RESUMEN
AIM: To review the effect of immunological changes induced by interstitial laser thermotherapy (ILT) on long-term outcome of patients with breast cancer. PATIENTS AND METHODS: Twenty-four patients with invasive breast cancer were treated with ILT followed by standard surgical excision. Immunohistological reactions on immunocompetent cells were performed on specimens obtained before and after ILT. Follow-up time was 116 (range=91-136) months. RESULTS: Significant prognostic factors were histologically-positive axillary lymph nodes and Ki67 positivity. ILT increased cytotoxic T (CD8(+)) lymphocytes within the tumor and mature dendritic cells (CD83(+)) and reduced the number of T-regulatory cells (Treg) CD25(+)/Forkhead box p3(+) (FOXP3(+)) lymphocytes in regional lymph nodes. These changes did not correlate with prognosis. The number of CD8(+) cells within the tumor, both before and after treatment, was significantly higher in patients with recurrence than in those without recurrence (p<0.01 and p<0.05, respectively). Patients with recurrent disease had a lower number of CD57(+) cells in tumor-free lymph nodes than did patients without recurrence (p<0.05). CONCLUSION: ILT did not have any long-term adverse effects. The clinical impact of the supposedly favourable immune changes after ILT should be examined in a larger patient population.
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Neoplasias de la Mama/inmunología , Neoplasias de la Mama/terapia , Linfocitos T CD8-positivos/inmunología , Hipertermia Inducida/métodos , Terapia por Láser/métodos , Ganglios Linfáticos/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Linfocitos T CD8-positivos/patología , Carcinoma Ductal de Mama/inmunología , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/inmunología , Carcinoma Lobular/secundario , Carcinoma Lobular/terapia , Células Dendríticas/inmunología , Células Dendríticas/patología , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Ganglios Linfáticos/patología , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Linfocitos T Reguladores/patología , Factores de TiempoRESUMEN
Lapatinib, in combination with capecitabine, has shown clinical activity in both first-line and refractory disease in patients with HER2-positive advanced breast cancer. Herein we describe the case of a plurimetastatic, heavily pretreated, HER2-positive breast cancer patient who experienced multiple cutaneous metastases successfully treated with lapatinib and capecitabine. An early complete response was obtained on all skin lesions, and no evidence of disease progression at other metastatic sites was observed for 22 months. The treatment was well tolerated, without dose-reductions or delays. In advanced breast cancer patients with skin metastases overexpressing HER2, previously treated with anthracyclines, taxanes and trastuzumab, lapatinib and capecitabine may represent a very active, safe and well-tolerated treatment option.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/secundario , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Quinazolinas/administración & dosificación , Receptor ErbB-2/análisis , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/secundario , Anciano , Antraciclinas/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias de la Mama/química , Capecitabina , Desoxicitidina/administración & dosificación , Progresión de la Enfermedad , Docetaxel , Cronoterapia de Medicamentos , Estradiol/administración & dosificación , Estradiol/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fulvestrant , Humanos , Inmunohistoquímica , Lapatinib , Letrozol , Nitrilos/administración & dosificación , Taxoides/administración & dosificación , Factores de Tiempo , Trastuzumab , Resultado del Tratamiento , Triazoles/administración & dosificación , Regulación hacia Arriba , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
PURPOSE: The duration of anti-HER2 blockage therapy in metastatic breast cancer patients is still unclear. We aimed to evaluate the effect of the anti-HER2 blockage therapy duration and other factors on survival in HER2 positive metastatic breast carcinoma (MBC) patients. METHODS: The medical records of 193 HER2 positive MBC patients, who did not have the opportunity to receive adjuvant trastuzumab therapy but had received trastuzumab in the metastatic setting were retrospectively evaluated. RESULTS: The median age at diagnosis was 45.0 years (range 21-83). Ninety-two (47.7%) patients received palliative trastuzumab < 6 months median, whereas 101 patients received trastuzumab ≥ 6 months median. The median number of trastuzumab cycles was 8 (range 1-51). Median survival after breast cancer recurrence was 31.0 months (range 24.3-37.7). The duration of trastuzumab therapy had a significant impact on the prognosis of recurrent breast cancer (22.0 vs 49.0 months, for ≤ 6 months of treatment duration, respectively; p<0.0001). Survival after breast cancer recurrence for the patients who received lapatinib plus capecitabine vs those who did not was significantly different (59 patients, p=0.005). Moreover, there was a statistically significant relationship between prolonged lapatinib plus capecitabine combination therapy and improved survival after disease recurrence (p=0.022). In the multivariate Cox regression analysis, treatment with trastuzumab > 6 months (p=0.003) was the only independent prognostic factor for survival after breast cancer recurrence. CONCLUSION: The duration of anti-HER2 blockage therapies, especially with trastuzumab, seems to improve survival of HER2-positive metastatic breast cancer patients who were not previously treated with adjuvant trastuzumab, regardless of other therapies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/mortalidad , Carcinoma Lobular/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Receptor ErbB-2/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Capecitabina , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/secundario , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Lapatinib , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Quinazolinas/administración & dosificación , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Trastuzumab , Adulto JovenRESUMEN
Chemotherapy regimens for early stage breast cancer have been tested by randomized clinical trials, and specified by evidence-based practice guidelines. However, little is known about the translation of trial results and guidelines to clinical practice. We extracted individual-level data on chemotherapy administration from the electronic medical records of Kaiser Permanente Northern California (KPNC), a pre-paid integrated healthcare system serving 29 % of the local population. We linked data to the California Cancer Registry, incorporating socio-demographic and tumor factors, and performed multivariable logistic regression analyses on the receipt of specific chemotherapy regimens. We identified 6,004 women diagnosed with Stage I-III breast cancer at KPNC during 2004-2007; 2,669 (44.5 %) received at least one chemotherapy infusion at KPNC within 12 months of diagnosis. Factors associated with receiving chemotherapy included <50 years of age [odds ratio (OR) 2.27, 95 % confidence interval (CI) 1.81-2.86], tumor >2 cm (OR 2.14, 95 % CI 1.75-2.61), involved lymph nodes (OR 11.3, 95 % CI 9.29-13.6), hormone receptor-negative (OR 6.94, 95 % CI 4.89-9.86), Her2/neu-positive (OR 2.71, 95 % CI 2.10-3.51), or high grade (OR 3.53, 95 % CI 2.77-4.49) tumors; comorbidities associated inversely with chemotherapy use [heart disease for anthracyclines (OR 0.24, 95 % CI 0.14-0.41), neuropathy for taxanes (OR 0.45, 95 % CI 0.22-0.89)]. Relative to high-socioeconomic status (SES) non-Hispanic Whites, we observed less anthracycline and taxane use by SES non-Hispanic Whites (OR 0.63, 95 % CI 0.49-0.82) and American Indians (OR 0.23, 95 % CI 0.06-0.93), and more anthracycline use by high-SES Asians/Pacific Islanders (OR 1.72, 95 % CI 1.02-2.90). In this equal-access healthcare system, chemotherapy use followed practice guidelines, but varied by race and socio-demographic factors. These findings may inform efforts to optimize quality in breast cancer care.
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Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Lobular/tratamiento farmacológico , Adulto , Anciano , Antraciclinas/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , California/epidemiología , Carcinoma Ductal de Mama/epidemiología , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/epidemiología , Carcinoma Lobular/secundario , Quimioterapia Adyuvante/estadística & datos numéricos , Registros Electrónicos de Salud , Femenino , Personal de Salud , Humanos , Modelos Logísticos , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Guías de Práctica Clínica como Asunto , Taxoides/uso terapéutico , Carga TumoralRESUMEN
Neoadjuvant chemotherapy has become the standard of care for locally advanced primary breast cancer. Anthracycline-based regimens have proven to be one of the most effective treatments in this setting. As certain cytotoxic antineoplastic agents, such as anthracyclines, generate reactive oxygen species as a by-product of their mechanism of action, we examined whether redox protein expression was involved in the response to anthracycline-based chemotherapy and with clinical outcome. Pre-treatment needle core biopsy and post-anthracycline treatment tumour sections were analysed from 98 cases. In all, 32 individuals had a complete clinical response and 17 had a complete pathological response. Immunohistochemical staining was performed for eight redox proteins: thioredoxin, thioredoxin reductase, thioredoxin interacting protein (TxNIP), glutathione S-transferase (GST) π, θ and α, catalase and manganese superoxide dismutase. GST π (P=0.05) and catalase (P=0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP (P=0.017) and thioredoxin reductase (P=0.022) were independent prognostic factors for distant metastasis-free survival and TxNIP for overall survival (P=0.014). In oestrogen receptor negative patients that are known to have a poor overall survival, a considerably worse prognosis was seen in cases that exhibited low expression of TxNIP (P=0.000003), stratifying patients into more defined groups. This study indicates the importance of redox regulation in determining breast cancer response to anthracycline-based chemotherapy and provides ways of further stratifying pre-chemotherapy patients to potentially allow more tailored treatments.
Asunto(s)
Antraciclinas/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/diagnóstico , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/secundario , Adulto , Biomarcadores de Tumor/metabolismo , Biopsia con Aguja Gruesa , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/metabolismo , Quimioterapia Adyuvante , Enzimas/metabolismo , Femenino , Humanos , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Metástasis Linfática , Mastectomía , Persona de Mediana Edad , Oxidación-Reducción , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: In breast cancer surgery, intraoperative frozen section (FS) analysis of sentinel lymph nodes (SLNs) enables axillary lymph node dissection (ALND) during the same operative procedure. In case of discordance between a "negative" FS analysis and definitive histology, an ALND as a second operation is advocated since additional lymph node metastases may be present. The clinical implications of the subsequent ALND in these patients were evaluated. MATERIALS AND METHODS: Between November 2000 and May 2008, 879 consecutive breast cancer patients underwent surgery including sentinel lymph node biopsy (SLNB) with intraoperative FS analysis of 2 central cuts from axillary SLNs. Following fixation and serial sectioning, SLNs were further examined postoperatively with hematoxylin and eosin (H&E) and immunohistochemical techniques. For patients with a discordant FS examination, the effect of the pathology findings of the subsequent ALND specimen on subsequent nonsurgical therapy were evaluated. RESULTS: FS analysis detected axillary metastases in the SLN(s) in 200 patients (23%), while the definitive pathology examination detected metastases in SLNs in another 151 patients (17%). A complementary ALND was performed in 108 of the 151 patients with discordant FS. Additional tumor positive axillary lymph nodes were found in 17 patients (16%), leading to "upstaging" in 7 (6%). Subsequent nonsurgical treatment was adjusted in 4 patients (4%): all 4 had more extensive locoregional radiotherapy; no patient received additional hormonal and/or chemotherapy. CONCLUSION: Discordance between intraoperative FS analysis and definitive histology of SLNs is common. In this selection of patients, a substantial proportion had additional lymph node metastases, but postsurgical treatment was rarely adjusted based on the findings of the complementary ALND.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Secciones por Congelación/normas , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Axila , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/secundario , Carcinoma Lobular/cirugía , Femenino , Estudios de Seguimiento , Humanos , Periodo Intraoperatorio , Ganglios Linfáticos/cirugía , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios ProspectivosRESUMEN
Gastrointestinal metastases are rare. May occur years after initial diagnosis and its symptoms are nonspecific, delaying its correct diagnosis and aggravating its prognosis. The most common histological subtype is lobular breast carcinoma. We present a 75-year-old woman with history of left mastectomy six years ago by infiltrating lobular carcinoma. She was treated with tamoxifen for five years. At present, there was no evidence of disease. She attended the hospital for intestinal subocclusion, being admitted for study. A barium enema revealed multiple strictures of the large bowel and a colonoscopy revealed an impassable stricture in the rectum-sigma. Due to the severity of symptoms, underwent total colectomy. The suspected diagnosis was Crohn's disease. The surgical specimen showed multiple stenosis of the light, with thickened wall and mucosa with granulations. Microscopic examination showed transmural infiltration of colonic wall by malignant cells CK7 positive and ER positive. Breast infiltrating lobular carcinoma has more special tendency to affect the digestive tract, even many years after the diagnosis of the primary tumor. In front of a patient with history of breast cancer and gastrointestinal symptoms, its mandatory to consider gastrointestinal metastases, making differential diagnosis with inflammatory bowel disease, infections or primary tumors, as the therapeutic actions are different.
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Neoplasias de la Mama/patología , Carcinoma Lobular/secundario , Neoplasias del Colon/secundario , Obstrucción Intestinal/etiología , Anciano , Femenino , HumanosRESUMEN
This study evaluated whether doxorubicin and cyclophosphamide are superior to cyclophosphamide, methotrexate and 5-fluorouracil as adjuvant chemotherapy in breast cancer patients. Between July 1976 and December 2004, 1045 breast cancer patients received adjuvant chemotherapy at the Radiotherapy Unit of the University of florence. 927 were administered i.v. CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2) and 5-fluorouracil 600 mg/m(2) on days 1 and 8, repeated every 28 days for a total of six cycles) and 118 i.v. DC (doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) on day 1 repeated every 21 days for a total of four cycles). All patients underwent adjuvant radiotherapy as well. The survival analysis, stratified according to treatment, did not show any significant difference in metastasis occurrence between the two groups (log rank test p=0.42). According to multivariate analysis four parameters emerged as independent prognostic factors for distant metastases in patients treated with the Cmf regimen: pt (p=0.0005), number of positive axillary lymph nodes (p=<0.0001), tamoxifen use (p=0.0109) and local relapses (p=<0.0001). Only number of positive axillary lymph nodes and local relapses were significant predictors of metastases occurrence according to multivariate analysis in the DC group, 17 and p=0.028, respectively. No significant difference between the two regimens was observed with regards to number of involved nodes. DC and CMF produced similar outcome in breast cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Lobular/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/mortalidad , Carcinoma Lobular/secundario , Quimioterapia Adyuvante , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/uso terapéutico , Humanos , Metástasis Linfática , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: High expression of total HER2 protein confers poor prognosis for breast cancer patients. HER2 is a member of the HER family consisting of four receptors, HER1 to HER4. HER receptor activity is regulated by a variety of mechanisms, and phosphorylation of the C-terminal part of the HER receptors is a marker for active signaling. The importance of phosphorylation and thereby activation of the HER1 to HER4 receptors, however, has not been investigated concomitantly in breast tumors. In the present study we examined the importance of active HER signaling in breast tumor biopsies and paired metastases, by evaluating the expression of phosphorylated HER1, HER2, HER3, Erk, Akt and the total level of HER4 and HER2. METHODS: Immunohistochemical analysis was performed on 268 primary breast tumors and 30 paired metastatic lesions from postmenopausal women with hormone receptor-positive breast tumors, who had received adjuvant tamoxifen therapy. The observed protein expression levels were analyzed for co-expression, for correlation to clinicopathological parameters and for prognostic value in relation to disease-free survival and overall survival. Lastly, the difference between protein levels in primary tumors versus metastasis was evaluated. RESULTS: In the primary tumors, 8%, 18%, 14% and 15% of cases were scored positive for total HER2, pHER1, pHER2 and pHER3 expression, respectively. HER4 was expressed with strong intensity in 68% and at moderate intensity in 29% of cases. The activated forms of Akt and Erk were quite uniformly expressed in the categories; negative, moderate or strong. In univariate analysis, expression of total HER2, pHER1, pHER2 and pHER3 was significantly associated with poor disease-free survival. Strong HER4 expression was associated with prolonged disease-free as well as with overall survival. Expression of pAkt and pErk was not correlated with survival. In multivariate analysis, pHER2 expression was clearly an independent marker for poor disease-free survival and overall survival when tested against tumor size, tumor grade, nodal status and HER2. Lastly, comparison of HER receptor expression in metastatic versus primary tumors showed a significant increase in expression of pHER1 and pHER3 in the metastases. CONCLUSIONS: In hormone receptor-positive breast cancer, determination of pHER2 yields additional prognostic information about poor prognosis compared with the current clinical standard for measuring HER2.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Tirosina/metabolismo , Anciano , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/secundario , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/mortalidad , Carcinoma Intraductal no Infiltrante/secundario , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidad , Carcinoma Lobular/secundario , Receptores ErbB/metabolismo , Femenino , Humanos , Técnicas para Inmunoenzimas , Hibridación Fluorescente in Situ , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Estadificación de Neoplasias , Fosforilación , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-3/metabolismo , Receptor ErbB-4 , Estudios Retrospectivos , Tasa de Supervivencia , Análisis de Matrices TisularesRESUMEN
BACKGROUND: Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. METHODS: After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. RESULTS: Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. CONCLUSIONS: Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.
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Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Paclitaxel/uso terapéutico , Adulto , Anciano , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/química , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/secundario , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Esquema de Medicación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Infusiones Intravenosas , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this study was to evaluate the efficacy and safety of neoadjuvant chemotherapy with infusional 5-fluorouracil (5-FU), adriamycin and cyclophosphamide (iFAC) in locally advanced breast cancer (LABC). PATIENTS AND METHODS: Eighty-two LABC patients were treated with neoadjuvant iFAC chemotherapy including infusional 5-FU (1000 mg/m2, continuous intravenous infusion, days 1-3), adriamycin (40 mg/m2, intravenous bolus, day 1) and cyclophosphamide (600 mg/m2, intravenous bolus, day 1) every 3 weeks until maximum tumor response. Patients subsequently received surgery, adjuvant chemotherapy, radiotherapy and hormonal therapy as appropriate. RESULTS: Downstaging occurred in 71 of the 82 patients (86.6%). Seventy-two patients (67 patients with downstaging and five patients without downstaging) were resectable (resectability rate, 87.8%). The clinical response rate was 84.2%, with a complete response (CR) rate of 17.1% and a pathological CR rate of 7.8%. During 891 cycles of chemotherapy, the most common grade 3/4 hematological toxicity was leukopenia (36.0%). There were no treatment-related deaths. The median follow-up period was 51 months, with a median overall survival (OS) of 66 months, and a 5 year OS rate of 50.9% for all patients. The 5 year OS and disease-free survival (DFS) rates of the 64 patients who underwent surgery were 55.8% and 44.7%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy with iFAC had a comparable response rate and DFS to the conventional bolus FAC regimen, with an acceptable toxicity in LABC using the AJCC 2002 staging system. An early response to neoadjuvant iFAC was a favorable prognostic factor.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/radioterapia , Carcinoma Lobular/secundario , Carcinoma Lobular/cirugía , Quimioterapia Adyuvante , Terapia Combinada , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intravenosas , Dosis Máxima Tolerada , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Dosificación Radioterapéutica , Tasa de SupervivenciaRESUMEN
The role of plasma oxidant-antioxidant status in survival after breast cancer surgery was investigated in a cohort of patients (n = 363) hospitalized in Southern France between 1989 and 1992. The median follow-up was 8 years after surgery for histologically confirmed breast cancer. Plasma analyses were performed after diagnosis and before surgery and adjuvant therapy. We found an inverse relationship between plasma lipoperoxides (MDA) and tumor size at diagnosis, together with higher lipoperoxide levels in node-negative tumors than in node-positive ones (TNM). The longitudinal approach revealed an increased risk of recurrence for patients with plasma lipoperoxides in the highest tertile of the sample (RR = 2.1, 95% CI 1.1-4.0). In addition, the risk of recurrence increased (RR = 1.7, 95%CI 1.0-3.0), after adjustment for the known prognostic factors (TNM), for patients with plasma lipid-adjusted vitamin E levels of over 22 micromol/l. The risk of breast cancer death was twice as great for patients with plasma lipid-adjusted vitamin E levels above this value. Excesses of plasma lipoperoxides and vitamin E appear to be factors in poor prognosis for breast cancer-specific survival (OVS) and disease-free survival (DFS), respectively, independent of tumor characteristics at diagnosis. Several hypotheses are advanced to explain the possible role of plasma vitamin E as a factor in poor prognosis for survival.
Asunto(s)
Antioxidantes/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Lobular/metabolismo , Oxidantes/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Neoplasias de la Mama/secundario , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/epidemiología , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/cirugía , Carcinoma Intraductal no Infiltrante/epidemiología , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Lobular/epidemiología , Carcinoma Lobular/secundario , Carcinoma Lobular/cirugía , Colesterol/sangre , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Peróxidos Lipídicos/sangre , Estudios Longitudinales , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Receptores de Estrógenos/metabolismo , Tasa de SupervivenciaAsunto(s)
Neoplasias Óseas/terapia , Neoplasias de la Mama/terapia , Carcinoma Lobular/terapia , Terapias Complementarias , Terapia Nutricional , Oncología por Radiación , Neoplasias Óseas/secundario , Carcinoma Lobular/secundario , Prestación Integrada de Atención de Salud , Femenino , Humanos , Persona de Mediana Edad , Consejos de Especialidades , Estados UnidosRESUMEN
Breast cancer treatment has undergone significant changes in concept, concurrent with alterations in our understanding of cancer biology and natural history. Within the last 10 years, oncologists have brought into question the traditional Halstedian concepts of the natural history of breast cancer and its appropriate management. The goal of treatment, once a primary cancer is detected in the breast, is to prevent metastasis and subsequent death of the patient. One hundred forty-two female patients over the age of 65 with histologically confirmed breast cancer were treated at Lankenau Hospital from 1982 to 1990. We treated 32 women over the age of 65 with quadrantectomy and tamoxifen as the sole form of therapy. No radiation, standard chemotherapy, nor axillary dissection was utilized. A cohort of 110 women of similar age, treated for breast cancer with "standard therapy" (total mastectomy or "segmental resection" and radiation with axillary nodal dissection) during the same time period, were also analyzed retrospectively. All segmental resections were followed by standard radiation doses to the ipsilateral breast and draining nodal basins with a local boost. Twenty-nine of 32 patients in the quad + tam group were available for follow-up 1 to 8 years following treatment (mean 52 months). The cumulative overall survival was 67 per cent and disease-free survival 92 per cent. No patient developed local recurrence. Follow-up analysis of the 110 women treated in "standard fashion" was complete in 88 patients 1 to 8 years post-treatment (mean 56 months). Cumulative overall survival was 82 per cent and disease-free survival 83 per cent. Local recurrence was noted in five per cent.(ABSTRACT TRUNCATED AT 250 WORDS)