aberration (LSA, >10 Mb) and similar altered chromosomal regions of LSA. These suggested non-BRCA HR gene-mutated TNBC shared similar characteristics with BRCA-mutated TNBC, indicating non-BRCA HR gene-mutated TNBC sensitive to platinum and PARP inhibitors. Among tumors with mutation of non-HR DDR genes, 3 PTEN and 1 MSH6 mutation also contained significant LSAs (BRCAness); however, they had different regions of genomic alteration to BRCA and HR gene-mutated tumors, might explain prior findings that PTEN- and MSH6-mutated cancer cells not sensitive to PARP inhibitors. Therefore, we hypothesize that the heterogeneous genomic background of BRCAness indicates different responsiveness to platinum and PARP inhibitors. Direct sequencing DDR genes in TNBC should be applied to predict their sensitivity toward platinum and PARP inhibitors.


Assuntos
Dano ao DNA/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Recombinação Homóloga/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Proteína BRCA1/genética , Proteína BRCA2/genética , Dano ao DNA/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação/genética , Platina/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteína Supressora de Tumor p53/genética
11.
Int J Cancer ; 146(8): 2296-2304, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31901133

RESUMO

The tumor-stroma ratio (TSR) was evaluated as a promising parameter for breast cancer prognostication in clinically relevant subgroups of patients. The TSR was assessed on hematoxylin and eosin-stained tissue slides of 1,794 breast cancer patients from the Nottingham City Hospital. An independent second cohort of 737 patients from the Netherlands Cancer Institute to Antoni van Leeuwenhoek was used for evaluation. In the Nottingham Breast Cancer series, the TSR was an independent prognostic parameter for recurrence-free survival (RFS; HR 1.35, 95% CI 1.10-1.66, p = 0.004). The interaction term was statistically significant for grade and triple-negative status. Multivariate Cox regression analysis showed a more pronounced effect of the TSR for RFS in grade III tumors (HR 1.89, 95% CI 1.43-2.51, p < 0.001) and triple-negative tumors (HR 1.86, 95% CI 1.10-3.14, p = 0.020). Comparable hazard ratios and confidence intervals were observed for grade and triple-negative status in the ONCOPOOL study. The prognostic value of TSR was not modified by age, tumor size, histology, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status or lymph node status. In conclusion, patients with a stroma-high tumor had a worse prognosis compared to patients with a stroma-low tumor. The prognostic value of the TSR is most discriminative in grade III tumors and triple-negative tumors. The TSR was not modified by other clinically relevant parameters making it a potential factor to be included for improved risk stratification.


Assuntos
Células Estromais/patologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Países Baixos/epidemiologia , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias de Mama Triplo Negativas/epidemiologia
12.
Cancer ; 126(1): 26-36, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31588557

RESUMO

BACKGROUND: Male breast cancer (MBC) is a rare disease for which there is limited understanding of treatment patterns and prognostic factors. METHODS: Men with TNM stage I to stage III breast cancer diagnosed between 2004 and 2014 in the National Cancer Data Base were included. Trends in treatment modalities were described using the average annual percentage change (AAPC) and estimated using Joinpoint software for the analysis of trends. Kaplan-Meier curves and the multivariate Cox proportional hazards regression model were used to compare survival between subgroups and to identify prognostic factors. RESULTS: A total of 10,873 MBC cases were included, with a median age at diagnosis of 64 years. Breast-conserving surgery was performed in 24% of patients, and 70% of patients undergoing breast conservation received radiotherapy. Approximately 44% of patients received chemotherapy, and 62% of patients with estrogen receptor-positive disease received endocrine therapy. Oncotype DX was ordered in 35% of patients with lymph node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. During the study period, there was a significant increase in the rates of total mastectomy, contralateral prophylactic mastectomy, radiotherapy after breast conservation, ordering of Oncotype DX, and the use of endocrine therapy (P < .05). On multivariate analysis, factors found to be associated with worse overall survival were older age, black race, higher Charlson Comorbidity Index, high tumor grade and stage of disease, and undergoing total mastectomy. Residing in a higher income area; having progesterone receptor-positive tumors; and receipt of chemotherapy, radiotherapy, and endocrine therapy were associated with better overall survival. CONCLUSIONS: Despite the lack of prospective randomized trials in patients with MBC, the results of the current study demonstrated that the treatment of this disease has evolved over the years. These findings further the understanding of the modern treatment and prognosis of MBC, and identify several areas for further research.


Assuntos
Neoplasias da Mama Masculina/epidemiologia , Mama/cirurgia , Prognóstico , Neoplasias de Mama Triplo Negativas/epidemiologia , Idoso , Mama/patologia , Neoplasias da Mama Masculina/genética , Neoplasias da Mama Masculina/cirurgia , Neoplasias da Mama Masculina/terapia , Receptor alfa de Estrogênio/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/cirurgia , Neoplasias de Mama Triplo Negativas/terapia , Estados Unidos/epidemiologia
13.
Pan Afr Med J ; 34: 67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819783

RESUMO

Introduction: Breast cancer is among the most common cancers among women in most of Africa. However, features of histologically confirmed breast cancers presenting in specific regional populations is limited. Our study describes the clinic-pathologic features of invasive breast cancer diagnosed in women undergoing biopsy for a clinically apparent mass in Senegal, West Africa. Methods: A prospective cohort of 522 Senegalese women presenting consecutively to Dantec Hospital (University of Dakar Tumor Institute) with a breast mass were included in the study cohort. Demographic data was collected by survey and 197 (37.7%) core needle biopsy-confirmed invasive breast cancers available for review were subsequently centrally reviewed at the University of Washington in Seattle to further to characterize the pathologic features and to perform immunohistochemistry for ER/PR and HER2. Results: Seventy six (76.1%) of the 522 Senegalese women presenting for biopsy of a clinically apparent breast mass were diagnosed with invasive breast cancer. The average age of a woman with invasive cancer was 46 years old, and most (83%) presented with Stage III or IV disease. The predominant histologic subtype among the 197 biopsy-confirmed cancers was invasive ductal carcinoma (98%), with few cases of invasive lobular carcinoma (2%). Cancers were classified into four clinically relevant treatment IHC groups by combined ER/PR status and HER2 status as follows: ER-/PR-, HER2- (n=92; 46.7%), ER-/PR-, HER2+ (n=20; 10.1%), ER+/PR+, HER2- (n=76; 38.6%) and ER+/PR+, HER2+ (n=9; 4.6%). Age at time of diagnosis was similar between these four subgroups although more HER2 positive cases were pre-menopausal (p=0.05). Stage of disease at presentation differed by IHC group (p=0.008), with HER2+ cancers significantly more likely to present with stage IV disease than other IHC groups, including ER-/PR-, HER2-. There were no significant differences between groups by age group, ethnicity, place of residence or birth, or parity. Conclusion: Our analysis of breast cancer cases in Senegal shows a distribution of clinically relevant IHC groups like that seen in the few prior studies of breast cancer in West Africa, with higher frequencies of triple negative cancers than in most United States and European populations. Mean age at presentation, delayed presentation, and genetic/regional risk factors likely influence these differences. A better understanding of the frequencies of the pathologic features of breast cancers in the West African population may help guide future genetic studies as well as appropriate clinical management of breast cancer in these populations.


Assuntos
Neoplasias da Mama/patologia , Pré-Menopausa , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Biópsia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Senegal/epidemiologia , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/epidemiologia
14.
Br J Cancer ; 121(12): 991-1000, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719684

RESUMO

BACKGROUND: Metastatic breast cancer (MBC) behaviour differs depending on hormone receptors (HR) and human epidermal growth factor receptor (HER2) statuses. METHODS: The kinetics of central nervous system (CNS) metastases (CNS metastasis-free survival, CNSM-FS) and subsequent patient's prognosis (overall survival, OS) according to the molecular subtype were retrospectively assessed in 16703 MBC patients of the ESME nationwide multicentre MBC database (Kaplan-Meier method). RESULTS: CNS metastases occurred in 4118 patients (24.6%) (7.2% at MBC diagnosis and 17.5% later during follow-up). Tumours were HER2-/HR+ (45.3%), HER2+/HR+ (14.5%), HER2+/HR- (14.9%) and triple negative (25.4%). Median age at CNS metastasis diagnosis was 58.1 years (range: 22.8-92.0). The median CNSM-FS was 10.8 months (95% CI: 16.5-17.9) among patients who developed CNS metastases. Molecular subtype was independently associated with CNSM-FS (HR = 3.45, 95% CI: 3.18-3.75, triple-negative and HER2-/HR+ tumours). After a 30-month follow-up, median OS after CNS metastasis diagnosis was 7.9 months (95% CI: 7.2-8.4). OS was independently associated with subtypes: median OS was 18.9 months (HR = 0.57, 95% CI: 0.50-0.64) for HER2+/HR+ , 13.1 months (HR = 0.72, 95% CI: 0.65-0.81) for HER2+/HR-, 4.4 months (HR = 1.55, 95% CI: 1.42-1.69) for triple-negative and 7.1 months for HER2-/HR+ patients (p <0.0001). CONCLUSIONS: Tumour molecular subtypes strongly impact incidence, kinetics and prognosis of CNS metastases in MBC patients. CLINICAL TRIAL REGISTRATION: NCT03275311.


Assuntos
Neoplasias da Mama Masculina/epidemiologia , Neoplasias do Sistema Nervoso/epidemiologia , Neoplasias de Mama Triplo Negativas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama Masculina/classificação , Neoplasias da Mama Masculina/genética , Neoplasias da Mama Masculina/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Cinética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias do Sistema Nervoso/genética , Neoplasias do Sistema Nervoso/patologia , Neoplasias do Sistema Nervoso/secundário , Prognóstico , Receptor ErbB-2/genética , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Adulto Jovem
15.
Nat Med ; 25(10): 1526-1533, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31570822

RESUMO

Whole-genome sequencing (WGS) brings comprehensive insights to cancer genome interpretation. To explore the clinical value of WGS, we sequenced 254 triple-negative breast cancers (TNBCs) for which associated treatment and outcome data were collected between 2010 and 2015 via the population-based Sweden Cancerome Analysis Network-Breast (SCAN-B) project (ClinicalTrials.gov ID:NCT02306096). Applying the HRDetect mutational-signature-based algorithm to classify tumors, 59% were predicted to have homologous-recombination-repair deficiency (HRDetect-high): 67% explained by germline/somatic mutations of BRCA1/BRCA2, BRCA1 promoter hypermethylation, RAD51C hypermethylation or biallelic loss of PALB2. A novel mechanism of BRCA1 abrogation was discovered via germline SINE-VNTR-Alu retrotransposition. HRDetect provided independent prognostic information, with HRDetect-high patients having better outcome on adjuvant chemotherapy for invasive disease-free survival (hazard ratio (HR) = 0.42; 95% confidence interval (CI) = 0.2-0.87) and distant relapse-free interval (HR = 0.31, CI = 0.13-0.76) compared to HRDetect-low, regardless of whether a genetic/epigenetic cause was identified. HRDetect-intermediate, some possessing potentially targetable biological abnormalities, had the poorest outcomes. HRDetect-low cancers also had inadequate outcomes: ~4.7% were mismatch-repair-deficient (another targetable defect, not typically sought) and they were enriched for (but not restricted to) PIK3CA/AKT1 pathway abnormalities. New treatment options need to be considered for now-discernible HRDetect-intermediate and HRDetect-low categories. This population-based study advocates for WGS of TNBC to better inform trial stratification and improve clinical decision-making.


Assuntos
Recidiva Local de Neoplasia/genética , Prognóstico , Neoplasias de Mama Triplo Negativas/genética , Sequenciamento Completo do Genoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA/genética , Intervalo Livre de Doença , Feminino , Genética Populacional , Mutação em Linhagem Germinativa/genética , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Regiões Promotoras Genéticas , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia
16.
Cancer Med ; 8(18): 7523-7531, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31642210

RESUMO

BACKGROUND: Triple-negative apocrine carcinoma (TNAC) of the breast is a very rare type of breast cancer. Furthermore, the clinicopathological features, prognosis, and potential impact of treatment strategies in TNAC remain unclear. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) program were used to identify breast cancer patients diagnosed between 2010 and 2016 with TNAC and triple-negative breast cancer (TNBC, IDC [invasive ductal carcinoma], NOS [not otherwise specified]). Chi-squared tests were used to examine the categorical variables between the two groups. Overall survival (OS) of TNAC and TNBC was assessed by Kaplan-Meier analyses and Cox regression. Breast cancer-specific survival (BCSS) was evaluated by Nelson-Aalen analyses and competing risk regression. RESULTS: We identified 31 362 patients from the SEER database, including 366 patients with TNAC and 30 996 patients with TNBC. TNAC was correlated with older age, lower T stage and lower tumor grade. Patients with TNAC had better OS compared with TNBC patients; the 5-year OS rates were 82.2% vs 73.5% (P < .001). The breast cancer-related death rate was significantly lower in patients with TNAC than in patients with TNBC, with a 5-year cumulative incidence of 9.1% vs 22.9% (P < .001). Chemotherapy was significantly associated with improved OS in TNAC patients, but radiotherapy was not associated with OS in TNAC patients. In the multivariable Cox regression, TNAC was still associated with improved OS (HR [hazard ratio], 0.61; 95% CI [confidence interval] 0.45-0.83; P = .002). In the multivariable competing risk regression, the significantly higher BCSS in patients with TNAC compared patients with TNBC remained (subdistribution HR [SHR], 0.42; 95% CI, 0.27-0.64; P < .001). CONCLUSION: Patients with TNAC had a better prognosis than patients with TNBC, and chemotherapy was associated with survival advantages in TNAC patients.


Assuntos
Carcinoma Ductal de Mama/epidemiologia , Neoplasias de Mama Triplo Negativas/epidemiologia , Adolescente , Adulto , Idoso , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , Programa de SEER , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto Jovem
17.
Cancer Epidemiol Biomarkers Prev ; 28(12): 1977-1985, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31533938

RESUMO

BACKGROUND: The impact of the immune landscape of the microenvironment on cancer progression is not well understood for triple-negative breast cancer (TNBC). We, therefore, aimed to examine the association of immune cell enrichment scores as a proxy for immune profiles of tumor microenvironment with TNBC prognosis. METHODS: We included 76 patients with TNBC diagnosed between 2008 to 2016 in West China Hospital and 158 patients with TNBC from The Cancer Genome Atlas. On the basis of transcriptome data, we calculated the overall ImmuneScore and type-specific enrichment scores for 34 types of immune cells, using xCell, a gene signature-based method. HRs of recurrence-free survival (RFS) and overall survival (OS) were calculated by Cox proportional hazards models. RESULTS: During the median follow-up time of 2.8 (0.1-9.8) years, 42 patients had a recurrence, and 34 patients died. The overall ImmuneScore and most immune cell enrichment scores were relatively higher in tumors than normal tissues. A higher enrichment score of plasma cells was associated with favorable RFS [HR 0.45; 95% confidence interval (CI), 0.27-0.73] and OS (HR 0.32; 95% CI, 0.17-0.61). The score of CD4+ central memory T cell (Tcm) was negatively associated with RFS (HR 1.52; 95% CI, 1.17-1.97). Besides, CD4+ Tcm enrichment score was higher in invasive tumors that were not ductal/lobular carcinoma (OR 1.59; 95% CI, 1.06-2.37). CONCLUSIONS: Our findings suggest that plasma cells and CD4+ Tcm in the tumor microenvironment may play a role in the subsequent progression of TNBC. IMPACT: This study provides evidence of the role of immune cells in TNBC progression that may have clinical utility.


Assuntos
Biomarcadores/análise , Carcinoma Ductal de Mama/imunologia , Carcinoma Lobular/imunologia , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Neoplasias de Mama Triplo Negativas/imunologia , Microambiente Tumoral/imunologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/epidemiologia , Carcinoma Lobular/patologia , China , Estudos de Coortes , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Prognóstico , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia
18.
Cancer Epidemiol Biomarkers Prev ; 28(11): 1771-1783, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31455670

RESUMO

Breast cancer is the most common cancer in Latina women. Although they have a lower incidence of the disease when compared with other population groups such as non-Hispanic white and African-American women, some studies have shown that Latina women have a higher risk of mortality when compared with non-Hispanic white women. This phenomenon can be explained in part by the higher prevalence of aggressive subtypes in Latina women, particularly the triple negative. Such differences in breast cancer-intrinsic subtype distribution between population groups might be a consequence of a variety of risk factors differentially present among population groups. Here, we provide a full description of risk factors that might be associated with the high prevalence of the triple-negative subtype in Latina women. We assessed demographic (socioeconomic status), modifiable (reproductive patterns, obesity, and physical activity), and nonmodifiable (family history, germline BRCA mutations, and genetic ancestry) risk factors. The observed inconsistencies among different epidemiologic studies in Latinas warrant further research focused on breast cancer subtype-specific risk factors in this population.


Assuntos
Neoplasias de Mama Triplo Negativas/epidemiologia , Adulto , Feminino , Hispano-Americanos , Humanos , Fatores de Risco , Adulto Jovem
19.
Adv Exp Med Biol ; 1152: 9-29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456177

RESUMO

Epidemiologic studies have contributed importantly to current knowledge of environmental and genetic risk factors for breast cancer. Worldwide, breast cancer is an important cause of human suffering and premature mortality among women. In the United States, breast cancer accounts for more cancer deaths in women than any site other than lung cancer. A variety of risk factors for breast cancer have been well-established by epidemiologic studies including race, ethnicity, family history of cancer, and genetic traits, as well as modifiable exposures such as increased alcohol consumption, physical inactivity, exogenous hormones, and certain female reproductive factors. Younger age at menarche, parity, and older age at first full-term pregnancy may influence breast cancer risk through long-term effects on sex hormone levels or by other biological mechanisms. Recent studies have suggested that triple negative breast cancers may have a distinct etiology. Genetic variants and mutations in genes that code for proteins having a role in DNA repair pathways and the homologous recombination of DNA double stranded breaks (APEX1, BRCA1, BRCA2, XRCC2, XRCC3, ATM, CHEK2, PALB2, RAD51, XPD), have been implicated in some cases of breast cancer.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Proteínas de Ligação a DNA/genética , Feminino , Predisposição Genética para Doença , Recombinação Homóloga , Humanos , Mutação , Gravidez , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/etiologia
20.
Breast J ; 25(6): 1225-1229, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31310384

RESUMO

Overall survival (OS), disease-free survival (DFS), and distant recurrence-free interval (DRFI) were evaluated from 169 patients diagnosed with early triple negative breast cancer. Overall, 5 and 10 years OS, DFS, and DRFI were 77% and 65%; 60% and 46%; and 74% and 73%, respectively. Forty-seven patients did not receive chemotherapy. A separate analysis was performed excluding those patients. In this subgroup, 5- and 10-year OS, DFS, and DRFI were 86% and 77%; 68% and 54%, 77% both at 5 and 10 years. Prognosis is better than previously described; adjuvant chemotherapy should be offered to fit elderly patients if clinically warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Administração dos Cuidados ao Paciente , Neoplasias de Mama Triplo Negativas/terapia , Fatores Etários , Idoso , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/estatística & dados numéricos , Administração dos Cuidados ao Paciente/tendências , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia
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