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1.
Reprod Biomed Online ; 44(6): 1031-1044, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35525718

RESUMEN

RESEARCH QUESTION: What are the real-life oncofertility practices in young women diagnosed with breast cancer? DESIGN: The FEERIC (FErtility, prEgnancy, contRaceptIon after breast Cancer in France) study is a web-based cohort study launched with the French collaborative research platform Seintinelles. The current work is based on the enrolment self-administered questionnaire of 517 patients with prior breast cancer diagnosis, free from relapse and aged 18 to 43 years at inclusion (from 12 March 2018 to 27 June 2019). RESULTS: Median age at breast cancer diagnosis was 33.6 years and 424 patients (82.0%) received chemotherapy. Overall, 236 (45.6%) patients were offered specialized oncofertility counselling, 181 patients underwent at least one fertility preservation procedure (FPP); 125 (24.2%) underwent one or more FPP with material preservation (oocytes n = 108, 20.9%; embryos n = 31, 6.0%; ovarian cryopreservation n = 6, 1.2%) and 78 patients received gonadotrophin-releasing hormone agonists (15.1%). With a median follow-up of 26.9 months after the end of treatments, 133 pregnancies had occurred in 85 patients (16.4%), including 20 unplanned pregnancies (15.0%). Most of the pregnancies were natural conceptions (n = 113, 87.6%), while 16 (12.4%) required medical interventions. For the planned pregnancies, median time to the occurrence of an ongoing pregnancy was 3 months. Patients who had an unplanned pregnancy reported lower rates of information on the consequences of the treatments on fertility (P = 0.036) at diagnosis. CONCLUSIONS: Most of the patients were not offered proper specialized oncofertility counselling at the time of breast cancer diagnosis. Naturally conceived pregnancies after breast cancer were much more frequent than pregnancies resulting from the use of cryopreserved gametes. Adequate contraceptive counselling seems as important as information about fertility and might prevent unplanned pregnancies.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Preservación de la Fertilidad , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Cohortes , Criopreservación , Femenino , Preservación de la Fertilidad/métodos , Humanos , Recurrencia Local de Neoplasia , Embarazo
2.
Lancet ; 393(10191): 2591-2598, 2019 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-31178155

RESUMEN

BACKGROUND: In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events. METHODS: PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901. FINDINGS: 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3-8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93-1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group. INTERPRETATION: The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months. FUNDING: The French National Cancer Institute.


Asunto(s)
Antineoplásicos Inmunológicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Trastuzumab/administración & dosificación , Adulto , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias de la Mama/metabolismo , Quimioterapia Adyuvante , Esquema de Medicación , Femenino , Francia , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Análisis de Supervivencia , Trastuzumab/efectos adversos , Resultado del Tratamiento , Adulto Joven
3.
Oncologist ; 24(7): e490-e500, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30578310

RESUMEN

BACKGROUND: The likelihood that health-related quality of life (HRQoL) could depend on factors other than clinical data increases with the duration of follow-up since diagnosis. The aim of this study was to identify determinants of long-term HRQoL in women with cervical, endometrial, and ovarian cancer. Secondary objectives were to describe their living conditions (sexual function, psychological distress, social and professional reinsertion). MATERIALS AND METHODS: In a cross-sectional survey, women diagnosed with cervical, endometrial, and ovarian cancers from 2006 to 2013 were selected through the French gynecological cancers registry of Côte d'Or. Validated questionnaires exploring HRQoL (short-form health survey; SF-12), anxiety and depression (Hospital Anxiety and Depression Scale), social support (Sarason's Social Support Questionnaire), sexual function (Female Sexual Function Index), and living conditions (EPICES questionnaire) were used to assess HRQoL and its determinants. Social and professional reinsertion were also investigated using study-specific questionnaires. Determinants of HRQoL were identified using a multivariable mixed-regression model for each composite score of the SF-12. RESULTS: In total, 195 gynecological cancer survivors participated in the survey. HRQoL was deteriorated for almost all the SF-12 dimensions. The main determinants of poor HRQoL were comorbidities, deprivation, lack of availability and satisfaction with social support, and psychological outcomes. Thirty-four percent of survivors of gynecological cancer reported a negative impact of cancer on their work, and 73% reported an impaired ability to work after treatment. CONCLUSIONS: Long-term HRQoL of survivors of gynecological cancer is not impacted by stage of disease. Specific interventions should focus on issues that promote social and professional reintegration and improve HRQoL. IMPLICATIONS FOR PRACTICE: This study shows that women with gynecological cancer have problems related to work and sexual dysfunction, even 5 years after diagnosis. The results of this study will help improve clinicians' awareness of the factors affecting the lives of gynecological cancer survivors, even long after diagnosis and treatment. They will also highlight for clinicians the areas that are of importance to gynecological cancer survivors, making it possible to guide management of these patients with a view to preventing deteriorated health-related quality of life after treatment. For the health authorities, the results of this study underline that more than 5 years after gynecological cancer, the initial stage of disease no longer affects quality of life, but there is a clear need for actions targeting socio-professional reintegration of survivors.


Asunto(s)
Supervivientes de Cáncer/estadística & datos numéricos , Neoplasias de los Genitales Femeninos/mortalidad , Calidad de Vida/psicología , Adulto , Anciano , Estudios Transversales , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
4.
BMC Cancer ; 18(1): 526, 2018 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-29728098

RESUMEN

BACKGROUND: The 21-gene Recurrence Score (RS) result predicts outcome and chemotherapy benefit in node-negative and node-positive (N+), estrogen receptor-positive (ER+) patients treated with endocrine therapy. The purpose of this study was to evaluate the prognostic impact of RS results in N+, hormone receptor-positive (HR+) patients treated with adjuvant chemotherapy (6 cycles of FEC100 vs. 3 cycles of FEC100 followed by 3 cycles of docetaxel 100 mg/m2) plus endocrine therapy (ET) in the PACS-01 trial (J Clin Oncol 2006;24:5664-5671). METHODS: The current study included 530 HR+/N+ patients from the PACS-01 parent trial for whom specimens were available. The primary objective was to evaluate the relationship between the RS result and distant recurrence (DR). RESULTS: There were 209 (39.4%) patients with low RS (< 18), 159 (30%) with intermediate RS (18-30) and 162 (30.6%) with high RS (≥ 31). The continuous RS result was associated with DR (hazard ratio = 4.14; 95% confidence interval: 2.67-6.43; p <  0.001), adjusting for treatment. In multivariable analysis, the RS result remained a significant predictor of DR (p <  0.001) after adjustment for number of positive nodes, tumor size, tumor grade, Ki-67 (immunohistochemical status), and chemotherapy regimen. There was no statistically significant interaction between RS result and treatment in predicting DR (p = 0.79). CONCLUSIONS: After adjustment for clinical covariates, the 21-gene RS result is a significant prognostic factor in N+/HR+ patients receiving adjuvant chemoendocrine therapy. TRIAL REGISTRATION: Not applicable.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias de la Mama/tratamiento farmacológico , Pruebas Genéticas/métodos , Recurrencia Local de Neoplasia/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Mama/patología , Mama/cirugía , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Ensayos Clínicos Fase III como Asunto , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Mastectomía , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia/genética , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo
5.
Breast Cancer Res ; 19(1): 98, 2017 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-28830573

RESUMEN

BACKGROUND: Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer. METHODS: A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS. RESULTS: The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1-97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival. CONCLUSIONS: In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients' outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis. TRIAL REGISTRATION: PHARE cohort: NCT00381901 , Sept. 26, 2006 - SIGNAL cohort: INCa RECF1098, Jan. 28, 2009.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Biomarcadores de Tumor , Neoplasias de la Mama/patología , Ensayos Clínicos Fase III como Asunto , Estudios de Cohortes , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Supervivencia , Carga Tumoral , Adulto Joven
6.
Ann Pathol ; 37(1): 133-141, 2017 Feb.
Artículo en Francés | MEDLINE | ID: mdl-28159406

RESUMEN

The role of the immune response in breast cancer is now well recognized and increasingly taken in account. The goal of this article is, in the first part, to underline its prognostic impact and to precise the immunosurvelliance, immunoselection and the immunosubversion concepts involved in the control and evasion of breast carcinoma. In the second part, therapeutic strategies for the restauration of anti-tumor immunity are developed. Vaccination strategies and checkpoints inhibitors blockade strategies are discussed as well as the immunogenic death linked to the conventional treatments of breast cancer.


Asunto(s)
Neoplasias de la Mama/inmunología , Inmunoterapia/métodos , Antígenos de Neoplasias/inmunología , Antígeno B7-H1/antagonistas & inhibidores , Neoplasias de la Mama/terapia , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Terapia Combinada , Células Dendríticas/fisiología , Femenino , Humanos , Inflamación , Modelos Inmunológicos , Terapia Molecular Dirigida , Monitorización Inmunológica , Mucina-1/inmunología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/inmunología , Fagocitosis , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor ErbB-2/inmunología , Escape del Tumor/inmunología , Microambiente Tumoral
7.
Breast Cancer Res ; 17: 56, 2015 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-25888246

RESUMEN

INTRODUCTION: Worldwide, many patients with HER2+ (human epidermal growth factor receptor 2-positive) early breast cancer (BC) do not receive adjuvant trastuzumab. Hazards of recurrence of these patients with respect to hormone receptor status of the primary tumor have not been described. METHODS: Using data from 1,260 patients randomized to placebo in the adjuvant TEACH trial, we report 10-year annual hazards of recurrence in HER2+ patients not treated with anti-HER2 therapy. RESULTS: Disease-free survival (DFS) was 75% after 5 and 61% after 10 years, respectively. Patients with HER2+ hormone receptor-positive (HR+ (hormone receptor-positive); ER+ (estrogen receptor-positive) or PR+ (progesterone receptor-positive)) disease had a significantly better DFS than patients with HER2+ HR- (ER-/PR-) disease (hazard ratio 0.72, P=0.02). This difference was explainable by a significantly higher hazard of recurrence in years 1 to 5 in HER2+ HR- compared to HER2+ HR+ patients, with a mean risk of recurrence of 9%/year for HR- versus 5%/year in HR+ patients (hazard ratio 0.59, P=0.002 for years 1 to 5). The high early risk of recurrence of HER2+ HR- patients declined sharply over time, so that it was similar to that seen in HER2+ HR+ patients in years 6 to 10 (hazard ratio 0.97, P=0.92 for years 6 to 10). CONCLUSIONS: Our results show that outcomes in HER2+ patients with early BC not receiving anti-HER2 therapy strongly depend on HR expression. The very high early risk of relapse seen in HER2+ HR- patients is particularly relevant in health care settings with limited access to adjuvant anti-HER2 treatment. The event rates shown for subpopulations of HER2+ BC patients suggest that in resource-constrained environments patients with HER2+ HR- early BC should be prioritized for consideration of adjuvant anti-HER2 therapy.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Receptor ErbB-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Terapia Molecular Dirigida , Recurrencia Local de Neoplasia , Pronóstico , Modelos de Riesgos Proporcionales , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/genética , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Resultado del Tratamiento , Adulto Joven
8.
Oncologist ; 20(2): 94-104, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25561512

RESUMEN

This review considers the potential utility of positron emission tomography (PET) tracers in the setting of response monitoring in breast cancer, with a special emphasis on glucose metabolic changes assessed with (18)F-fluorodeoxyglucose (FDG). In the neoadjuvant setting of breast cancer, the metabolic response can predict the final complete pathologic response after the first cycles of chemotherapy. Because tumor metabolic behavior highly depends on cancer subtype, studies are ongoing to define the optimal metabolic criteria of tumor response in each subtype. The recent multicentric randomized AVATAXHER trial has suggested, in the human epidermal growth factor 2-positive subtype, a clinical benefit of early tailoring the neoadjuvant treatment in women with poor metabolic response after the first course of treatment. In the bone-dominant metastatic setting, there is increasing clinical evidence that FDG-PET/computed tomography (CT) is the most accurate imaging modality for assessment of the tumor response to treatment when both metabolic information and morphologic information are considered. Nevertheless, there is a need to define standardized metabolic criteria of response, including the heterogeneity of response among metastases, and to evaluate the costs and health outcome of FDG-PET/CT compared with conventional imaging. New non-FDG radiotracers highlighting specific molecular hallmarks of breast cancer cells have recently emerged in preclinical and clinical studies. These biomarkers can take into account the heterogeneity of tumor biology in metastatic lesions. They may provide valuable clinical information for physicians to select and monitor the effectiveness of novel therapeutics targeting the same molecular pathways of breast tumor.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Tomografía de Emisión de Positrones , Neoplasias de la Mama/patología , Femenino , Fluorodesoxiglucosa F18/uso terapéutico , Humanos , Pronóstico , Radiografía , Receptor ErbB-2/metabolismo
9.
BMC Cancer ; 15: 169, 2015 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-25879949

RESUMEN

BACKGROUND: Overexpression of HER2 is observed in 20 to 30% of breast carcinomas. The use of trastuzumab has improved the treatment of these patients, especially when it is associated with docetaxel. To optimize the use of this treatment, it seems important to select putative complete responders before treatment administration. METHODS: In this study, we analyzed by quantitative PCR the expression of 28 genes in HER2-overexpressing tumors treated with trastuzumab + docetaxel-based chemotherapy. We then correlated their expression profile with those of trastuzumab-sensitive and resistant cell lines to classify tumors as having a sensitive (pCR) or resistant (non-pCR) profile. Finally, we used public datasets from the GEO website to validate the reduced gene-expression profile obtained. RESULTS: We identified an 8-gene-expression combination that predicted the response to treatment with an accuracy of 76%. Based on public microarray data, we showed that the expression profile was specific to first-line trastuzumab + docetaxel-based treatment with an accuracy of 85%. CONCLUSIONS: Our results showed that by profiling the expression of 8 genes it was possible to predict the response to first-line trastuzumab + docetaxel-based chemotherapy. The use of cancer cell lines as the reference allowed a proper fit with the specificity of different tissues, such as lung or gastric cancers, which could also be eligible to concomitant HER2 inhibition by treatment with trastuzumab or tyrosine kinase inhibitors and docetaxel.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Proteínas de Neoplasias/biosíntesis , Taxoides/administración & dosificación , Trastuzumab/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Bases de Datos Genéticas , Docetaxel , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Receptor ErbB-2/biosíntesis
10.
Anticancer Drugs ; 26(10): 1009-16, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26352219

RESUMEN

Trastuzumab has transformed the treatment of HER2-positive breast cancer. Because of impending European patent expiry in 2017, numerous trastuzumab biosimilars are currently undergoing comparability exercises for marketing authorization. Although biosimilar products have been approved in Europe since 2006, many obstacles are expected for trastuzumab, resulting from its nature as a monoclonal antibody, its impact on overall survival, and its extensive biochemical complexities. Unsolved questions need to be addressed for the evaluation of biosimilars' activity in terms of appropriate clinical endpoint definitions for such anticancer drugs, specific assessment pathways and comparative testing of biosimilars, untested ensuing de facto combination of trastuzumab biosimilars with cytotoxics, and immunogenicity monitoring among immunocompromised patients. In such a context of uncertainties, the recent approval by the French parliament of biosimilar substitution, which would allow dispensing trastuzumab biosimilars in place of the originator, should interrogate the oncological community. A think tank of experts was created to delineate specificities and challenges stemming from trastuzumab biosimilars.


Asunto(s)
Antineoplásicos/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Trastuzumab/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Medicamentos Genéricos/uso terapéutico , Europa (Continente) , Humanos , Terapia Molecular Dirigida , Receptor ErbB-2/metabolismo
11.
Future Oncol ; 11(16): 2283-97, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26260807

RESUMEN

AIM: Microarray studies identified a subgroup of molecular apocrine tumors (estrogen receptor [ER] negative/androgen receptor [AR] positive) that express luminal genes including FOXA1. FOXA1 may direct AR to sites normally occupied by ER in luminal tumors, inducing an estrogen-like gene program that stimulated proliferation. MATERIALS & METHODS: Expression of AR and FOXA1 was evaluated by immunohistochemistry in 592 patients with nonmetastatic triple-negative breast cancer (TNBC). RESULTS: Coexpression of AR and FOXA1 was found in 15.2% of patients. These tumors were more frequently lobular, found in older patients and exhibited a lower nuclear grade and a greater degree of node involvement. They less often exhibited lymphocytic infiltrate, pushing margins, syncytial architecture, central fibrosis or necrosis. CONCLUSION: TNBC with coexpression of AR and FOXA1 seems to behave like luminal tumors with a morphological profile distinct from other TNBC. These biomarkers could be useful to identify a subgroup of TNBC and could have future therapeutic implications.


Asunto(s)
Expresión Génica , Factor Nuclear 3-alfa del Hepatocito/genética , Receptores Androgénicos/genética , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Factor Nuclear 3-alfa del Hepatocito/metabolismo , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Oportunidad Relativa , Receptores Androgénicos/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Carga Tumoral
12.
Eur J Nucl Med Mol Imaging ; 41(3): 428-37, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24196916

RESUMEN

PURPOSE: The objective of this study was to assess the impact on management and the prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for initial staging of newly diagnosed large breast cancer (BC) when compared with conventional staging. METHODS: We prospectively included 142 patients with newly diagnosed BC and at least grade T2 tumour. All patients were evaluated with complete conventional imaging (CI) procedures (mammogram and/or breast ultrasound, bone scan, abdominal ultrasound and/or CT, X-rays and/or CT of the chest), followed by FDG PET/CT exploration, prior to treatment. The treatment plan based on CI staging was compared with that based on PET/CT findings. CI and PET/CT findings were confirmed by imaging and clinical follow-up and/or pathology when assessable. Progression-free survival (PFS) was analysed using the Cox proportional hazards regression model. RESULTS: According to CI staging, 79 patients (56%) were stage II, 46 (32%) stage III and 17 (12%) stage IV (distant metastases). Of the patients, 30 (21%) were upstaged by PET/CT, including 12 (8%) from stage II or III to stage IV. On the other hand, 23 patients (16%) were downstaged by PET/CT, including 4 (3%) from stage IV to stage II or III. PET/CT had a high or medium impact on management planning for 18 patients (13%). Median follow-up was 30 months (range 9-59 months); 37 patients (26%) experienced recurrence or progression of disease during follow-up and 17 patients (12%) died. The Cox model indicated that CI staging was significantly associated with PFS (p = 0.01), but PET/CT staging provided stronger prognostic stratification (p < 0.0001). Moreover, Cox regression multivariate analysis showed that only PET/CT staging remained associated with PFS (p < 0.0001). CONCLUSION: FDG PET/CT provides staging information that more accurately stratifies prognostic risk in newly diagnosed large BC when compared with conventional explorations alone.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Carcinoma/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Imagen Multimodal , Tomografía de Emisión de Positrones , Radiofármacos , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Carcinoma/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico
13.
Eur J Nucl Med Mol Imaging ; 41(8): 1525-33, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24647576

RESUMEN

PURPOSE: To investigate the value of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET/CT) to predict a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. MATERIAL AND METHODS: Fifty-seven consecutive women with HER2-positive breast cancer, treated with trastuzumab plus taxane-based NAC, were prospectively included. Maximum Standardized Uptake Value of the primary tumor and axillary nodes were measured at baseline (PET1.SUVmax) and after the first course of NAC (PET2.SUVmax). Tumor metabolic volumes were assessed to determine Total Lesion Glycolysis (TLG). The tumor metabolic response (ΔSUVmax and ΔTLG) was calculated. RESULTS: In univariate analysis, negative hormonal receptor status (p = 0.04), high tumor grade (p = 0.03), and low tumor PET2.SUVmax (p = 0.001) were predictive of pCR. Tumor ΔSUVmax correlated with pCR (p = 0.03), provided that tumors with low metabolic activity at baseline were excluded. ΔTLG did not correlate with pCR. In multivariate analysis, tumor PET2.SUVmax < 2.1 was the best independent predictive factor (Odds ratio =14.3; p = 0.004) with both negative and positive predictive values of 76 %. Although the metabolic features of the primary tumor did not depend on hormonal receptor status, both the baseline metabolism and early response of axillary nodes were higher if estrogen receptors were not expressed (p = 0.01 and p = 0.03, respectively). CONCLUSION: In HER2-positive breast cancer, very low tumor residual metabolism after the first cycle of NAC (SUVmax < 2.1) was the main predictor of pCR. These results should be further explored in multicenter studies and incorporated into the design of clinical trials.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias de la Mama/diagnóstico por imagen , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Carcinoma Ductal de Mama/diagnóstico por imagen , Genes erbB-2 , Terapia Neoadyuvante , Tomografía de Emisión de Positrones , Taxoides/uso terapéutico , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/genética , Femenino , Fluorodesoxiglucosa F18 , Humanos , Persona de Mediana Edad , Imagen Multimodal , Valor Predictivo de las Pruebas , Radiofármacos , Tomografía Computarizada por Rayos X , Trastuzumab , Resultado del Tratamiento
14.
Eur J Nucl Med Mol Imaging ; 41(3): 416-27, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24258007

RESUMEN

PURPOSE: The objective of this study was to evaluate, in the luminal human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype, the prognostic value of tumour glucose metabolism at baseline and of its early changes during neoadjuvant chemotherapy (NAC). METHODS: This prospective study included 61 women with hormone-sensitive HER2-negative breast cancer treated with NAC. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed at baseline. Hepatic activity was used as a reference to distinguish between low metabolic and hypermetabolic tumours. In hypermetabolic tumours, a PET exam was repeated after the first course of NAC. The relative change in the maximum standardized uptake value of the tumour (∆SUV) was calculated. RESULTS: Nineteen women had low metabolic luminal breast cancers at baseline, correlated with low proliferation indexes. Forty-two women had hypermetabolic tumours, corresponding to more proliferative breast cancers with higher Ki-67 expression (p = 0.017) and higher grade (p = 0.04). The median follow-up period was 64.2 months (range 11.5-93.2). Thirteen women developed recurrent disease, nine of whom died. Worse overall survival was associated with larger tumour size [>5 cm, hazard ratio (HR) = 6.52, p = 0.009] and with hypermetabolic tumours achieving a low metabolic response after one cycle of NAC (ΔSUV < 16%, HR = 10.63, p = 0.004). Five-year overall survival in these poor responder patients was 49.2%. Overall survival in women with low metabolic tumours or hypermetabolic/good response tumours was 100 and 96.15%, respectively. CONCLUSION: In luminal HER2-negative breast tumours, tumour metabolism at baseline and changes after the first course of NAC are early surrogate markers of patients' survival. A subgroup of women with hypermetabolic/poorly responding tumours, correlated with poor prognosis at 5 years, can be identified early. These results may guide future studies by tailoring the NAC regimen to the metabolic response.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Carcinoma/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Terapia Neoadyuvante , Tomografía de Emisión de Positrones , Radiofármacos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/terapia , Carcinoma/tratamiento farmacológico , Femenino , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Resultado del Tratamiento
15.
Br J Clin Pharmacol ; 77(3): 498-508, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24283925

RESUMEN

AIMS: Vinflunine (VFL) ditartrate, a novel tubulin-targeted inhibitor, is registered for the treatment of patients with advanced or metastatic urothelial transitional cell carcinoma. This phase I study assessed the effect of renal impairment on the pharmacokinetics and tolerability of VFL. METHODS: VFL was infused in patients with advanced/metastatic solid tumours once every 3 weeks with anticipated dose reduction on the first cycle stratified according to the creatinine clearance (CLcr ) values. Pharmacokinetic data were collected on the first two cycles in renally impaired patients (CLcr ≤ 60 ml min(-1) ) and were compared with a control cohort of patients (CLcr > 60 ml min(-1) ). RESULTS: Thirty-three patients (46-86 years) were treated, 13 in group 1 (40 ml min(-1) ≤ CLcr ≤ 60 ml min(-1) ) and 20 in group 2 (20 ml min(-1) ≤ CLcr < 40 ml min(-1) ). The renal dysfunction induced a mean decrease in VFL clearance of 12% in group 1 and 28% in group 2, compared with the control group. The anticipated dose reduction given in renally impaired patients (i.e. 280 mg m(-2) and 250 mg m(-2) in groups 1 and 2, respectively) yielded similar drug exposure to control patients. The tolerance profile of VFL in patients with renal dysfunction was similar to that observed in patients with CLcr > 60 ml min(-1) . CONCLUSION: In conclusion, the recommended doses of intravenous VFL administered once every 3 weeks in cancer patients with renal impairment are 280 mg m(-2) when CLcr is between 40 and 60 ml min(-1) and 250 mg m(-2) when CLcr is between 20 and <40 ml min(-1) .


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Enfermedades Renales/complicaciones , Riñón/fisiopatología , Neoplasias/tratamiento farmacológico , Moduladores de Tubulina/administración & dosificación , Vinblastina/análogos & derivados , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/farmacocinética , Esquema de Medicación , Femenino , Francia , Humanos , Infusiones Intravenosas , Enfermedades Renales/diagnóstico , Enfermedades Renales/fisiopatología , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/diagnóstico , Resultado del Tratamiento , Moduladores de Tubulina/efectos adversos , Moduladores de Tubulina/farmacocinética , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/farmacocinética
16.
Lancet Oncol ; 14(1): 88-96, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23234763

RESUMEN

BACKGROUND: Worldwide, many patients with HER2-positive early stage breast cancer do not receive trastuzumab-the standard adjuvant treatment. We investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer, started at any time after diagnosis. METHODS: This study was a placebo-controlled, multicentre, randomised phase 3 trial. Women outpatients from 405 [corrected] centres in 33 countries [corrected] with HER2-positive early-breast cancer who had previously received adjuvant chemotherapy but not trastuzumab were randomly assigned (1:1) to receive daily lapatinib (1500 mg) or daily placebo for 12 months. Randomisation was done with a computer-generated sequence, stratified by time since diagnosis, lymph node involvement at diagnosis, and tumour hormone-receptor status. Investigators, site staff, and patients were masked to treatment assignment. The primary endpoint was disease-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00374322. FINDINGS: Between August, 2006, and May, 2008, 3161 women were enrolled and 3147 were assigned to lapatinib (n=1571) or placebo (n=1576). After a median follow-up of 47·4 months (range 0·4-60·0) in the lapatinib group and 48·3 (0·7-61·3) in the placebo group, 210 (13%) disease-free survival events had occurred in the lapatinib group versus 264 (17%) in the placebo group (hazard ratio [HR] 0·83, 95% CI 0·70-1·00; p=0·053). Central review of HER2 status showed that only 2490 (79%) of the randomised women were HER2-positive. 157 (13%) of 1230 confirmed HER2-positive patients in the lapatinib group and in 208 (17%) of 1260 in the placebo group had a disease-free survival event (HR 0·82, 95% 0·67-1·00; p=0·04). Serious adverse events occurred in 99 (6%) of 1573 patients taking lapatinib and 77 (5%) of 1574 patients taking placebo, with higher incidences of grade 3-4 diarrhoea (97 [6%] vs nine [<1%]), rash (72 [5%] vs three [<1%]), and hepatobiliary disorders (36 [2%] vs one [<1%]). INTERPRETATION: Our data show that there was no significant difference in disease-free survival between groups when analysed in the intention-to-treat population. However, exploratory analyses restricted to patients who had HER2-positive disease confirmed by central fluorescence in-situ hybridisation review suggested marginal benefit with lapatinib in terms of disease-free survival. Thus lapatinib might be an option for women with HER2-positive breast cancer who do not or cannot receive adjuvant trastuzumab. FUNDING: GlaxoSmithKline.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Supervivencia sin Enfermedad , Quinazolinas/administración & dosificación , Receptor ErbB-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Femenino , Humanos , Lapatinib , Ganglios Linfáticos/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Quinazolinas/efectos adversos , Trastuzumab
17.
Lancet Oncol ; 14(8): 741-8, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23764181

RESUMEN

BACKGROUND: Since 2005, 12 months of adjuvant trastuzumab has been the standard treatment for patients with HER2-positive early-stage breast cancer. However, the optimum duration of treatment has been debated. We did a non-inferiority trial of a shorter exposure of 6 months versus the standard 12 months of trastuzumab for patients with early breast cancer. METHODS: We did an open-label, randomised, phase 3 trial in 156 centres in France. Patients with HER2-positive early breast cancer who had received at least four cycles of chemotherapy, had breast-axillary surgery, and had received up to 6 months of trastuzumab (administered by intravenous infusions over 30-90 min every 3 weeks; initial loading dose 8 mg/kg; 6 mg/kg thereafter) before randomisation were eligible. Patients were randomly assigned via central randomisation procedure with web-based software to continue trastuzumab for another 6 months (12 months total duration; control group) or to discontinue trastuzumab at 6 months (6 months total duration; experimental group). Randomisation was stratified by concomitant or sequential administration of trastuzumab with chemotherapy, oestrogen-receptor status, and centre using a minimisation algorithm. The primary endpoint was disease-free survival, with a prespecified non-inferiority margin of 1·15. Analyses were done in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00381901. FINDINGS: 1691 patients were randomly assigned to receive 12 months of trastuzumab and 1693 to receive 6 months of trastuzumab; 1690 patients in each group were included in the intention-to-treat analyses. After a median follow-up of 42·5 months (IQR 30·1-51·6), 175 disease-free survival events were noted in the 12-month group and 219 in the 6-month group. 2-year disease-free survival was 93·8% (95% CI 92·6-94·9) in the 12-month group and 91·1% (89·7-92·4) in the 6-month group (hazard ratio 1·28, 95% CI 1·05-1·56; p=0·29). 119 (93%) of the 128 cardiac events (clinical or based on assessment of left ventricular ejection fraction) occurred while patients were receiving trastuzumab. Significantly more patients in the 12-month group experienced a cardiac event than did those in the 6-month group (96 [5·7%] of 1690 patients vs 32 [1·9%] of 1690 patients, p<0·0001). INTERPRETATION: After 3·5 years follow-up, we failed to show that 6 months of treatment with trastuzumab was non-inferior to 12 months of trastuzumab. Despite the higher rates of cardiac events, 12 months of adjuvant trastuzmab should remain the standard of care. FUNDING: French National Cancer Institute.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Mastectomía , Inhibidores de Proteínas Quinasas/administración & dosificación , Receptor ErbB-2/análisis , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/química , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/secundario , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Esquema de Medicación , Detección Precoz del Cáncer , Femenino , Francia , Cardiopatías/inducido químicamente , Humanos , Infusiones Intravenosas , Estimación de Kaplan-Meier , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Primarias Secundarias , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Inhibidores de Proteínas Quinasas/efectos adversos , Radioterapia Adyuvante , Receptor ErbB-2/genética , Factores de Tiempo , Trastuzumab , Resultado del Tratamiento , Adulto Joven
18.
BMC Cancer ; 13: 460, 2013 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-24099585

RESUMEN

BACKGROUND: Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary objectives were to report dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were secondary objectives. METHODS: Cabazitaxel was administered weekly (1-hour intravenous infusion at 1.5-12 mg/m² doses) for the first 4 weeks of a 5-week cycle in patients with solid tumours. Monitoring of DLTs was used to determine the MTD and the recommended weekly dose. RESULTS: Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m², which was declared the MTD. Gastrointestinal disorders were the most common adverse event. Eight patients developed neutropenia (three ≥ Grade 3); one occurrence of febrile neutropenia was reported. There were two partial responses (in breast cancer) and 13 patients had stable disease (median duration of 3.3 months). Increases in C(max) and AUC(0-t) were dose proportional for the 6-12 mg/m² doses. CONCLUSION: The MTD of weekly cabazitaxel was 12 mg/m² and the recommended weekly dose was 10 mg/m². The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov as NCT01755390.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Taxoides/uso terapéutico , Adulto , Anciano , Antineoplásicos Fitogénicos/farmacología , Terapia Combinada , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/diagnóstico , Taxoides/farmacología , Resultado del Tratamiento
19.
BMC Cancer ; 13: 172, 2013 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-23547558

RESUMEN

BACKGROUND: Lipids A, the lipophilic partial structure of lipopolysaccharides, induce regression of several tumor types in animal models. Rather than exerting direct cytotoxic effect, these compounds trigger the immune system which in turn stimulates secretion of cytokines, and activates the inducible nitric oxide synthase, as well as immune cell infiltration of tumors. OM-174 is an analogue of lipid A with dual action on Toll-like receptors 2 and 4. In an experimental model of peritoneal carcinomatosis induced in BDIX rats by intraperitoneal injection of syngeneic PROb colon cancer cells, it induced a complete regression of tumors. The present phase I trial was conducted to determine the maximum tolerated dose, the recommended phase II dose and biological response associated with OM-174 administered as intravenous infusion. METHODS: Patients received OM-174 twice weekly for a total of 5, 10 or 15 injections of either 600, 800 or 1000 µg/m(2). Blood samples for pharmacokinetic analysis and cytokine dosages were collected. NK cells activity and Toll-like receptors 4 polymorphism analysis were also performed. RESULTS: Seventeen patients were included. The highest dose administered was 1000 µg/m(2) repeated in 15 injections. The most common toxicities were a chills, fever, nausea/vomiting, diarrhea, fatigue and headache. No patient experienced haematological side effects. As no dose limiting toxicity was observed, despite a grade 3 respiratory complication, the maximal tolerated dose and recommended dose were not established. Three patients exhibited disease stabilization with a mean duration of 4 months. Pharmacokinetic profile of OM-174 was characterized by a low distribution volume and clearance. Analysis of TLR 4 polymorphysm showed that most (16/17) patients carried the wild type alleles. A progressive increase in NK cell number and activity was observed only in patients receiving 1000 µg/m(2) of OM-174. A peak of IL-8 and IL-10 concentrations were observed after each OM-174 injection. Peaks of TNF-alpha and IL-6 concentrations were detected after the first infusion and decreased progressively suggesting tolerance. CONCLUSION: OM-174 therapy was well tolerated at biologically active concentrations. Whereas the recommended dose was not determined, further studies are planned in combination with chemotherapy as animal models suggest a strong synergistic antitumor effect. TRIAL REGISTRATION: NCT01800812 (ClinicalTrials.gov Identifier).


Asunto(s)
Antineoplásicos/administración & dosificación , Lipopolisacáridos/administración & dosificación , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Adulto , Anciano , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Citocinas/sangre , Modelos Animales de Enfermedad , Esquema de Medicación , Femenino , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Lipopolisacáridos/farmacología , Lipopolisacáridos/uso terapéutico , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/genética , Polimorfismo Genético , Ratas , Receptor Toll-Like 4/genética , Resultado del Tratamiento
20.
J Pathol ; 224(3): 389-400, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21437909

RESUMEN

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Quimioterapia Adyuvante , Métodos Epidemiológicos , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Pronóstico , Receptor ErbB-2/metabolismo , Resultado del Tratamiento
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