RESUMEN
BACKGROUND: To identify patients most likely to respond to everolimus, a mammalian target of rapamycin (mTOR) inhibitor, a prospective biomarker study was conducted in hormone receptor-positive endocrine-resistant metastatic breast cancer patients treated with exemestane-everolimus therapy. METHODS: Metastatic tumor biopsies were processed for immunohistochemical staining (p4EBP1, PTEN, pAKT, LKB1, and pS6K). ESR1, PIK3CA and AKT1 gene mutations were detected by NGS. The primary endpoint was the association between the p4EBP1 expression and clinical benefit rate (CBR) at 6 months of everolimus plus exemestane treatment. RESULTS: Of 150 patients included, 107 were evaluable for the primary endpoint. p4EBP1 staining above the median (Allred score ≥6) was associated with a higher CBR at 6 months (62% versus 40% in high-p4EBP1 versus low-p4EBP1, χ2 test, p = 0.026) and a longer progression-free survival (PFS) (median PFS of 9.2 versus 5.8 months in high-p4EBP1 versus low-p4EBP1; p = 0.02). When tested with other biomarkers, only p4EBP1 remained a significant predictive marker of PFS in multivariate analysis (hazard ratio, 0.591; p = 0.01). CONCLUSIONS: This study identified a subset of patients with hormone receptor-positive endocrine-resistant metastatic breast cancer and poor outcome who would derive less benefit from everolimus and exemestane. p4EBP1 may be a useful predictive biomarker in routine clinical practice. CLINICAL TRIAL REGISTRATION: NCT02444390.
Asunto(s)
Neoplasias de la Mama , Everolimus , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Androstadienos/uso terapéutico , Biomarcadores , Receptor ErbB-2/metabolismoRESUMEN
PURPOSE: The use of oral cancer drugs (OAD) has increased over the last two decades. The objective of this study was to measure the impact of a nurse-led telephone follow-up in the therapeutic management of patients treated with an OAD regarding toxicity, medication adherence and quality of life. METHODS: A randomized, multicenter, controlled trial was conducted. All consecutive over 18-year-old patients, treated in medical oncology, radiotherapy, or hematology departments, receiving OAD for any cancer were invited to participate to the study. A total of 183 patients treated for solid or hematological cancers with an OAD were randomly assigned to receive a nurse-led telephone follow-up or standard care for 24 weeks. Data were collected between 2015 and 2018. RESULTS: Nurse telephone follow-up did not improve the global score toxicity in the intervention group. However, telephone calls directed by trained nurses induced a significant decrease in number of patients with grade 3 adverse events throughout the follow-up [OR 0.45 (IC à 95%) (0.23, 0.9)](P = 0.03). There was no significant difference in quality of life and medication adherence between groups at any follow-up time point. CONCLUSIONS: In this first French real-life study, the advice provided by qualified nurses via phone calls improved the management of grade 3 toxicities but failed to demonstrate an improvement of all grades of toxicities. More prospective studies are needed to confirm the impact of telephone calls on the toxicities related to OAD. TRIAL REGISTRATION: Clinical trial registration is NCT02459483. Protection committee SUD-ESTI registration is 2015-A00527-42 on 13 April 2015. National Agency for the Safety of Medicines and Health Products registration is 150619-B on the 27 may 2015.
Asunto(s)
Antineoplásicos/uso terapéutico , Cumplimiento de la Medicación/psicología , Calidad de Vida/psicología , Anciano , Antineoplásicos/farmacología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
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 JovenRESUMEN
The need to accurately identify cancer outpatients at high risk of thrombotic complications is still unmet. In a prospective, multicenter cohort study (ONCOlogie et Chambres ImPlantables [ONCOCIP]), consecutive adult patients with a solid tumor and implanted port underwent 12-month follow-up. Our primary objective was to identify risk factors for (1) catheter-related thrombosis, defined as ipsilateral symptomatic upper-limb deep-vein thrombosis with or without pulmonary embolism, and (2) venous thromboembolism other than catheter-related, defined as any symptomatic superficial- or deep-vein thrombosis (other than catheter-related) or pulmonary embolism, and incidental pulmonary embolism. All events were objectively confirmed and centrally adjudicated. Rate assessments integrated competing risk of death. Overall, 3032 patients were included (median age: 63 years; women: 58%). The most frequent cancer locations were breast (33.7%), lung (18.5%), and colorectal (15.6%), cancer being metastatic in 43.2% of patients. Most patients (97.1%) received chemotherapy. By 12 months, 48 (1.6%) patients had been lost to follow-up and 656 (24.6%) had died; 3.8% (n = 111) of patients had experienced catheter-related thrombosis, and 9.6% (n = 276) venous thromboembolism other than catheter-related. By multivariate analysis, use of cephalic vein for catheter insertion predicted catheter-related thrombosis, whereas ongoing antiplatelet therapy was protective; risk factors for venous thromboembolism other than catheter-related were advanced age, previous venous thromboembolism, cancer site, and low hemoglobin level or increased leukocyte count before chemotherapy. In conclusion, this large prospective cohort study showed a high rate of venous thromboembolism in patients with a solid tumor and implanted port. Risk factors for catheter-related thrombosis differed from those for venous thromboembolism not catheter-related. This trial was registered at www.clinicaltrials.gov as #NCT02025894.
Asunto(s)
Catéteres/efectos adversos , Neoplasias/mortalidad , Embolia Pulmonar/mortalidad , Tromboembolia Venosa/mortalidad , Trombosis de la Vena/mortalidad , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Francia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias/patología , Neoplasias/terapia , Estudios Prospectivos , Embolia Pulmonar/etiología , Embolia Pulmonar/patología , Factores de Riesgo , Tasa de Supervivencia , Tromboembolia Venosa/etiología , Tromboembolia Venosa/patología , Trombosis de la Vena/etiología , Trombosis de la Vena/patologíaRESUMEN
PURPOSE: Endocrine therapy (ET) used to reduce the risk of recurrence in hormone receptor-expressing disease (75% of breast cancers) is associated with worsening of climacteric symptoms with a negative impact on quality of life (QoL). Homeopathy might allow a better management of hot flushes (HF). METHODS: In this multicenter randomized double-blind placebo-controlled phase III study ( ClinicalTrials.gov NCT01246427), we enrolled ≥ 18 years old women with histologically proven non metastatic localized breast cancer, with Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) ≤ 1, treated for at least 1 month with adjuvant ET, and complaining about moderate to severe HF. Patients should not be scheduled for chemotherapy or radiotherapy, and had no associated pathology known to induce HF. After a 2- to 4-week placebo administration, we randomly assigned (1:1) patients with HFS ≥ 10 using an interactive web-based centralized platform to BRN-01 homeopathic medicine complex (Actheane®) in arm A or Placebo (Arm P). Randomization was stratified by adjuvant ET (taxoxifen/aromatase inhibitor) and recruiting site. HF scores (HFS) were calculated as the mean of HF frequencies before randomization, at 4, and at 8 weeks post-randomization (pre-, 4w,- and 8w-) weighted by a 4-level intensity scale. Primary endpoint was assessed at 4-week post-randomization, as the variation between pre- and 4w-HFS. Secondary endpoints included HFS variation between pre- and 8w-HFS, compliance and tolerance assessed 8 weeks after randomization, and QoL and satisfaction assessed at 4- and 8-week post-randomization. RESULTS: Two hundred ninety-nine patients were included, and 138 (46.2%) randomized (A, 65; P, 73). Median 4w-HFS absolute variation (A, - 2.9; P, - 2.5 points, p = 0.756) and relative decrease (A, - 17%; P, - 15%, p = 0.629) were not statistically different. However, 4w-HFS decreased for 46 (75%) in A vs 48 (68%) patients in P arm. 4w-QoL was stable or improved for respectively 43 (72%) vs 51 (74%) patients (p = 0.470). CONCLUSIONS: The efficacy endpoint was not reached, and BRN-01 administration was not demonstrated as an efficient treatment to alleviate HF symptoms due to adjuvant ET in breast cancer patients. However, the study drug administration led to decreased HFS with a positive impact on QoL. Without any recommended treatment to treat or alleviate the HF-related disabling symptoms, Actheane® could be a promising option, providing an interesting support for better adherence to ET, thereby reducing the risk of recurrence with a good tolerance profile.
Asunto(s)
Neoplasias de la Mama/terapia , Homeopatía/métodos , Sofocos/tratamiento farmacológico , Adolescente , Adulto , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Método Doble Ciego , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Humanos , Materia Medica/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Calidad de Vida , Tamoxifeno/uso terapéutico , Resultado del TratamientoRESUMEN
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 JovenRESUMEN
BACKGROUND: Trabectedin plus pegylated liposomal doxorubicin (PLD) proved efficacious as second-line treatment for patients with recurrent ovarian cancer (ROC). METHODS: We report a single-center retrospective analysis of the efficacy and tolerance of trabectedin 1.1 mg/m2 every 3 weeks in a cohort of real-life ROC patients. RESULTS: From February 2012 to January 2014, 17 patients were treated with trabectedin alone or combined with PLD. Median age was 61 years (range: 48-78). Performance status was 0-1 in 16 patients (94%). Disease response rate was 53% and disease control rate was 76%. At the end of the follow-up, 8 patients (47%) were alive. Median overall survival was 17.6 months (95% CI 13.6 to not reached). Median progression-free survival was 6.7 months (95% CI 5.4-10.0). The most frequent grade 3-4 toxicities were neutropenia (n = 4, 24%) and nausea/vomiting (n = 4, 24%). CONCLUSION: Trabectedin combined with PLD seems efficient in and well tolerated by real-life ROC patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dioxoles/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Ováricas/patología , Polietilenglicoles/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Tetrahidroisoquinolinas/administración & dosificación , Trabectedina , Resultado del TratamientoRESUMEN
INTRODUCTION: In Europe, breast cancer is the most common cancer among women. His treatment (TTT) can have a significant impact on daily life. AIMS: Explore the experienced short-term side effects (SE) of chemotherapy and hormonal therapy by women themselves, the information delivered and the place of the general practitioner (GP). METHOD: Qualitative study by individual interview, conducted from January to May 2015, with 14 women followed for no metastatic breast cancer after chemotherapy and possible initiation of hormone therapy, at the Cancer Institute of the Loire (France). RESULTS: The SE of chemotherapy, except vomiting, have appeared very trying (fatigue, pains oral and cutaneous involvement), punctuated and accentuated by the cures. They were resounding on daily life, requiring family or professional assistance. Falling dander, considered stigmatizing, violated the person and femininity. The women have estimated to be well informed. They had appreciated the initial response of the pivot nurse. The least expected SE of hormone therapy, hot flashes and articular pains might limit activities. To counteract these side effects, mostly accepted to prevent recidivism, a remedy for complementary therapies was frequent. The GP was solicited for some SE, sometimes for complementary medicine (CM). CONCLUSION: Over the cures, women suggested support meetings, a more sustainable action of the pivot nurse, a better attention to their complaints and a more personalized information. The development of TTT less EI provider was desired. The effect of CM on SE should be explored.
Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Alopecia/inducido químicamente , Alopecia/psicología , Antineoplásicos Hormonales/efectos adversos , Neoplasias de la Mama/psicología , Terapias Complementarias/estadística & datos numéricos , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/psicología , Fatiga/inducido químicamente , Fatiga/psicología , Femenino , Fiebre/inducido químicamente , Humanos , Persona de Mediana Edad , Enfermedades de la Boca/inducido químicamente , Dolor/inducido químicamente , Educación del Paciente como Asunto , Investigación Cualitativa , Calidad de VidaRESUMEN
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 JovenRESUMEN
BACKGROUND: The objective of the CHEOPS trial was to assess the benefit of adding aromatase inhibitor (AI) to metronomic chemotherapy, oral vinorelbine, 50 mg, three times a week for pre-treated, HR + /HER2- metastatic breast cancer patients. METHODS: In this multicentric phase II study, patients had to have progressed on AI and one or two lines of chemotherapy. They were randomized between oral vinorelbine (Arm A) and oral vinorelbine with non-steroidal AI (Arm B). RESULTS: 121 patients were included, 61 patients in Arm A and 60 patients in Arm B. The median age was 68 years. 109 patients had visceral metastases. They all had previously received an AI. The study had been prematurely stopped following the third death due to febrile neutropenia. Median PFS trend was found to be different with 2.3 months and 3.7 months in Arm A and Arm B, respectively (HR 0.73, 95%CI 0.50-1.06, p value = 0.0929). No statistical difference was shown in OS and better tumor response. 56 serious adverse events corresponding to 25 patients (21%) were reported (respectively, 12 (20%) versus 13 (22%) for arms A and B) (NS). CONCLUSION: The addition of AI to oral vinorelbine over oral vinorelbine alone in aromatase inhibitor-resistant metastatic breast cancer was associated with a non-significant improvement of PFS. Several unexpected serious adverse events were reported. Metronomic oral vinorelbine schedule, at 50 mg three times a week, requires close biological monitoring. The question of hormonal treatment and chemotherapy combination remains open.
Asunto(s)
Neoplasias de la Mama , Humanos , Anciano , Femenino , Vinorelbina/uso terapéutico , Neoplasias de la Mama/patología , Inhibidores de la Aromatasa/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Vinblastina/efectos adversos , Metástasis de la Neoplasia , Resultado del TratamientoRESUMEN
The benefit of taxanes in the adjuvant setting for node-negative (N0) early breast cancer (EBC) has not yet been established. We conducted a meta-analysis of randomized adjuvant trials comparing docetaxel-containing versus non-taxane-containing regimens. The purpose of this study was to determine whether the incorporation of docetaxel improves disease-free survival (DFS) and overall survival (OS) in early stage breast cancer. Studies were retrieved by searching major databases and the proceedings of leading breast cancer conferences. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for DFS and OS and obtained pooled estimates using an inverse-variance model. Fourteen randomized phase III studies were included (25,067 patients). The pooled HR estimate was 0.84 (95% CI 0.78-0.89; P < 0.001) favoring docetaxel for DFS and 0.86 (0.78-0.94; P < 0.001) for OS. In N0 patients (4,274 patients), the pooled HR estimate for DFS was 0.86 (0.73-1.00; P = 0.05). The HR for OS was equal to 1 (0.75-1.34). The improvement in DFS with docetaxel-containing regimens was observed across all subgroups (age, under or over 50; number of involved nodes; hormone receptor or HER2 status (including triple negative status), or administration schedule (sequential or concomitant). The addition of docetaxel to a non-taxane-containing regimen improves DFS and OS in high risk EBC patients. The benefit in DFS was seen across all subgroups regardless of nodal status, age, hormone receptor or HER2 status (including triple negative status), or administration schedule.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Adulto , Anciano , Antineoplásicos/administración & dosificación , Neoplasias de la Mama/mortalidad , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Docetaxel , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Taxoides/administración & dosificación , Adulto JovenRESUMEN
PURPOSE: Everolimus, an oral inhibitor of the mammalian target of rapamycin, improves progression-free survival in combination with endocrine therapy (ET) in postmenopausal women with aromatase inhibitor-resistant metastatic breast cancer. However, the benefit of adding everolimus to ET in the adjuvant setting in early breast cancer is unknown. PATIENTS AND METHODS: In this randomized double-blind phase III study, women with high-risk, hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer were randomly assigned to everolimus or placebo for 2 years combined with standard ET. Stratification factors included ET agent, receipt of neoadjuvant versus adjuvant chemotherapy, progesterone receptor status, duration of ET before random assignment, and lymph node involvement. The primary end point was disease-free survival (DFS). The trial is registered with ClinicalTrials.gov (identifier: NCT01805271). RESULTS: Between June 2013 and March 2020, 1,278 patients were randomly allocated to receive everolimus or placebo. At the first interim analysis, the trial was stopped for futility and a full analysis undertaken once data snapshot complete. One hundred forty-seven patients have had a DFS event reported and at 3 years, DFS did not differ between patients who received ET plus everolimus (88% [95% CI, 85 to 91]) or ET plus placebo (89% [95% CI, 86 to 91; hazard ratio, 0.95; 95% CI, 0.69 to 1.32; P = .77]). Grade ≥ 3 adverse events were reported in 22.9% of patients (29.9% with everolimus v 15.9% with placebo, P < .001). 53.4% everolimus-treated patients permanently discontinued experimental treatment early compared with placebo-treated 22.3%. CONCLUSION: Among high-risk patients, everolimus added to adjuvant ET did not improve DFS. Tolerability was a concern, with more than half of patients stopping everolimus before study completion. Everolimus cannot be recommended in the adjuvant setting.
Asunto(s)
Neoplasias de la Mama , Everolimus , Humanos , Femenino , Neoplasias de la Mama/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Receptor ErbB-2/metabolismo , Supervivencia sin Enfermedad , Quimioterapia Adyuvante , Método Doble CiegoRESUMEN
A 75-year-old female patient, nonsmoker was addressed to our institution for a fracture of C5 vertebra with spinal cord compression by a tumor mass invading surrounding soft tissue. She had a previous history of breast ductal carcinoma and endometrioid carcinoma. Biopsy of the tumor mass showed a TTF-1-positive carcinoma. Molecular study showed a E545K mutation of PIK3CA. Lung imaging showed multiple nodules evocative of metastasis rather than a primitive tumor. Reviewing of slides of endometrioid carcinoma showed areas positive for TTF1, and the same E545K mutation was found in endometrial tumor. The final diagnosis was endometrioid metastatic carcinoma with aberrant TTF-1 expression. A subset of endometrial neoplasm expresses TTF-1, this situation might be confusing especially in case of metastatic disease.
Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/genética , Proteínas de Unión al ADN/biosíntesis , Neoplasias Endometriales , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Mutación Missense , Proteínas de Neoplasias , Factores de Transcripción/biosíntesis , Anciano , Sustitución de Aminoácidos , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Proteínas de Unión al ADN/genética , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Factores de Transcripción/genéticaRESUMEN
OBJECTIVES: HERmione study was conducted to assess, in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBC), the safety profile of subcutaneous (SC) formulation of trastuzumab in real-life in France. MATERIALS AND METHODS: This prospective, non-interventional study included 511 patients planned to be treated in both neoadjuvant and adjuvant settings with a follow-up of 12 months maximum in 101 sites. The safety analyses concerned 505 patients. Primary endpoint was the description of systemic safety and local tolerability of the SC trastuzumab. RESULTS: The median age of patients was 58 years. Over the study, 2449 adverse events (AEs) occurred in 422 (83.6%) patients (asthenia, arthralgia, radiation skin injury, myalgia, hot flush and diarrhea in ≥10% of patients): 92 AEs (3.8%) were grade ≥3 (radiation skin injury in 1.8% of patients and febrile neutropenia in 1.4% of patients), 76 (3.1%) were serious (mainly febrile neutropenia in 1.4% of patients) and 336 (13.7%) were treatment-related (mainly injection site pain in 9.1% of patients). Congestive Heart Failure occurred in 58 (11.5%) patients and was related to treatment in 4.6% of patients. Only 34 AEs (1.4%) in 27 (5.4%) patients led to permanent treatment discontinuation. One death was assessed as not treatment-related. Quality of life (QoL) analyses showed no deterioration of global health status. CONCLUSION: The HERmione study showed that, in a real-life setting, the safety of SC trastuzumab administered in HER2-positive eBC patients is consistent with data reported from previous clinical trials, without new safety concerns or QoL deterioration.
Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Trastuzumab/efectos adversos , Neoplasias de la Mama/metabolismo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Francia/epidemiología , Humanos , Inyecciones Subcutáneas , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Receptor ErbB-2/metabolismo , Resultado del TratamientoRESUMEN
PURPOSE: Genomic tests can identify ER-positive HER2-negative localized breast cancer patients who may not benefit from adjuvant chemotherapy. Such tests seem especially interesting in "intermediate" clinico-pathological risk categories. The psychological impact of the decision uncertainty in these women remains largely unexplored. We assessed the clinical and psychological impact of EndoPredict® (EpClin), a clinico-genomic test, in these patients. METHODS: This multicenter, single arm prospective study (NCT02773004) enrolled patients for which adjuvant chemotherapy was uncertain, based on predefined criteria. The primary endpoint was the proportion of change between initial adjuvant decision and final administration of chemotherapy. Secondary endpoints included post-test (Day 17) and 1-year patient reported outcomes. RESULTS: One third of 200 evaluable patients had a high EpClin score (≥3.32867; 10 years cumulative risk of distance failure ≥10%). The overall change rate of chemotherapy decision was 72/200 (35.8%, 95% CI 29.2-42.4). Chemotherapy was withdrawn in 57 cases (28.4% [22.2-34.8]) and added in 15 (7.5% [3.8-11.2]. 6 changes (8%) were based on patients' decisions. Anxiety and distress levels increased at Day 17 when adding chemotherapy after the test result (p < 10-7 and 0.00022 respectively), while stable in other situations. At 1-year, all patients had returned to the baseline anxiety and distress levels (mean anxiety 51.5, +/- SD = 2.5 [max. 80], mean distress 3±1 [max. 10]). CONCLUSIONS: EndoPredict ® (EpClin) is clinically useful in deciding whether or not to administer adjuvant chemotherapy in patients with intermediate risk. A single-step decision is preferable since adding chemotherapy at a later stage increases anxiety and distress.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Reglas de Decisión Clínica , Toma de Decisiones Clínicas/métodos , Genes erbB-2 , Pruebas Genéticas/métodos , Receptores de Estrógenos/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Ansiedad/diagnóstico , Ansiedad/etiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/psicología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Femenino , Marcadores Genéticos , Genómica , Humanos , Mastectomía , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Distrés Psicológico , Medición de Riesgo , IncertidumbreRESUMEN
Benefits of physical activity are widely demonstrated for early stage cancers but few studies have focused on metastatic disease. The purpose of this study was to determine the impact of physical activity on survival in patients with metastatic breast cancer. We conducted a secondary analysis of the national, multicentric, non-randomized, prospective cohort SNPs to Risk of Metastasis (StoRM) study. The level of physical activity was self-reported at inclusion and divided into three categories of physical activity: light level, moderate level, and vigorous level. Overall, 833 patients (56.2%) completed the physical activity questionnaire at baseline on average physical activity during the previous year: 11.6% had a light level of physical activity, 69.0% achieved moderate levels of physical activity and 19.3% reported vigorous levels of physical activity. After adjustment for confounding, physical activity was not statistically significantly associated with overall survival in the whole population. Subgroup analysis identified that both vigorous and moderate physical activity were associated with statistically significantly improved overall survival compared to light physical activity level only in the HER2 positive subgroup (HR 0.23; 95% CI 0.07-0.70, p = 0.01 and HR 0.38; 95% CI 0.15-0.96, p = 0.04). Physical activity done during the previous year was associated with survival in HER2 positive metastatic breast cancer patients. These results suggest that overall survival in metastatic breast cancer patients could be improved through physical activity which should be considered as a complementary intervention for these individuals. The study showed that moderate/vigorous levels of physical activity were associated with better overall survival, and that these associations remained statistically significant in multivariate analysis in the HER2 positive subgroup. These results have clinical relevance and justify the recommendations for physical activity interventions in metastatic breast cancer.
Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/fisiopatología , Ejercicio Físico , Anciano , Antropometría , Índice de Masa Corporal , Neoplasias de la Mama/genética , Interpretación Estadística de Datos , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Polimorfismo de Nucleótido Simple , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Receptor ErbB-2/metabolismo , Encuestas y Cuestionarios , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/fisiopatologíaRESUMEN
Endocrine treatment represents the cornerstone of endocrine-sensitive pre-menopausal early breast cancer. The estrogen blockade plays a leading role in the therapeutic management with surgery, radiotherapy and selective antiestrogen treatment. For several years, selective estrogen receptor modulators, such as tamoxifen, have revolutionized medical care of hormone receptors-positive breast cancer and have conquered the therapeutic arsenal while becoming the gold standard of treatment. Other combinations associating the ovarian function suppression using LHRH agonists with tamoxifen or aromatase inhibitors have been recently investigated, leading to mitigated opinions regarding the clinical benefit of these associations. We propose here a comprehensive overview on existing data and their actualization concerning LHRH analogues, whilst emphasizing benefit-risk balance for this targeted population.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Hormona Liberadora de Gonadotropina/análogos & derivados , Guías de Práctica Clínica como Asunto , Premenopausia , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Humanos , Ovario/efectos de los fármacos , Medición de Riesgo , Tamoxifeno/uso terapéuticoRESUMEN
OBJECTIVES: The objectives of this study were to identify actionable genomic alterations in the gynaecological subpopulation of the ProfiLER programme and to report clinical efficacy of recommended targeted treatment (RTT). METHODS: The ProfiLER programme (NCT01774409) is a multicentric prospective trial aiming to implement molecular profiling in patients with advanced refractory cancers. In this programme, tumour DNA is analysed by targeted next-generation sequencing (69 genes) and by whole genome array comparative genomic hybridisation. Clinical cases and genomic profiles are presented in a dedicated molecular tumour board to guide treatment strategies. We report here an analysis of patients with gynaecological cancers included in this trial. RESULTS: From February 2013 to February 2017, 309 patients with gynaecologic cancer were included; 279 (90%) had sufficient quality, and 131 patients (42.4%) had at least one actionable genomic alteration in cancer cells. Four alterations were shared by at least 3% of the patients: 27 (9.7%) PIK3CA mutations, 15 (5.4%) KRAS mutations, 11 (3.9%) ERBB2 amplifications and 9 (3.2%) CDKN2A deletions. Forty-one treatments were initiated among 39 patients (12.6% of the screened population): 8 (20%) had a partial response, and other 10 (24%) had a stable disease. The median progression-free survival was 2.7 months. The median overall survival was 15.6 months for patients who received a RTT. CONCLUSION: Molecular profiling identified actionable alterations in 42.4% of patients with advanced refractory gynaecologic cancer, but only 12.6% were treated with a RTT. Among them, 46% derived clinical benefit (5.8% of the screened population).
Asunto(s)
Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Neoplasias de los Genitales Femeninos/genética , Transcriptoma , Adulto , Anciano , Anciano de 80 o más Años , Toma de Decisiones Clínicas , Hibridación Genómica Comparativa , Progresión de la Enfermedad , Femenino , Francia , Amplificación de Genes , Eliminación de Gen , Predisposición Genética a la Enfermedad , Neoplasias de los Genitales Femeninos/mortalidad , Neoplasias de los Genitales Femeninos/patología , Neoplasias de los Genitales Femeninos/terapia , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Persona de Mediana Edad , Mutación , Selección de Paciente , Fenotipo , Valor Predictivo de las Pruebas , Supervivencia sin Progresión , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Secuenciación Completa del GenomaRESUMEN
AIM: Adjuvant clinical trials in early human epidermal growth factor receptor 2 (HER2)-positive breast cancer have assessed either sequential or concomitant incorporation of trastuzumab with chemotherapy; only the North Central Cancer Treatment Group (NCCTG)-N9831 trial prospectively compared both modalities. In routine trastuzumab has been incorporated into a concurrent regimen with taxane chemotherapy instead of sequential modality on the basis of a positive risk-benefit ratio. This present study assessed sequential versus concomitant administration of adjuvant trastuzumab. METHODS: A population combining patients from Protocol for Herceptin® as Adjuvant therapy with Reduced Exposure (PHARE) a randomised phase III clinical trial (NCT00381901) and SIGNAL (RECF1098) a prospective study specifically designed for Genome-wide Association Studies (GWAS) analyses was studied. In this cohort with 58 months of median follow-up, the comparison in the HER2-positive group of adjuvant trastuzumab and chemotherapy modalities was based on a propensity score methodology. Treatment modalities were based on physician's choice and comparisons adjustment were made by a propensity score methodology. Overall Survival (OS) and Disease-Free Survival (DFS) were estimated using the Kaplan-Meier method, and comparisons between groups were based on the log rank test. RESULTS: The SIGNAL/PHARE cohort included 11,728 breast cancer cases treated in adjuvant setting; some 5502 of them with HER2-positive tumour: 34.5% (1897/5502) were treated by sequential and 65.5% (3605/5502) by concomitant modality of administration for taxane-chemotherapy and trastuzumab. The adjusted comparison found similar OS (HR = 1.01; 95% CI: 0.86-1.19) and similar DFS (HR = 1.08; 95% CI: 0.96-1.21). CONCLUSION: These results suggest that the sequential administration of trastuzumab given after the completion of adjuvant chemotherapy might be as valid as the concomitant administration of trastuzumab and taxane chemotherapy in the adjuvant setting.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Trastuzumab/administración & dosificación , Adulto , Anciano , Neoplasias de la Mama/metabolismo , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estudios Prospectivos , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismoRESUMEN
Human epidermal growth factor receptor 2-positive breast cancer is a subtype of interest regarding its outcome and the impressive impact of human epidermal growth factor receptor 2 targeted therapy. Constitutional variants may be involved in the aetiology of human epidermal growth factor receptor 2-positive breast cancer, and we propose a case-case study to test the hypothesis that single nucleotide polymorphisms may be associated with human epidermal growth factor receptor 2 status. A Genome-Wide Association Study was used in a cohort of 9836 patients from the SIGNAL/PHARE study (NCT00381901-RECF1098). The main goal was to identify variants specifically related to human epidermal growth factor receptor 2-positive breast cancer. A two-staged genotyping strategy was carried out to cover as large a proportion of the genome as possible. All subjects were genotyped using the Illumina HumanCore Exome chip set. Principal Components Analysis and k-means were then used to characterize the ancestry of the participants. A random sample of subjects from the main "European" cluster was genotyped with the Omni5 chip set. These data were then used to impute missing genotypes from the remaining subjects genotyped only using the HumanCore Exome array. From the 9836 patients, a total of 8703 cases including 3230 patients with human epidermal growth factor receptor 2-positive breast cancer were analyzed. Despite having 80% power to detect an odds ratio of 1.23 in this population, no variant achieved genome-wide significance for association with the occurrence of human epidermal growth factor receptor 2-positive breast cancer vs. any other subtype of breast tumour. Our study was unable to identify constitutional polymorphisms that are strongly associated with human epidermal growth factor receptor 2-positive status among breast cancer patients.