Lifestyle improvement reduces the consumption of ultra-processed foods in adults with metabolic syndrome.

BACKGROUND AND AIMS: The high consumption of ultra-processed products is a concern because it is positively associated with the incidence of chronic non-communicable diseases, as metabolic syndrome (MetS). The aim is to evaluate the effects of three different interventions to modify lifestyle on the consumption of ultra-processed foods in adults with MetS. METHODS AND RESULTS: This was a randomized clinical trial, in which the participants were divided into three groups: Standard Intervention (SI), Group Intervention (GI) and Individual Intervention (II). The interventions were carried out over a three-month period and the data was collected in a 24-h food record, taken at the beginning and end of the intervention. The food they ate was classified into four groups according to the degree of processing (unprocessed or minimally processed foods, processed culinary ingredients, processed foods, and ultra-processed foods) in accordance with the NOVA food classification. Seventy adults took part in the study with a mean age of 51.2 ± 6.6 years old; most of whom were female (55.7%). The amount of ultra-processed food consumed by the three groups (SI, GI and II) was significantly reduced (46%, 34%, and 33%, respectively). The amount of processed food consumed only reduced in the II group. The Total Energy Value (TEV) consumed by the SI and II groups decreased. CONCLUSIONS: The interventions that were intended to alter lifestyles were able to reduce the amount of ultra-processed food consumed, which can have an impact on the prevention and treatment of MetS. REGISTRATION: registered in the Brazilian Registry of Clinical Trials, ReBEC, under number: RBR-9wz5fc.

Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study‡.

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary end points included 2-year failure rate and cardiac safety. Results: A total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR is 1.13 (90% CI 0.89-1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-year overall survival (OS) is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90% CI 0.74-1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22-0.50, P < 0.0001). Conclusions: This study failed to show the non-inferiority of a shorter trastuzumab administration. One-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse. Trial Registration: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

Effects of the use of respiratory physiotherapy in children admitted with acute viral bronchiolitis.

OBJECTIVE: To evaluate the effects of the use of respiratory physiotherapy in children admitted with acute viral bronchiolitis (AVB). METHODS: A literature review was done searching the Pubmed, LILACS, PEDro, and Scielo databases. The following key words were used: bronchiolitis, physiotherapy, techniques, physical therapy, and chest physiotherapy. Both controlled and uncontrolled clinical trials, without limits as to date, were selected. RESULTS: Fifteen articles were included and the use of different techniques of respiratory physiotherapy showed positive results in eight studies. Most (11) were controlled clinical trials, and only two had a double-blind design. Of the 14 studies with a control group, in six this group was submitted to nasopharyngeal aspiration. The most widely used techniques were manual vibration and postural drainage (eight studies), and then tapping/percussion (seven studied). The maneuvers considered as current, e.g., prolonged slow expiration, expiratory flow acceleration, and rhinopharyngeal retrograde clearance, were used in four, four, and two studies, respectively. CONCLUSIONS: The use of respiratory physiotherapy in children with AVB remains controversial. The heterogeneity of techniques evaluated in the studies limits the interpretation of efficacy, although its use was considered safe. Recent findings indicating a reduction in the length of the hospital stay remain to be confirmed.

[Iron intake and HFE gen in male adults from Buenos Aires]. / Ingesta de hierro y gen HFE en varones adultos de Buenos Aires.

Excess iron (Fe) intake in subjects carrying certain mutations in the HFE gene may result in Fe overload. To estimate risk of Fe overload, 166 male blood donors (19-65 years) from Buenos Aires city were investigated. Daily Fe intake (FeI), hem Fe intake, and Fe intake from SO4Fe enriched flours were estimated (SARA Computer Program and Food Composition Table, USDA). Serum ferritin and transferrin saturation were determined; criteria for Fe overload was serum ferritin > 300 ng/ml and transferrin saturation = 50%. HFE genotypes C282Y, H63D and S65C were analyzed by PCR-RFLP in blood samples. No participant presented FeI lower than the estimated average requirement (6 mg Fe/day) and 3.0% was over the upper level (45 mg Fe/day). Hem Fe and Fe from flour enrichment were 9.4% and 47.7% of daily Fe intake, respectively. A significant association was observed between the increase in serum ferritin (ng/ml) and the increase in FeI (p = 0.0472); 2.3% of the donors presented serum ferritin > 300 ng/ml and transferrin saturation = 50%. Genotypes associated with hereditary hemochromatosis (H63D, S65C and C282Y) were found in 29.3% of the donors. The percentage of transferrin saturation was higher in subjects carrying mutation than in wild type subjects (p = 0.0167). Although penetrance of hereditary hemochromatosis in the studied group was only 1.2%, an excessive Fe intake could enhance adverse effects in individuals unaware of any family history of Fe overload.

Ingesta de hierro y gen HFE en varones adultos de Buenos Aires / Iron intake and HFE gen in male adults from Buenos Aires

El consumo excesivo de hierro (Fe) en portadores de mutaciones en el gen HFE puede resultar en sobrecarga. Para evaluar el riesgo de sobrecarga de Fe fueron investigados 166 varones adultos donantes de sangre de la ciudad de Buenos Aires. Se estimó la ingesta diaria de Fe (IFe), de Fe hemínico y de Fe proveniente de harinas enriquecidas con SO4Fe. Se determinó ferritina sérica y porcentaje de saturación de transferrina (criterio de sobrecarga de Fe: ferritina sérica > 300 ng/ml y saturación de transferrina ≥ 50%). Las mutaciones C282Y, H63D y S65C fueron investigadas en sangre mediante PCR-RFLP. Todos los participantes cubrieron ampliamente el requerimiento estimado promedio de Fe (6 mg Fe/día) y 3.0% superó el máximo tolerable (45 mg Fe/día). El Fe hemínico correspondió al 9.4% de la IFe y el de harinas enriquecidas al 47.7%. Se observó una asociación entre el aumento de IFe y el de ferritina sérica (p = 0.0472), y el 2.3% de los donantes presentaron ferritina sérica > 300 ng/ml y saturación de transferrina ≥ 50%. El 29.3% de los donantes eran portadores de los genotipos H63D, S65C o C282Y, asociados a hemocromatosis hereditaria, y tenían valores de saturación de transferrina significativamente mayores a los de los donantes wild type (p = 0.0167). Si bien la incidencia clínica de hemocromatosis hereditaria fue baja en el grupo estudiado (1.2%), el consumo excesivo de Fe plantea un riesgo potencial para la salud de individuos que ignoran sus antecedentes familiares de sobrecarga de Fe.

Excess iron (Fe) intake in subjects carrying certain mutations in the HFE gene may result in Fe overload. To estimate risk of Fe overload, 166 male blood donors (19-65 years) from Buenos Aires city were investigated. Daily Fe intake (FeI), hem Fe intake, and Fe intake from SO4Fe enriched flours were estimated (SARA Computer Program and Food Composition Table, USDA). Serum ferritin and transferrin saturation were determined; criteria for Fe overload was serum ferritin > 300 ng/ml and transferrin saturation ≥ 50%. HFE genotypes C282Y, H63D and S65C were analyzed by PCR-RFLP in blood samples. No participant presented FeI lower than the estimated average requirement (6 mg Fe/day) and 3.0% was over the upper level (45 mg Fe/day). Hem Fe and Fe from flour enrichment were 9.4% and 47.7% of daily Fe intake, respectively. A significant association was observed between the increase in serum ferritin (ng/ml) and the increase in FeI (p = 0.0472); 2.3% of the donors presented serum ferritin > 300 ng/ml and transferrin saturation ≥ 50%. Genotypes associated with hereditary hemochromatosis (H63D, S65C and C282Y) were found in 29.3% of the donors. The percentage of transferrin saturation was higher in subjects carrying mutation than in wild type subjects (p = 0.0167). Although penetrance of hereditary hemochromatosis in the studied group was only 1.2%, an excessive Fe intake could enhance adverse effects in individuals unaware of any family history of Fe overload.

A simple and reproducible prognostic index in luminal ER-positive breast cancers.

BACKGROUND: The group of estrogen receptor (ER)-positive breast cancers (both luminal-A and -B) behaves differently from the ER-negative group. At least in early follow-up, ER expression influences positively patients' prognosis. This low aggressive biology flattens out the differences of clinical management. Thus we aimed to produce a prognostic index specific for ER-positive (ERPI) cancers that could be of aid for clinical decision. PATIENTS AND METHODS: The test set comprised 495 consecutive ER-positive breast cancers. Tumor size, number of metastatic lymph nodes and androgen receptor expression were the only independent variables related to disease-specific survival. These variables were used to create the ERPI, which was applied to the entire test set and to selected subpopulations (grade 2 (G2)-tumors, luminal-A and -B breast cancers). A series of 581 ER-positive breast cancers, collected from another hospital, was used to validate ERPI. RESULTS: In the test population, 96.9% of patients classified as ERPI-good showed a good prognosis compared with 79.6% classified as ERPI-poor (P < 0.001). ERPI effectively discriminated outcome in luminal-A and luminal-B and in G2-tumors. In the validation series, the ERPI maintained its value. CONCLUSION: ERPI is a practical tool in refining the prediction of outcome of patients with ER-positive breast cancer.

Ventilatory muscle strength in cystic fibrosis patients: a literature review.

UNLABELLED: The ventilatory mechanic changes that occur in cystic fibrosis (CF) patients may lead to alterations in the respiratory muscle strength levels. However, the findings regarding the strength profile in these patients are still contradictory. OBJECTIVE: To evaluate, trough a literature review, the respiratory muscle strength behavior in CF patients. We have performed a search in Medline/Pubmed, Scielo, IBECS and LILACS databases selecting observational cross-sectional, prospective or retrospective studies, as well as randomized clinical trials, published between 1981 and 2011, using the following terms: cystic fibrosis, respiratory muscle strength, inspiratory maximal pressure and muscle training. The majority of the studies 71.24% have shown normal or above normal respiratory muscle strength, whilst 28.57% demonstrated reduced or near-normal values. Most of these findings were attributed to an increased work of breathing as a result of airway obstruction and chronic persistent cough. Taken together, the analyses of selected studies have showed conflicting findings regarding respiratory muscle strength behavior in these patients. However, most of the studies seem to indicate that CF patients presented maximum respiratory pressures normal or above predicted values.

Impact of dental care in the prevention of bisphosphonate-associated osteonecrosis of the jaw: a single-center clinical experience.

BACKGROUND: Osteonecrosis of the jaw (ONJ) is associated with bisphosphonate (BP) therapy and invasive dental care. An Interdisciplinary Care Group (ICG) was created to evaluate dental risk factors and the efficacy of a preventive restorative dental care in the reduction of ONJ risk. PATIENTS AND METHODS: This prospective single-center study included patients with bone metastases from solid tumors. Patients who received at least one BP infusion between October 2005 and 31 August 2009 underwent one or more ICG evaluation and regular dental examinations. We also retrospectively evaluated patients with bone metastases from solid tumors who did not undergo dental preventive measures. RESULTS: Of 269 patients, 211 had received at least one infusion of BP therapy: 62% were BP naive and 38% had previous BP exposure. Of these 211 patients followed for 47 months, 6 patients developed ONJ (2.8%). Of 200 patients included in the retrospective analysis, 11 patients developed ONJ (5.5%). CONCLUSIONS: In comparison with published ONJ rates and those extrapolated from the retrospective analysis, the observed ONJ rate in the prospective group was lower, suggesting that implementation of a preventive dental program may reduce the risk of ONJ in metastatic patients treated with i.v. BP therapy.

Vascular endothelial growth factor genetic polymorphisms and haplotypes in female patients with bisphosphonate-related osteonecrosis of the jaws.

OBJECTIVE: To investigate the polymorphisms of the vascular endothelial growth factor (VEGF) gene in relation to female patients who developed bisphosphonate-related osteonecrosis of the jaws (BRONJ). METHODS: Test subjects were 30 Italian female patients with BRONJ (Group A). Control subjects were 30 female patients with a history of intravenous bisphosphonate use without any evidence of osteonecrosis (Group B) and 125 unrelated healthy volunteers (Group C). Three single-nucleotide polymorphisms were investigated: -634 G>C, occurring in 5' untranslated region (UTR); +936 C>T, occurring in 3' UTR; and -2578 C>A of the promoter region. RESULTS: The frequency of the VEGF CAC (+936/-2578/-634) haplotype was increased in patients with BRONJ, compared with female disease-negative controls [odds ratio (OR) = 2.76, 95% CI = 1.09-4.94, P = 0.039; corrected P value: P(c) = 0.117], and was also increased compared with female healthy controls (OR = 2.11, 95% CI = 1.14-3.89, P = 0.024; corrected P value: P(c) = 0.072). The CC homozygotes of -634G>C of VEGF gene and AA homozygotes of -2578C>A have also been significantly correlated in female patients who developed BRONJ compared with healthy controls (OR = 2.04, 95% CI = 1.12-3.70, P = 0.008; corrected P value: P(c) = 0.024). CONCLUSIONS: These results suggest a possible haplotype effect of VEGF polymorphisms expression in BRONJ Italian female patients. Studies with different and larger populations possibly using TagSNP to represent all haplotypes within the VEGF gene are needed to further delineate the genetic contribution of this gene to BRONJ.

Biology, prognosis and response to therapy of breast carcinomas according to HER2 score.

BACKGROUND: The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. PATIENTS AND METHODS: A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. RESULTS: Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. CONCLUSIONS: The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

Patients with advanced stage breast carcinoma immunoreactive to biotinylated Herceptin are most likely to benefit from trastuzumab-based therapy: an hypothesis-generating study.

BACKGROUND: Biotin-labeled trastuzumab (BiotHER) can be used to test for HER2 by immunohistochemistry. We previously showed that BiotHER immunoreactivity is highly correlated with HER2 amplification and indicated that it could be associated with better clinical outcome in advanced breast cancer patients receiving trastuzumab. PATIENTS AND METHODS: Tumor specimens and clinical information from 234 patients who received trastuzumab-based treatments were collected from 10 institutions. HER2 amplification and BiotHER immunoreactivity were assessed centrally. The effect of BiotHER positivity on response rate (RR), time to progression and survival were studied by univariate and multivariate analysis in patients presenting HER2-amplified breast cancer. The pathologic reviews of the assays were blinded to patient outcomes. RESULTS: BiotHER was positive in 109/194 (56%) HER2-amplified breast cancers and in one not amplified tumor. RRs were 74% [95% (confidence interval) CI 64%-81%] and 47% (95% CI 36%-58%) in BiotHER-positive and -negative tumors, respectively (P < 0.001). BiotHER immunoreactivity was independently associated with increased probability of tumor response (odds ratio 3.848; 95% CI 1.952-7.582), with reduced risk of disease progression [hazard ratio (HR) 0.438; 95% CI 0.303-0.633] and with reduced risk of death (HR 0.566; 95% CI 0.368-0.870) by multivariate analysis. CONCLUSION: The results support a role for BiotHER testing in better tailoring trastuzumab-based treatments in patients with advanced HER2-amplified breast cancers.

Weekly cisplatin plus capecitabine in metastatic breast cancer patients heavily pretreated with both anthracycline and taxanes.

BACKGROUND: Treating patients with anthracycline- and taxane-pretreated metastatic breast cancer is challenging. This study evaluated the activity and safety of a combination of cisplatin and capecitabine in this setting. PATIENTS AND METHODS: Thirty-nine consecutive patients entered the study. All had experienced failures or relapse after previous treatment with anthracyclines and taxanes plus/minus other chemotherapeutic regimens. The present treatment consisted of intravenous cisplatin 20 mg/m(2) every week for 6 weeks, followed by 1 week of rest, and oral capecitabine 1,000 mg/m(2) twice daily for 14 days, followed by a 7-day rest period. RESULTS: Objective response was obtained in 14 patients (35.9%), with complete remission in 3 (7.7%). Median time to progression was 5.2 months and survival was 10.9 months in the entire population and 8.7 and 16.5 months in the responding patients, respectively. The dose-limiting toxicity for the regimen was leucopenia, while gastrointestinal discomfort was the most frequent cause of capecitabine reduction or delay. CONCLUSIONS: The cisplatin and capecitabine combination regimen is active and manageable. It seems to be non-cross resistant to anthracyclines and taxanes.

A modified Trastuzumab antibody for the immunohistochemical detection of HER-2 overexpression in breast cancer.

The immunohistochemical determination of HER-2 to identify patients with advanced breast cancer candidates for Trastuzumab treatment proved neither accurate nor fully reliable, possibly because none of the current reagents detects the specific antigenic site target of Trastuzumab. To circumvent this problem, we conjugated the NH2 groups of Trastuzumab with biotin, and the compound obtained, designated BiotHER, was added directly to tissue sections. Biotin-labelling was revealed with horseradish peroxidase-conjugated streptavidin. Specificity and sensitivity of BiotHER immunostaining with respect to HER-2 amplification were tested on 164 breast carcinoma samples. BiotHER staining was detected on the tumour cell membrane of 12% of all specimens and in 49% specimens with gene amplification, while absent in nonamplified tumours. Predictivity of BiotHER status with respect to the clinical outcome was analysed in 54 patients with HER-2 amplified advanced breast cancer treated with Trastuzumab plus chemotherapy. BiotHER staining, detected in 50% of tumours with HER-2 amplification, was an independent predictor of clinical outcome. In fact, BiotHER positivity was independently associated with increased likelihood of tumour response and reduced risk of tumour progression and death. Biotinylated Trastuzumab can thus be used for immunohistochemical detection of HER-2 overexpression in breast cancer, and has the potential to identify patients likely to benefit from Trastuzumab treatment.

Clinical and pharmacokinetic phase II study of pegylated liposomal doxorubicin and vinorelbine in heavily pretreated recurrent ovarian carcinoma.

BACKGROUND: This multicenter phase II study evaluated feasibility, clinical efficacy, toxicity and pharmacokinetics of the combination of pegylated liposomal doxorubicin (PLD) and vinorelbine (VNR) in patients with platinum-paclitaxel pretreated recurrent ovarian cancer. PATIENTS AND METHODS: All patients received prior treatment with platinum and paclitaxel. Thirty-two heavily pretreated (median number of chemotherapy regimens two, range one to six) ovarian cancer patients received treatment with PLD 30 mg/m(2) and VNR 30 mg/m(2) every three weeks for six cycles. Ten patients entered the pharmacokinetic study, five receiving the PLD-VNR and five the VNR-PLD sequence. RESULTS: In 30 patients evaluated for response and toxicity, the overall response rate was 37% and 10% of patients achieved stable disease. Median time to progression and overall survival were 5.5 months (range 1-10) and 9 months (range 2-16), respectively. Toxicity was generally mild and reversible. VNR AUC(tot) and plasma levels were considerably higher in the PLD-VNR sequence. CONCLUSIONS: The PLD-VNR regimen exhibits significant activity in heavily pretreated patients, is well tolerated and is associated with encouraging survival. Preliminary pharmacokinetic results suggest the PLD-VNR sequence for further clinical applications. This regimen should be considered as a treatment option in patients with chemotherapy-resistant ovarian cancer.

Paclitaxel, vinorelbine and 5-fluorouracil in breast cancer patients pretreated with adjuvant anthracyclines.

We investigated the activity and toxicity of a combination of vinorelbine (VNB), paclitaxel (PTX) and 5-fluorouracil (5-FU) continuous infusion administered as first-line chemotherapy in metastatic breast cancer patients pretreated with adjuvant anthracyclines. A total of 61 patients received a regimen consisting of VNB 25 mg m(-2) on days 1 and 15, PTX 60 mg m(-2) on days 1, 8 and 15 and continuous infusion of 5-FU at 200 mg m(-2) every day. Cycles were repeated every 28 days. Disease response was evaluated by both RECIST and World Health Organization (WHO) criteria. Objective responses were recorded in 39 of 61 patients (64.0%) assessed by WHO and in 36 of 50 patients (72.0%) assessable by RECIST criteria. Complete remission occurred in 15 (24.6%) and 14 patients (28.0%), respectively. The median time to progression and overall survival of entire population was 10.6 and 27.3 months, respectively, and median duration of complete response was 14.8 months. The dose-limiting toxicity was myelosuppression (leucopenia grade 3/4 in 52.5% of patients). Grade 3/4 nonhaematologic toxicities included mucositis/diarrhoea in 13.1%, skin in 3.3% and cardiac in 1.6% of patients. Grade 2/3 neurotoxicity was observed in five patients (7.2%). The VNB, PTX and 5-FU continuous infusion combination regimen was active and manageable. Complete responses were frequent and durable.

Ultrasonographically-guided fine-needle aspiration of axillary lymph nodes: role in breast cancer management.

The knowledge of the status of axillary lymph nodes (LN) of patients with breast cancer is a fundamental prerequisite in the therapeutic decision. In the present work, we evaluated the impact of fine-needle aspiration cytology (FNAC) of ultrasonographically (US) selected axillary LN in the diagnosis of LN metastases and subsequently in the treatment of patients with breast cancer. Axillary US was performed in 298 patients with diagnosed breast cancer (267 invasive carcinomas and 31 ductal carcinoma in situ DCIS), and in 95 patients it was followed by FNAC of US suspicious LN. Smears were examined by routine cytological staining. Cases of uncertain diagnosis were stained in immunocytochemistry (ICC) with a combination of anticytokeratin and anti-HMFG2 antibodies. Eighty-five FNAC were informative (49 LN were positive for metastases, 36 were negative). In 49 of 267 patients with invasive breast carcinoma (18%), a preoperative diagnosis of metastatic LN in the axilla could be confirmed. These patients could proceed directly to axillary dissection. In addition, US-guided FNAC presurgically scored 49 out of 88 (55%) metastatic LN. Of all others, with nonsuspicious LN on US (203 cases including 31 DCIS), in which no FNAC examination was performed, 28 invasive carcinomas (16%) turned out to be LN positive on histological examination. Based on these data, US examination should be performed in all patients with breast cancer adding ICC-supported FNAC only on US-suspect LN. This presurgical protocol is reliable for screening patients with LN metastases that should proceed directly to axillary dissection or adjuvant chemotherapy, thus avoiding sentinel lymph node biopsy.

Multimodal treatment with primary single-agent epirubicin in operable breast cancer: 5-year experience of the Michelangelo Cooperative Group.

BACKGROUND: To assess the efficacy of primary single-agent epirubicin (120 mg/m(2) every 3 weeks for three cycles) in reducing tumor burden in operable breast cancer >or=2.5 cm in largest diameter at diagnosis and its effect on the rate of conservative surgery. PATIENTS AND METHODS: A total of 319 eligible patients, who were all candidates for mastectomy, were enrolled on to a multicenter prospective non-randomized study. Tumor response was assessed clinically and pathologically. Relapse-free and overall survival were assessed on major prognostic variables. RESULTS: After primary epirubicin, complete disappearance of invasive neoplastic cells accounted for only 2.6% of patients, but 40% of patients had their primary tumor downstaged to

Paclitaxel administration on days 1 and 8 every 21 days in anthracycline-pretreated metastatic breast cancer patients. A multicenter phase II trial.

Paclitaxel is now included in second- and even first-line regimens in advanced breast cancer. The optimal dose and schedule of this drug, however, still remain a matter of investigation. A group of 57 consecutive patients with advanced breast cancer previously treated with anthracycline-containing regimens were submitted to treatment with single-agent paclitaxel administered at 130 mg/m2 on days 1 and 8 every 21 days. Of the 57 patients, 56 were fully evaluable, and of these 25 had an absolute anthracycline resistance, 14 a relative resistance and 17 were potentially sensitive. The median age of the patients was 57 years (range 33-71 years), their median performance status was 1 (0-3), and 27 (47%) had liver involvement, 17 (30%) lung involvement, 30 (53%) bone involvement and 15 (26%) skin/lymph node involvement. Toxicity was recorded in 295 cycles. This scheme was well tolerated, the dose-limiting toxicities being hematological and neurological. Grade 3/4 leukopenia was observed in 20% of patients at nadir, while grade 3 leukopenia was observed in 3% of patients at recycle. Only one patient experienced febrile neutropenia. Grade 2/3 neurotoxicity was observed in 26% of patients, leading to drug withdrawal in three. The treatment was given on an outpatient basis in all patients and the median relative dose intensity of 86.6 mg/m2 per week was 100% of the planned dose (range 75-100%). Three patients (5%) attained a complete clinical response and 12 (21%) a partial response for an overall response rate of 26% (95% confidence interval 18-38%), while 30 (53%) attained disease stabilization and 11 progressed (19%). Time to progression in responding patients was 10.3 months, and the median overall survival of the entire population was 15.4 months. To conclude, paclitaxel administration on days 1 and 8 every 21 days was active and manageable in advanced breast cancer patients previously treated with anthracyclines. The response obtained was durable.

Independent factors predict supranormal CA 15-3 serum levels in advanced breast cancer patients at first disease relapse.

Data currently available are insufficient to demonstrate a real utility for CA 15-3 in the diagnosis, staging or surveillance of breast cancer patients following primary treatment. The aim of this study was to determine if there was a correlation between supranormal CA 15-3 serum levels and clinical and biological variables in breast cancer patients at first disease relapse. From October 1988 to March 1998, 430 consecutive patients entered the study. Overall CA 15-3 sensitivity was 60.7%. Elevated CA 15-3 levels were found more frequently in patients with liver metastases (74.6%) and in those with pleural effusion (75.7%). CA 15-3 sensitivity was 70.4% in patients with estrogen-receptor-positive (ER+) primary tumors and 45.9% in those with estrogen-receptor-negative (ER-) tumors (p < 0.0001). In patients with a limited extent of disease, marker sensitivity was 57.7% in ER+ tumors and 25.7% in ER- tumors (p < 0.0001). Logistic regression analysis showed ER status, disease extent and pleural effusion as independent variables associated with CA 15-3 positivity. The multivariate Cox analysis showed ER and disease extent as independent variables predicting overall survival, whereas CA 15-3 failed to be statistically significant. CA 15-3 was an independent variable only when the disease extent variable was removed. This study suggests that CA 15-3 in advanced breast cancer patients is a marker of both disease extent and ER status. The direct relationship with ER status indicates that CA 15-3 diagnostic sensitivity in the early detection of disease recurrence could be greater in ER+ patients than in ER- ones. Furthermore, this suggests that patients with elevated CA 15-3 levels could have disease that is more sensitive to hormone manipulation than those with normal CA 15-3 values.