Process strategy to fabricate a hierarchical porosity gradient in diatomite-based foams by 3D printing.

Motivated by the hierarchical micro and nanoscale features in terms of porosity of diatomite, the production of ceramic-graded porous foams with tailored porosity, obtained by using it as raw material, has been proposed. The main challenge during the foam-production process has been the preservation of diatomite nanometric porosity and the addition of other levels of hierarchical porosity. The coupled use of two techniques of direct foaming (chemical and mechanical), combined with the use of 3D printing inverse replica method, assured the achievement of porosity of, respectively, microscopic and macroscopic dimensions. Optical and scanning electron microscopies have been performed for an in-depth characterization of the final microstructure. XRD analysis has been carried out to check the influence of sacrificial templates on the matrix mineralogical composition. The porosity of the diatomite-based foams has been investigated by means of nitrogen-adsorption analysis and mercury-intrusion porosimetry. The experimental tests confirmed the presence of different porous architectures ranging over several orders of magnitudes, giving rise to complex systems, characterized by hierarchical levels of porosity. The presence of porosity of graded dimensions affects the final mechanical performances of the macroporous diatomite-based foams, while their mineralogical composition does not result to be affected by the addition of templates.

Mechanical and chemical properties of composite materials made of dredged sediments in a fly-ash based geopolymer.

Dredging activity in harbours and channels produces huge quantities of sediments, generally considered as waste soil (WS) to be disposed: the management of such sediments is a great environmental problem for many countries worldwide. Among the recycling possibilities, the use of dredged sediments for the manufacture of geopolymer-based materials seems to be an interesting alternative to disposal, due to their low cost and easy availability. In order to analyse the possibility to use these geopolymer materials as building materials - for instance as precast construction elements in maritime projects - a multi-disciplinary research activity has been developed at the Federico II University of Napoli (Italy). Some experimental tests have been carried out on different geopolymeric specimens made by mixing sediments from Napoli 'harbour and industrial fly ashes produced by a power plant in the South of Italy. A siliceous sand was used for comparison as an inert reference material. Chemical, morphological and mechanical properties of different specimens have been studied by X-ray diffraction, Scanning Electron Microscopy (SEM), Fourier transformed infrared spectroscopy (FTIR) and finally unconfined compression tests. The experimental results highlight that the use of dredged sediments in combination with fly ash can lead to geopolymeric matrices with interesting mechanical performances. Some differences in the microstructure of the geocomposite built with the siliceous sand or the dredged materials were found. In terms of environmental impacts, on the basis of standard leaching tests and according to Italian thresholds, the adopted dredged mixtures satisfy the prescribed limit for inert or non hazardous waste.

Body weight and risk of molecular breast cancer subtypes among postmenopausal Mediterranean women.

Breast cancer (BC) is the most common malignant tumor in women, obesity is associated with increased BC incidence and mortality and high levels of circulating insulin may negatively impact on cancer incidence. In the present study, we investigated whether the strength of several anthropometric and metabolic parameters varies between BC molecular subtypes. Eligible cases were 991 non-metastatic BC patients recruited between January 2009 and December 2013. Anthropometric, clinical and immunohistochemical features were measured. Multivariate logistic regression models were built to assess HER2 positive BC risk, comparing (a) triple positive (TP) with luminal A, luminal B and triple negative (TN) and (b) HER2-enriched group with luminal A, luminal B and TN. We stratified patients in pre- and post-menopause: significant differences emerged for luminal A in relation to age: they were more likely to be older compared to other groups. Among postmenopausal patients, the adjusted multivariate analysis showed that high BMI and high waist circumference were inversely correlated to TP subtype when compared to luminal B (OR=0.48 and OR=0.49, respectively). Conversely, HOMA-IR was a risk factor for TP when compared to luminal A and TN (OR=2.47 and OR=3.15, respectively). Our findings suggest a potential role of higher abdominal fat in the development of specific BC molecular subtypes in postmenopausal women. Moreover, they support a potential role of insulin resistance in the development of HER2 positive BC, although this role appears to be stronger when hormone receptors are co-expressed, suggesting a difference in the etiology of these two BC subtypes.

Intraoperative radiotherapy in early breast cancer.

BACKGROUND: Intraoperative radiotherapy (IORT) constitutes a paradigm shift from the conventional 3-5 weeks of whole-breast external beam radiotherapy (EBRT). IORT enables delivery of radiation at the time of excision of the breast tumour, targeting the area at highest risk of recurrence, while minimizing excessive radiation exposure to healthy breast tissue. The rationale for IORT is based on the observation that over 90 per cent of local recurrences after breast-conserving surgery occur at or near the original operation site. METHODS: This article reviews trials of IORT delivered with different techniques and devices. RESULTS: IORT is a very attractive option for delivering radiotherapy, reducing the traditional fractionated treatment to a single fraction administered at the time of surgery. IORT has been shown to be associated with reduced toxicity and has several potential benefits over EBRT. Only two randomized clinical trials have been published to date. The TARGIT-A and ELIOT trials have demonstrated that IORT is associated with a low rate of local recurrence, although higher than that after EBRT (TARGIT-A: 3·3 versus 1·3 per cent respectively, P = 0·042; ELIOT: 4·4 versus 0·4 per cent, P < 0·001). However, the local recurrence rate for IORT fell within the predefined 2·5 per cent non-inferiority margin in TARGIT-A, and the 7·5 per cent equivalence margin in ELIOT. CONCLUSION: Longer follow-up data from existing trials, optimization of patient criteria and cost-effectiveness analyses are needed. Based on the current evidence, IORT can be offered as an alternative to EBRT to selected patients within agreed protocols, and outcomes should be monitored within national registries.

Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves prognosis in locally advanced breast cancer patients: an update of the Southern Italy Cooperative Oncology Group (SICOG) randomised trial 9908.

BACKGROUND: The present article reports the updated survival outcome of the 200 patients enrolled in the Southern Italy Cooperative Oncology Group 9908 trial, which compared 12 weekly cycles of cisplatin-epirubicin-paclitaxel (PET) with 4 triweekly (once every 3 weeks) cycles of epirubicin-paclitaxel (ET) in patients with locally advanced breast cancer (LABC). METHODS: The effects of treatment, pathologically documented response (pathological response), pre- and post-treatment biomarkers on relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) are analysed. RESULTS: At a median follow-up of 74 (range 48-105 months) months, the 5-year RFS, DMFS, and OS were 64 % versus 53% (P = 0.11), 73% versus 55% (P = 0.04), and 82% versus 69% (P = 0.07) in PET and ET, respectively. At multivariate analysis, after adjusting treatment effect for pretreatment biomarkers, PET independently predicted better DMFS (P = 0.018) and OS (P = 0.03), whereas the impact on RFS was of borderline significance (0.057). PET treatment was significantly better than ET treatment only in high-grade or highly proliferating tumours. The better outcome in PET arm was the results of both the higher rate of patients with optimal pathological response and the lower rate of patients with biologically aggressive residual tumour. CONCLUSIONS: The PET weekly regimen significantly improves both DMFS and OS in LABC patients, compared with the triweekly ET combination. The therapeutic advantage is limited to patients with highly aggressive tumours.

Outcome analysis of breast cancer patients receiving breast-conserving surgery in Southern Italy.

The purpose of the current analysis was to evaluate the outcome of patients enrolled at the National Cancer Institute of Naples between 1997 and 2000, who underwent breast-conserving surgery. Between January 1997 and December 2000, 946 patients had been diagnosed with T1 or T2 (<3 cm) breast carcinoma. At the time of the present analysis (31-12-2005), all patients had been followed for >5 years. A Cox proportional hazards model was performed. Overall, 7-year Locoregional Relapse-free survival (LRFS) and Distant Relapse-free Survival (DRFS) rates were 95.9% and 88.4%, respectively. Seven-year DRFS was 91.2% and 79.3% in T1 and T2 stage, respectively (p<0.0001). Multivariate Cox analysis indicated that number of positive lymph-nodes and hormone receptor status were significantly associated with prognosis. Our findings confirm that early diagnosed breast cancer, treated with breast-conserving surgery, is associated with a very good prognosis in patients referred to an Institution which may be considered as representative of similar Cancer Institutes of Southern Italy. The risk of local relapse was found to be very low (4%), although a longer follow-up is needed to draw definitive conclusions.

Characterization of 2 novel and 2 recurring BRCA1 germline mutations in breast and/or ovarian carcinoma patients from the area of Naples.

We have analyzed 18 families with high incidence of breast cancer or breast and ovarian cancer for the presence of BRCA1 mutations. We identified 4 mutations in the BRCA1 gene in 4 unrelated probands who belong to families with at least 1 case of breast and 1 case of ovarian cancer. Two of the mutations reported in this study are novel (GAA(1172)-->TAA in family Naples 14, GAA(1765)-->TAA in family Naples 20) whereas the others are already present in the Breast Cancer Information Core Electronic Database (http://nchgr.nih.gov/ Intramural research/Lab transfer/Bic/) (5382insC in family Naples 18 and 2080delA in family Naples 19). Conversely, no mutation in the BRCA1 gene was detected in 14 families characterized by 2 or more cases of breast cancer only, even if bilateral and with early-onset. These results indicate that germline mutations in the BRCA1 gene highly predispose for a cancer syndrome that involves the presence of both breast and ovarian cancer.

Gemcitabine/cyclophosphamide/5-fluorouracil/folinic acid triplet combination in anthracycline- and taxane-refractory breast cancer patients: a Southern Italy Cooperative Oncology Group phase I/II study.

We sought to define the recommended dose of cyclophosphamide (CTX) for subsequent phase II assessment when combined with fixed doses of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and 5-fluorouracil/folinic acid in metastatic breast cancer patients previously treated with anthracyclines and taxanes. Patients age 70 or less, with an Eastern Cooperative Oncology Group performance status 0 to 2, were enrolled. Patients received gemcitabine 1,000 mg/m(2), 5-fluorouracil 425 mg/m(2), folinic acid 100 mg/m(2), and escalating doses of CTX (in 100-mg/m(2) increments), starting at 500 mg/m(2), on days 1 and 8 every 3 weeks. Since March 1999, 46 patients, with a median age of 51 years (range, 38 to 74 years), entered the trial in seven cohorts. Cyclophosphamide dose escalation was stopped at 600 mg/m(2) when three of six patients experienced dose-limiting toxicity (one each with grade 3 thrombocytopenia, grade 3 neutropenia, and persistent grade 2 neutropenia), and then continued with granulocyte colony-stimulating factor support. The CTX dose of 800 mg/m(2) was proven safe and was chosen for phase II study. Two complete and 15 partial responses provided an overall response rate of 37% (95% confidence interval, 23% to 51%). Gemcitabine/CTX/5-fluorouracil/folinic acid is well tolerated by metastatic breast cancer patients pretreated with anthracyclines/taxanes, up to a CTX dose of 800 mg/m(2). The phase II study is ongoing. Semin Oncol 28 (suppl 10):50-56.

Cisplatin-epirubicin-paclitaxel weekly administration with G-CSF support in advanced breast cancer. A Southern Italy Cooperative Oncology Group (SICOG) phase II study.

PURPOSE: It has been shown in vitro that both cisplatin and epirubicin increase the antitumor activity of paclitaxel. Weekly administration could give a substantial improvement in the therapeutic index of cisplatin and paclitaxel. This study was aimed at defining the antitumor activity of a weekly cisplatin-epirubicin-paclitaxel (PET) administration in locally advanced or metastatic breast cancer patients. PATIENTS AND METHODS: Sixty-eight breast cancer patients with advanced disease, who had not received prior chemotherapy (except adjuvant), received weekly cisplatin 30 mg/sqm, paclitaxel 120 mg/sqm and epirubicin 50 mg/sqm plus G-CSF (day 3-5), for a maximum of 12 cycles. Thirty-five patients had stage IIIB and 33 stage IV disease (14 with visceral metastases). RESULTS: All patients were evaluable for response on an intent to treat basis. Overall, 21 complete and 38 partial responses have been recorded for an 87% ORR (95% CI = 76-94%). Fourteen CRs and 19 PRs have been registered in the 35 patients with locally advanced disease for a 94% ORR (95% CI = 81-99%) while 7 CRs and 19 PRs were observed in the 33 patients with metastatic disease for a 79% ORR (95% CI-61-91%). Surgery was performed in 33/35 women with locally advanced disease. Four of these patients (11%) showed no invasive cancer on pathologic examination, and in an additional 8 patients tumor < 1 cm was found in the breast. Only 4/33 patients who underwent surgery relapsed. The projected one-year RFS was greater than 80%. At an 11-month median follow-up (range, 3-19), 11 patients had progressed and 5 had died among the 33 patients with metastatic disease, the median progression-free survival in this group being 14 months. Severe hematologic toxicity was uncommon, grade 3-4 neutropenia and thrombocytopenia occurring in 32% and 4% of patients, respectively. Only 2 episodes of neutropenic sepsis were registered. Packed red blood cell transfusions were required in 7 patients. Vomiting, diarrhoea, mucositis and skin toxicity were severe in 6%, 9%, 10%, and 9% of patients, respectively. Peripheral neuropathy was observed in 47% of patients. CONCLUSIONS: The weekly PET administration is a well tolerated and very effective approach in advanced breast cancer patients. It can produce a 40% clinical complete response rate, with a more than 10% pCR rate in patients with T4 disease, and an about 80% ORR in those with distant metastases. A phase III trial comparing PET with a standard every 3 weeks epirubicin-taxol administration is underway.

Identification of a new subset of cells exhibiting dendritic phenotypes in patients affected by breast proliferative disorders.

We report that a subset of circulating cells reacting with a monoclonal antibody raised against a protein marker is significantly increased in the peripheral blood of women carrying benign or malignant breast diseases, particularly in patients under 55 years of age with ductal mammary carcinomas. These cells were statistically (confidence level of 99%) less represented in a control population including healthy women or women carrying carcinomas of origin other than breast. Double staining analysis showed that they harbor markers of dendritic cells and exhibit endo- cytic activity, as determined by their ability to internalize FITC-dextran particles. Their dendritic morphology was further demonstrated by electron microscopy of sorted antibody-positive cells. However, expression of surface molecules, such as CD34 and CD14, usually not present in differentiated populations of dendritic cells was also observed. Adherent cells of patients with breast ductal carcinoma including mostly cells of this new subset were efficient stimulators of mixed lymphocyte reaction, attaining maximal stimulatory activity attained after TNFalpha treatment. In conclusion, we have shown that a subset of cells characterized by a phenotype suggestive of a yet undescribed stage of maturation of the dendritic cell lineage is accumulated in the blood of patients affected by breast proliferative disorders.

Weekly docetaxel plus gemcitabine or vinorelbine in refractory advanced breast cancer patients: a parallel dose-finding study. Southern Italy Cooperative Oncology Group (SICOG).

PURPOSE: The objective of this study was to determine the docetaxel MTD when combined with gemcitabine or vinorelbine in advanced breast cancer patients who had received previous anthracycline-based chemotherapy for advanced disease. PATIENTS AND METHODS: Advanced breast cancer patients aged between 18 and 70 with ECOG PS 0-2 who had not responded to, or had relapsed after, first-line anthracycline-based chemotherapy, were randomized to receive either gemcitabine 1000 mg/m2 or vinorelbine 25 mg/m2 in combination with escalating doses of docetaxel (starting from 30 mg/m2), all on days 1 and 8 every three weeks. Escalation was stopped if > 33% of patients treated at a given dose level showed DLT at the first cycle. RESULTS: A total of 34 patients with locally advanced (8) or metastatic disease (26) were treated, for a total of 94 cycles delivered. Nineteen patients received docetaxel in combination with gemcitabine and 15 with vinorelbine. All patients had been pretreated with anthracyclines, and 24 of 34 had also received weekly dose-dense paclitaxel. A docetaxel dose of 40/m2 proved to be safe when combined on days 1 and 8 with gemcitabine, while a dose of 35 mg/m2 was tolerated in combination with vinorelbine. Overall, nine episodes of DLT, all of them neutropenia, occurred at the first cycle. Considering all 94 cycles, grades 3 or 4 neutropenia and thrombocytopenia occurred in 15 (44%), and 7 (20%) patients. Non-hematologic toxicity was mild, except for three cases of grade 2 peripheral neuropathy. All patients were assessed for response on an 'intent-to-treat' basis. Overall, five partial responses were recorded (docetaxel + gemcitabine = 3 and docetaxel + vinorelbine = 2), for a 15% (95% CI: 5%-31%) overall response rate. Only 1 of 24 (4%) patients who had received weekly dose-dense paclitaxel responded to treatment. CONCLUSIONS: The weekly docetaxel administration in combination with either gemcitabine or vinorelbine is a well-tolerated treatment for heavily pretreated advanced breast cancer patients. This approach, although sometimes capable of achieving a major response, does not seem advisable in advanced breast cancer patients refractory to both anthracyclines and paclitaxel.

Changing patterns of breast cancer stage at diagnosis in southern italy: hospital data as indicators of progressive changes.

BACKGROUND: In southern Italy diagnostic delay in breast cancer patients has been demonstrated to be related to the level of education and residency in rural areas. In order to verify whether late breast cancer diagnosis was actually in decline as a result of improving socioeconomic conditions and ongoing prevention programs, we evaluated clinical data from the tumor registry of the National Cancer Institute, Naples. METHODS: Four thousand two hundred forty consecutive breast cancer patients admitted to our institution from 1986 to 1997 were grouped into four 3-year periods according to their admission date. Using multiple logistic regression, chi(2) for trend and beta-coefficient were calculated in each pT and pN categories in order to discover the trend for the 1986-1997 period. RESULTS: A progressive, statistically significant decrease in the number of patients with advanced cancer at the time of diagnosis was observed over the study period. In particular, chi(2) values for trend for each pT category, over the study period, were pT1 119.4 (P < 0.001) with positive chi-coefficient, pT2 13.4 (P = 0.003) with negative beta, and pT3-pT4 152.2 (P < 0.001) with the strongest negative beta. CONCLUSIONS: Changing patterns of breast cancer stage at diagnosis have been demonstrated in women living in Southern Italy. They are consistent with an increasing orientation toward prevention. Data from hospital tumor registries are a useful source of information on diagnostic delay.

Circulating antibodies against the breast tumor marker GCDFP-15/gp17 in mammary carcinoma patients and in patients carrying benign breast conditions.

Sera samples from 111 women, including 73 breast cancer patients and 38 patients with benign diseases of the breast, were examined. These were compared with samples from healthy women or from patients carrying tumors of origin other than breast as controls. This was done to determine whether antibodies against GCDFP-15/gp17, a protein of gross cystic disease fluid also secreted by mammary apocrine tumor cells, could be found. We observed that 2.6% of mammary disease patients affected by benign conditions and 5.5% of patients carrying malignant mammary gland tumors expressed statistically significant amounts of antibodies against GCDFP-15/gp17 (p < 0.01). The highest circulating anti-GCDFP-15/gp17 antibody levels occurred in patients with highly malignant ductal or lobular carcinoma of the breast and in patients with dysplasia. No correlation was found between the presence of circulating antibodies and the size of the tumor or the age of the patients. A bimodal correlation with the percent of invaded lymph nodes was observed instead. IgM and IgG isotypes were detected among the circulating anti-GCDFP-15/gp17 antibodies, suggesting the involvement of a T-cell-mediated immunoresponse. Our findings raise the possibility that the anti-GCDFP-15/gp17 immune response may be useful as a tool for investigating some aspects of the mechanisms of breast disease progression and that GCDFP-15/gp17 may be explored as an antigen for anti-tumor vaccination. Int. J. Cancer (Pred. Oncol.) 84:568-572, 1999.

Cisplatin-epirubicin-paclitaxel weekly administration in advanced breast cancer: a phase I study of the Southern Italy Cooperative Oncology Group.

PURPOSE: Both cisplatin and epirubicin have been shown to enhance the antitumor activity of paclitaxel in vitro. Weekly administration could result in a substantial improvement in the therapeutic index of cisplatin and paclitaxel. This study was aimed at determining the MTDs of epirubicin and paclitaxel given weekly with a fixed dose of cisplatin. PATIENTS AND METHODS: Sixty-three breast cancer patients with advanced disease (24 locally advanced and 39 metastatic), who had not received prior chemotherapy (except adjuvant), received weekly cisplatin (CDDP) doses of 30 mg/m2 together with escalating doses of paclitaxel (PTX) and epirubicin (EPI) for a minimum of six cycles. The dose escalation was stopped if DLT occurred during the first six treatment cycles in > 33% of patients of a given cohort. RESULTS: Nine different dose levels were tested, for a total of 506 weekly cycles delivered. G-CSF support on days 3-5 of each week was also given in the last four cohorts (24 patients). An overall 11 patients showed DLT in the first six cycles. EPI and PTX doses up to 40 and 85 mg/m2/week, respectively, were safely delivered without G-CSF support. However, the actually delivered mean dose intensity was only 64% in this cohort. Therefore, the dose escalation continued with the addition of filgrastim from day 3 to day 5 each week. Doses of EPI and PTX up to 50 and 120 mg/m2/week were administered without observing DLT in the first six cycles in more than one third of the patients enrolled. No toxic deaths were observed. Only two patients had to be hospitalized because of sepsis. Grade 3-4 neutropenia, thrombocytopenia, and anemia occurred in 25, 9, and 16 patients, respectively. Alopecia was almost universal. Other nonhematologic toxicities were generally mild, being of grade 3-4 in only eight patients (fatigue and loss of appetite in two cases, diarrhoea in four cases, peripheral neuropathy and mucositis in one case). Fifteen complete and 37 partial responses have been registered for an 82% (95% CI = 71-91) overall clinical response rate (ORR). Eight complete and 14 partial responses occurred in the 24 patients with locally advanced disease, for a 92% (95% CI = 73-99) ORR, as compared to seven complete and 23 partial responses in the 39 women with metastatic disease, 77% (95% CI = 61-89). A clear dose-response relationship was not observed, since an overall response rate of at least 70% was achieved at all dose levels. However, the ORR increased to 92% in the last four cohorts which included patients who received higher doses of EPI and PTX with G-CSF support. All of the 24 patients with locally advanced disease underwent modified radical mastectomy with axillary dissection. Three of them showed no invasive cancer on pathologic examination, and in another five patients a tumor smaller than 1 cm was found in the surgical specimen of the breast. At a nine-month median follow-up (range 2-14), 11 patients have progressed and three have died. Twenty-three out of 24 patients who underwent surgery are still free from progression. The one-year projected progression-free survival is 77% for the whole population. CONCLUSIONS: The CDDP/EPI/PTX weekly administration is a well tolerated and very effective approach in advanced breast cancer patients. Full doses of all the three drugs can be delivered even in absence of G-CSF support. A very impressive increment of the dose-intensity can be obtained, however, by adding filgrastim. A phase II study is under way to better define the therapeutic efficacy of this regimen in patients with advanced breast cancer.

Weekly paclitaxel-cisplatin administration with G-CSF support in advanced breast cancer. A phase II study.

PURPOSE: In a previous phase I study we found the MTDs of paclitaxel and cisplatin when given together weekly, with or without G-CSF support, in patients with advanced solid tumors. The present study was conducted to define the toxicity and efficacy of this regimen, when used with G-CSF support, in chemotherapy-naive or pretreated patients with advanced breast cancer, and to compare the antiproliferative activity of paclitaxel-cisplatin and paclitaxel-doxorubicin combinations on two human breast cancer cell lines. METHODS: Patients with metastatic breast cancer received weekly paclitaxel (as a 3-hour i.v. infusion) at the dose of 85 mg/m2 (75 mg/m2 in pretreated women) followed by cisplatin (40 mg/m2) for a minimum of 6 weeks. An additional 6 weekly cycles were delivered in patients showing absence of documented disease progression after the first 6 weeks. After the 12th cycle only patients who had shown a substantial tumor shrinkage received 6 further cycles. G-CSF 5 microg/kg was also given, SC on days 3 to 5 of each week, for the whole duration of chemotherapy. The combination of paclitaxel with cisplatin or doxorubicin was also tested in vitro on two breast cancer cell lines (MCF-7 and MDAMB-231). RESULTS: Forty-three women with metastatic breast cancer entered this trial between June 1995 and January 1997. Twenty-seven patients were previously untreated for their metastatic disease (but 23 had previously received adjuvant chemotherapy). The dominant site of disease involvement was visceral in 23, bone in 13, and soft tissues in 7 patients. Seven complete and 15 partial responses were observed in unpretreated patients, while no complete and 6 partial responses were achieved in the pretreated population. The overall response rate, assessed on an 'intent to treat' basis, was 81% (26% CRs) in patients unpretreated for metastatic disease and 37% in those who had received one or more previous chemotherapy regimens. Eighteen responder patients had previously received anthracyclines either as adjuvant chemotherapy (12) or in the treatment of metastatic disease (6). At a median potential follow-up of 12 (range, 3-21) months, 14/27 unpretreated and 12/16 pretreated patients had shown disease progression. The median time to treatment failure was 13 and 7 months, respectively, in the 2 subgroups. The 1-year survival probability was 95% in unpretreated patients. The treatment showed a moderate toxicity in both subgroups of patients. Both hematological toxicity and peripheral neuropathy occurred more frequently in pretreated patients. Treatment-related deaths did not occur, and severe myelosuppression was observed only in pretreated patients with massive liver involvement. Delays in chemotherapy administration were very uncommon, especially during the first 6 treatment cycles, and the average actually delivered dose intensity exceeded 90% in unpretreated patients. The in vitro data on MCF-7 and MDA-MB-231 human breast cancer cell lines showed that exposure to the combination of cisplatin and paclitaxel produced a tumor cell killing similar to that achievable with equivalent concentrations of doxorubicin and paclitaxel. CONCLUSIONS: Weekly paclitaxel and cisplatin with G-CSF support is an active and particularly well tolerated treatment for patients with either unpretreated or pretreated metastatic breast cancer. This approach seems quite effective also in patients relapsing after anthracycline-based adjuvant chemotherapy. In view of the negligible hematological toxicity associated with this regimen, further clinical trials testing the addition of non cross-resistant drugs to this combination should be performed.

Retinoic acid receptors alpha, beta and gamma, and cellular retinol binding protein-I expression in breast fibrocystic disease and cancer.

Retinoids seem to act as agents of chemoprevention and differentiation in breast diseases. Their action is mediated by nuclear receptors, retinoic acid receptors (RAR alpha, RAR beta, RAR gamma) and retinoid X receptors (RXR alpha, RXR beta, RXR gamma) and modulated by cellular retinol binding proteins (CRBP). There are few published data on CRBP expression. In this study, we evaluated the expression of RAR alpha, beta and gamma and CRBP type I (CRBP-I) gene expression in fibrocystic disease (FD) and in breast cancer (BC), studying 14 FD and 20 BC surgical samples by reverse transcription (RT)-PCR. We also evaluated mRNA concentrations in cancer samples by a semiquantitative PCR method, co-amplifying RAR alpha, RAR beta and CRBP-I genes with an unrelated gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as internal control. All benign and malignant breat tissues expressed RAR alpha, beta and gamma, and CRBP-I mRNAs. A greater concentration of RAR beta mRNA was detected in cancer tissues with lower oestrogen and progesterone receptor concentrations, whereas RAR alpha was detected in variable concentrations that were not related to those of steroid receptors. The CRBP-I concentration was similar in all samples studied. We demonstrated that all three RARs and CRBP-I transcripts are expressed in FD, and that RAR beta, RAR gamma and CRBP-I mRNAs also are present in BC tissues. This indicates that both malignant and benign breast tissues may be target for retinoids, justifying the use of natural and synthetic vitamin A derivatives in the chemoprevention of breast disease.

Breast cancer estrogen and progesterone receptors.

Data from 2933 consecutive cases of primary breast carcinoma, observed in our Institute from 1984 to 1994, having documented estrogen (ER) and progesterone (PR) receptor levels, were obtained from the Institute's Hospital Tumor Registry and analysed after being categorised as follows: age, less than or equal to 60 vs. >60; menopausal status, pre-menopausal vs. post-menopausal; histology, ductal vs. lobular vs. others; tumor size, T-1 vs. T-2, T-3, T-4; nodal status, N-0, vs. N+; histologic grade, 1-2 vs. 3; focality, unifocal vs. multifocal; ER status, <10 fmol/mg protein vs. greater than or equal to 15. At multivariate analysis, using a logistic model including age, histology, tumor size, nodal status, histologic grade, uni-multifocality and PGF/ER status, significant associations were, for ER status: PGR status (OR = 34.01, 95% CI:20.08-57.80), histology (OR = 3.24, 95% CI:1.85-5.67), histologic grade (OR = 2.18, 95% CI:1.38-3.42), menopausal status (OR = 2.17, 95% CI:1.26-3.74), age (OR = 34.01, 95% CI:20.08-57.80), menopausal status (OR = 5.27, 95% CI:1.43-3.33), age (OR = 1.71, 95% CI:1.13-2.59). The finding that estrogen receptor positivity was more prevalent among tumors with lobular histology seems to suggest the possibility of fundamental differences in tumor biology ductal and lobular cancers.

Sociodemographic factors associated with the diagnostic staging of breast cancer in southern Italy.

BACKGROUND: There are marked regional differences in breast cancer mortality rates in Italy, probably linked to factors such as diagnostic delay, therapeutic strategies, and biologic and sociodemographic differences. To investigate a possible link between sociodemographic factors (e.g. age, education, and residence) and delay in the diagnosis of breast cancer, data were evaluated from all such patients from our Institute living in the Campania Region of Southern Italy for 1991-1993. METHODS: Patients were grouped into Tis-T1/N0-N+ versus T2-4/N0-N+ and the variables examined were age (< 40, 41-50, 51-60, > 60 years), education (< or = 5 vs. > 5 school years) and residence (urban vs. rural). An analysis was made using the Pearson's Chi-square test and the multiple logistic regression. RESULTS: Statistically significant differences were found for both residence (P = 0.04) and education level (P = 0.03) in the older than 60 years age group, but only for residence (P = 0.03) in the 51-60 years age group. The risks according to Mantel-Haenszel were 1.28 for education (P = 0.08) and 1.32 for residence in rural municipalities (P = 0.05). The odds ratio for residence in rural municipalities, adjusted by education and by the education-residence interaction, was 2.26 (95% confidence interval [CI], 1.12-4.54) in the 51-60 years age group and 1.74 (95% CI, 1.01-3.00) in the older than 60 years age group. CONCLUSIONS: These data clearly indicate that residents of rural municipalities, as well as poorly educated subjects, are more likely than their respective counter-parts to have a delayed diagnosis of breast cancer.