Inflammatory Breast Cancer: A Distinct Clinicopathological Entity Transcending Histological Distinction.

INTRODUCTION: Although well recognized in breast oncology literature, histologic subtypes have not been previously described in inflammatory breast cancer (IBC). The purpose of this study was to describe lobular subtype in IBC and assess the impact of histology on patient outcomes. METHODS: We performed a retrospective analysis of 659 IBC patients at MD Anderson Cancer Center between January 1984 and December 2009. Patients with Invasive Lobular, Mixed Invasive Ductal and Lobular, or Invasive Ducal Carcinomas (ILC, MIC, IDC, respectively) comprise the subject of this report. Patient characteristics and survival estimates were compared by using chi-square test and Kaplan-Meier method with log-rank statistic. Cox proportional hazards models were fit to determine association of histology with outcomes after adjustment for other characteristics. RESULTS: A total of 30, 37, and 592 patients were seen to have invasive lobular, mixed, or ductal histology, respectively. Grade 3 tumors were more common in the ductal group (78%) than in the lobular (60%) or mixed (61%) group (P = 0.01). The 3-year overall survival rates were 68%, 64%, and 62% in the lobular, mixed, and ductal groups, respectively (P = 0.68). After adjustment, histology did not have a significant effect on death in the lobular group (HR = 0.70, 95% confidence interval [CI]: 0.26-1.94; P = 0.50) or mixed group (HR = 0.53, 95% CI: 0.25-1.13; P = 0.10) compared with the ductal group. CONCLUSION: In this cohort of IBC patients, lobular histology was seen in 4.5% cases. Histology does not appear to have a significant effect on survival outcomes in IBC patients, unlike in patients with non-inflammatory breast cancer (n-IBC), indicating the distinct biological behavior of the IBC phenotype.

Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer†.

BACKGROUND: Everolimus synergistically enhances taxane-induced cytotoxicity in breast cancer cells in vitro and in vivo in addition to demonstrating a direct antiproliferative activity. We aim to determine pharmacodynamics changes and response of adding everolimus to standard neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Phase II study in patients with primary TNBC randomized to T-FEC (paclitaxel 80 mg/m(2) i.v. weekly for 12 weeks, followed by 5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2) every 3 weeks for four cycles) versus TR-FEC (paclitaxel 80 mg/m(2) i.v. and everolimus 30 mg PO weekly for 12 weeks, followed by FEC). Tumor samples were collected to assess molecular changes in the PI3K/AKT/mTOR pathway, at baseline, 48 h, 12 weeks, and at surgery by reverse phase protein arrays (RPPA). Clinical end points included 12-week clinical response rate (12-week RR), pathological complete response (pCR), and toxicity. RESULTS: Sixty-two patients were registered, and 50 were randomized, 27 received T-FEC, and 23 received TR-FEC. Median age was 48 (range 31-75). There was downregulation of the mTOR pathway at 48 h in the TR-FEC arm. Twelve-week RR by ultrasound were 29.6% versus 47.8%, (P = 0.075), and pCR were 25.9% versus 30.4% (P = 0.76) for T-FEC and TR-FEC, respectively. mTOR downregulation at 48 h did not correlate with 12-week RR in the TR-FEC group (P = 0.58). Main NCI grade 3/4 toxicities included anemia, neutropenia, rash/desquamation, and vomiting in both arms. There was one case of grade 3 pneumonitis in the TR-FEC arm. No grade 3/4 stomatitis occurred. CONCLUSION: The addition of everolimus to paclitaxel was well tolerated. Everolimus downregulated mTOR signaling but downregulation of mTOR at 48 h did not correlate with 12-week RR in the TR-FEC group. CLINICAL TRIAL NUMBER: NCT00499603.

Outcome of metastatic breast cancer in selected women with or without deleterious BRCA mutations.

The aim of this study was to compare the time-to progression and overall survival (OS) in patients with metastatic breast cancer (MBC) with and without deleterious BRCA1/2 mutations. 195 women with MBC who were referred for BRCA genetic testing between 1997 and 2011 were included in the study. Logistic regression models and Cox proportional hazards models were fit to determine the associations between clinical variables and outcomes. Of 195 women with MBC, 21 % (n = 41) were positive for BRCA1/2 mutations. The number of metastatic sites at the time of metastatic disease was not different between BRCA1 versus BRCA2 carriers versus non-carriers (P = 0.77). The site of first metastasis was visceral-only in 70 % of BRCA1 carriers compared to 9 % in BRCA2 carriers and 37 % in non-carriers (P = 0.001). Median follow-up was 2.8 years. BRCA non-carriers and BRCA2 carriers had a longer time-to progression and OS compared to BRCA1 carriers (median time-to progression = 1.3 vs. 0.9 vs. 0.7 years; P = 0.31, and median OS = 4.88 vs. 4.94 vs. 1.34 years; P = 0.0065). In a multivariate model, no association was identified between BRCA positivity and time-to-event outcomes (P > 0.28). In addition, patients with triple-negative MBC carried a poorer prognosis irrespective of their BRCA status (P = 0.058 and P = 0.15 for the interaction term of BRCA status and triple-negative for time-to progression and OS, respectively). Our data indicate that BRCA1 carriers diagnosed with MBC have worse outcomes compared to BRCA2 carriers and non-carriers. However, the differences in outcome did not reach statistical significance likely due to small sample sizes.

Surveillance of childhood vaccine-preventable diseases at health facilities in Jeddah, Saudi Arabia.

A cross-sectional study was conducted at 33 randomly selected health facilities in Jeddah, Saudi Arabia, to assess health facilities' performance and health workers' knowledge of surveillance activities for childhood vaccine-preventable diseases. The WHO surveillance assessment questionnaire and a specially designed knowledge questionnaire were used. There were deficiencies in some surveillance items. The percentages of health facilities that had the surveillance manual and correctly filled clinical registers were 57.6% and 60.6% respectively. In the 6 months preceding the study, 36.4% of facilities lacked the appropriate surveillance forms while only 18.2% had received supervision reviews. Only one-quarter of health workers had a satisfactory knowledge score.

Pharmacoepidemiological study of self-medication in adults attending pharmacies in Alexandria, Egypt.

A cross-sectional study was conducted to determine the extent and pattern of self-medication among adults, to identify their knowledge and practice concerning the purchased drugs and to calculate prescribing and purchaser care indicators. Following WHO methods, 35 pharmacies were randomly selected from districts in Alexandria city, Egypt. Of 1294 clients interviewed at these pharmacies, 1050 (81.1%) purchased self-medication; the commonest reason given was a belief that the condition was minor. The most frequently dispensed drugs were those for the respiratory system. The mean number of drugs per encounter was 1.10, mean cost LE 7.29 and mean dispensing time 2.53 minutes. Purchasers' knowledge and practice regarding the purchased drugs were poor.

An epidemiological study on survival of oropharyngeal cancer cases in Alexandria, Egypt.

A retrospective cohort study was conducted to determine the 5-year survival and prognostic factors for survival for 407 oropharyngeal cancer cases registered in the 3 main hospitals in Alexandria, Egypt, from 1996-2000. Survival analysis was conducted using Kaplan-Meier curves, and multivariate Cox regression analysis. The overall 5-year survival rate was 30.8%. Multivariate analysis showed that significant prognostic factors for survival were tumour stage (hazard ratio = 2.39; 95% CI: 1.41-11.72), tumour site and patient's age. Secondary prevention of oral cancers can be conducted through examination of the oral cavity to find precancerous and early cancerous lesions and hence improve survival.

An educational programme on dengue fever prevention and control for females in Jeddah high schools.

A mass communication campaign was conducted at 20 randomly selected female high schools and 2 school supervision centres in Jeddah to improve knowledge, attitudes and practices of students, teachers and supervisors about dengue fever. A total of 5977 pre- and post-intervention questionnaires were completed and the intervention was conducted using lectures and audiovisual aids. A marked improvement in all areas of knowledge, attitudes and practices was observed after the programme in all groups. Students obtained the highest improvement in mean knowledge scores after the programme compared to the other 2 groups. There is a need to expand such programmes to all Jeddah schools.

An educational programme on dengue fever prevention and control for females in Jeddah high schools

A mass communication campaign was conducted at 20 randomly selected female high schools and 2 school supervision centres in Jeddah to improve knowledge, attitudes and practices of students, teachers and supervisors about dengue fever. A total of 5977 pre- and post-intervention questionnaires were completed and the intervention was conducted using lectures and audiovisual aids. A marked improvement in all areas of knowledge, attitudes and practices was observed after the programme in all groups. Students obtained the highest improvement in mean knowledge scores after the programme compared to the other 2 groups. There is a need to expand such programmes to all Jeddah schools

Pharmacoepidemiological study of self-medication in adults attending pharmacies in Alexandria, Egypt

A cross-sectional study was conducted to determine the extent and pattern of selfmedication among adults, to identify their knowledge and practice concerning the purchased drugs and to calculate prescribing and purchaser care indicators. Following WHO methods, 35 pharmacies were randomly selected from districts in Alexandria city, Egypt. Of 1294 clients interviewed at these pharmacies, 1050 [81.1%] purchased self-medication; the commonest reason given was a belief that the condition was minor. The most frequently dispensed drugs were those for the respiratory system. The mean number of drugs per encounter was 1.10, mean cost LE 7.29 and mean dispensing time 2.53 minutes. Purchasers' knowledge and practice regarding the purchased drugs were poor

Surveillance of childhood vaccinepreventable diseases at health facilities in Jeddah, Saudi Arabia

A cross-sectional study was conducted at 33 randomly selected health facilities in Jeddah, Saudi Arabia, to assess health facilities' performance and health workers' knowledge of surveillance activities for childhood vaccine-preventable diseases. The WHO surveillance assessment questionnaire and a specially designed knowledge questionnaire were used. There were deficiencies in some surveillance items. The percentages of health facilities that had the surveillance manual and correctly filled clinical registers were 57.6% and 60.6% respectively. In the 6 months preceding the study, 36.4% of facilities lacked the appropriate surveillance forms while only 18.2% had received supervision reviews. Only one-quarter of health workers had a satisfactory knowledge score

An epidemiological study on survival of oropharyngeal cancer cases in Alexandria, Egypt

A retrospective cohort study was conducted to determine the 5-year survival and prognostic factors for survival for 407 oropharyngeal cancer cases registered in the 3 main hospitals in Alexandria, Egypt, from 1996-2000. Survival analysis was conducted using Kaplan-Meier curves, and multivariate Cox regression analysis. The overall 5-year survival rate was 30.8%. Multivariate analysis showed that significant prognostic factors for survival were tumour stage [hazard ratio = 2.39; 95% CI: 1.41-11.72], tumour site and patient's age. Secondary prevention of oral cancers can be conducted through examination of the oral cavity to find precancerous and early cancerous lesions and hence improve survival

Defining prognosis for women with breast cancer and CNS metastases by HER2 status.

BACKGROUND: The purpose of this retrospective study was to determine, in a cohort of patients with breast cancer and central nervous system (CNS) metastases, the effect of trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive disease and to compare this with that of patients with HER2-negative disease. METHODS: Five hundred and ninety-eight patients with invasive breast cancer, CNS metastases and known HER2 status were identified. Time to CNS metastases and survival after CNS metastases were estimated by the Kaplan-Meier method, and Cox models were fitted to determine the association between HER2 status, trastuzumab treatment and outcomes after adjustment for other patient characteristics. RESULTS: In the multivariable model, patients with HER2-negative disease [Hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.15-1.95, P = 0.003] and patients with HER2-positive disease who did not receive trastuzumab (HR 2.13, 95% CI 1.51-3.00, P < 0.0001) had shorter times to CNS metastases compared with patients with HER2-positive disease who had received trastuzumab as first-line therapy for metastases. Furthermore, patients with HER2-negative disease (HR 1.66, 95% CI 1.31-2.12, P < 0.0001) and patients with HER2-positive disease who had never received trastuzumab (HR 1.34, 95% CI 0.78-2.30, P = 0.28) had an increased hazard of death compared with patients with HER2-positive disease who had received trastuzumab before or at the time of CNS metastases diagnosis. CONCLUSION: In our cohort of patients with breast cancer and CNS metastases, patients with HER2-positive disease treated with trastuzumab had longer times to development of and better survival from CNS metastases compared with patients with HER2-positive disease who had never received trastuzumab and patients with HER2-negative breast cancer.

Assessment of safety of frozen foods.

This study aimed to assess the microbiological quality of 90 frozen food samples (50 samples of raw frozen vegetables including molokeya, okra, green peas, peas + carrot, and artichoke, 20 of frozen poultry products and 20 of frozen meat products), and to assess the level of women practice during handling. A cross-sectional study was conducted. Results showed that the mean aerobic mesophilic plate count of frozen vegetables was 3.4 x 10(5) +/- 7.3 x 10(5) cfu/g. The mean mold and yeast count was 3.9 x 10(3) +/- 1.1 x 10(4) cfu/g. The mean coliform count was 3.9 x 10 +/- 6.6 x 10 m.o./g. In case of meat product, the mean aerobic count was 2.3 x 10(5) +/- 3.2 x 10(5), that of mold and yeast was 2.5 x 10(5) +/- 8.8 x 10(5) cfu/g and that of coliform was 3.2 x 10(2) +/- 3.8 x 10(2) m.o./g. Poultry products on the other hand had a mean aerobic count of 6.8 x 10(5) +/- 1.6 x 10(6), a mean mold and yeast count of 3.5 x 10(5) +/- 7.4 x 10(5) cfu/g and a mean coliform count of 6.4 x 10(2) +/- 5.2 x 10(2) m.o./g. Fecal coliforms were detected only in 60.0% of meat product samples and in 45.0% of poultry product samples. On the other hand Staph aureus was detected only in 10.0% of poultry product samples. Difference between the 5 types of vegetables was statistically significant (P = 0.00, and 0.02, respectively) for total plate and mold and yeasts counts. Among the 113 interviewed women, 80 used frozen food products. Twenty six of them (32.5%) had scores < 50%, those were classified as being bad as they were handling frozen food improperly which would contribute to outbreaks of food borne diseases. Less than 4% of the users used satisfactory practice during handling frozen foods. Illiteracy affected significantly the level of practice.

Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial.

PURPOSE: Preclinical studies have demonstrated that the adenovirus type 5 E1A gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial. PATIENTS AND METHODS: An E1A gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12). RESULTS: E1A gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression was accompanied by HER-2/neu downregulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites. CONCLUSION: These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.

Phase I-II vinorelbine (Navelbine) by continuous infusion in patients with metastatic breast cancer: cumulative toxicities limit dose escalation.

Vinorelbine (Navelbine) has significant activity against breast carcinoma and is less neurotoxic than vinblastine. Because vinblastine has improved activity when administered by continuous infusion, we conducted a Phase I-II study to determine the maximum tolerated dose (MTD) of vinorelbine when given by continuous infusion and the response rates to it in heavily pretreated metastatic breast cancer patients. Between April 1994 and August 1997, 87 patients were entered in the study. All were female and had proven metastatic breast cancer. Ninety-five percent of them had received prior doxorubicin treatment, and 74% had received prior paclitaxel treatment. In Phase I of the study, all patients received 8 mg of vinorelbine by intravenous (i.v.) bolus followed by a continuous infusion of vinorelbine over 96 hr. When the MTD was determined, patients were entered in the Phase II arm to assess treatment responses and cumulative toxic reactions. In the Phase I arm (43 patients, 182 cycles), we determined the MTD of vinorelbine to be 8 mg by i.v. bolus followed by a continuous infusion of 11 mg/m2/day over 4 days. The dose-limiting toxic reaction was grade 3-4 granulocytopenia in 35% of the cycles and neutropenic fever in 15% of the cycles. Forty-four patients (193 cycles) were treated at the MTD. Seven (16%) of them had a response (2 complete responses, 5 partial responses). The median durations of response and survival were 4.3 and 8.6 months, respectively. However, cumulative toxic reactions (neutropenic fever and stomatitis) in 22 patients (50%) required dose reductions. A continuous infusion of vinorelbine can be safely administered but with a narrow therapeutic index because of cumulative toxic reactions. We recommend a modified MTD of vinorelbine: 8 mg by i.v. bolus followed by a continuous infusion of 10 mg/m2/day over 4 days. However, this treatment schedule offers no apparent advantage over the commonly used weekly vinorelbine schedule.

Phase I study of vinorelbine and paclitaxel by 3-hour simultaneous infusion with and without granulocyte colony-stimulating factor support in metastatic breast carcinoma.

BACKGROUND: The purpose of the study was to determine the maximum tolerated dose (MTD) of vinorelbine and paclitaxel given concomitantly in patients with advanced breast carcinoma, the toxicity of this combination, and whether the addition of granulocyte colony-stimulating factor (G-CSF) would allow administration of higher doses of the combination. METHODS: Between January 1994 and January 1995, 38 patients were entered on this study. All patients received vinorelbine and paclitaxel administered simultaneously over 3 hours and repeated every 21 days as frontline therapy for metastatic breast carcinoma. Twenty-five patients (Group 1) did not receive prophylactic G-CSF, and 13 patients (Group 2) received prophylactic G-CSF. Toxic effects were documented prospectively using the National Cancer Institute grading system. RESULTS: One hundred eighty-seven (Group 1) and 111 (Group 2) cycles were administered. For Group 1, Grade 3-4 granulocytopenia was encountered in 72% of the cycles and neutropenic fever in 30% of the cycles. For Group 2, Grade 3-4 granulocytopenia and neutropenic fever were encountered in 23% and 4% of the cycles, respectively. Grade 3-4 fatigue and myalgia, respectively, were encountered in 11% and 3% of the cycles in Group 1, whereas they were reported in 12% and 1% of the cycles in Group 2. The MTD of this combination without prophylactic G-CSF was 25 mg/m2 of vinorelbine and 150 mg/m2 of paclitaxel, the dose-limiting toxicity (DLT) being neutropenic fever and myalgia. The MTD of this combination with G-CSF was 36 mg/m2 of vinorelbine and 150 mg/m2 of paclitaxel, the DLT being myalgia and fatigue. CONCLUSIONS: The authors conclude that vinorelbine and paclitaxel can be safely administered concomitantly and are well tolerated. Phase II studies are recommended to test the efficacy of this schedule.

Prevalence and possible risk factors of Helicobacter pylori infection among children attending Damanhour Teaching Hospital.

Helicobacter pylori (H. pylori) is a major cause of gastrointestinal disease in children. The factors influencing the acquisition and prevalence of H. pylori infection remain incompletely understood. In the present study, the prevalence and possible risk factors of H. pylori infection were studied among children aged 1.5-16 years who were attending the pediatric outpatient clinic of Damanhour Teaching Hospital. Blood samples were drawn and IgG seroprevalence of H. pylori among the studied children was determined using ELISA kits. A specially designed questionnaire inquired about personal, socioeconomic, household characteristics, feeding history during infancy and the child's health data was completed for every child. Results revealed that the overall seroprevalence of H. pylori infection was 50.5 %. The prevalence was widely age dependent: it was 60.6% among those age > or = 5 years and only 25.9% among those < 5 years (OR = 4.4; 95% CI = 1.6-11.9). Increased crowding in bed was also an associated factor; the prevalence among children where > or = 3 share a bed was 59.7% compared to only 26.9% among those where < 3 persons share a bed (OR = 4.1; 95% CI = 1.5-10.9). The prevalence among children who were breast fed for < 1 year was 64.7% compared to only 42.4% among those who were fed for > or =1 year (OR = 2.5; 95% CI = 1.1-5.9). After controlling for possible confounding in a Stepwise Multiple Logistic Regression model, independent predictors for H. pylori infection were: increasing age (> or = 5 years), overcrowding in bed (> or = 3/ bed) and shorter duration of breast-feeding (< 1 year) during infancy. It could be concluded that, H. pylori was highly prevalent among the sampled children and the possible risk factors are related to the community. So, there is a need to early diagnose, treat and eradicate infection during childhood to prevent its complications during adulthood.

Phase I study of vinorelbine by 96-hour infusion in advanced metastatic breast cancer.

The purpose of this study was to evaluate the maximum tolerated dose and the toxicity profile of vinorelbine administered by continuous infusion for 96 hours to patients who had received prior chemotherapy for metastatic breast cancer. Forty-three patients with metastatic breast cancer were treated with vinorelbine 8 mg intravenously for 10 minutes (day 1) followed by continuous infusion of vinorelbine for 96 hours. Treatments were repeated every 3 weeks. Eighty-eight percent of the patients had had two or more prior chemotherapeutic regimens: 91% had prior doxorubicin therapy and 77% had prior paclitaxel therapy. All 43 patients were evaluable for toxicity. The median age was 49 years. All patients had a performance status less than or equal to 2 and a life expectancy more than 12 weeks. Eight dose levels were evaluated, and a total of 182 cycles were given. National Cancer Institute grade III or IV granulocytopenia was observed in 64 (35%) cycles, neutropenic fever in 27 (15%) cycles, fatigue (National Cancer Institute grade III or IV) in 18 (10%) cycles, and hand-foot syndrome in 8 (4%) cycles. In 17 (9%) cycles, patients were hospitalized. The maximum tolerated dose of this regimen was determined to be vinorelbine 8 mg intravenously for 10 minutes (day 1) followed by continuous vinorelbine infusion 11 mg/m2 for 96 hours. The dose-limiting toxicity was neutropenic fever and stomatitis.

Colitis associated with docetaxel-based chemotherapy in patients with metastatic breast cancer.

BACKGROUND: Docetaxel and vinorelbine as combined treatment for metastatic breast cancer can have the dose-limiting toxic effects of mucositis and neutropenic fever. We report unexpected ischaemic colitis in six patients associated with docetaxel-based therapy, three of whom were treated in a phase I study designed to establish the maximum tolerated dose of this combination with the prophylactic use of granulocyte-colony-stimulating factor. METHODS: Between August, 1997, and December, 1998, 14 patients with metastatic breast cancer were treated with vinorelbine, docetaxel, and granulocyte-colony-stimulating factor in a phase I study. Three patients developed colitis similar to that seen in typhlitis. Three additional patients were identified during scheduled review of toxic effects in patients participating in clinical trials involving docetaxel. FINDINGS: Three patients on combined vinorelbine and docetaxel developed colitis-like symptoms. Two patients died, one from necrotic bowel and the other from neutropenic fever and colitis. Two of the patients presented on day 7 and day 8 of chemotherapy, respectively, with neutropenic fever and abdominal pain; the third patient developed neutropenia without fever and abdominal pain on day 8. The other three patients were treated with docetaxel, docetaxel and pamidronate disodium, or docetaxel and cyclophosphamide. All three patients presented with abdominal pain on days 10, 5, and 4, respectively. One had non-neutropenic fever, another had neutropenic fever, and the third was afebrile and non-neutropenic at the time of presentation with abdominal pain. Three patients had blood in their diarrhoea, abdominal tenderness, or both. Computed tomography of the abdomen and pelvis showed features of colitis in three patients. INTERPRETATION: This serious complication may result from the use of docetaxel and may be exacerbated by its combination with vinorelbine. Study of hospital-based patients treated with taxane-based chemotherapy is underway to find out the frequency of such complications.