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1.
Nature ; 610(7931): 343-348, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36071165

RESUMO

Cancer progression is driven in part by genomic alterations1. The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations2, leading to the concept that generation of genomic profiling in patients with cancer could allow the selection of effective therapies3,4. Although DNA sequencing has been implemented in practice, it remains unclear how to use its results. A total of 1,462 patients with HER2-non-overexpressing metastatic breast cancer were enroled to receive genomic profiling in the SAFIR02-BREAST trial. Two hundred and thirty-eight of these patients were randomized in two trials (nos. NCT02299999 and NCT03386162) comparing the efficacy of maintenance treatment5 with a targeted therapy matched to genomic alteration. Targeted therapies matched to genomics improves progression-free survival when genomic alterations are classified as level I/II according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)6 (adjusted hazards ratio (HR): 0.41, 90% confidence interval (CI): 0.27-0.61, P < 0.001), but not when alterations are unselected using ESCAT (adjusted HR: 0.77, 95% CI: 0.56-1.06, P = 0.109). No improvement in progression-free survival was observed in the targeted therapies arm (unadjusted HR: 1.15, 95% CI: 0.76-1.75) for patients presenting with ESCAT alteration beyond level I/II. Patients with germline BRCA1/2 mutations (n = 49) derived high benefit from olaparib (gBRCA1: HR = 0.36, 90% CI: 0.14-0.89; gBRCA2: HR = 0.37, 90% CI: 0.17-0.78). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with metastatic breast cancer.


Assuntos
Neoplasias da Mama , Tomada de Decisão Clínica , Genoma Humano , Genômica , Metástase Neoplásica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Tomada de Decisão Clínica/métodos , Análise Mutacional de DNA , Progressão da Doença , Feminino , Genes BRCA1 , Genes BRCA2 , Genoma Humano/genética , Humanos , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico
2.
J Transl Med ; 21(1): 408, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353806

RESUMO

BACKGROUND: Uterine clear cell carcinomas (CCC) represent less than 5% of uterine cancers. Their biological characteristics and clinical management remain uncertain. A multicenter study to explore both clinical and molecular features of these rare tumors was conducted. METHODS: This multicenter retrospective national study was performed within the French TMRG (Rare Gynecologic Malignant Tumors) network. Clinical data and, when available, FFPE blocks were collected. Clinical features, treatments, and outcome (progression-free survival (PFS) and overall survival (OS)) were analyzed and correlated to the protein (tissue micro-array), RNA (Nanostring nCounter® technology), and DNA (array-Comparative Genomic hybridization and target-next generation sequencing) levels using the tumor samples available. RESULTS: Sixty-eight patients with uterine CCC were enrolled, 61 from endometrial localization and 5 with cervix localization. Median age at diagnosis was 68.9 years old (range 19-89.7). Most tumors were diagnosed at an early stage (78% FIGO stage I-II). Hysterectomy (performed in 90%) and lymph node dissection (80%) were the most frequent surgical treatment. More than 70% of patients received external beam radiotherapy and 57% received brachytherapy. Nearly half (46%) of the patients received chemotherapy. After a median follow-up of 24.7 months, median PFS was 64.8 months (95 CI [5.3-124.4]) and median OS was 79.7 (IC95 [31.0-128.4]). Low hormone receptor expression (13% estrogen-receptor positive), frequent PI3K pathway alterations (58% PTEN loss, 50% PIK3CA mutations), and P53 abnormalities (41%) were observed. Mismatch repair deficiency was identified in 20%. P16 expression was associated with shorter PFS (HR = 5.88, 95 CI [1.56-25], p = 0.009). Transcriptomic analyzes revealed a specific transcriptomic profile notably with a high expression of immune response-associated genes in uterine CCC displaying a very good overall prognosis. CONCLUSIONS: Uterine CCC reported to be potentially MSI high, hormone receptors negative, and sometimes TP53 mutated. However, some patients with immune response-associated features and better prognosis may be candidate to treatment de-escalation and immunotherapy.


Assuntos
Carcinoma , Neoplasias Uterinas , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Hibridização Genômica Comparativa , Neoplasias Uterinas/genética , Neoplasias Uterinas/terapia , Hormônios
3.
Qual Life Res ; 32(4): 1085-1094, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36418525

RESUMO

INTRODUCTION: Several studies have shown that emotional competence (EC) impacts cancer adjustment via anxiety and depression symptoms. The objective was to test this model for the quality of life (QoL) of partners: first, the direct effect of partners' EC on their QoL, anxiety and depression symptoms after cancer diagnosis (T1), after chemotherapy (T2) and after radiotherapy (T3); Second, the indirect effects of partners' EC at T1 on their QoL at T2 and T3 through anxiety and depression symptoms. METHODS: 192 partners of women with breast cancer completed a questionnaire at T1, T2 and T3 to assess their EC (PEC), anxiety and depression symptoms (HADS) and QoL (Partner-YW-BCI). Partial correlations and regression analyses were performed to test direct and indirect effects of EC on issues. RESULTS: EC at T1 predicted fewer anxiety and depression symptoms at each time and all dimensions of QoL, except for career management and financial difficulties. EC showed different significant indirect effects (i.e. via anxiety or depression symptoms) on all sub-dimensions of QoL, except for financial difficulties, according to the step of care pathway (T2 and T3). Anxiety and depression played a different role in the psychological processes that influence QoL. CONCLUSION: Findings confirm the importance of taking emotional processes into account in the adjustment of partners, especially regarding their QoL and the support they may provide to patients. It, thus, seems important to integrate EC in future health models and psychosocial interventions focused on partners or caregivers.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Qualidade de Vida/psicologia , Estudos Longitudinais , Depressão/psicologia , Emoções , Ansiedade/psicologia
4.
J Oncol Pharm Pract ; 29(8): 1990-1997, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36945877

RESUMO

INTRODUCTION: Cases of osteonecrosis of the jaw have been reported by dental surgeons to the pharmacovigilance center in Rennes, France, occurring among patients treated with palbociclib, a cyclin-dependent kinase 4/6 inhibitor. Although this event was not expected with the drug, a safety signal was raised. Describing a local case series, the aim of our study was to identify specific patterns that might suggest a triggering role for these drugs, and to discuss pathophysiological hypotheses. MATERIALS AND METHODS: A retrospective case series of patients exposed to cyclin-dependent kinase 4/6 inhibitors between 2016 and 2020 with a diagnosis of osteonecrosis of the jaw at the Rennes Dental Care Center was analyzed. The descriptive analysis was conducted on patient demographics, breast cancer characteristics, osteonecrosis of the jaw, biological data, and exposure to cyclin-dependent kinase 4/6 inhibitors. RESULTS: We identified eight cases, most of them at stages 0-1 (62.5%). Four patients were still exposed to palbociclib at the time of diagnosis and four had discontinued the treatment before the diagnosis. Chronological imputability could not be excluded given the drug's half-life and the variable intervals of dental monitoring from one patient to another. All patients had at least one dental osteonecrosis risk factor (including dental extraction, dentures, and denosumab exposure at the time of diagnosis). Neutropenia and mucositis were not systematically reported at the time of diagnosis. The anatomopathological characteristics were nonspecific. CONCLUSION: We did not identify a specific pattern that could suggest a triggering role of palbociclib in the development of ONJ.


Assuntos
Conservadores da Densidade Óssea , Osteonecrose , Humanos , Conservadores da Densidade Óssea/efeitos adversos , Estudos Retrospectivos , Quinase 4 Dependente de Ciclina , Osteonecrose/induzido quimicamente , Difosfonatos/efeitos adversos , Denosumab/efeitos adversos
5.
N Engl J Med ; 381(25): 2416-2428, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31851799

RESUMO

BACKGROUND: Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS: We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. RESULTS: Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation. (Funded by ARCAGY Research and others; PAOLA-1 ClinicalTrials.gov number, NCT02477644.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Ftalazinas/administração & dosagem , Piperazinas/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Ftalazinas/efeitos adversos , Piperazinas/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Intervalo Livre de Progressão , Qualidade de Vida
6.
Psychooncology ; 31(5): 848-855, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34989072

RESUMO

OBJECTIVE: Emotional competence (EC) is considered a substantial resource in the adjustment of cancer patients, especially via its effect on anxiety and depression symptoms. This research aimed at assessing the impact of intrapersonal EC in young women (≤45 years) with breast cancer (YWBC) on their specific quality of life (i.e. subjective experience related to daily difficulties and perceived repercussions of the disease and treatments) related to chemotherapy, via anxiety and depression symptoms. METHODS: Two hundred fifty YWBC from 24 French centers completed a self-reported questionnaire after diagnosis (T1) and after the chemotherapy phase (T2), comprising the Young Women Breast Cancer Inventory, the Profile of EC and the Hospital Anxiety and Depression Scale. The indirect effect of EC (T1) on subjective experience (T2) via anxiety and depression symptoms (T2) was tested using regressions and the Macro PROCESS. RESULTS: Emotional competence predicted fewer anxiety and depression symptoms at T1 and T2, and a better subjective experience at T2 via fewer anxiety and depression symptoms. Depression symptoms appeared to be a stronger mediator than anxiety symptoms on four dimensions (Support from close relatives, feeling of couple cohesion, body image and sexuality, management of children and everyday life), whereas anxiety symptoms appeared to be a stronger mediator on two dimensions (negative affectivity and apprehension about the future, deterioration of relationships). CONCLUSIONS: These results support the importance of developing psycho-affective interventions to reinforce the EC of YWBC during chemotherapy in order to facilitate the cognitive and emotional processes necessary for a better adjustment and subjective experience.


Assuntos
Neoplasias da Mama , Angústia Psicológica , Ansiedade/psicologia , Neoplasias da Mama/psicologia , Criança , Depressão/psicologia , Feminino , Humanos , Qualidade de Vida/psicologia
7.
Oncologist ; 26(10): e1870-e1879, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34216177

RESUMO

BACKGROUND: Neurokinin (NK) 1 receptor antagonists (RAs), administered in combination with a 5-hydroxytryptamine-3 (5-HT3 ) RA and dexamethasone (DEX), have demonstrated clear improvements in chemotherapy-induced nausea and vomiting (CINV) prevention over a 5-HT3 RA plus DEX. However, studies comparing the NK1 RAs in the class are lacking. A fixed combination of a highly selective NK1 RA, netupitant, and the 5-HT3 RA, palonosetron (NEPA), simultaneously targets two critical antiemetic pathways, thereby offering a simple convenient antiemetic with long-lasting protection from CINV. This study is the first head-to-head NK1 RA comparative study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC). MATERIALS AND METHODS: This was a pragmatic, multicenter, randomized, single-cycle, open-label, prospective study designed to demonstrate noninferiority of single-dose NEPA to a 3-day aprepitant regimen in preventing CINV in chemotherapy-naive patients receiving AC/non-AC MEC in a real-life setting. The primary efficacy endpoint was complete response (no emesis/no rescue) during the overall (0-120 hour) phase. Noninferiority was achieved if the lower limit of the 95% confidence interval (CI) of the difference between NEPA and the aprepitant group was greater than the noninferiority margin set at -10%. RESULTS: Noninferiority of NEPA versus aprepitant was demonstrated (risk difference 9.2%; 95% CI, -2.3% to 20.7%); the overall complete response rate was numerically higher for NEPA (64.9%) than aprepitant (54.1%). Secondary endpoints also revealed numerically higher rates for NEPA than aprepitant. CONCLUSION: This pragmatic study in patients with cancer receiving AC and non-AC MEC revealed that a single dose of oral NEPA plus DEX was at least as effective as a 3-day aprepitant regimen, with indication of a potential efficacy benefit for NEPA. IMPLICATIONS FOR PRACTICE: In the absence of comparative neurokinin 1 (NK1 ) receptor antagonist (RA) studies, guideline committees and clinicians consider NK1 RA agents to be interchangeable and equivalent. This is the first head-to-head study comparing one NK1 RA (oral netupitant/palonosetron [NEPA]) versus another (aprepitant) in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy. Noninferiority of NEPA versus the aprepitant regimen was demonstrated; the overall complete response (no emesis and no rescue use) rate was numerically higher for NEPA (65%) than aprepitant (54%). As a single-dose combination antiemetic, NEPA not only simplifies dosing but may offer a potential efficacy benefit over the current standard-of-care.


Assuntos
Antieméticos , Antineoplásicos , Antibióticos Antineoplásicos/uso terapêutico , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Aprepitanto , Método Duplo-Cego , Humanos , Isoquinolinas/uso terapêutico , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Palonossetrom/uso terapêutico , Estudos Prospectivos , Quinuclidinas/uso terapêutico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/prevenção & controle
8.
BMC Cancer ; 20(1): 975, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036567

RESUMO

BACKGROUND: Currently, oral targeted therapies are known to be effective and are frequently used to treat metastatic cancer patients, but fatigue is a frequently reported early side effect of these treatments. This fatigue may impact the patient's treatment adherence and result in a negative impact on quality of life. Physical exercise significantly improved the general well-being and quality of life of advanced cancer patients. However, there is no specific physical activity program adapted for patients with advanced disease. METHODS: QUALIOR is a two-part, randomized, open-label, and multicenter with two arms phase II/III trial. Patients (phase II: n = 120; phase III: n = 312) with metastatic cancer (breast cancer, kidney cancer, lung cancer, and other cancers [including but not limited to colon cancer, melanoma, sarcoma, or hepatocarcinoma]) treated with a first- or second-line oral targeted therapy without chemotherapy will be included. Patients will be randomized (2:1) to a 3-month supervised home-based standardized physical activity program or to a recommended adapted physical activity (via a booklet). The primary objective of the phase II is to evaluate the feasibility of the supervised program. The primary objective of the phase III is the evaluation of the benefit of the supervised home-based program compare to the recommended program in terms of fatigue and quality of life at 3 months. The secondary objectives aim to evaluate the impact of the supervised program on fatigue over time, pain, physical capacities, psychosocial and cognitive functions, general quality of life, frequency of dose reduction and patients' adherence to the targeted therapy, overall survival, and progression-free survival. This study will also evaluate the medico-economic impact of supervised program compared to the recommended adapted physical activity program. DISCUSSION: The aim of this study is to evaluate home-based physical exercise program for metastatic cancer patients treated with oral targeted therapies to help patients to cope with fatigue and improve quality of life. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov since May 2017 ( NCT03169075 ).


Assuntos
Terapia por Exercício/métodos , Metástase Neoplásica/terapia , Administração Oral , Estudos de Viabilidade , Feminino , Humanos , Masculino
9.
Gynecol Oncol ; 159(1): 129-135, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32723678

RESUMO

PURPOSE: Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is a rare and rapidly lethal disease affecting young women. Cytoreductive surgery associated with chemotherapy followed by a high dose chemotherapy regimen (HDC) demonstrated improved outcomes in a unique prospective and several retrospective studies, and this report aimed to confirm these results in an independent and larger cohort. METHODS: Between 2006 and 2018, we conducted a multicentric prospective study on 44 women diagnosed with SCCOHT. Patients were treated homogeneously with optimal cytoreductive surgery and chemotherapy protocol for four to six cycles (PAVEP). In case of complete response, patients received HDC with stem-cell support, followed by pelvic radiotherapy. The primary endpoint was the event-free survival (EFS) in the per-protocol cohort. Secondary analysis explored the effect of HDC with outcomes. RESULTS: Mean age at diagnosis was 33 years old (range 13.8-75.8). 14 patients presented with stage FIGO I, 21 with stage III and 9 with stage IV. Median follow-up was 53.4 months. 38 patients underwent optimal surgery with up to 6 cycles of PAVEP. 30 received HDC, and 21 pelvic radiotherapy. 21 relapses were reported leading to death for 18 patients. Median EFS in the per-protocol cohort was 18.2 months, and 2-year EFS rate was 40%. HDC was significantly associated with better overall survival (p < .001). Grades 3/4 adverse events were frequent but, in most cases, manageable, although one grade-5 adverse-event occurred during HDC. CONCLUSION: Intensive regimen containing multidrug chemotherapy, HDC and pelvic radiotherapy, for the management of SCCOHT, demonstrated encouraging survival and should be proposed for all patients. However, the significant toxicity cost associated is of concern and it should be restricted to expert centers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Pequenas/terapia , Hipercalcemia/terapia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/patologia , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/mortalidade , Hipercalcemia/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Ovário/patologia , Ovário/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Transplante de Células-Tronco , Transplante Autólogo , Adulto Jovem
10.
J Psychosoc Oncol ; 37(1): 50-68, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30295567

RESUMO

PURPOSE: This study aimed to compare the self-reported perceptions of the repercussions of the disease and its treatments and emotional distress in young women with breast cancer and their partners. DESIGN: Cross-sectional study using self-reported questionnaires. SAMPLE: 491 couples in which women were aged <45 years when diagnosed with non-metastatic breast cancer in four different groups of treatment: during chemotherapy with or without Trastuzumab; under Trastuzumab with or without hormone therapy; during hormone therapy; and during the follow-up period. METHODS: Patients and partners completed a questionnaire assessing their self-reported perceptions of the disease and treatments (Patient YW-BCI and Partner YW-BCI for the partners) and their emotional distress (CESD; STAI). FINDINGS: Patients reported more difficulties than partners in the management of child(ren) and everyday life, body image and sexuality, negative affectivity about the disease and apprehension about the future, career management, and finances. While the difficulties were generally more marked in the chemotherapy and Trastuzumab groups than in the hormone therapy and follow-up groups, the negative affectivity about the disease and apprehension about the future was high in all four groups, especially in patients. The partners reported more difficulties in sharing with close relatives, and even more in those groups reflecting the latest treatment phases. No difference appeared between patients and partners in couple cohesion and deterioration of relationships with relatives. Partners were less anxious than patients but as depressed as them. CONCLUSIONS: Difficulties of patients and partners seem particularly severe in the early care pathway, maybe reflecting better adjustment in women under surveillance and their partners. A longitudinal study will substantiate this finding and enable a better identification of some explanatory processes of these differences and similarities in the daily self-reported repercussions of the disease throughout the cancer care pathway. Implications for psychosocial oncology: It seems important to support young women with breast cancer and their partners, as our results evidence distress in both and differences according to the type of treatment the woman is currently receiving. Healthcare providers need consistent methods to identify and respond to couples' distress and reduce significant disparities in support.


Assuntos
Atitude Frente a Saúde , Neoplasias da Mama/psicologia , Parceiros Sexuais/psicologia , Adulto , Neoplasias da Mama/terapia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato
11.
Future Oncol ; 13(29): 2667-2680, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29191056

RESUMO

AIM: Evaluate the influence of emotional distress of young women with breast cancer and their spouses on their daily subjective experience of the disease, through application of the Actor-Partner Interdependence Model. PATIENTS & METHODS: A total of 112 women under 45 years of age were diagnosed with nonmetastatic breast cancer and their spouses answered self-reported measures of anxiety, depression and subjective experience of the disease and its treatment. RESULTS: The patient's emotional distress influenced more the subjective experience of her spouse than the spouse's emotional distress influenced the patient. The spouse's difficulties depended as much on his own distress level as on the patient's distress level. CONCLUSION: These data confirm the importance of implementing couple-focused interventions.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/psicologia , Emoções , Cônjuges/psicologia , Estresse Psicológico , Adulto , Ansiedade/epidemiologia , Ansiedade/etiologia , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Breast Cancer Res Treat ; 152(3): 569-80, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26160250

RESUMO

Cognitive impairment, especially verbal episodic memory and executive function impairments, has been considered to be a possible adverse effect of aromatase inhibitors (AI). This phase III open-label study compared the impact of tamoxifen and AI on verbal episodic memory (Rey auditory verbal learning test-RAVLT) and other cognitive functions (visual memory, psychomotor speed, and executive functions) after 6 and 12 months of treatment in breast cancer patients undergoing adjuvant hormonotherapy. Menopausal chemo-naïve patients with resectable breast cancer were randomly assigned (1:1) at the end of the radiotherapy to receive tamoxifen or AI. Neuropsychological assessments, self-reported quality of life, and depression assessments were performed at baseline, before any hormonal treatment, and at 6 and 12 months. Mixed design analysis models of variance was used to compare the evolution of the scores between the groups during follow-up. A total of 74 evaluable patients were enrolled (Tamoxifen arm, n = 37; AI arm, n = 37; letrozole n = 18; anastrozole n = 16; exemestane n = 3). The median age at inclusion was 61 years (range, minimum 49-maximum 69). The patient and breast cancer characteristics were well balanced between arms. After 6 months, no significant differential effect of AI or tamoxifen was observed on the RAVLT. Moreover, considering the other cognitive measures and the quality of life questionnaires, there were also no differences between the groups during the 1-year follow-up. In this study, AI has not demonstrated worse adverse effects on cognitive functions than tamoxifen during a 1-year follow-up.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Transtornos Cognitivos/induzido quimicamente , Idoso , Anastrozol , Androstadienos/efeitos adversos , Androstadienos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Quimioterapia Adjuvante , Feminino , Humanos , Letrozol , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Pós-Menopausa , Desempenho Psicomotor/efeitos dos fármacos , Qualidade de Vida , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Triazóis/efeitos adversos , Triazóis/uso terapêutico
13.
Mol Oncol ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287892

RESUMO

Erb-b2 receptor tyrosine kinase 2 (ERBB2)-activating mutations are therapeutically actionable alterations found in various cancers, including metastatic breast cancer (MBC). We developed multiplex digital PCR assays to detect and quantify ERBB2 mutations in circulating tumor DNA from liquid biopsies. We studied the plasma from 272 patients with hormone-receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) MBC to detect 17 ERBB2 mutations using a screening assay. The assay was developed on the three-color Crystal dPCR™ naica® platform with a two-step strategy for precise mutation identification. We found that nine patients (3.3%) harbored at least one ERBB2 mutation. The mutation rate was higher in patients with lobular histology (5.9%) compared to invasive breast carcinoma of no special type (2.6%). A total of 12 mutations were found with the following frequencies: L755S (25.00%), V777L (25.00%), S310Y (16.67%), L869R (16.67%), S310F (8.33%), and D769H (8.33%). Matched tumor samples from six patients identified the same mutations with an 83% concordance rate. In summary, our highly sensitive multiplex digital PCR assays are well suited for plasma-based monitoring of ERBB2 mutational status in patients with MBC.

14.
Expert Rev Anticancer Ther ; 23(7): 699-708, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37198729

RESUMO

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) is a group of rare tumors characterized by abnormal trophoblastic proliferation following pregnancy including invasive moles, choriocarcinomas, and intermediate trophoblastic tumors (ITT). Although the treatment and follow-up of GTN has been heterogeneous, globally the emergence of expert networks has helped to harmonize its management. AREAS COVERED: We provide an overview of the current knowledge, diagnosis, and management strategies in GTN and discuss innovative therapeutic options under investigation. While chemotherapy has been the historical backbone of GTN treatment, promising drugs such as immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway and anti-angiogenic tyrosine kinase inhibitors are currently being investigated remodeling the therapeutical landscape of trophoblastic tumors. EXPERT OPINION: Chemotherapy regimens for GTN have potential long-term effects on fertility and quality of life, making innovative and less toxic therapeutic approaches necessary. Immune checkpoint inhibitors have shown promise in reversing immune tolerance in GTN and have been evaluated in several trials. However, immunotherapy is associated with rare but life-threatening adverse events and evidence of immune-related infertility in mice, highlighting the need for further research and careful consideration of its use. Innovative biomarkers could help personalize GTN treatments and reduce chemotherapy burden in some patients.


Assuntos
Doença Trofoblástica Gestacional , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Animais , Camundongos , Inibidores de Checkpoint Imunológico/efeitos adversos , Qualidade de Vida , Doença Trofoblástica Gestacional/terapia , Doença Trofoblástica Gestacional/tratamento farmacológico , Neoplasias Uterinas/terapia
15.
Clin Chim Acta ; 545: 117366, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37105452

RESUMO

BACKGROUND: Early detection of ESR1 mutations is a key element for better personalization of the management of patients with HR+/HER2- Metastatic Breast Cancer (MBC). Analysis of circulating tumor DNA from liquid biopsies is a particularly well-suited strategy for longitudinal monitoring of such patients. MATERIALS AND METHODS: Using the naica® three-color digital PCR platform, we developed a screening assay allowing the detection of 11 ESR1 mutations and designed a sequential strategy for precise mutation identification. We then applied this strategy in the analysis of plasma circulating cell-free DNA from 109 HR+/HER2- MBC patients and performed a double-blind comparison study on a subset of patients with the multiplex assay used at the Institut Curie (IC) for the PADA-1 study. RESULTS: Thirty-one patients (28.4%) harboured at least one ESR1 mutation, with the following frequencies: D538G (41.03%), Y537S (25.64%), E380Q (10.26%), Y537N (10.26%), "(536-540)" (7.69%), Y537C (2.56%), and L536R (2.56%). The presence of ESR1 mutation(s) was significantly associated with liver metastases (p = 0.0091). A very good agreement (91%) was observed with the IC assay. CONCLUSION: Our assays have proven to be robust and highly sensitive and are very well-suited for monitoring ESR1 mutations in the plasma of MBC patients.


Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , DNA Tumoral Circulante , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Mutação , DNA Tumoral Circulante/genética , Reação em Cadeia da Polimerase Multiplex
16.
Cancers (Basel) ; 14(9)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35565475

RESUMO

The surgical specificities of advanced low-grade serous ovarian carcinoma (LGSOC) have been little investigated. Our objective was to describe surgical procedures/complications in primary (PDS) compared to interval debulking surgery (neoadjuvant chemotherapy and interval debulking surgery, NACT-IDS) and to assess the survival (progression-free (PFS) and overall survival (OS)) in patients with advanced LGSOC. We retrospectively analyzed advanced LGSOC from a nationwide registry (January 2000 to July 2017). A total of 127 patients were included (48% PDS and 35% NACT-IDS). Peritoneal carcinomatosis was more severe (p = 0.01 to 0.0001, according to sites), surgery more complex (p = 0.03) and late postoperative morbidity more frequent (p = 0.03) and more severe in the NACT-IDS group. PFS and OS were similar in patients with CC0 and CC1 residual disease after PDS or IDS. Prognosis was poorest for NACT-IDS patients with CC2/CC3 resection (PFS: HR = 2.31, IC95% (1.3-4.58); p = 0.005; OS: HR = 4.98, IC95% (1.59-15.61); p = 0.006). NACT has no benefit in terms of surgical outputs in patients with advanced LGSOC. Patients with complete resection or minimal residual disease (CC0 and CC1) have similar prognoses. On the other hand, patients with CC2 and more residual disease have similar survival rates compared to nonoperated patients. Primary cytoreduction with complete or with minimal residuals should be preferred when feasible.

17.
Int J Biol Markers ; 36(2): 57-63, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34027694

RESUMO

PURPOSE: Genomic signatures, such as EndoPredict®, may help clinicians to decide which adjuvant treatment is the most appropriate. METHODS: We propose the EndoPredict® assay for unclear cases of adjuvant treatment in patients treated in our comprehensive cancer center. We prospectively and retrospectively report the decision of adjuvant treatment before and after the EndoPredict® assay, respectively, compared to the PREDICT's tool scores. RESULTS: From November 2016 to March 2019, 159 breast cancer tumors were analyzed and presented before and after the EndoPredict® assay. Before the EndoPredict® results, clinicians recommended chemotherapy for 57 patients (57/159, 36%). A total of 108 patients (108/159, 68%) were classified as EPclin high-risk score. There was only a slight agreement between clinicians' decisions and EPclin risk score. The EPclin score led to 37% changes in treatment (59/159); chemotherapy was favored in 80% of cases (47/59). The PREDICT tool recommended chemotherapy for 16 high-risk patients (16/159, 10%). CONCLUSION: Although genomic tests were developed in order to de-escalate adjuvant treatment, in our comprehensive cancer center the use of the EndoPredict® assay led to an increase in prescribed chemotherapy.


Assuntos
Quimioterapia Adjuvante/métodos , Tomada de Decisões/efeitos dos fármacos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
18.
Sci Rep ; 11(1): 17316, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34453076

RESUMO

With the approval of new therapies targeting the PI3K pathway, the detection of PIK3CA mutations has become a key factor in treatment management for HR+/HER2- metastatic breast cancer (MBC). We developed multiplex digital PCR (dPCR) assays to detect and quantify PIK3CA mutations. A first screening assay allows the detection of 21 mutations, with a drop-off system targeting the 542-546 hotspot mutations combined with the simultaneous detection of N345K, C420R, H1047L and H1047R mutations. In the case of a positive result, a sequential strategy based on other assays that we have developped allows for precise mutation identification. Clinical validity was determined by analyzing plasma circulating free DNA (cfDNA) from 213 HR+/HER2- MBC samples, as well as DNA extracted from 97 available matched tumors from 89 patients. Our assays have shown reliable specificity, accuracy and reproducibility, with limits of blank of three and four droplets for the screening assay. Sixty-eight patients (32%) had at least one PIK3CA mutation detectable in their plasma, and we obtained 83.1% agreement between the cfDNA analysis and the corresponding tumors. The high sensitivity and robustness of these new dPCR assays make them well-suited for rapid and cost-effective detection of PIK3CA mutations in the plasma of MBC patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Ácidos Nucleicos Livres/análise , Classe I de Fosfatidilinositol 3-Quinases/genética , Adolescente , Sequência de Bases , Neoplasias da Mama/diagnóstico , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Humanos , Lactente , Recém-Nascido , Mutação , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , Adulto Jovem
19.
Nat Med ; 27(2): 250-255, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33462450

RESUMO

The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n = 199) were randomized to either durvalumab (10 mg kg-1 every 2 weeks) or maintenance chemotherapy. In the overall population, durvalumab did not improve progression-free survival (adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.00-1.96; P = 0.047) or overall survival (OS; adjusted HR: 0.84, 95% CI: 0.54-1.29; P = 0.423). In an exploratory subgroup analysis, durvalumab improved OS in patients with triple-negative breast cancer (TNBC; n = 82; HR: 0.54, 95% CI: 0.30-0.97, P = 0.0377). Exploratory analysis showed that the HR of death was 0.37 (95% CI: 0.12-1.13) for patients with PD-L1+ TNBC (n = 32) and 0.49 (95% CI: 0.18-1.34) for those with PD-L1- TNBC (n = 29). In patients with TNBC, exploratory analyses showed that the HR for durvalumab efficacy (OS) was 0.18 (95% CI: 0.05-0.71; log-rank test, P = 0.0059) in patients with CD274 gain/amplification (n = 23) and 1.12 (95% CI: 0.42-2.99; log-rank test, P = 0.8139) in patients with CD274 normal/loss (n = 32). Tumor infiltration by lymphocytes (CD8, FoxP3 and CD103 expressions) and homologous recombination deficiency did not predict sensitivity to durvalumab in exploratory analyses. This latter finding should be interpreted with caution since only one patient presented a germline BRCA mutation. The present study provides a rationale to evaluate single-agent durvalumab in maintenance therapy in patients with TNBC. Exploratory analyses identified CD274 amplification as a potential biomarker of sensitivity. Maintenance chemotherapy was more effective than durvalumab in patients with hormone receptor-positive and Her2-negative disease.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/genética , Mama/efeitos dos fármacos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Quimioterapia de Manutenção/métodos , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , Receptor ErbB-2/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
20.
Nutrients ; 12(10)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050321

RESUMO

Supervised exercise dietary programs are recommended to relieve cancer-related fatigue and weight increase induced by adjuvant treatment of early breast cancer (EBC). As this recommendation lacks a high level of evidence, we designed a multicenter randomized trial to evaluate the impact of an Adapted Physical Activity Diet (APAD) education program on fatigue. We randomized 360 women with EBC who were receiving adjuvant chemotherapy and radiotherapy to APAD or usual care at eight French cancer institutions. Data were collected at baseline, end of chemotherapy, end of radiotherapy, and 6 months post-treatment. The primary endpoint was the general cancer-related fatigue score using the MFI-20 questionnaire. Fatigue correlated with the level of precariousness, but we found no significant difference between the two groups in terms of general fatigue (p = 0.274). The APAD arm has a smaller proportion of patients with confirmed depression at the end of follow-up (p = 0.052). A transient modification in physical activity levels and dietary intake was reported in the experimental arm. However, a mixed hospital- and home-based APAD education program is not enough to improve fatigue caused by adjuvant treatment of EBC. Cancer care centers should consider integrating more proactive diet-exercise supportive care in this population, focusing on precarious patients.


Assuntos
Neoplasias da Mama/terapia , Quimiorradioterapia Adjuvante/efeitos adversos , Dietoterapia/métodos , Terapia por Exercício/métodos , Fadiga/etiologia , Fadiga/terapia , Educação em Saúde/métodos , Hospitais , Fenômenos Fisiológicos da Nutrição/fisiologia , Neoplasias da Mama/complicações , Feminino , Humanos , Organização e Administração , Avaliação de Programas e Projetos de Saúde , Qualidade de Vida , Resultado do Tratamento
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