RESUMEN
BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, ß = 0.8) 379 events had to be observed in the bevacizumab arms. RESULTS: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. CONCLUSIONS: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. CLINICAL TRIAL NUMBER: NCT 00567554, www.clinicaltrials.gov.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Sirolimus/análogos & derivados , Adulto , Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab , Neoplasias de la Mama/metabolismo , Quimioterapia Adyuvante , Quimioterapia Combinada , Everolimus , Femenino , Humanos , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Sirolimus/administración & dosificación , Sirolimus/uso terapéutico , Análisis de SupervivenciaRESUMEN
PURPOSE: To assess the toxicity and efficacy of preoperative chemotherapy with doxorubicin and docetaxel in patients with primary operable breast cancer. PATIENTS AND METHODS: Forty-two patients with histologically confirmed primary breast cancer tumors of at least 2 cm in diameter received doxorubicin (50 mg/m(2) intravenously [IV] over 15 minutes) and docetaxel (75 mg/m(2) IV over 1 hour) every 14 (24 patients) or 21 (18 patients) days for four cycles. RESULTS: The median size of the primary tumor decreased significantly, from 4 cm (range, 2 to 10 cm) to 2 cm (range, 0 to 5 cm) on physical examination and from 3.4 cm (range, 1 to 8 cm) to 1. 8 cm (range, 0 to 4 cm) on sonography (P <.001). The overall response rate as assessed by physical examination was 93%, and complete remission of the primary tumor occurred in 33% of patients. The remission rate as assessed by sonographic measurement was 67%. Two patients (5%) had histologically confirmed complete responses. Sonography was more reliable than palpation in predicting histologically determined response. No grade 4 toxicity was noted, and grade 3 toxicity was reported with alopecia (95%), lethargy (17%), loss of appetite (10%), stomatitis (7%), leukopenia (5%), skin desquamation (5%), infection (5%), motor neuropathy (2%), and nausea (2%). The 3-week schedule was associated with less toxicity than the 2-week schedule. CONCLUSION: Preoperative combination chemotherapy with doxorubicin and docetaxel is highly effective and feasible in primary operable breast cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Taxoides , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante/métodos , Docetaxel , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/análogos & derivados , Estadísticas no ParamétricasRESUMEN
PURPOSE: To investigate the effect of adding tamoxifen to a preoperative dose-dense doxorubicin and docetaxel regimen on the pathologic response of primary operable breast cancer. PATIENTS AND METHODS: Patients (tumor size > or = 3 cm, N0 to 2, M0) were prospectively randomized to receive every 14 days a total of four cycles of doxorubicin 50 mg/m2 and docetaxel 75 mg/m(2), either with (ADocT) or without (ADoc) simultaneous tamoxifen. Granulocyte colony-stimulating factor (G-CSF) was routinely given on days 5 to 10. Surgery followed 8 to 10 weeks after the start of treatment. RESULTS: Within 14 months, 250 patients were included in the study at 56 centers. Of 992 planned cycles, 97.9% were administered. Pathologically complete remission (pCR) with no detectable viable tumor cells was achieved in 9.7%. There was a nonsignificant difference of -1.2% in favor of ADoc, with a 95% confidence interval of -8.6% to 6.2%. A further 2.4% had only noninvasive tumor residues, and 13.8% had focal invasive residues. Complete and partial responses detected by palpation were observed in 28.9% and 52.4%, respectively. The response rates (complete and partial) by best appropriate imaging methods were 77.5% and 67.5% for ADocT and ADoc, respectively. Breast conservation was possible in 68.8% of the patients. A tendency toward more frequent toxic events was observed with ADocT treatment. Significant predictors of pCR to chemotherapy were negative lymph node and negative estrogen receptor status. CONCLUSION: A dose-dense regimen of ADoc with G-CSF offers high compliance, moderate toxicity, and rapid efficacy as a form of preoperative chemotherapy in operable breast cancer. Concurrent treatment with tamoxifen for 8 weeks could not improve the pathologic response rate.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Taxoides , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/cirugía , Terapia Combinada , Docetaxel , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/análogos & derivados , Cooperación del Paciente , Cuidados Preoperatorios , Estudios Prospectivos , Tamoxifeno/administración & dosificación , Tamoxifeno/efectos adversosRESUMEN
In a multicentre trial, 78 patients with a variety of malignancies, who had experienced insufficient control of emesis (greater than or equal to 3 episodes within 24 hours) while receiving standard antiemetics during previous chemotherapy, were randomly assigned to receive tropisetron 5mg once daily for 5 days or conventional antiemetic drugs. No attempt was made to standardise the conventional antiemetic treatment, which was given according to the usual practice of the participating institutions. Emesis was evaluated by counting emetic episodes and nausea by asking the patients to record on a diary chart the duration and severity of the nausea. Emesis was much better controlled with tropisetron than with standard drugs, complete control during the first 24 hours being achieved in 42% and 8% of patients, respectively, (p less than 0.001). Nausea was of significantly shorter duration (6.9 vs 10.3 hours; p less than 0.01) and was less severe (p less than 0.005) in the tropisetron group. The patients' overall assessment of treatment outcome was markedly better for tropisetron than for the standard antiemetic therapy. The superior efficacy of tropisetron was especially marked during the first 24 hours. For delayed nausea, no significant difference between treatments was seen. No serious adverse effects were observed.
Asunto(s)
Antieméticos/uso terapéutico , Antineoplásicos/uso terapéutico , Indoles/uso terapéutico , Náusea/prevención & control , Vómitos/prevención & control , Adulto , Anciano , Antieméticos/efectos adversos , Antineoplásicos/efectos adversos , Femenino , Humanos , Indoles/efectos adversos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Neoplasias/tratamiento farmacológico , Tropisetrón , Vómitos/inducido químicamenteRESUMEN
A complex analysis of oncogene over-expression in ovarian cystadenocarcinomas of 20 patients was performed. Radioactively labelled cDNAs were synthesized from total cellular RNA from tumor cells and hybridized to dot blot filters. On each filter more than 20 different plasmids containing cloned oncogene fragments were immobilized. In concordance with published data fms was found over-expressed in 40% of the tumors. Elevated expression levels of the EGF receptor was also frequently detected. 35% of the tumors showed elevated N-ras mRNA levels. All those tumors' showed a highly dedifferentiated phenotype and were classified as G3-tumors. More over, simultaneous over-expression of different oncogenes correlated surprisingly strongly with tumor grading.
RESUMEN
Total genomic DNA obtained from 24 ovarian carcinomas was examined for genomic imbalances by comparative genomic hybridization (CGH). A varying number of gains and losses (1 up to 31) of specific chromosomal segments was detected per tumor. Chromosomal segments which were most often present in increased copy numbers were (in decreasing order): 1q21, 8q24, 8q23, 3q26, 12p12-p13, 20q, 7q31, and 7q33-qter. Loss of material was found most frequently at 16q12, 13q13-q14, Xq, 8p21-p22, 5q13-q14, and 5q21. All these chromosomal segments involved in gains and losses may carry gene loci playing a more or less causal role in the process of ovarian malignancies. Based on these findings CGH can be regarded as a valuable tool for rapid screening of genomic imbalances in human tumors.
RESUMEN
More than 60 breast cancer specimens were screened for their expression status of 25 different proto-oncogenes. The screening method is based on in vitro synthesis of a radioactive cDNA copied from the total cellular RNA of tumor tissue. This cDNA is hybridized to cloned oncogene probes which are immobilized to a GeneScreen membrane. Frequently multiple oncogenes were found expressed although expression levels were rather moderate. 25-30% of the analyzed tumors showed significant expression of either erbB, src, raf1, lck or H-ras. Although neu expression--an oncogene believed to be particular relevant as prognostic parameter for mamma carcinoma--was screened for most of the tumors with a heterologous gene probe, expression signals could be detected in about 20% cases. The only notable correlation with classical clinical parameters such as tumor size and proliferation stage, hormone receptor status and different DNA indices was the observation that tumors lacking the progesterone receptor frequently express multiple oncogenes. Advantages and limitations of the cDNA/dot-blot screening for oncogene expression are discussed.
Asunto(s)
Neoplasias de la Mama/genética , Oncogenes , Proto-Oncogenes , Animales , Neoplasias de la Mama/patología , Clonación Molecular , Femenino , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Immunoblotting , Proteínas Proto-Oncogénicas/análisis , ARN Neoplásico/genética , ARN Neoplásico/aislamiento & purificaciónRESUMEN
The international consensus conference from St. Gallen concerning the treatment of early breast cancer concluded in 2003, that sentinel node biopsy was now accepted as method allowing axillary staging in breast cancer. This procedure may avoid complete lymph node dissection in appropriate cases. Since numerous questions associated with the technique are still not defined and the procedure itself is not yet standardized, the German Society of Senology defined the conditions for the routine clinical use of sentinel node biopsy in an interdisciplinary consensus meeting.
Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela/normas , Femenino , Alemania , Humanos , Estadificación de Neoplasias/normas , Garantía de la Calidad de Atención de Salud , RadiografíaRESUMEN
Breast preservation has become an important option in the treatment of breast cancer patients. The selection of patients should be based upon history, actual clinical situation, mammographic and morphologic parameters. After careful evaluation of all those factors the surgical treatment and eventually an adjuvant postsurgical irradiation can be tailormade according to the associated individual risk-profile.
Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía Segmentaria/métodos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Metástasis Linfática , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapiaAsunto(s)
Neoplasias de la Mama/terapia , Neoplasias de los Genitales Femeninos/terapia , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Terapia Combinada , Femenino , Estudios de Seguimiento , Neoplasias de los Genitales Femeninos/mortalidad , Neoplasias de los Genitales Femeninos/patología , Humanos , Metástasis Linfática , Estadificación de Neoplasias , Tasa de SupervivenciaAsunto(s)
Histeroscopía , Leiomioma/tratamiento farmacológico , Premedicación , Pamoato de Triptorelina/administración & dosificación , Neoplasias Uterinas/tratamiento farmacológico , Adulto , Terapia Combinada , Femenino , Humanos , Histeroscopios , Leiomioma/cirugía , Persona de Mediana Edad , Neoplasias Uterinas/cirugíaAsunto(s)
Neoplasias de la Mama/cirugía , Mastectomía Segmentaria/métodos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
An unusual uterine tube anomaly in a 33-year old Nigerian woman is described. The ampullae of both uterine tubes completely lacked the muscular layer. The peritoneum was in direct contact with the tubal mucosa.
Asunto(s)
Trompas Uterinas/anomalías , Infertilidad Femenina/patología , Músculo Liso/anomalías , Adulto , Trompas Uterinas/patología , Femenino , Humanos , Músculo Liso/patologíaRESUMEN
Scanning electron microscopic examination of the myocardium in cardiomyopathies is a valuable complementary method beside light and transmissionelectron microscopy for the differential diagnosis of this rare disease. In two cases of congestive cardiomyopathy no marked alterations of the myocardial architecture could be found whereas in one case of nonobstructive hypertrophic cardiomyopathy myocardial cell alterations and structure disorders could be demonstrated in an almost stereologic view. The pathogenesis of heart failure in this disease was clearly shown. Similar changes were not observed in hearts without cardiomyopathy or in other forms of cardiac hypertrophy.
Asunto(s)
Cardiomiopatías/patología , Autopsia , Cardiomiopatías/diagnóstico , Diagnóstico Diferencial , Humanos , Microscopía Electrónica de Rastreo , Miocardio/patologíaRESUMEN
In 124 patients suffering from a local recurrence after primary treatment of a breast cancer the course of disease was checked in a retrospective manner. This particular study points out the dependence of the clinical outcome on morphological indicators. The results show that local recurrence is mostly accompanied by a generalisation of the disease and on the whole by a poor prognosis. After five years only 29% of the patients with local recurrence are still alive. Of the morphological indicators the lymphatic carcinomatosis is the most important factor related with poor prognosis. Infiltration of the pectoralis muscle has no influence on the further course. Only in few cases breast tissue that has been left after the first surgical therapy can be regarded as the starting point of a local recurrence. To avoid a further local recurrence the excision with clear tumour margins is necessary. If an incomplete removal has been carried out or in cases of narrow resection margins one has to reckon with new local recurrencies in half of all cases despite adjunctive radiotherapy. The results suggest that in cases of local recurrence beside the local treatment systemic therapy with hormones or chemotherapy might be important.
Asunto(s)
Neoplasias de la Mama/patología , Mama/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de la Mama/cirugía , Carcinoma/patología , Carcinoma in Situ/patología , Carcinoma Intraductal no Infiltrante/patología , Terapia Combinada , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Músculos Pectorales/patología , PronósticoRESUMEN
This retrospective investigation comprises a follow-up observation of 51 patients with borderline tumours of the ovaries, who had been treated at the Department of Gynaecology of the University of Erlangen between January 1st 1966 and December 31st 1986. The average age was approx. ten years younger that of patients with invasive carcinomas and 65% of the patients were in stage I. For women in stage Ia desiring children, unilateral adnexectomy is sufficient in the context of meticulous staging laparotomy. The remaining ovary should be further exposed by wedge excision. Once the family is complete, hysterectomy and adnexectomy should then be carried out retrospectively in view of the high risk of bilaterality. In ovarian tumours of borderline malignancy stages II and III, the surgical therapy should correspond to the procedure for invasive carcinomas, with the objective of postoperative freedom from tumour. Lymphonodectomy is not obligatory in view of the very rare involvement of lymph nodes. The question as to the necessity of adjuvant therapy is still open. Our observations indicate, that combination chemotherapy, containing cisplatinum is effective as adjuvant therapy in advanced stages as well as in recurrences, which cannot be completely resected surgically. 18% of our patients with borderline tumours suffered a recurrence or tumour progression, in consequence of which five died (10%). The recurrences were manifested clinically after 33 months at the earliest, and after 164 months at the latest, so that the follow-up in these patients should extend over a period of more than ten years.
Asunto(s)
Neoplasias Ováricas/cirugía , Lesiones Precancerosas/cirugía , Adenocarcinoma Mucinoso/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Endometriosis/cirugía , Femenino , Estudios de Seguimiento , Alemania Occidental/epidemiología , Humanos , Mesonefroma/cirugía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Lesiones Precancerosas/mortalidad , Lesiones Precancerosas/patología , Tasa de SupervivenciaRESUMEN
We report on two young patients with massively elevated CA-125 serum level of 290 and 264 U/ml respectively, who clinically exhibited suddenly occurring ascites. The diagnosis of ovarian carcinoma or ruptured ovarian cystoma led to a laparotomy. During the operation, a disseminating granulomatous inflammation was evident, which was identified histologically and microbiologically as miliary tuberculosis with peritoneal invasion. CA-125 was immunohistochemically localised, sharply demarcated around the tuberculous granuloma. A possible explanation for this finding is the inflammatory mesothelial proliferation. A similarity in antigenic structures of membrane components of M. tuberculosis and CA-125 cannot be excluded. Serum CA-125 levels tested 6 months after the treatment of the tuberculosis showed a value within the normal range (less than 35 U/ml).
Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores/análisis , Peritonitis Tuberculosa/diagnóstico , Adolescente , Ascitis/patología , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Neoplasias Ováricas/diagnóstico , Peritoneo/patología , Peritonitis Tuberculosa/patologíaRESUMEN
BACKGROUND AND METHODS: The clinical staging system of cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) entails a large measure of subjectivity. This study analyzed the results of 1028 patients with cervical cancer at three reference centers. All patients had radical surgery, and all surgical specimens were processed as histologic giant sections with precise volumetry of the tumor. RESULTS: The interpretation of the histologic findings of parametrial invasion, vascular involvement, and lymph node involvement was found to differ somewhat among the three centers. However, all these findings were associated with tumor size. Survival rates correlated more consistently with tumor volume than with clinical or histologic stage. Five-year survival rates ranged from 91% for patients with tumors smaller than 2.5 cm3 to 70% for those with tumors 10-50 cm3. The 5-year survival rate of 24 patients with tumors larger than 50 cm3 (71% of whom had lymph nodes with positive findings) was 48%. Survival rates were identical among the three centers for patients with tumors smaller than 10 cm3, despite different degrees of surgical radicality. In contrast, more radical surgery was associated with significantly better survival rates in patients with larger tumors. CONCLUSIONS: The results of this study indicate that volumetry of the tumor permits a more accurate assessment of therapeutic results in patients with cervical cancer than does the FIGO classification. Pretherapeutic assessment of tumor volume is possible with magnetic resonance imaging. It seems that maximum parametrial resection is not necessary for patients with smaller tumors (smaller than 10 cm3), but truly radical surgery in patients with bulky tumors achieves better results than those usually expected in Stage IIb cervical cancer and at least comparable to those of radiation therapy.
Asunto(s)
Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Adulto , Femenino , Humanos , Histerectomía , Escisión del Ganglio Linfático , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de SupervivenciaRESUMEN
Twenty-eight small breast cancers and 17 other breast cancer specimens from which appropriate semi-thin sections had been prepared were examined by electron microscopy and special staining techniques for alterations in the basement membranes and the basal lamina. In each case disruptions of the basement membranes were invariably observed at the point of initial invasion. Two types of invasion were noted: (1) bud-like protrusions of intraduct cancer with disruption of the basement membranes at the point of invasion; (2) extensive basement membrane defects with single cancer cell invasion. Our study confirms that invasive breast cancer originates in intraductal or lobular carcinoma in situ.
Asunto(s)
Membrana Basal/ultraestructura , Neoplasias de la Mama/ultraestructura , Carcinoma in Situ/ultraestructura , Carcinoma Intraductal no Infiltrante/ultraestructura , Femenino , Humanos , Microscopía Electrónica , Invasividad NeoplásicaRESUMEN
The case of a 66-year-old female with chronic skin lesions is described, which clinically resembled parakeratosis variegata but histologically showed the pattern of "pagetoid reticulosis" (Woringer-Kolopp). The intraepidermal pagetoid cells were lymphoid cells which, by electron microscopy, could be identified as small Sézary cells. The intraepidermal presence of numerous atypical reticulum cells does not support the theory of "pagetoid reticulosis" as a separate nosological entity, but rather stresses the epidermotropic character of (pre-)mycosis fungoides just known from intraepidermal Pautrier microabscesses.