RESUMEN
BACKGROUND: The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. PATIENTS AND METHODS: Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics. RESULTS: EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P < 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P < 0.0001). CONCLUSIONS: The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.
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Neoplasias de la Mama , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Pronóstico , Receptor ErbB-2/metabolismo , Método Doble Ciego , Anciano , Adulto , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Everolimus/uso terapéutico , Everolimus/farmacología , Supervivencia sin Enfermedad , Biomarcadores de Tumor/metabolismoRESUMEN
BACKGROUND: Resection of breast cancer liver metastases (BCLM) combined with systemic treatment is increasingly accepted but not offered as therapeutic option. New evidence of the additional value of surgery in these patients is scarce while prognoses without surgery remains poor. PATIENTS AND METHODS: For this case matched analysis, all nationally registered patients with BCLM confined to the liver in the Netherlands (systemic group; N = 523) were selected and compared with patients who received systemic treatment and underwent hepatectomy (resection group; N = 139) at a hepatobiliary centre in France. Matching was based on age, decade when diagnosed, interval to metastases, maximum metastases size, single or multiple tumours, chemotherapy, hormonal or targeted therapy after diagnosis. Based on published guidelines, palliative systemic treatment strategies are similar in both European countries. RESULTS: Between 1983 and 2013, 3894 patients were screened for inclusion. Overall median follow-up was 80 months (95% CI 70-90 months). The median, 3- and 5-year overall survival of the whole population was 19 months, 29% and 19%, respectively. The resection and systemic group had median survival of 73 vs. 13 months (P < 0.001), respectively. Three and 5-year survival was 18% and 10% for the systemic group and 75% and 54% for the resection group, respectively. After matching, the resection group had a median overall survival of 82 months with a 3- and 5-year overall survival of 81% and 69%, respectively, compared with a median overall survival of 31 months in the systemic group with a 3- and 5-year overall survival of 32% and 24%, respectively (HR 0.28, 95% CI 0.15-0.52; P < 0.001). CONCLUSIONS: For patients with BCLM, liver resection combined with systemic treatment results in improved overall survival compared to systemic treatment alone. Liver resection should be considered in selected cases.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Europa (Continente)/epidemiología , Femenino , Francia/epidemiología , Hepatectomía/estadística & datos numéricos , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Países Bajos/epidemiología , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Mortality is high in patients with locally advanced triple-negative breast cancer (TNBC), especially in those with residual tumour after neoadjuvant chemotherapy (NAC). The aim of this study was to determine if pretreatment (18)F-FDG PET/CT staging and pathological findings after NAC could together allow stratification of patients into prognostic groups. METHODS: Initial staging with (18)F-FDG PET/CT was performed prospectively in 85 consecutive patients with stage II/III TNBC. Correlations between PET findings and disease-specific survival (DSS) were examined. In patients without distant metastases on PET staging, the impact of pathological response to NAC on DSS was examined. Patterns of recurrence were also analysed. RESULTS: (18)F-DG PET/CT revealed distant metastases in 11 of 85 patients (12.9 %). Among 74 M0 patients, 23 (31.1 %) showed a pathological complete response (pCR) at surgery, while 51 had residual invasive disease (no pCR). DSS differed considerably among the three groups of patients (log-rank P < .001): among patients with occult metastases on baseline PET/CT, 2-year DSS was 18.2 %, and among patients without initial metastases on PET/CT, 5-year DSS was 61.3 % in patients without pCR after NAC and 95.2 % in those with pCR. Of the 51 patients who did not achieve pCR, 21 relapsed (17 developed distant metastases). The sites of distant recurrence were: lung/pleura (nine patients), brain (eight patients), liver (six patients), distant lymph nodes (six patients) and bone (five patients). CONCLUSION: In patients with clinical stage II/III TNBC, (18)F-FDG PET/CT findings at initial staging and pathological response at the end of NAC allow three groups of patients with quite different prognoses to be defined. Extraskeletal recurrences predominated. Specific follow-up strategies in patients with TNBC who do not achieve pCR deserve investigation.
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Neoplasias de la Mama/diagnóstico por imagen , Carcinoma/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Imagen Multimodal , Tomografía de Emisión de Positrones , Radiofármacos , Tomografía Computarizada por Rayos X , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Carcinoma/tratamiento farmacológico , Carcinoma/patología , Quimioterapia , Femenino , Humanos , Terapia Neoadyuvante , Metástasis de la Neoplasia , Estadificación de Neoplasias , PronósticoRESUMEN
Trastuzumab improves care of patients with HER2+ breast cancer and allows a major gain in terms of survival. T-DM1 and pertuzumab are two new treatments, which give very encouraging results in metastatic breast cancer. Their place in neo-adjuvant and adjuvant setting still remains to be defined. Bevacizumab have its place in metastatic breast cancer. In adjuvant setting, results are disappointing and in neo-adjuvant setting, we need more studies on subgroups, which can benefit more. Development of the PARP inhibitors was slowed down by recent negative results in metastatic breast cancer but studies continue with more targeted patient's. Finally, everolimus, inhibitor of mTOR, allows to by pass the hormono-resistance in metastatic phase. Its toxicity must be taken into account in particular in adjuvant setting.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Ado-Trastuzumab Emtansina , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias de la Mama/química , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Lapatinib , Maitansina/análogos & derivados , Maitansina/uso terapéutico , Terapia Neoadyuvante , Metástasis de la Neoplasia/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Quinazolinas/uso terapéutico , Receptor ErbB-2/análisis , Receptor ErbB-2/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Trastuzumab/uso terapéuticoRESUMEN
PURPOSE OF INVESTIGATION: To describe the French practices regarding contraception after breast cancer in the 2000's. MATERIALS AND METHODS: A total of 2,500 forms were sent to gynecologists practicing in France. Inclusion criteria were premenopausal patients who had a history of breast cancer and who had been prescribed contraception after diagnosis. Between June 1, 2002 and January 1, 2003, 197 evaluable responses were retrieved. RESULTS: The median age of the sample was 38.5 years. The most commonly used form of contraception was an intrauterine device (n = 144, 73.1%). Hormonal contraception was prescribed for 42 patients (21.3%), and other methods were used in 29 patients (14.7%) (Condoms n = 14, tubal sterilization n = 7, and others n = 8). Recurrence occurred in 27 patients (13%); 2.9% in the progestin group, 16.3% in the IUD group, and 14.8% with the other methods). CONCLUSIONS: It is necessary to evaluate current contraception practices after breast cancer to evaluate the efficacy and safety of contraception in these patients.
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Neoplasias de la Mama , Carcinoma , Anticoncepción/métodos , Ginecología , Recurrencia Local de Neoplasia , Pautas de la Práctica en Medicina , Adulto , Condones/estadística & datos numéricos , Anticonceptivos Hormonales Orales/uso terapéutico , Femenino , Francia , Humanos , Dispositivos Intrauterinos/estadística & datos numéricos , Persona de Mediana Edad , Progestinas/uso terapéutico , Estudios Retrospectivos , Esterilización Tubaria/estadística & datos numéricos , Adulto JovenRESUMEN
BACKGROUND: Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in these cancers. METHODS: We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with two different neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide-anthracycline (AC) association (historically called SIM) or a conventional sequential association of cyclophosphamide and anthracycline, followed by taxanes (EC-T). We compared pathological responses and survival rates of these two groups and studied their association with tumours features. RESULTS: Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was statistically higher for TN than for non-TN patients (P=0.019), although we showed that the TN status was associated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN was associated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07-0.86), P=0.028). CONCLUSIONS: AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers. These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Anciano , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Epirrubicina/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Sobrevivientes , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/cirugía , Adulto JovenRESUMEN
This study was designed to identify predictive signatures of pathological complete response (pCR) in breast cancer treated by taxane-based regimen, using clinicopathological variables and transcriptomic data (Affymetrix Hgu133 Plus 2.0 devices). The REMAGUS 02 trial (n = 153,training set) and the publicly available M.D. Anderson data set (n = 133, validation set) were used. A re-sampling method was applied. All predictive models were defined using logistic regression and their classification performances were tested through Area Under the Curve (AUC) estimation. A stable set of 42 probesets (31 genes) differentiate pCR or no pCR samples. Single-or 2-probesets signatures, mainly related to ER pathway, were equally predictive of pCR with AUC greater then 0.80. Models including probesets associated with ESR1, MAPT, CA12 or PIGH presented good classification performances. When clinical variables were entered into the model, only CA12 and PIGH, remained informative (p = 0.05 and p = 0.005) showing that a combination of a few genes provided robust and reliable prediction of pCR.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Transcriptoma , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/química , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Anhidrasas Carbónicas/genética , Quimioterapia Adyuvante , Receptor alfa de Estrógeno/genética , Femenino , Humanos , Proteínas de la Membrana/genética , Persona de Mediana Edad , Terapia Neoadyuvante , Análisis de Secuencia por Matrices de Oligonucleótidos , Valor Predictivo de las Pruebas , ARN/análisis , Receptores de Estrógenos/análisis , Taxoides/administración & dosificación , Resultado del Tratamiento , Proteínas tau/genéticaRESUMEN
BACKGROUND: Pathologic complete response (pCR) to neoadjuvant treatment (NAT) is associated with improved survival of patients with HER2+ breast cancer. We investigated the ability of interim positron emission tomography (PET) regarding early prediction of pathology outcomes. METHODS: During 61 months, consecutive patients with locally advanced or large HER2+ breast cancer patients without distant metastases were included. All patients received NAT with four cycles of epirubicin+cyclophosphamide, followed by four cycles of docetaxel+trastuzumab. ¹8F-fluorodeoxyglucose (¹8F-FDG)-PET/computed tomography (CT) was performed at baseline (PET1) and after two cycles of chemotherapy (PET2). Maximum standardised uptake values were measured in the primary tumour as well as in the axillary lymph nodes. The correlation between pathologic response and SUV parameters (SUVmax at PET1, PET2 and ΔSUVmax) was examined with the t-test. The predictive performance regarding the identification of non-responders was evaluated using receiver operating characteristics (ROC) analysis. RESULTS: Thirty women were prospectively included and 60 PET/CT examination performed. At baseline, 22 patients had PET+ axilla and in nine of them ¹8F-FDG uptake was higher than in the primary tumour. At surgery, 14 patients (47%) showed residual tumour (non-pCR), whereas 16 (53%) reached pCR. Best prediction was obtained when considering the absolute residual SUVmax value at PET2 (AUC=0.91) vs 0.67 for SUVmax at PET1 and 0.86 for ΔSUVmax. The risk of non-pCR was 92.3% in patients with any site of residual uptake >3 at PET2, no matter whether in breast or axilla, vs 11.8% in patients with uptake ≤3 (P=0.0001). The sensitivity, specificity, PPV, NPV and overall accuracy of this cutoff were, respectively: 85.7%, 93.8%, 92.3%, 88.2% and 90%. CONCLUSION: The level of residual ¹8F-FDG uptake after two cycles of chemotherapy predicts residual disease at completion of NAT with chemotherapy+trastuzumab with high accuracy. Because many innovative therapeutic strategies are now available (e.g., addition of a second HER2-directed therapy or an antiangiogenic), early prediction of poor response is critical.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Transporte Biológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Ciclofosfamida/uso terapéutico , Docetaxel , Epirrubicina/uso terapéutico , Femenino , Fluorodesoxiglucosa F18 , Humanos , Terapia Neoadyuvante , Tomografía de Emisión de Positrones , Radiofármacos , Tasa de Supervivencia , Taxoides/uso terapéutico , Trastuzumab , Resultado del TratamientoRESUMEN
BACKGROUND: Molecular circadian clocks can modify cancer chemotherapy effects, with a possible moderation according to sex differences. We investigated whether sex determine the optimal delivery schedule of chemotherapy for metastatic colorectal cancer. PATIENTS AND METHODS: A meta-analysis was performed using individual data from three international Phase III trials comparing 5-fluorouracil, leucovorin and oxaliplatin administered in chronomodulated (chronoFLO) or conventional (CONV) infusions. The data from 345 females and 497 males were updated at 9 years. The main end point was survival. RESULTS: Overall survival was improved in males on chronoFLO when compared with CONV (P = 0.009), with respective median values of 20.8 (95% CL, 18.7 to 22.9) and 17.5 months (16.1 to 18.8). Conversely, median survival was 16.6 months (13.9 to 19.3) on chronoFLO and 18.4 months (16.6 to 20.2) on CONV in females (P = 0.012). The sex versus schedule interaction was a strong predictive factor of optimal treatment schedule, with a hazard ratio of 1.59 (1.30 to 1.75) for overall survival (P = 0.002) in multivariate analysis. CONCLUSIONS: Males lived significantly longer on chronomodulated chemotherapy rather than on conventional chemotherapy. The current chronoFLO schedule deserves prospective assessment as a safe and more effective first-line treatment option than conventional delivery for male patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Relojes Circadianos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Anciano , Cronoterapia , Esquema de Medicación , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Compuestos Organoplatinos/uso terapéutico , Factores Sexuales , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine the malignancy rate of nonpalpable breast lesions, categorised according to the Breast Imaging Reporting and Data System (BI-RADS) classification in the setting of a Breast Care Unit. METHODS: All nonpalpable breast lesions from consecutive patients referred to a dedicated Breast Care Unit were prospectively reviewed and classified into 5 BI-RADS assessment categories (0, 2, 3, 4, and 5). RESULTS: A total of 2708 lesions were diagnosed by mammography (71.6%), ultrasound (8.7%), mammography and ultrasound (19.5%), or MRI (0.2%). The distribution of the lesions by BI-RADS category was: 152 in category 0 (5.6%), 56 in category 2 (2.1%), 742 in category 3 (27.4%), 1523 in category 4 (56.2%) and 235 in category 5 (8.7%). Histology revealed 570 malignant lesions (32.9%), 152 high-risk lesions (8.8%), and 1010 benign lesions (58.3%). Malignancy was detected in 17 (2.3%) category 3 lesions, 364 (23.9%) category 4 lesions and 185 (78.7%) category 5 lesions. Median follow-up was 36.9 months. CONCLUSION: This pragmatic study reflects the assessment and management of breast impalpable abnormalities referred for care to a specialized Breast Unit. Multidisciplinary evaluation with BI-RADS classification accurately predicts malignancy, and reflects the quality of management. This assessment should be encouraged in community practice appraisal.
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Biopsia , Neoplasias de la Mama/clasificación , Mama/patología , Clasificación Internacional de Enfermedades , Imagen por Resonancia Magnética , Mamografía , Lesiones Precancerosas/clasificación , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Unidades Hospitalarias , Humanos , Comunicación Interdisciplinaria , Mamografía/métodos , Auditoría Médica , Persona de Mediana Edad , Palpación , Lesiones Precancerosas/diagnóstico , Estudios Prospectivos , Derivación y Consulta , Medición de Riesgo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) are currently the most commonly used methods to assess HER2 status. PCR-based assays allow quantitative determination of HER2 amplification (Q-PCR) or overexpression (Q-RT-PCR), but are not routinely used. We evaluated the relevance of Q-RT-PCR for HER2 status determination. METHODS: We compared IHC and Q-RT-PCR in 466 breast tumours. In discordant or equivocal cases, five additional methods (IHC with two other antibodies, FISH, silver in situ hybridisation (SISH) and Q-PCR) were combined to determine HER2 status. Two cases with HER2 intra-tumour heterogeneity were further explored by allelic profiles analysis and HUMARA clonality determination after microdissection. RESULTS: We observed 97.3% concordance between Q-RT-PCR and non-equivocal IHC. Twelve out of 466 cases (3%) revealed discordances between the two methods. The power of Q-RT-PCR to predict HER2 status (defined by seven methods) was similar to that of IHC. Although rare, some discordances between techniques might be due to HER2 intra-tumour heterogeneity and we report two examples, one tumour containing two distinct clones, another tumour consisting of HER2 amplified and non-amplified subclones. CONCLUSION: Q-RT-PCR and IHC are highly concordant methods for HER2 status assessment, and Q-RT-PCR allows a highly reliable quantitative assessment and could be a useful adjunct to IHC.
Asunto(s)
Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Alelos , Dosificación de Gen , Genes erbB-2 , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Receptores AndrogénicosRESUMEN
The authors discuss the various roles of 18F-FDG PET/CT in the management of breast cancer. Roles of new tracers such as F-18 fluoro-L-thymidine (a marker of cell proliferation), 18-fluoro-17-B-estradiol (marker of estrogen receptor) and sodium fluoride (marker of bone matrix) are also mentioned. There is little justification for the use of FDG-PET/CT in patient with clinically T1 (< or = 2 cm) N0 tumours. Notably, it cannot be used as a substitute to SLNB "sentinel lymph node biopsy" for axillary staging due to limited sensitivity for the detection of small metastases. The case is different in higher risk patients, and especially so in patients with locally advanced disease. FDG-PET/CT in these patients might depict lymph node involvement in the level III of Berg or in supraclavicular or internal mammary basins. It might also uncover occult distant metastases, notably, early osteomedullary infiltration. Thus, for these tumors, initial PET/CT can enable better intramodality treatment planning or a change in treatment. PET/CT as a whole-body examination is also very efficient in case of suspicion of recurrence. On the other hand, many studies show that this functional imaging could be used to assess early response to neoadjuvant chemotherapy or to chemotherapy of metastatic disease. 18FDG-PET/CT could thus become an unavoidable modality to answer various clinical situations.
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Neoplasias de la Mama/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/terapia , Didesoxinucleósidos , Estradiol/análogos & derivados , Femenino , Fluorodesoxiglucosa F18 , Humanos , Escisión del Ganglio Linfático , Recurrencia Local de Neoplasia/diagnóstico por imagen , Fluoruro de Sodio , Resultado del TratamientoRESUMEN
As compared to conventional axillary dissection, the sentinel node technique is accompanied by reduced morbidity and shorter hospital stay. Based on available data, the use of this technique does not seem to yield higher rates of axillary recurrence. A combination of both radioisotope detection and blue dye increases the identification rate, while also reducing false-negative rate. Surgical results are optimized when preoperative lymphoscintigraphy mapping is obtained in addition to peroperative probe detection. Considering the site of injection, the subareolar injection can be easy to apply even in case of non-palpable tumours, and gives higher count rates. However, the intraparenchymal, peritumoral, injection is necessary to evidence cases of extra-axillary drainage (internal mammary, infra- or supraclavicular) that is present in about 20% of patients. With the advent of hybrid cameras (SPECT-CT), the topography of these extra-axillary nodes can be given with high precision. Use of the sentinel node technique has been accompanied by an increase in the percent of patients with node involvement, due to an increased detection of micrometastases inferior or equal to 2 mm. Following an overview of basic principles, and of the main results with the sentinel node technique we focus the discussion on several points that are still open to debate, such as: 1) which group of patients can benefit from the sentinel node technique? 2) What is the optimal methodology? 3) What is the prognostic significance of micrometastases and of isolated tumour cells? 4) What attention should be given to extra-axillary drainage?
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Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias de la Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/patología , Colorantes , Femenino , Humanos , Escisión del Ganglio Linfático/efectos adversos , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Protección Radiológica/métodos , Radiofármacos/administración & dosificación , Recurrencia , Biopsia del Ganglio Linfático Centinela/normas , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Invasive lobular carcinoma accounts for 4 to 10% of breast cancers. The clinical and radiological diagnosis is difficult to make. Its progression is slower than that of ductal cancer, and the prognostic factors are more favourable. Its metastases are more frequently located in the digestive tract and the ovaries. It is more frequently bilateral. Its prognosis is not different from that of infiltrating ductal carcinomas. The choice of therapies depends on the individual characteristics of each patient and of the biological features of each tumour. However, lobular carcinomas seem to be less responsive to chemotherapy.
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Neoplasias de la Mama/diagnóstico , Carcinoma Lobular/diagnóstico , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/patología , Diagnóstico Diferencial , Femenino , Humanos , Pronóstico , Radiografía , Resultado del TratamientoRESUMEN
The incidence of lobular cancers in situ is increasing, especially in post-menopausal women. Whereas this form of disease was regarded for a long time as nothing but a risk factor of the occurrence of later infiltrating carcinoma, it now tends to represent a precancerous state whose progression to subsequent infiltrating carcinoma does not inevitably occur. The clinical and radiological diagnosis remains difficult and the choice of therapies varies according to teams, ranging from mere surveillance to mastectomy.
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Neoplasias de la Mama/diagnóstico , Carcinoma in Situ/diagnóstico , Carcinoma Lobular/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma in Situ/epidemiología , Carcinoma in Situ/patología , Carcinoma in Situ/terapia , Carcinoma Lobular/epidemiología , Carcinoma Lobular/patología , Carcinoma Lobular/terapia , Femenino , Humanos , Incidencia , Posmenopausia , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/patología , Lesiones Precancerosas/terapia , Pronóstico , Factores de RiesgoRESUMEN
S 16020, a new 9-OH olivacine derivative, is a novel topoisomerase II inhibitor with activity in cell lines presenting the classical multidrug resistance phenotype. This report summarizes, in addition to pharmacokinetic data, the whole phase I clinical experience of S 16020 using three different infusion schedules. Asthenia and skin toxicity were the main side effects. In an attempt to understand the skin toxicity mechanism, experiments in animals were performed, the results of which are reported. S 16020 showed rapid tumor necrotizing activity in some patients, with soft tissue metastases of epidermoïd tumors and pain at the tumor site. To document the side effects of S 16020 and tumor site reactions (pain, edema, inflammatory signs), inflammatory parameters and some cytokines were measured. In our patients there was no hemolysis and no detection of anti-S 16020 antibodies, confirming the absence of immunogenicity of the compound. Based on the overall data of the three infusion schedules of S 16020, the dose of 100 mg/m(2) over 3 h every 3 weeks was selected for phase II studies.
Asunto(s)
Carbazoles/administración & dosificación , Carbazoles/farmacocinética , Dosis Máxima Tolerada , Neoplasias/tratamiento farmacológico , Piridinas/administración & dosificación , Piridinas/farmacocinética , Adulto , Anciano , Disponibilidad Biológica , Carbazoles/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Elipticinas , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias/patología , Piridinas/efectos adversos , Medición de Riesgo , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
Chronotherapy has consisted in the adaptation of chemotherapeutic drug delivery to circadian (approximately 24-hour) rhythms. This can be achieved in fully ambulatory patients using multichannel programmable pumps. Up to approximately 1500 patients with metastatic colorectal cancer have been registered in one of 15 trials testing the relevance of this treatment method with 5-fluorouracil +/- leucovorin +/- oxaliplatin. Chronotherapy was shown as significantly less toxic and more effective than constant rate infusion in 2 consecutive multicenter trials. High efficacy and good tolerability permitted secondary surgical resection of previously inoperable metastases, with apparent survival improvement (3-year survival > or = 20%) and cures in some patients. This strategy is currently undergoing further testing within the European Organization for Research and Treatment of Cancer. Nevertheless, combining chronotherapy with surgery of colorectal cancer metastases can be readily offered to patients as a safer therapeutic option for optimizing outcome.
Asunto(s)
Antineoplásicos/administración & dosificación , Cronoterapia , Neoplasias Colorrectales/patología , Animales , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Metástasis de la Neoplasia/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , OxaliplatinoRESUMEN
The rest/activity circadian cycle has been used as a reference for chemotherapy administration at specific times to improve tolerability and efficacy. Because cancer processes may be associated with alterations of circadian rhythms, the rest/activity cycle was monitored noninvasively to assess its relationship with tumor response, survival, and quality of life in 200 patients with metastatic colorectal cancer. Patients wore an actigraph, a wristwatch that records the number of accelerations per minute, for 3 days before receiving chronomodulated chemotherapy. The circadian rhythms in activity were estimated by two robust parameters: the autocorrelation coefficient at 24 h (r24), and the dichotomy index (IAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación
, Ritmo Circadiano/fisiología
, Neoplasias Colorrectales/tratamiento farmacológico
, Neoplasias Colorrectales/fisiopatología
, Adulto
, Anciano
, Neoplasias Colorrectales/mortalidad
, Esquema de Medicación
, Fatiga/fisiopatología
, Femenino
, Fluorouracilo/administración & dosificación
, Humanos
, Hidrocortisona/sangre
, Leucovorina/administración & dosificación
, Masculino
, Persona de Mediana Edad
, Análisis Multivariante
, Metástasis de la Neoplasia
, Compuestos Organoplatinos/administración & dosificación
, Oxaliplatino
, Pronóstico
, Estudios Prospectivos
, Calidad de Vida
, Índice de Severidad de la Enfermedad
, Trastornos del Sueño-Vigilia/fisiopatología
, Análisis de Supervivencia
, Resultado del Tratamiento
RESUMEN
PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)-leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m(2)/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m(2), as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU-LV occurred in = 5% of the patients (= 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU-LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P <. 001). The median progression-free survival time was 6.1 months with 5-FU-LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU-LV (P =.048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU-LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.