Search PubMed⌕ Search

Biomedical subjects

E Marubini

Publications and source records attributed to E Marubini.

At least 19 recordsLinked to original sources
PubMed2006

Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer.

PURPOSE: The synthetic retinoid fenretinide administered for 5 years for prevention of second breast cancer showed no difference after a median of 8 years, but a possible reduction in premenopausal women. We conducted a long-term analysis in a subgroup of women who were regularly followed up in a single center. PATIENTS AND METHODS: We analyzed data after a median follow-up of 14.6 years (IQ range, 12.3-16.3 years) from 1739 women aged 30-70 (872 in the fenretinide arm and 867 in the observation arm), representing 60% of the initial cohort of 2867 women. The main efficacy endpoint was second primary breast cancer (contralateral or ipsilateral). RESULTS: The number of second breast cancers was 168 in the fenretinide arm and 190 in the control arm (hazard ratio = 0.83, 95% CI, 0.67-1.03). There were 83 events in the fenretinide arm and 126 in the observation arm in premenopausal women (HR = 0.62, 95% CI, 0.46-0.83), and 85 and 64 events in postmenopausal women (HR = 1.23, 95% CI, 0.63-2.40). The younger were the women, the greater was the risk reduction associated with fenretinide, which attained 50% in women aged 40 years or younger and disappeared after age 55 (P-age*treatment interaction = 0.023). There was no difference in cancers in other organs, distant metastases or survival. CONCLUSIONS: Fenretinide induces a significant risk reduction of second breast cancer in premenopausal women, which is remarkable at younger ages, and persists several years after treatment cessation. Since adverse events are limited, a trial in young women at high-risk is warranted.

Adult↗
PubMed2003

Vascular endothelial growth factor in node-positive breast cancer patients treated with adjuvant tamoxifen.

In 212 postmenopausal women with node-positive oestrogen receptor-positive (ER(LBA)) breast cancer subjected to radical surgery and adjuvant tamoxifen, the risk of 6-year relapse increased with increasing values of intratumoral vascular endothelial growth factor (VEGF) in patients whose tumours had a low/intermediate ER(LBA) content compared to patients with high-ER(LBA) tumours. These findings indicate that tumour progression, activated or sustained by high VEGF levels, may be counteracted in high-ER(LBA) cancers by tamoxifen, which in contrast fails to contrast the metastatic potential in low-ER(LBA) tumours.

Aged↗
PubMed2003

Prognosis in node-negative primary breast cancer: a neural network analysis of risk profiles using routinely assessed factors.

BACKGROUND: The present study investigated complex time-dependent effects of routinely assessed factors on the risk of breast cancer recurrence over follow-up time, with a partial logistic artificial neural network (PLANN) model. PATIENTS AND METHODS: PLANN was applied to data from 1793 patients with node-negative breast cancer, not submitted to any adjuvant treatment and with a minimal potential follow-up of 10 years. RESULTS: The shape of the hazard function changed according to histology, which showed a time-dependent effect, partly modulated by estrogen receptors (ERs). Age and progesterone receptors (PgR) showed protective effects; the latter was more evident for short follow-up and high ER values. Tumour size and ER content showed time-dependent unfavourable effects at early and long follow-up times, respectively. Predicted values of disease recurrence probability at 2 years of follow-up showed that low steroid-receptor content, young age and large tumour size were associated with the highest risk of relapse. Although the oldest patients with high ER content seem to be those most protected overall, high risk predictions tend to spread also to higher steroid-receptor contents, intermediate ages and small tumour size, with an increase in follow-up time. CONCLUSION: PLANN with suitable visualisation techniques provided thorough insights into the dynamics of breast cancer recurrence for improving individual risk staging of node-negative breast cancer patients.

Breast Neoplasms↗
PubMed2002

Prognostic role of serum CA15.3 in 362 node-negative breast cancers. An old player for a new game.

The aims of the present investigation were to evaluate the association between serum CA15.3 levels and other biological and clinical variables and its prognostic role in patients with node-negative breast cancer. We evaluated 362 patients operated upon primary breast cancer from 1982 to 1992 (median follow-up 69 months). Serum CA15.3 was measured by an immunoradiometric assay. The association between variables was investigated by a Principal Component Analysis (PCA) and the prognostic role of CA15.3 on relapse-free survival (RFS) was investigated by Cox regression models adjusting for age, oestrogen receptor (ER), tumour stage, and ER x age interaction, with both the likelihood ratio test and Harrell's c statistic. The prognostic contribution of CA 15.3 was highly significant. Log relative hazard of relapse was constant until approximately 10 (U/ml) of CA15.3 and increased thereafter with increasing marker levels. CA15.3 showed a significant contribution using as a cut-off point a value of 31 U/ml. However, the contribution to the model of the marker as a continuous variable is much greater. From these findings, we can conclude that: (i) CA15.3 is a prognostic marker in node-negative breast cancer; (ii) its relationship with prognosis is continuous, with the risk of relapse increasing progressively from approximately 10 U/ml.

Aged↗
PubMed2001

Modelling cause-specific hazards with radial basis function artificial neural networks: application to 2233 breast cancer patients.

The clinical course of a disease is often characterized by the possible occurrence of different types of events acting in a competing way. From a statistical point of view this translates into the need of modelling the dependence of cause-specific hazards as a function of covariates. Generalized linear models with Poisson error have previously been adopted for the analysis of competing risks as a function of discrete covariates. In the present paper an artificial neural network extension for the flexible joint estimation of cause-specific hazards depending on both discrete and continuous covariates is proposed. This approach is based on radial basis function networks which have the advantage of allowing parameter estimation by the adoption of standard software for generalized linear models. We have applied this method to data from 2233 breast cancer patients to investigate the effects of age, tumour size, number of metastatic axillary nodes, histology and tumour site on cause-specific hazards for intra-breast tumour recurrences and distant metastases. The adoption of a radial basis function network made it possible to highlight effects that were not considered by previous analyses of the same data.

Adult↗
PubMed2001

Safety of the synthetic retinoid fenretinide: long-term results from a controlled clinical trial for the prevention of contralateral breast cancer.

PURPOSE: To describe the pattern of occurrence of adverse events commonly arising during treatment with fenretinide, a synthetic retinoid under investigation for cancer prevention. PATIENTS AND METHODS: The series includes 2,867 women accrued in a trial aimed at assessing the effect of fenretinide on the prevention of second breast malignancy. Women were randomly assigned to receive no treatment (1,435 patients) or 5-year fenretinide treatment (1,432 patients). In terms of disease recurrence in the breast, the trial showed a possible beneficial effect of the compound in premenopausal women, and an opposite trend in postmenopausal women. End points considered for safety assessment were the occurrence of diminished dark adaptation, dermatologic disorders, gastrointestinal symptoms, disorders of the ocular surface, and abnormal laboratory values. RESULTS: The most common adverse events were diminished dark adaptation (cumulative incidence, 19.0%) and dermatologic disorders (18.6%). Less common events were gastrointestinal symptoms (13.0%) and disorders of the ocular surface (10.9%). In comparison, incidence figures in the control arm were 2.9% for diminished dark adaptation, 2.9% for dermatologic disorders, 5.4% for gastrointestinal symptoms, and 3.2% for disorders of the ocular surface. Symptoms occurring during fenretinide treatment tended to recover with time. No between-group difference was observed for the occurrence of laboratory data abnormalities. Overall, 63 (4.4%) treatment discontinuations were caused by adverse events. CONCLUSION: Given the number of patients involved in the study and the prolonged intake of the drug, the experience on fenretinide tolerability can be considered sufficiently reassuring to justify further testing of the retinoid.

Administration, Oral↗
PubMed2001

Response to cyclophosphamide, methotrexate, and fluorouracil in lymph node-positive breast cancer according to HER2 overexpression and other tumor biologic variables.

PURPOSE: There is considerable interest in biologic markers able to predict the response of cancer patients to therapy. HER2 overexpression is a potential indicator of responsiveness to doxorubicin and paclitaxel and of unresponsiveness to tamoxifen in breast carcinoma patients. However, the significance of HER2 overexpression in responsiveness to cyclophosphamide, methotrexate, and fluorouracil (CMF) has remained unclear. In this study, we investigated this issue in the 386 breast cancer patients in the first CMF controlled clinical trial with a 20-year follow-up. PATIENTS AND METHODS: Node-positive breast carcinoma patients were randomly assigned to receive either no further treatment after radical mastectomy (179 women) or 12 monthly cycles of adjuvant CMF chemotherapy (207 women). Overexpression of HER2 and the status of other tumor variables was assessed by immunohistochemistry in at least 324 (84%) of the 386 patients. Statistical analyses were performed to assess the efficacy of CMF treatment for the subgroups defined by HER2 and the status of other variables using a Bayesian approach. The end points considered were relapse-free survival (RFS) and cause-specific survival (CSS). RESULTS: Bayesian analysis of the treatment effect for HER2 and other variables indicated a clinical benefit from CMF treatment in all subgroups defined according to variables status. In particular regarding HER2 status, Bayesian estimates of RFS hazard ratios were equal to 0.484 and 0.641 and estimates of CSS hazard ratios were equal to 0.495 and 0.730 for HER2-positive and -negative tumors, respectively. CONCLUSION: CMF treatment showed a clinical benefit in the considered subgroups, defined according to HER2 and other tumor variables status. Patients with HER2-positive or HER2-negative tumors benefit from CMF treatment, and the poor prognosis associated with the HER2 overexpression in the untreated group could be completely overcome by the chemotherapy treatment.

Aged↗
PubMed2001

Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study.

PURPOSE: Because interferon gave promising results in the management of metastatic renal cell carcinoma in the 1980s, a multicentric randomized controlled trial was planned to compare adjuvant recombinant interferon alfa-2b (rIFNalpha2b) with observation after radical nephrectomy in patients with Robson stages II and III renal cell carcinoma. Overall and event-free survival were to be evaluated together with prognostic factors. PATIENTS AND METHODS: Overall and event-free survival curves for 247 patients (124 controls and 123 treated) were estimated by the Kaplan-Meier method and compared using the log-rank test. Cox's multiple regression models were adopted to perform a joint analysis of treatment and prognostic factors. RESULTS: The 5-year overall and event-free survival probabilities were 0.665 and 0.671, respectively, for controls and 0.660 and 0.567, respectively, for the treated group; the differences were not statistically significant (2P = .861 for overall and 2P = .107 for event-free survival with the log-rank test). Regarding prognostic factors, only grade, pT, and pN demonstrated a significant prognostic role. First-order interactions of treatment with pT and pN category were investigated; a significant interaction was found between pN and treatment. A harmful effect of rIFNalpha2b in the 97 treated pN0 patients and a protective effect in the 13 treated pN2/pN3 patients were statistically significant. CONCLUSION: Adjuvant rIFNalpha2b is not indicated after radical nephrectomy for renal cell carcinoma. The protective effect in the small group of pN2/pN3 patients requires further investigation.

Adult↗
PubMed2001

Ticlopidine versus aspirin after myocardial infarction (STAMI) trial.

OBJECTIVES: We sought to compare the efficacy of aspirin and ticlopidine in survivors of acute myocardial infarction (AMI) treated with thrombolysis. BACKGROUND: The role of ticlopidine in secondary prevention after AMI has not yet been explored. METHODS: Of 4,696 patients with AMI treated with thrombolysis who were screened, 261 died in the hospital (5.6%) and 1,470 were enrolled in this randomized, double-blind, multicenter trial and allocated to treatment with either aspirin (160 mg/day) or ticlopidine (500 mg/day). The most frequent reasons for exclusion were refusal to give informed consent, planned myocardial revascularization, risk of noncompliance with study procedures, need for anticoagulant therapy and contraindications to the study treatments. The primary end point was the first occurrence of any of the following events during the six-month follow-up: fatal and nonfatal AMI, fatal and nonfatal stroke, angina with objective evidence of myocardial ischemia, vascular death or death due to any other cause. RESULTS: The primary end point was recorded in 59 (8.0%) of the 736 aspirin-treated and 59 (8.0%) of the 734 ticlopidine-treated patients (p = 0.966). Vascular death was the first event in five patients taking aspirin and in six patients taking ticlopidine (0.7% vs. 0.8%; p = NS); nonfatal AMI in 18 and 8 (2.4% vs. 1.1%; p = 0.049); nonfatal stroke in 3 and 4 (0.4% vs. 0.5%; p = NS); and angina in 33 and 40 (4.5% vs. 5.4%; p = NS), respectively. The frequency of adverse reactions was not significantly different between the two groups. CONCLUSIONS: No difference was found between the ticlopidine and aspirin groups in the rate of the primary combined end point of death, recurrent AMI, stroke and angina.

Adult↗
PubMed2001

Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial.

BACKGROUND: Breast-conserving surgery followed by radiotherapy is a widely accepted form of treatment in patients with breast cancer of limited extent. Many attempts have been made to identify subgroups of patients who might avoid radiotherapy. PATIENTS AND METHODS: Between 1987 and 1989, 579 women with carcinoma of the breast were randomly assigned to quadrantectomy, axillary dissection and radiotherapy (299) and to quadrantectomy with axillary dissection without radiotherapy (280). Eligible patients were women with a breast carcinoma less than 2.5 cm in maximum diameter up to 70 years of age. Primary endpoints were intra-breast tumour reappearance (IBTR) and all-cause mortality. RESULTS: The number of IBTRs was significantly higher in patients treated with surgery alone (59 cases out of 273; 10-year crude cumulative incidence of 23.5%) than in patients treated with surgery plus radiotherapy (16 cases out of 294; 10-year crude cumulative incidence of 5.8%). The difference in IBTR frequency between the two treatments appeared to be particularly high in women up to 45 years of age, tending to decrease with increasing age up to no apparent difference in women older than 65 years. Overall survival curves for the two groups, did not differ significantly (P = 0.326). However, a limited survival advantage was evident after radiotherapy for node-positive women. CONCLUSIONS: After breast-conserving surgery radiotherapy appears indicated in all patients up to 55 years of age, in patients with positive axillary nodes, and in patients with extensive intraductal component at histology. The data suggest that radiotherapy may be avoided in patients older than 65, and may be optional in women aged 56-65 years with negative nodes.

Adult↗
PubMed2000

Time-dependent relevance of steroid receptors in breast cancer.

PURPOSE: To analyze the time-dependent prognostic role of the investigated variables, considered, when appropriate, on a continuous scale, for the purpose of evaluating and describing the interrelationships between clinically relevant patient and tumor characteristics (age, size and histology, and estrogen receptor [ER] and progesterone receptor content) and the risk of new disease manifestation. PATIENTS AND METHODS: We applied a flexible statistical model to a case series of 1,793 patients with axillary lymph node-negative breast cancer with a minimal potential follow-up of 10 years. To avoid a potential confounding effect of adjuvant treatment, only patients given local-regional therapy until relapse were considered. RESULTS: ER content and tumor size (adjusted for all the other covariates) showed a time-dependent relationship with the risk of new disease manifestations. In particular, ER content failed to show a prognostic effect within the first years of follow-up; thereafter, a positive association with risk of relapse was observed. For tumor size, within the first years of follow-up, the risk of relapse was directly related to size for only tumors up to 2.5 cm in diameter; thereafter, the impact on prognosis progressively decreased. CONCLUSION: The availability of a long follow-up on a large breast cancer series, as well as the use of innovative statistical approaches, allowed us to explore the functional relation between steroid receptors and clinical outcome and to generate a hypothesis on the involvement of ER in favoring long-term metastasis development.

Adult↗
PubMed2000

Content and quality of currently published phase II cancer trials.

PURPOSE: A number of statistical methods have been proposed for the design and analysis of phase II studies based on dichotomous outcomes. To investigate to what extent such methods are in current use, we conducted a survey of published studies. MATERIALS AND METHODS: We identified studies by conducting a computerized literature search of MEDLINE. We considered trials on systemic antineoplastic treatments described as phase II or pilot. The search was limited to articles written in English and published in 1997. RESULTS: Three hundred eight trials were identified. The majority, ie, 295 (95.8%), had been conducted as single-arm studies, with objective tumor response as the primary efficacy end point. An identifiable statistical design was reported for only 58 (19.7%) of these trials. The quality in reporting the statistical design and compliance with the design in carrying out the study or results interpretation were frequently poor. The frequency of reporting the statistical design was not shown to increase over the years of study start and was not associated with sample size or study duration. Instead, a significant association was found with trial results (which were less frequently positive among studies with a statistical design) and with the impact factor of the publishing journal. CONCLUSION: This survey shows that the quality of the statistical component of published phase II cancer trials is generally poor and raises suspicion that low quality is likely to bias study findings. Journals might improve the methodologic standard of published articles through a more vigilant reviewing policy.

Clinical Trials, Phase II as Topic↗
PubMed2000

Improvement of walking distance by defibrotide in patients with intermittent claudication--results of a randomized, placebo-controlled study (the DICLIS study). Defibrotide Intermittent CLaudication Italian Study.

Defibrotide is an antithrombotic drug which enhances prostacyclin production and activates fibrinolytic system. The aim of this study was to investigate the improvement of walking distance in patients with intermittent claudication treated with defibrotide. DICLIS was a double blind, placebo-controlled study which included patients with walking distance autonomy at a standardized treadmill test < or =350 > or =100 meters. A total of 310 patients were randomly allocated to placebo (n = 101), defibrotide 800 mg/day (n = 104) or defibrotide 1200 mg/day (n = 105). During a one year follow-up, the Absolute Walking Distance (AWD) was measured six times (0, 30, 60, 90, 180, 360 days). Similar improvement in walking distance was found in the three groups until the 90th day; thereafter placebo group showed no further increase, while AWD continued to increase in the defibrotide groups. Between the 180th and 360th day visits, AWD was significantly higher (P <0.01) in patients given defibrotide than in patients given placebo. No difference in efficacy was observed between the two dosages of defibrotide. No differences in side effects were observed among the three groups. The results of the present trial suggest that long-term administration of defibrotide improves walking distance in patients with intermittent claudication.

Adult↗
PubMed1999

Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer.

BACKGROUND: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies. We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. METHODS: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence were determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. RESULTS: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P =.642) or ipsilateral breast cancer (P =.177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes =.045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0. 92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82-2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1. 89). There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. CONCLUSIONS: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed.

Adult↗
PubMed1999

The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-year results of a randomised trial.

The lymph nodes of the internal mammary chain represent a primary station draining the lymph from the breast and their removal or their irradiation has been considered an important step in breast cancer treatment. From January 1964 to January 1968, 737 patients with breast cancer were randomised at the National Cancer Institute in Milan to undergo either Halsted mastectomy or extended mastectomy with internal mammary node dissection. Patients with non-disseminated carcinoma classified as T1, T2, T3, N0, N1 were eligible for the study. No patients received postoperative radiotherapy or systemic therapy. After 30 years of follow-up, the overall survival curves and the specific survival curves do not show any difference between the patients of the two groups. Among the 558 patients who died in the 30 year interval period, 395 (71%) died from breast carcinoma (201 in the Halsted group and 194 in the extended mastectomy group) and 163 from other causes. This study shows that the removal of internal mammary nodes does not improve the survival of patients treated for breast carcinoma. This finding supports the theory that treatment of regional nodes does not influence the survival of cancer patients. The prognostic value of internal mammary node status is, however, high and a biopsy on a selected lymph node should be considered for staging purposes.

Adult↗
PubMed1999

Reoperation for locally recurrent breast cancer in patients previously treated with conservative surgery.

BACKGROUND: This study aimed to analyse the possibility of surgical rescue of intrabreast tumour recurrence (IBTR) following conservative operation for breast cancer, i.e. quadrantectomy, axillary dissection and radiotherapy. METHODS: Of 2544 patients treated with this approach, 209 presented with an IBTR as the first and only sign of relapse. Some 197 patients were considered suitable for further surgery; 12 were inoperable. Six patients declined operation. RESULTS: Reoperative surgery was total mastectomy in 134 patients (70 per cent) and further local resection in 57 (30 per cent). Median follow-up after second surgery was 73 (range 1-192) months. The overall survival probability at 60 months was 70 per cent after mastectomy and 85 per cent following further local excision. There was no difference in disease-free survival between the two operative groups. Second IBTR was more common at 5 years in the re-excision group (19 versus 4 per cent). CONCLUSION: Since the type of surgery did not seem to affect survival, breast conservation can be considered in selected patients with IBTR.

Breast Neoplasms↗