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1.
Future Oncol ; 18(19): 2339-2349, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35465733

RESUMEN

ALPHABET is a randomized phase III trial assessing alpelisib + trastuzumab with or without fulvestrant in previously treated HER2-positive PIK3CA-mutated advanced breast cancer. Patients will be included in two cohorts according to hormone receptor (HR) status. In the experimental arms, patients in the HR-negative cohort will receive trastuzumab + alpelisib, and patients in the HR-positive cohort will receive the same treatment plus fulvestrant. Patients in the control arms will receive trastuzumab + physician's choice chemotherapy (eribuline, capecitabine or vinorelbine). Key eligibility criteria include 1-4 previous lines of anti-HER2 therapy and prior trastuzumab emtansine. The primary end point is investigator-assessed progression-free survival. The study aims to recruit a total of 300 patients.


ALPHABET is a clinical study investigating the potential use of alpelisib for the treatment of certain subtypes of breast cancer. Alpelisib is a novel drug that is given orally. It specifically targets a protein called PI3K. PI3K is hyperactivated in some tumors, allowing uncontrolled growth. This study is enrolling patients with HER2-positive advanced breast cancer whose tumor tests positive for a mutation in the PIK3CA gene, which encodes PI3K. Patients are allocated at random to receive either a combination treatment of trastuzumab (an anti-HER2-targeted therapy) with alpelisib or standard chemotherapy and trastuzumab without alpelisib. The efficacy of each treatment will be determined by comparing how long patients in each group live for without further tumor growth. Additional analyses will also look at the side effects experienced by patients, as well as their quality of life.


Asunto(s)
Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Ensayos Clínicos Fase III como Asunto , Femenino , Fulvestrant/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor ErbB-2/genética , Receptores de Estrógenos , Tiazoles , Trastuzumab
2.
Breast Cancer Res ; 23(1): 38, 2021 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-33761970

RESUMEN

BACKGROUND: Circulating tumor cells (CTCs) are prognostic in patients with advanced breast cancer (ABC). However, no data exist about their use in patients treated with palbociclib. We analyzed the prognostic role of CTC counts in patients enrolled in the cTREnd study, a pre-planned translational sub-study of TREnd (NCT02549430), that randomized patients with ABC to palbociclib alone or palbociclib plus the endocrine therapy received in the prior line of treatment. Moreover, we evaluated RB1 gene expression on CTCs and explored its prognostic role within the cTREnd subpopulation. METHODS: Forty-six patients with ER-positive, HER2-negative ABC were analyzed. Blood samples were collected before starting palbociclib treatment (timepoint T0), after the first cycle of treatment (timepoint T1), and at disease progression (timepoint T2). CTCs were isolated and counted by CellSearch® System using the CellSearch™Epithelial Cell kit. Progression-free survival (PFS), clinical benefit (CB) during study treatment, and time to treatment failure (TTF) after study treatment were correlated with CTC counts. Samples with ≥ 5 CTCs were sorted by DEPArray system® (DA). RB1 and GAPDH gene expression levels were measured by ddPCR. RESULTS: All 46 patients were suitable for CTCs analysis. CTC count at T0 did not show significant prognostic value in terms of PFS and CB. Patients with at least one detectable CTC at T1 (n = 26) had a worse PFS than those with 0 CTCs (n = 16) (p = 0.02). At T1, patients with an increase of at least three CTCs showed reduced PFS compared to those with no increase (mPFS = 3 versus 9 months, (p = 0.004). Finally, patients with ≥ 5 CTCs at T2 (n = 6/23) who received chemotherapy as post-study treatment had a shorter TTF (p = 0.02). Gene expression data for RB1 were obtained from 19 patients. CTCs showed heterogeneous RB1 expression. Patients with detectable expression of RB1 at any timepoint showed better, but not statistically significant, outcomes than those with undetectable levels. CONCLUSIONS: CTC count seems to be a promising modality in monitoring palbociclib response. Moreover, CTC count at the time of progression could predict clinical outcome post-palbociclib. RB1 expression analysis on CTCs is feasible and may provide additional prognostic information. Results should be interpreted with caution given the small studied sample size.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Células Neoplásicas Circulantes/patología , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Recuento de Células , Progresión de la Enfermedad , Femenino , Humanos , Células Neoplásicas Circulantes/efectos de los fármacos , Células Neoplásicas Circulantes/metabolismo , Supervivencia sin Progresión , Receptor ErbB-2/deficiencia , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Proteínas de Unión a Retinoblastoma/metabolismo , Resultado del Tratamiento , Ubiquitina-Proteína Ligasas/metabolismo
3.
Cancer ; 127(5): 700-708, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33290610

RESUMEN

BACKGROUND: Endocrine therapy resistance is a major cause of distant recurrence (DR) in hormone receptor-positive breast cancer. This study evaluated differences in survival after DR in patients treated with different adjuvant endocrine therapy regimens in the Breast International Group (BIG) 1-98 trial. METHODS: BIG 1-98 compared 5 years of adjuvant treatment among 4 arms: tamoxifen (T), letrozole (L), tamoxifen followed by letrozole (TL), and letrozole followed by tamoxifen (LT). After a median follow-up of 8.1 years, 911 of 8010 patients (T, 302; L, 285; TL, 170; and LT, 154) had DR as the site of first recurrence. Univariate and multivariate Cox analyses were performed to determine features associated with post-DR survival. RESULTS: The median follow-up time after DR was 59 months (interquartile range, 29-88 months). Among all patients with DR, 38.1% were 65 years old or older at enrollment, 61.9% had tumors larger than 2 cm, and 69.7% were node positive. Neoadjuvant or adjuvant chemotherapy was administered to 35.6% of the patients. There was no difference in post-DR survival by treatment arm (median survival, 20.8 months for T, 17.9 months for L, 17.3 months for TL, and 20.8 months for LT; P = .21). In multivariate analysis, older patients (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.15-1.59) and patients with tumors larger than 2 cm (HR, 1.19; 95% CI, 1.00-1.41), 4 or more positive nodes (HR, 1.31; 95% CI, 1.05-1.64), progesterone receptor (PR)-negative tumors (HR, 1.25; 95% CI, 1.02-1.52), or shorter disease-free survival (DFS) had significantly worse post-DR survival. CONCLUSIONS: Treatment with adjuvant T, L, or their sequences was not associated with differences in survival after DR. Significant differences in survival were observed by age, primary tumor size, nodal and PR status, and DFS, and this suggests that traditional baseline high-risk features remain prognostic in the metastatic setting.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Neoplasias de la Mama/química , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Receptor alfa de Estrógeno/genética , Femenino , Humanos , Letrozol/uso terapéutico , Metástasis Linfática , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Tamoxifeno/uso terapéutico
4.
N Engl J Med ; 379(2): 122-137, 2018 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-29863451

RESUMEN

BACKGROUND: In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials. METHODS: Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy. RESULTS: In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group. CONCLUSIONS: Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).


Asunto(s)
Androstadienos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/prevención & control , Tamoxifeno/uso terapéutico , Adulto , Androstadienos/efectos adversos , Antineoplásicos Hormonales/efectos adversos , Inhibidores de la Aromatasa/efectos adversos , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Premenopausia , Receptor ErbB-2 , Tamoxifeno/efectos adversos , Adulto Joven
6.
Breast Cancer Res Treat ; 181(2): 347-359, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32274665

RESUMEN

PURPOSE: Sexual dysfunction is an important concern of premenopausal women with early breast cancer. We investigated predictors of sexual problems in two randomized controlled trials. METHODS: A subset of patients enrolled in TEXT and SOFT completed global and symptom-specific quality-of-life indicators, CES-Depression and MOS-Sexual Problems measures at baseline, six, 12 and 24 months. Mixed models tested the association of changes in treatment-induced symptoms (baseline to 6 months), depression at 6 months, and age at randomization with changes in sexual problems over 2 years. RESULTS: Sexual problems increased by 6 months and persisted at this level. Overall, patients with more severe worsening of vaginal dryness, sleep disturbances and bone or joint pain at 6 months reported a greater increase in sexual problems at all time-points. Depression scores were significantly associated with sexual problems in the short-term. All other symptoms had a smaller impact on sexual problems. Age was not associated with sexual problems at any time-point. CONCLUSION: Among several key symptoms, vaginal dryness, sleep disturbance, and bone and joint pain significantly predicted sexual problems during the first 2 years. Early identification of these symptoms may contribute to timely and tailored interventions.


Asunto(s)
Antineoplásicos Hormonales/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/efectos adversos , Trastorno Depresivo/epidemiología , Disfunciones Sexuales Fisiológicas/etiología , Trastornos del Sueño-Vigilia/epidemiología , Tamoxifeno/efectos adversos , Adulto , Neoplasias de la Mama/patología , Neoplasias de la Mama/psicología , Trastorno Depresivo/inducido químicamente , Trastorno Depresivo/patología , Femenino , Estudios de Seguimiento , Salud Global , Humanos , Incidencia , Agencias Internacionales , Persona de Mediana Edad , Premenopausia , Pronóstico , Calidad de Vida , Disfunciones Sexuales Fisiológicas/patología , Trastornos del Sueño-Vigilia/inducido químicamente , Trastornos del Sueño-Vigilia/patología
7.
Lancet Oncol ; 20(3): 371-382, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30765258

RESUMEN

BACKGROUND: HER2-positive breast cancers usually contain large amounts of T-cell infiltrate. We hypothesised that trastuzumab resistance in HER2-positive breast cancer could be mediated by immune mechanisms. We assessed the safety and anti-tumour activity of pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, added to trastuzumab in trastuzumab-resistant, advanced HER2-positive breast cancer. METHODS: We did this single-arm, multicentre, phase 1b-2 trial in 11 centres based in five countries. Eligible participants were women aged 18 years or older, who had advanced, histologically confirmed, HER2-positive breast cancer; documented progression during previous trastuzumab-based therapy; an Eastern Cooperative Oncology Group performance status of 0 or 1; and a formalin-fixed, paraffin-embedded metastatic tumour biopsy for central assessment of programmed cell death 1 ligand 1 (PD-L1) status. In phase 1b, we enrolled patients with PD-L1-positive tumours in a 3 + 3 dose-escalation of intravenous pembrolizumab (2 mg/kg and 10 mg/kg, every 3 weeks) plus 6 mg/kg of intravenous trastuzumab. The primary endpoint of the phase 1b study was the incidence of dose-limiting toxicity and recommended phase 2 dose; however, a protocol amendment on Aug 28, 2015, stipulated a flat dose of pembrolizumab of 200 mg every 3 weeks in all Merck-sponsored trials. In phase 2, patients with PD-L1-positive and PD-L1-negative tumours were enrolled in parallel cohorts and received the flat dose of pembrolizumab plus standard trastuzumab. The primary endpoint of the phase 2 study was the proportion of PD-L1-positive patients achieving an objective response. This trial is registered in ClinicalTrials.gov, number NCT02129556, and with EudraCT, number 2013-004770-10, and is closed. FINDINGS: Between Feb 2, 2015, and April 5, 2017, six patients were enrolled in phase 1b (n=3 received 2 mg/kg pembrolizumab, n=3 received 10 mg/kg pembrolizumab) and 52 patients in phase 2 (n=40 had PD-L1-positive tumours, n=12 had PD-L1-negative tumours). The data cutoff for this analysis was Aug 7, 2017. During phase 1b, there were no dose-limiting toxicities in the dose cohorts tested. Median follow-up for the phase 2 cohort was 13·6 months (IQR 11·6-18·4) for patients with PD-L1-positive tumours, and 12·2 months (7·9-12·2) for patients with PD-L1-negative tumours. Six (15%, 90% CI 7-29) of 40 PD-L1-positive patients achieved an objective response. There were no objective responders among the PD-L1-negative patients. The most common treatment-related adverse event of any grade was fatigue (12 [21%] of 58 patients). Grade 3-5 adverse events occurred in 29 (50%) of patients, treatment-related grade 3-5 adverse events occurred in 17 (29%), and serious adverse events occurred in 29 (50%) patients. The most commonly occurring serious adverse events were dyspnoea (n=3 [5%]), pneumonitis (n=3 [5%]), pericardial effusion (n=2 [3%]), and upper respiratory infection (n=2 [3%]). There was one treatment-related death due to Lambert-Eaton syndrome in a PD-L1-negative patient during phase 2. INTERPRETATION: Pembrolizumab plus trastuzumab was safe and showed activity and durable clinical benefit in patients with PD-L1-positive, trastuzumab-resistant, advanced, HER2-positive breast cancer. Further studies in this breast cancer subtype should focus on a PD-L1-positive population and be done in less heavily pretreated patients. FUNDING: Merck, International Breast Cancer Study Group.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/genética , Trastuzumab/administración & dosificación , Adolescente , Adulto , Anciano , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/genética , Trastuzumab/efectos adversos , Resultado del Tratamiento
8.
Breast Cancer Res ; 21(1): 71, 2019 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-31142370

RESUMEN

Currently, there is limited data regarding the effectiveness of standard subsequent line therapies such as endocrine therapy, chemotherapy, or targeted agents after progression on CDK4/6 inhibitor-based regimens. This paper describes time-to-treatment failure beyond progression on palbociclib or palbociclib+endocrine therapy in patients enrolled in the phase II, multicenter TREnd trial. Our results indicate that there is limited benefit from post-palbociclib treatment, regardless of the type of therapy received. A small population of long responders were identified who demonstrated ongoing benefit from a subsequent line of endocrine therapy after progression to palbociclib-based regimens. A translational research program is ongoing on this population of outliers.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Piperazinas/uso terapéutico , Piridinas/uso terapéutico , Antineoplásicos Hormonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Estimación de Kaplan-Meier , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Posmenopausia , Pronóstico , Piridinas/administración & dosificación , Piridinas/efectos adversos , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Resultado del Tratamiento
9.
Br J Cancer ; 120(10): 959-967, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30967649

RESUMEN

BACKGROUND: In the phase III SOLE trial, the extended use of intermittent versus continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Intermittent therapy with 3-month breaks may be beneficial for patients' quality of life (QoL). METHODS: In the SOLE QoL sub-study, 956 patients completed the Breast Cancer Prevention Trial (BCPT) symptom and further QoL scales up to 24 months after randomisation. Differences in change of QoL from baseline between the two administration schedules were tested at 12 and 24 months using repeated measures mixed-models. The primary outcome was change in hot flushes at 12 months. RESULTS: There was no difference in hot flushes at 12 months between the two schedules, but patients receiving intermittent letrozole reported significantly more improvement at 24 months. They also indicated less worsening in vaginal problems, musculoskeletal pain, sleep disturbance, physical well-being and mood at 12 months. Overall, 25-30% of patients reported a clinically relevant worsening in key symptoms and global QoL. CONCLUSION: Less symptom worsening was observed during the first year of extended treatment with the intermittent administration. For women experiencing an increased symptom burden of extended adjuvant endocrine therapy, an intermittent administration is a safe alternative. CLINICAL TRIAL INFORMATION: Clinical trial information: NCT00651456.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Letrozol/administración & dosificación , Ganglios Linfáticos/efectos de los fármacos , Adulto , Anciano , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/efectos adversos , Supervivencia sin Enfermedad , Esquema de Medicación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Letrozol/efectos adversos , Ganglios Linfáticos/patología , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Calidad de Vida
10.
Pharmacogenomics J ; 19(6): 556-563, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-30723313

RESUMEN

Dihydropyrimidine dehydrogenase (DPYD) is a highly polymorphic gene and classic deficient variants (i.e., c.1236G>A/HapB3, c.1679T>G, c.1905+1G>A and c.2846A>T) are characterized by impaired enzyme activity and risk of severe adverse drug reactions (ADRs) in patients treated with fluoropyrimidines. The identification of poor metabolizers by pre-emptive DPYD screening may reduce the rate of ADRs but many patients with wild-type genotype for classic variants may still display ADRs. Therefore, the search for additional DPYD polymorphisms associated with ADRs may improve the safety of treatment with fluoropyrimidines. This study included 1254 patients treated with fluoropyrimidine-containing regimens and divided into cohort 1, which included 982 subjects suffering from gastrointestinal G≥2 and/or hematological G≥3 ADRs, and cohort 2 (control group), which comprised 272 subjects not requiring dose reduction, delay or discontinuation of treatment. Both groups were screened for DPYD variants c.496A>G, c.1236G>A/HapB3, c.1601G>A (DPYD*4), c.1627A>G (DPYD*5), c.1679T>G (DPYD*13), c.1896T>C, c.1905 + 1G>A (DPYD*2A), c.2194G>A (DPYD*6), and c.2846A>T to assess their association with toxicity. Genetic analysis in the two cohorts were done by Real-Time PCR of DNA extracted from 3 ml of whole blood. DPYD c.496A>G, c.1601G>A, c.1627A>G, c.1896T>C, and c.2194G>A variants were found in both cohort 1 and 2, while c.1905+1G>A and c.2846A>T were present only in cohort 1. DPYD c.1679T>G and c.1236G>A/HapB3 were not found. Univariate analysis allowed the selection of c.1905+1G>A, c.2194G>A and c.2846A>T alleles as significantly associated with gastrointestinal and hematological ADRs (p < 0.05), while the c.496A>G variant showed a positive trend of association with neutropenia (p = 0.06). In conclusion, c.2194G>A is associated with clinically-relevant ADRs in addition to the already known c.1905+1G>A and c.2846A>T variants and should be evaluated pre-emptively to reduce the risk of fluoropyrimidine-associated ADRs.


Asunto(s)
Dihidrouracilo Deshidrogenasa (NADP)/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Polimorfismo de Nucleótido Simple/genética , Pirimidinas/efectos adversos , Alelos , Estudios de Cohortes , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Pirimidinas/uso terapéutico
11.
Breast J ; 25(6): 1225-1229, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31310384

RESUMEN

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


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Manejo de Atención al Paciente , Neoplasias de la Mama Triple Negativas/terapia , Factores de Edad , Anciano , Quimioterapia Adyuvante/métodos , Supervivencia sin Enfermedad , Femenino , Humanos , Italia/epidemiología , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Manejo de Atención al Paciente/métodos , Manejo de Atención al Paciente/estadística & datos numéricos , Manejo de Atención al Paciente/tendencias , Pronóstico , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/epidemiología , Neoplasias de la Mama Triple Negativas/patología
12.
Lancet Oncol ; 19(10): 1385-1393, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30196031

RESUMEN

BACKGROUND: We previously reported the 5-year results of the phase 3 IBCSG 23-01 trial comparing disease-free survival in patients with breast cancer with one or more micrometastatic (≤2 mm) sentinel nodes randomly assigned to either axillary dissection or no axillary dissection. The results showed no difference in disease-free survival between the groups and showed non-inferiority of no axillary dissection relative to axillary dissection. The current analysis presents the results of the study after a median follow-up of 9·7 years (IQR 7·8-12·7). METHODS: In this multicentre, randomised, controlled, open-label, non-inferiority, phase 3 trial, participants were recruited from 27 hospitals and cancer centres in nine countries. Eligible women could be of any age with clinical, mammographic, ultrasonographic, or pathological diagnosis of breast cancer with largest lesion diameter of 5 cm or smaller, and one or more metastatic sentinel nodes, all of which were 2 mm or smaller and with no extracapsular extension. Patients were randomly assigned (1:1) before surgery (mastectomy or breast-conserving surgery) to no axillary dissection or axillary dissection using permuted blocks generated by a web-based congruence algorithm, with stratification by centre and menopausal status. The protocol-specified primary endpoint was disease-free survival, analysed in the intention-to-treat population (as randomly assigned). Safety was assessed in all randomly assigned patients who received their allocated treatment (as treated). We did a one-sided test for non-inferiority of no axillary dissection by comparing the observed hazard ratios (HRs) for disease-free survival with a margin of 1·25. This 10-year follow-up analysis was not prespecified in the trial's protocol and thus was not adjusted for multiple, sequential testing. This trial is registered with ClinicalTrials.gov, number NCT00072293. FINDINGS: Between April 1, 2001, and Feb 8, 2010, 6681 patients were screened and 934 randomly assigned to no axillary dissection (n=469) or axillary dissection (n=465). Three patients were ineligible and were excluded from the trial after randomisation. Disease-free survival at 10 years was 76·8% (95% CI 72·5-81·0) in the no axillary dissection group, compared with 74·9% (70·5-79·3) in the axillary dissection group (HR 0·85, 95% CI 0·65-1·11; log-rank p=0·24; p=0·0024 for non-inferiority). Long-term surgical complications included lymphoedema of any grade in 16 (4%) of 453 patients in the no axillary dissection group and 60 (13%) of 447 in the axillary dissection group, sensory neuropathy of any grade in 57 (13%) in the no axillary dissection group versus 85 (19%) in the axillary dissection group, and motor neuropathy of any grade (14 [3%] in the no axillary dissection group vs 40 [9%] in the axillary dissection group). One serious adverse event (postoperative infection and inflamed axilla requiring hospital admission) was attributed to axillary dissection; the event resolved without sequelae. INTERPRETATION: The findings of the IBCSG 23-01 trial after a median follow-up of 9·7 years (IQR 7·8-12·7) corroborate those obtained at 5 years and are consistent with those of the 10-year follow-up analysis of the Z0011 trial. Together, these findings support the current practice of not doing an axillary dissection when the tumour burden in the sentinel nodes is minimal or moderate in patients with early breast cancer. FUNDING: International Breast Cancer Study Group.


Asunto(s)
Neoplasias de la Mama/cirugía , Escisión del Ganglio Linfático/métodos , Mastectomía/métodos , Ganglio Linfático Centinela/cirugía , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/mortalidad , Metástasis Linfática , Mastectomía/efectos adversos , Mastectomía/mortalidad , Micrometástasis de Neoplasia , Factores de Riesgo , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela , Factores de Tiempo
13.
Lancet Oncol ; 19(1): 87-100, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29223745

RESUMEN

BACKGROUND: Activation of the PI3K/AKT/mTOR pathway occurs frequently in breast cancer that is resistant to endocrine therapy. Approved mTOR inhibitors effectively inhibit cell growth and proliferation but elicit AKT phosphorylation via a feedback activation pathway, potentially leading to resistance to mTOR inhibitors. We evaluated the efficacy and safety of buparlisib plus fulvestrant in patients with advanced breast cancer who were pretreated with endocrine therapy and mTOR inhibitors. METHODS: BELLE-3 was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Postmenopausal women aged 18 years or older with histologically or cytologically confirmed hormone-receptor-positive, HER2-negative, locally advanced or metastatic breast cancer, who had relapsed on or after endocrine therapy and mTOR inhibitors, were recruited from 200 trial centres in 22 countries. Eligible patients were randomly assigned (2:1) via interactive response technology (block size of six) to receive oral buparlisib (100 mg per day) or matching placebo starting on day 1 of cycle 1, plus intramuscular fulvestrant (500 mg) on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles. Randomisation was stratified by visceral disease status. The primary endpoint was progression-free survival by local investigator assessment as per the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 in the full analysis population (all randomised patients, by intention-to-treat). Safety was analysed in all patients who received at least one dose of treatment and at least one post-baseline safety assessment. This study is registered with ClinicalTrials.gov, number NCT01633060, and is ongoing but no longer enrolling patients. FINDINGS: Between Jan 15, 2013, and March 31, 2016, 432 patients were randomly assigned to the buparlisib (n=289) or placebo (n=143) groups. Median progression-free survival was significantly longer in the buparlisib versus placebo group (3·9 months [95% CI 2·8-4·2] vs 1·8 months [1·5-2·8]; hazard ratio [HR] 0·67, 95% CI 0·53-0·84, one-sided p=0·00030). The most frequent grade 3-4 adverse events in the buparlisib versus placebo group were elevated alanine aminotransferase (63 [22%] of 288 patients vs four [3%] of 140), elevated aspartate aminotransferase (51 [18%] vs four [3%]), hyperglycaemia (35 [12%] vs none), hypertension (16 [6%] vs six [4%]), and fatigue (ten [3%] vs two [1%]). Serious adverse events were reported in 64 (22%) of 288 patients in the buparlisib group versus 23 (16%) of 140 in the placebo group; the most frequent serious adverse events (affecting ≥2% of patients) were elevated aspartate aminotransferase (six [2%] vs none), dyspnoea (six [2%] vs one [1%]), and pleural effusion (six [2%] vs none). On-treatment deaths occurred in ten (3%) of 288 patients in the buparlisib group and in six (4%) of 140 in the placebo group; most deaths were due to metastatic breast cancer, and two were considered treatment-related (cardiac failure [n=1] in the buparlisib group and unknown reason [n=1] in the placebo group). INTERPRETATION: The safety profile of buparlisib plus fulvestrant does not support its further development in this setting. Nonetheless, the efficacy of buparlisib supports the rationale for the use of PI3K inhibitors plus endocrine therapy in patients with PIK3CA mutations. FUNDING: Novartis Pharmaceuticals Corporation.


Asunto(s)
Aminopiridinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Estradiol/análogos & derivados , Antagonistas del Receptor de Estrógeno/administración & dosificación , Morfolinas/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Anciano , Aminopiridinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/química , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Método Doble Ciego , Estradiol/administración & dosificación , Estradiol/efectos adversos , Antagonistas del Receptor de Estrógeno/efectos adversos , Femenino , Fulvestrant , Humanos , Persona de Mediana Edad , Morfolinas/efectos adversos , Fosfatidilinositol 3-Quinasa/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Inhibidores de Proteínas Quinasas/efectos adversos , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo , Resultado del Tratamiento
14.
Lancet Oncol ; 19(1): 127-138, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29158011

RESUMEN

BACKGROUND: In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women. METHODS: We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4-6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2·5 mg/day orally for 5 years) or intermittent use of letrozole (2·5 mg/day orally for 9 months followed by a 3-month break in years 1-4 and then 2·5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing. FINDINGS: Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53-72), disease-free survival was 85·8% (95% CI 84·2-87·2) in the intermittent letrozole group compared with 87·5% (86·0-88·8) in the continuous letrozole group (hazard ratio 1·08, 95% CI 0·93-1·26; p=0·31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3-5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3-5 CNS cerebrovascular ischaemia, 16 (nine [<1%] vs seven [<1%]) had grade 3-5 CNS haemorrhage, and 40 (19 [1%] vs 21 [1%]) had grade 3-5 cardiac ischaemia. In total, 23 (<1%) of 4851 patients died while on trial treatment (13 [<1%] of 2417 patients in the intermittent letrozole group vs ten [<1%] of 2411 in the continuous letrozole group). INTERPRETATION: In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them. FUNDING: Novartis and the International Breast Cancer Study Group.


Asunto(s)
Antineoplásicos/administración & dosificación , Inhibidores de la Aromatasa/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Nitrilos/administración & dosificación , Posmenopausia , Triazoles/administración & dosificación , Anciano , Antineoplásicos/efectos adversos , Inhibidores de la Aromatasa/efectos adversos , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Letrozol , Persona de Mediana Edad , Nitrilos/efectos adversos , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Factores de Tiempo , Resultado del Tratamiento , Triazoles/efectos adversos
15.
BMC Genomics ; 19(1): 960, 2018 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-30583719

RESUMEN

BACKGROUND: New single-cell isolation technologies are facilitating studies on the transcriptomics of individual cells. Bio-Rad ddSEQ is a droplet-based microfluidic system that, when coupled with downstream Illumina library preparation and sequencing, enables the monitoring of thousands of genes per cell. Sequenced reads show unique features that do not permit the use of freely available tools to perform single cell demultiplexing. RESULTS: We present ddSeeker, a tool to perform initial processing and quality metrics of reads generated through Bio-Rad ddSEQ/Illumina experiments. Its application to the Illumina test dataset demonstrates that ddSeeker performs better than Illumina BaseSpace software, enabling a higher recovery of valid reads. We also show its utility in the analysis of an in-house dataset including two read sets characterized by low and high sequencing quality. ddSeeker and its source code are available at https://github.com/cgplab/ddSeeker . CONCLUSIONS: ddSeeker is a freely available tool to perform initial processing and quality metrics of reads generated through Bio-Rad ddSEQ/Illumina single cell transcriptomic experiments.


Asunto(s)
ARN/genética , Análisis de Secuencia de ARN , Análisis de la Célula Individual/métodos , Programas Informáticos , Transcriptoma/genética , Algoritmos , Biología Computacional , Perfilación de la Expresión Génica
16.
Breast Cancer Res Treat ; 170(2): 329-341, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29564743

RESUMEN

PURPOSE: HER2-positive (HER2+) breast cancers show heterogeneous response to chemotherapy, with the ER-positive (ER+) subgroup deriving less benefit. Loss of retinoblastoma tumor suppressor gene (RB1) function has been suggested as a cardinal feature of breast cancers that are more sensitive to chemotherapy and conversely resistant to CDK4/6 inhibitors. We performed a retrospective analysis exploring RBsig, a gene signature of RB loss, as a potential predictive marker of response to neoadjuvant chemotherapy in ER+/HER2+ breast cancer patients. METHODS: We selected clinical trials of neoadjuvant chemotherapy ± anti-HER2 therapy in HER2+ breast cancer patients with available information on gene expression data, hormone receptor status, and pathological complete response (pCR) rates. RBsig expression was computed in silico and correlated with pCR. RESULTS: Ten studies fulfilled the inclusion criteria and were included in the analysis (514 patients). Overall, of 211 ER+/HER2+ breast cancer patients, 49 achieved pCR (23%). The pCR rate following chemotherapy ± anti-HER2 drugs in patients with RBsig low expression was significantly lower compared to patients with RBsig high expression (16% vs. 30%, respectively; Fisher's exact test p = 0.015). The area under the ROC curve (AUC) was 0.62 (p = 0.005). In the 303 ER-negative (ER-)/HER2+ patients treated with chemotherapy ± anti-HER2 drugs, the pCR rate was 43%. No correlation was found between RBsig expression and pCR rate in this group. CONCLUSIONS: Low expression of RBsig identifies a subset of ER+/HER2+ patients with low pCR rates following neoadjuvant chemotherapy ± anti-HER2 therapy. These patients may potentially be spared chemotherapy in favor of anti-HER2, endocrine therapy, and CDK 4/6 inhibitor combinations.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos/genética , Genes de Retinoblastoma , Mutación con Pérdida de Función , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/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 , Femenino , Perfilación de la Expresión Génica , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Clasificación del Tumor , Estadificación de Neoplasias , Curva ROC , Transcriptoma , Resultado del Tratamiento , Adulto Joven
17.
Breast Cancer Res Treat ; 170(2): 351-360, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29589138

RESUMEN

PURPOSE: We investigated the occurrence and the prognostic and predictive relationship of a selected number of somatic mutations in triple-negative breast cancer (TNBC) patients having known clinical outcomes treated within the IBCSG Trial 22-00. METHODS: A matched case-control sampling selected patients enrolled in the IBCSG Trial 22-00 who had TNBC tumors, based on local assessment. Cases had invasive breast cancer recurrence (at local, regional, or distant site) according to the protocol definition. Matched controls had not recurred. Mutational analysis was performed with OncoCarta panel v1.0 using Mass Array System. The panel includes 19 genes belonging to different functional pathways as PI3K pathway, receptor tyrosine kinase, and cell cycle-metabolic group. Conditional logistic regression assessed the association of mutation status with breast cancer recurrence. RESULTS: Mutation assessment was successful for 135 patients (49 cases, 86 controls). A total of 37 (27.4%) of the 135 patients had at least one mutation in the selected genes. PIK3CA was the most common mutated gene (18/135; 13.3%), followed by BRAF, KIT and PDGFRA (each 4/135, 3.0%) and AKT1 (3/135; 2.2%). TNBC patients with at least one mutation had increased odds of recurrence compared with those with wild-type tumors (odds ratio (OR) 2.28; 95% CI 0.88-5.92), though this difference was not statistically significant (p = 0.09). We found no evidence that these mutations were predictive for the value of maintenance metronomic chemotherapy. CONCLUSIONS: Mutations in the tested oncogenes were not associated with breast cancer recurrence in this TNBC subset of patients. The question of whether any of these mutated genes (e.g., PIK3CA) may represent a useful therapeutic target in TNBC may be answered by ongoing clinical trials and/or larger dataset analysis.


Asunto(s)
Biomarcadores de Tumor , Mutación , Neoplasias de la Mama Triple Negativas/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Oportunidad Relativa , Pronóstico , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Carga Tumoral , Adulto Joven
18.
BMC Cancer ; 18(1): 932, 2018 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-30261866

RESUMEN

BACKGROUND: Several trials evaluated the role of ovarian function suppression for the adjuvant treatment of premenopausal patients with hormone receptor-positive early breast cancer. Based on the results of the SOFT and TEXT trials, international guidelines recommend the addition of ovarian function suppression to standard adjuvant endocrine therapy for patients at higher risk of relapse. METHODS: The ERA project (Evaluation of Risk factors in the Adjuvant treatment of breast cancer in premenopausal patients) was devised with the objective of obtaining a consensus on the identification of risk factors and the use of ovarian function suppression in the adjuvant treatment of these women. To this aim, a panel of 31 Italian oncologists with expertise in breast cancer participated in a Delphi consensus study in June 2017. RESULTS: A total of 29 statements related to prognostic factors, therapeutic strategies and ovarian function suppression were defined and voted to gain final consensus. For each topic we report data supporting the acquired consensus and the relevant issues discussed. CONCLUSIONS: The SOFT and TEXT trials have changed the standard adjuvant treatment of premenopausal patients with hormone receptor-positive early breast cancer, but the available treatment options require a careful risk assessment and toxicities evaluation to ensure the greatest clinical benefit for each patient.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Antagonistas de Estrógenos/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Quimioterapia Adyuvante , Técnica Delphi , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/uso terapéutico , Humanos , Italia , Pruebas de Función Ovárica , Premenopausia , Tamoxifeno/uso terapéutico
19.
Pharmacol Res ; 106: 92-100, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26921662

RESUMEN

In the era of precision medicine in oncology, pharmacogenomic assessment is a vital step in delivering personalized care. Increasing evidence points towards the importance of assessing molecular features of the advanced disease, rather than relying on the primary tumor sample, in order to appreciate the evolution of the tumor and to target relevant features. Circulating tumor cells (CTCs) represent a novel method of tumor sampling, as they offer a contemporaneous picture of the current disease state without the need for invasive needle biopsy. As they may derive from any number of metastatic sites, the potential to capture the heterogeneity of the disease is increased. Improvements in CTC capture, enrichment and isolation technology now allow sophisticated interrogation of these cells, such that pharmacogenomic assessment of CTCs is now possible, and the clinical potential is being explored. We review current and potential uses for CTCs for pharmacogenomic analysis.


Asunto(s)
Neoplasias/genética , Neoplasias/patología , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Pruebas de Farmacogenómica/métodos , Humanos , Medicina de Precisión/métodos
20.
Adv Exp Med Biol ; 882: 217-34, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26987537

RESUMEN

Metabolomics refers to the study of the whole set of metabolites in a biological sample that constitute a reflection of cellular functions. Cancer cells display significantly altered cellular processes, and thus metabolites, compared to normal cells. This can be detected in a number of ways, and is already exploited to a limited extent in the diagnosis of cancer. The host response to the tumor is perhaps equally important, as it either rejects or permits tumor growth, and this may also potentially result in a measurable metabolite signature. Analysis then of entire pools of metabolites may yield critical information about both tumor presence and host response, and represent a possible novel collective biomarker for cancer behaviour that could allow prediction of relapse, response to therapy, or progression. Isolating meaningful differences in the sea of metabolites and within the context of significant metabolic heterogeneity both within and between patients remains a great challenge. This chapter will review current metabolomic research in breast cancer, with a focus on efforts to translate the technology into clinical practice.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Metabolómica , Animales , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Femenino , Humanos , Metabolómica/métodos , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo
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