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Objective: The aim of the present retrospective study was to compare two breast-conserving techniques, segmental resection and standard lumpectomy, for the treatment of breast cancer regarding their oncological safety. Quality of life aspects were evaluated by assessing the respective postsurgical cosmetic results. Patients and Methods: 190 women with breast cancer located in the superior and lateral quadrant were included in the study. Sixty patients were treated with segmental resection (group 1), whereas 130 underwent standard lumpectomy (group 2). Tumor sizes were determined and excised tissue specimens were analyzed for positive or negative resection margins. Patients were given a 16-item questionnaire for the postsurgical self-assessment of the cosmetic outcome. Results: No statistically significant difference was found concerning the number of positive resection margins between the groups (25 vs. 30%, p = 0.46). Exceptions were ventral margins, which predominated in group 2 (p = 0.016). Group 1 revealed a significantly larger maximum tumor size with negative margins as compared to group 2 (26.6 vs. 17.0 mm). General satisfaction with the cosmetic results was comparable between groups. Conclusions: Segmental resection surgery, as a method of breast conservation therapy, can be used to treat larger breast lesions as compared to standard lumpectomy. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We evaluated the survival benefit, safety, feasibility, and tolerability of dose-dense (DD) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer. Randomised patients (n=216) received DD or conventional-schedule (CS) chemotherapy. Dose-dense regimen patients (n=108) received epirubicin 90 mg m-2 plus paclitaxel 175 mg m-2 in four 14-day cycles, then cyclophosphamide 600 mg m-2, methotrexate 40 mg m-2, and fluorouracil 600 mg m-2 (CMF 600/40/600) in three 14-day cycles, plus filgrastim 5 microg kg day-1 as growth support in every cycle. Conventional-schedule regimen patients (n=108) received epirubicin 90 mg m-2 plus cyclophosphamide 600 mg m-2 in four 21-day cycles, then CMF 600/40/600 in three 21-day cycles, plus filgrastim if required. After a median follow-up of 38.4 months, 71 patients (33%) relapsed or died: DD, 33 patients (15 deaths); CS, 38 patients (22 deaths). Dose dense showed a trend for improved disease-free survival (DFS) and overall survival (OS). Four-year rates of DFS and OS were 64 and 85% for DD, and 58 and 75% for CS. All seven cycles were administered to 208 patients (96%). Rates of cycle delay, discontinuation, dose reduction, and adverse events were similar in both groups. Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF, supported by filgrastim, is safe and improves survival for patients with node-positive breast cancer. [ABSTRACT FROM AUTHOR]

Background: Several studies showed that pathologic complete response (pCR) is a surrogate for disease free survival (DFS) and overall survival (OS). Combinations of trastuzumab and anthracyclines in HER2-positive breast cancer are highly active but associated with a high incidence of cardiotoxicity. The risk of cardiac damage can be significantly reduced through liposomal encapsulation of anthracyclines. This phase I/II study was initiated to evaluate the combination of non-pegylated liposomal doxorubicin (NPLD), paclitaxel and lapatinib as primary treatment for patients with early stage, HER2-positive primary breast cancer. Patients and Methods: Patients with newly diagnosed HER2-positive (IHC 3+ or FISH+) early stage (T1c N1-2 or T2 N0-2) breast cancer were treated with NPLD (60mg/m²; day 1), paclitaxel (175mg/m², day 1) and lapatinib (750-1500 mg orally daily) in 3-week intervals for up to 6 cycles. The primary endpoints were dose-limiting toxicities (DLT) and pathological complete response (pCR). Secondary endpoints include safety, incidence of cardiac events, and clinical response. Exploratory endpoints include molecular markers for sensitivity or resistance to chemotherapy and/or lapatinib evaluated. Results: A total of 84 patients have been included. No dose-limiting toxicity were observed and the maximum tolerated doses were NPLD 60mg/m², paclitaxel 175mg/m² and lapatinib 1500mg. Recommended phase 2 doses (P2D) were NPLD 60mg/m², paclitaxel 175mg/m² and lapatinib 1250mg. The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents. No cardiac event has been observed to date. Preliminary efficacy data confirm a pCR breast rate of 41.7% and pCR rate in breast and lymph nodes of 37.5%, in 32 evaluable patients treated at ≥ P2D. Conclusions: The combination of NPLD, paclitaxel and lapatinib is well tolerated and has high antitumor activity in patients with HER2-positive primary breast cancer. Updated results of all 84 patients will be presented. [ABSTRACT FROM AUTHOR]

Background: Increases in overweight and obesity among youths have resulted in the diagnosis of Type 2 diabetes mellitus (T2DM) at earlier ages. The impact of lifestyle-related factors has been implicated; however, its relation to morbidity and mortality and sex differences remain unclear. We aimed to document the changes in risk factors and sex differences associated with T2DM-related morbidity and mortality during 1995-2015., Method: We used mortality rates and morbidity estimates from the Global Burden of Diseases Study 2016 using Disability-Adjusted Life Years (DALY). Multiple linear regression analyses were used to determine associations between T2DM-related mortality and related risk factors. DALYs were grouped by country income level, and were stratified by sex., Results: Increases in mortality were observed for both sexes, and females tended to have higher mortality rates per 100,000 persons. Body mass index (BMI) continued to be the leading risk factor for T2DM-related mortality, and increases in BMI were more common in low- and middle-income countries (LIC and MIC). Low physical activity was strongly associated with mortality rates, followed by dietary risks and smoking (2.4; 1.4; 0.8 per 100,000 persons, respectively). Similar patterns were observed after adjustments for income level, sex, and age. DALYs continued to show increasing trends across all income levels during 1995-2015 (high-income (HIC):16%; MIC: 36%; LIC: 12%). Stratification by sex showed similar results; males had fewer T2DM DALYs than females, though a greater increase was observed among males., Conclusion: Overall, T2DM related mortality was higher among females. Compared to in HIC, there appeared to be a considerable increase in the burden of T2DM in MIC and LIC, where BMI is the leading risk factor for T2DM-related mortality. Prevention programs should emphasize related risk factors according to the existing standard of care.

Purpose: Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer. Their effect in early breast cancer is controversial. Ibandronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile. It therefore qualifies as potential agent for adjuvant use., Patients and Methods: The GAIN (German Adjuvant Intergroup Node-Positive) study was an open-label, randomized, controlled phase III trial with a 2 × 2 factorial design. Patients with node-positive early breast cancer were randomly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ibandronate 50 mg per day orally for 2 years or observation. In all, 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival (DFS) by ibandronate from 75% to 79.5% by using a two-sided α = .05 and 1-β of 80%. We report here the efficacy analysis for ibandronate, which was released by the independent data monitoring committee because the futility boundary was not crossed after 50% of the required DFS events were observed., Results: Between June 2004 and August 2008, 2,015 patients were randomly assigned to ibandronate and 1,008 to observation. Patients randomly assigned to ibandronate showed no superior DFS or overall survival (OS) compared with patients randomly assigned to observation (DFS: hazard ratio, 0.945; 95% CI, 0.768 to 1.161; P = .589; OS: HR, 1.040; 95% CI, 0.763 to 1.419; P = .803). DFS was numerically longer if ibandronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years (test for interaction P = .093)., Conclusion: Adjuvant treatment with oral ibandronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy.

Background: Elderly breast cancer patients are underrepresented in clinical trials and this leads to a lack of knowledge regarding the tolerance and side effects of modern chemotherapy regimens, especially in dose-dense (dd) or dose-intensified combination., Patients and Methods: In this analysis, data from 4 German, randomized (neo-)adjuvant trials, including anthracycline-based chemotherapy, were evaluated for toxicity, compliance and feasibility. Patients were grouped according to age., Results: Of the 4,775 patients, 73.6% were < 60 years, 15.8% were 60-64 years and 10.6% were > 64 years. The patients' compliance decreased with increasing age, the rate of therapy discontinuations was 10.3%; 16.0% were > 64 years old (p < 0.001). The rate of dose reductions also increased with increasing age in the docetaxel/doxorubicin/cyclophosphamide (TAC) (p overall = 0.02) and 5-fluorouracil/epirubicin-cyclophosphamide (FE120C) (p overall < 0.001) treatment groups. Neutropenia grade 3 + 4 in patients of > 64 years was 77% in FE120C- compared to 55% in TAC-treated patients (with primary granulocyte colony-stimulating factors (G-CSFs)). The incidence of febrile neutropenia (FN) was lowest in the regimens without additional taxanes. FN in patients aged > 64 years was lower in the FE120C- than in TAC-and dd-doxorubicin/docetaxel-treated groups., Conclusion: The range and intensity of toxicity increased with age. Neutropenia did not increase significantly in the dd groups; the highest rate was seen in FE120C-treated patients. FE120C without G-CSFs is not an option in patients older than 64 years.

BACKGROUND: The aim of this article was to evaluate the prognostic value of the MammaPrint(TM) signature in women $$ 60 years with invasive breast cancer. PATIENTS AND METHODS: 60 female patients were included in this prospective study. Eligibility criteria included: pT1c-3, pN0-1a, grade 2/3, hormone receptor-positive and HER2-negative tumor. The clinical risk was determined by Adjuvant! Online (AOL). RESULTS: 38 patients (63%) where considered to be low-risk patients by the 70-gene signature, while 22 (37%) were considered to be high-risk patients. No statistically significant differences between low- and high-risk groups could be detected for conventional prognostic parameters, particularly not for Ki-67. By AOL, 33 patients (55%) were considered to be at high risk, of which 20 had a discordant MammaPrint(TM) result. The discordance rate between the profile and AOL was 48%, which is higher than in previous publications. When the 70-gene signature was used in combination with the clinical risk assessment, the recommendation for adjuvant systemic treatment differed in 11 patients (18%). CONCLUSIONS: In the intermediate-risk subgroup, the 70-gene signature could be useful to decide in elderly patients whether they may benefit from adjuvant chemotherapy or not. Conventional clinicopathological factors were not suitable for a prediction of the 70-gene signature results in these patients.

Background/aim: The aim of the present study was to investigate the effects of conventional and dose-dense chemotherapy on serum levels of soluble adhesion molecules sICAM-1 and sVCAM-1 in node-positive patients with breast cancer., Patients and Methods: sICAM-1 and sVCAM-1 were measured in the blood serum of 147 patients with breast cancer and with 1 to 3 affected lymph nodes prior to and after conventional or dose-dense chemotherapy within a randomized phase III study (NOGGO trial)., Results: The increase in sICAM-1 (p<0.0001) and sVCAM-1 (p<0.001) levels after chemotherapy was statistically significant within the entire sample and the dose-dense study arm. sVCAM-1 levels were not altered by conventional chemotherapy, but were markedly and significantly increased after the dose-dense regimen. Higher sICAM-1 concentrations were found in postmenopausal patients, and the difference was significant before, but not after treatment. There was no significant correlation with other prognostic criteria., Conclusion: Both sVCAM-1 and sICAM-1 levels changed significantly after adjuvant chemotherapy, the effect being more marked under the dose-dense regimen. The possible prognostic relevance of adhesion molecule concentration and the effect of different modes of chemotherapy remains to be determined.

Background: Transvaginal video-assisted cholecystectomy with rigid instruments is a new procedure that combines natural orifice surgery (NOS) with classic laparoscopy. This hybrid technique requires conventional laparoscopy via an umbilical incision. To date it is unclear if this procedure is safe and feasible in routine practice., Methods: We report on a case series of 128 women who consented to transvaginal cholecystectomy. Data, including visual analog scores (VAS), were collected prospectively via a standard digital spreadsheet. Patients completed satisfaction questionnaires within 10 days after discharge from hospital. We report on outcomes, age, body mass index, operating time, complications, pain scores, and patient satisfaction., Results: In 115 (89.8%) patients the procedure was performed as a transvaginal operation. In 11 women (8.6%), we converted to standard laparoscopy, and in 2 cases (1.6%), we converted to an open procedure. Mean age was 52.4 years (range = 23-78 years) and mean body mass index was 27.8 (range = 18.8-42). Mean operating time was 60.6 min (range = 22-110 min). Other procedures were combined with hybrid cholecystectomy in six cases. Complications following transvaginal access included one vaginal bleeding, one perforation of the urinary bladder, and one superficial lesion of the rectum. In one case the hepatic duct had to be stented due to leakage after the procedure via endoscopic retrograde cholangiography. Mean VAS on day 1 was 2.26 (± 0.31 SEM) and on day 2 it was 1.53 (± 0.35 SEM). In a postoperative questionnaire, 95% of patients indicated that they would recommend this procedure to other patients., Conclusions: Transvaginal cholecystectomy is a safe and easy-to-learn procedure. Possible complications are different than those of standard laparoscopic procedures. Trauma to the abdominal wall and scarring is minimal. Postoperative pain scores were not different than those of standard laparoscopy and a high percentage of patients are satisfied with the procedure.

SUMMARY: In women with estrogen receptor(ER)- and ErbB2 (HER2)-positive breast cancer, a vicious cycle is established between ER mechanisms of action and the growth factor receptor network, leading to enhanced cell proliferation and endocrine resistance. As such, co-targeting ErbB1 and ErbB2 with lapatinib in combination with hormonal therapy is an attractive approach to enhance the efficacy of either tamoxifen or estrogen deprivation. As demonstrated in the EGF30008 trial, a combined targeted strategy with letrozole and lapatinib significantly increased progression-free survival and clinical benefit rates in patients with metastatic breast cancer that co-expresses ER and ErbB2. Therefore, women who are not in an acutely life-threatening situation should be considered for upfront treatment with hormonal therapy (e.g. aromatase inhibitors) in combination with an anti-ErbB2 therapy.

Introduction: Despite the fact that people older than 65 years of age have the highest incidence of developing breast cancer, these patients are excluded from clinical trials in most cases. Furthermore, most physicians tend towards therapy regimens without the use of dose-dense, highly active taxane-based treatments because of a lack of data regarding toxicities of these compounds in older patients., Methods: Pooled side-effect data were analyzed from four prospective, randomized clinical trials in which patients of different age groups (< 60 years, between 60 and 64 years, and > 64 years) with primary breast cancer received taxane-based chemotherapy., Results: Dose delays, dose reductions, hospitalization, and therapy discontinuation increased with age. Hematologic toxicities and some nonhematologic toxicities were generally more common in older patients. Leucopenia increased from 55.3% in patients aged < 60 years to 65.5% in patients aged > 64 years (P < 0.001), and neutropenia increased from 46.9% to 57.4% (P < 0.001). There was no difference, however, in clinically more relevant febrile neutropenia between the different age groups. Thrombopenia shows a similar age-dependent increase, whereas there is no difference between the age groups concerning anemia. Hot flushes and elevated liver enzymes decreased with increasing age., Conclusions: The present pooled analysis of a substantial cohort of older primary breast cancer patients demonstrates that taxane-containing (neo)adjuvant chemotherapy is feasible in older patients and that toxicity can be reduced by sequential therapy regimens.

The insulin-like growth factor 1 (IGF1) and its binding protein IGFBP3 (insulin-like growth factor binding protein 3) play a pivotal role during the growth and development of tissues. The purpose of this study was to evaluate the influence of anthracycline- and taxane-containing adjuvant chemotherapy in breast cancer patients on the circulating plasma levels of IGF1 and its main binding protein, IGFBP3. This investigation was part of a prospective randomized phase III study in which breast cancer patients were treated with either conventional or dose-intensified adjuvant chemotherapy. The factors were quantified in the plasma of 151 patients with a commercially available sandwich enzyme immunoassay. Before therapy, both parameters were within the normal range in most patients (n=145 and n=144). After therapy, both factors had increased significantly by 29% (IGF1) and 19% (IGFBP3), with the highest increase being observed in the dose-intensified group. Correlations with patient and tumor characteristics revealed a relatively higher increase in both parameters in premenopausal patients, patients with lower-grade tumors, more positive lymph nodes, larger tumor volume, and positive hormone receptor status. No correlation was found with the HER2 expression of the tumors.

To evaluate the feasibility and tolerability of dose-dense adjuvant chemotherapy for older patients with node-positive breast cancer, a retrospective subset analysis compared dose delays and dose reductions for women aged > or = 60 years with those of younger women. Patients were randomized to a dose-dense (DD, 14-day cycle) or conventional-schedule (CS, 21-day cycle) regimen. DD patients (n = 104; 25 aged > or = 60 years) received epirubicin 90 mg/m2 plus paclitaxel 175 mg/m2 (four cycles), then cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2 and fluorouracil 600 mg/m2 (CMF 600/40/600) (three cycles), plus filgrastim 5 microg/kg per day in every cycle. CS patients (n = 107; 27 aged > or = 60 years) received epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 (four cycles), then CMF 600/40/600 (three cycles), plus filgrastim if required. Delays were more common in older patients in both the DD and CS groups (DD, 17% versus 6%; CS, 11% versus 6%), as were Grades 3-4 leukopenia (26% versus 12%) and neutropenia (33% versus 25%). All older DD and 89% of older CS patients received all seven chemotherapy cycles, with 99% of cycles at full dose. This study demonstrates that a dose-dense regimen combining epirubicin and paclitaxel can be administered to patients > or = 60 years of age with a tolerable safety profile.

Due to improved life expectancy and the increase in incidence of breast cancer in old age, ever more older women are developing this disease. Although there is only limited evidence-based data from randomized trials on the treatment, older patients are still under-represented in clinical studies, and currently there is no clear consensus on chemotherapy treatment for older women with breast cancer. Adjuvant therapy strategies, in particular, suffer from a lack of uniform standards and reflect a generally less aggressive treatment. Recently published studies have shown that older women suffering from breast cancer can also profit from a treatment based on therapeutic standards and consensus guidelines. In spite of developments in adjuvant chemotherapy using increased amounts of therapeutic agent to improve survival, many older patients receive instead reduced quantities of chemotherapeutic agent. Thus, the questions arise, whether undertreatment of older patients with breast cancer can lead to a poorer outcome or whether new therapy strategies (e.g., dose-intensive chemotherapy) can be used with older patients. A common reason for dose reductions is neutropenia, but studies have shown that it is manageable by using granulocyte colony-stimulating factors (G-CSFs). In this review, the current status of clinical research in the area of adjuvant treatment and the necessity for clinical studies that take into account the special therapeutic requirements of older women are discussed.

Background: The goal of the present study was to investigate the changes in concentration of the important lymph-angiogenesis factors vascular endothelium-derived growth factor (VEGF) and VEGF-D under adjuvant chemotherapy., Materials and Methods: The blood plasma of a total of 142 patients with breast carcinoma and with 1 to 3 affected lymph nodes was investigated, using the quantitative sandwich enzyme immunoassay technique, prior to and following chemotherapy, within the framework of a randomized phase III study: the patients received either conventional or dose-intensified chemotherapy., Results: In general, there was a significant reduction in VEGF levels after chemotherapy only in patients with large tumors (T3) (p = 0.043). There was also an almost significant reduction in patients with an overexpression of c-erbB-2 (Dako Score +3, p = 0.052). In contrast, the clearest reduction in VEGF-D occurred in patients with a positive hormone receptor status (p = 0.04) or in patients with a low expression of c-erbB-2 (Dako Score +1, p = 0.05). A significant effect of chemotherapy on VEGF-D was determined only in patients who had a baseline level that was above the normal (conventionel treatment p = 0.005; dose-intensified treatment p = 0.004)., Conclusion: Both VEGF and VEGF-D levels changed after chemotherapy, depending on the patient and tumor characteristics. With respect to changes in the plasma levels of VEGF and VEGF-D, there were no significant differences between dose-intensified and conventional chemotherapy.

The primary objective was to determine the optimal doses for gemcitabine (prolonged infusion), liposomal doxorubicin (Myocet) and docetaxel as primary (neoadjuvant) chemotherapy for locally advanced breast cancer. Secondary objectives included evaluation of the safety and efficacy of the regimen. Patients (n=19) with histologically confirmed stage II or III breast cancer were treated with liposomal doxorubicin (50-60 mg/m2) and docetaxel (60-75 mg/m2) on day 1, and gemcitabine as 4-h infusion (350-400 mg/m2) on day 4. Treatment was repeated every 3 weeks for a maximum of 6 cycles. The maximum tolerated doses were gemcitabine 350 mg/m2, liposomal doxorubicin 60 mg/m2 and docetaxel 75 mg/m2. Dose-limiting toxicities were stomatitis, diarrhea and infection. The predominant hematologic toxicity was mild-to-moderate myelosuppression with grade 3/4 neutropenia in 20% of cycles. Non-hematologic toxicity was generally mild, with no grade 4 toxicities being observed. Predominant non-hematologic toxicity was stomatitis, which occurred in 95% of patients. Grade 3 toxicities were reported for stomatitis, nausea, diarrhea, infection and constipation. No cases of cardiac, renal, pulmonary or neurotoxicity were observed. The clinical response rate was 83% and histologically confirmed, clinically complete remissions occurred in two patients (11%). We conclude that the combination of gemcitabine (prolonged infusion), liposomal doxorubicin and docetaxel is safe and highly effective in patients with locally advanced breast cancer as defined by maximum tolerated doses. The evaluated schedule is suitable for phase II studies.

Sequential, dose-dense epirubicin plus docetaxel was evaluated as primary systemic therapy for women with inoperable, locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients (LABC n=27; IBC n=7) received 3 cycles of epirubicin 120 mg/m2 every 2 weeks followed by 3 cycles of docetaxel 100 mg/m2 every 2 weeks, with granulocyte colony-stimulating factor. Grade 3-4 toxicities were observed in 21 of 195 cycles (10.8%). Grade 3 anemia and leukopenia each occurred in 1% of cycles. Following chemotherapy, all patients underwent surgery. Eight patients (23.5%) had a clinical complete response and 15 (44.1%) had a partial response. In patients with IBC, median skin thickness decreased from 5.85 mm (range: 3.1-6.2 mm) to 4 mm (range: 2.7-5.1 mm) (p<0.005). Sequential, dose-dense epirubicin plus docetaxel achieved a high response rate among patients with LABC or IBC with only moderate toxicity.

Background: Granulosa cell tumor of the ovary is an uncommon neoplasm. The majority of patients are diagnosed in early stages of disease and overall prognosis is favorable. The stage at time of diagnosis is the only prognostic factor that is unequivocally related to survival. Other prognostic factors have not been well defined and are discussed in the literature controversially., Materials and Methods: In a multi-institutional retrospective study we analyzed all relevant clinical data of patients with histologically proven granulosa cell tumor of the ovary. We applied the Kaplan-Meier method in order to estimate overall survival rates and evaluate prognostic factors., Results: The median follow-up was 75 months (range, 6-315 months). Overall survival was 87% and 76% after 5 and 10 years, respectively. Eighty percent of granulosa cell tumors were diagnosed stage I (FIGO). The survival rate after recurrence was 56.8% after 10 years. Mitotic rate (p=0.003), tumor stage (p<0.001) and residual tumor disease (p<0.001) were associated with a poor prognosis (p<0.001). Age and rupture of the tumor could not be confirmed to be of prognostic value., Conclusion: The results of our study showed that the mitotic index may be a valuable prognostic factor. Complete tumor resection should always be attempted, since residual tumor disease is associated with a poor prognosis. Prospective studies are needed in order to confirm our findings.

This phase II study evaluated the activity and toxicity of gemcitabine plus cisplatin as first-line treatment of patients with advanced ovarian cancer. Chemonaive patients >/=60-year-old with FIGO stage IIIC or IV epithelial ovarian carcinoma were enrolled. Patients received cisplatin 75 mg /m2 on day 1 and gemcitabine 1250 mg /m2 on day 1 (before cisplatin) and day 8 of a 21-day cycle. Of 44 female patients (median age, 70 years), 72.7% had stage IIIC disease and 67.4% had a Karnofsky performance status >/=80. Of the 37 response-evaluable patients (35 with measurable lesion[s] >/=2 cm), there were seven (18.9%) pathologic complete responses, two (5.4%) pathologic partial responses, two (5.4%) clinical complete responses, and 12 (32.4%) clinical partial responses, for an overall response rate of 62.2% (95% CI, 44.8%-77.5%), and a pathologic response rate of 24.3% (95% CI, 11.8%-41.2%). Median survival was 27.7 months (95% CI, 14.3-40.8 months). Grade 3/4 neutropenia and thrombocytopenia occurred in 59.5% and 30.2% of patients, respectively, with neutropenic fever in one patient. Grade 3 nausea /vomiting and alopecia occurred in 25.6% and 9.5% of patients, respectively. We conclude that gemcitabine plus cisplatin is active and feasible as first-line treatment of advanced epithelial ovarian cancer in patients >/=60 years. Further clinical trials adding gemcitabine to current standard, first-line treatment seem warranted in younger as well as older patients.

Objectives: Carboplatin and paclitaxel can be applied safely and effectively as single agents for the treatment of ovarian cancer on a weekly basis. A multicenter, phase-I study was conducted to investigate the maximum tolerated dose of a weekly combination regimen., Methods: We enrolled 21 patients with primary, surgically resected, advanced ovarian cancer (FIGO III/ IV) and a median age of 59 (range, 35 to 79) years. For a fixed dose of paclitaxel at 100 mg/m(2), carboplatin was administered at levels equating an area under the curve of 2.0 (6 patients), 2.5 (7 patients), and 3.0 (8 patients), respectively. Treatment schedule consisted of six cycles with drug delivery once a week, followed by a 2-week break, and another six cycles. After a treatment-free interval of 28 days, three more cycles were administered., Results: No dose-limiting toxicity was observed at the first level. Three patients developed dose-limiting toxicity (thrombocytopenia, neutropenic fever, and grade 3 neuropathy) receiving carboplatin at area under the curve 2.5. Another three patients developed dose-limiting toxicity at the highest carboplatin dose, of whom two encountered refractory thrombocytopenia, whereas another experienced neutropenic fever despite prophylactic granulocyte-colony-stimulating factor use. Alopecia was documented in 17 patients. Neurotoxicity was usually mild to moderate. CA-125 concentrations normalized (<35 U/ml) in 13 of 19 patients (68%) by the end of therapy. A 50% response was observed in 16 of 19 subjects., Conclusions: Weekly carboplatin and paclitaxel is a well-tolerated combination regimen in patients with primary, advanced ovarian cancer. The recommended dose for a phase II study is carboplatin at 100 mg/m(2) and carboplatin at area under the curve 2.0., ((c) 2002 Elsevier Science (USA).)

We have developed a 2-stage protocol for BRCA1 and BRCA2 mutation screening from blood spot paper. Stage 1 screening was aimed to analyze patients at highest risk for the most common disease-associated sequence variants listed in the BIC database. Accordingly, stage1 testing implied detection of 18 disease- associated BRCA1 and 9 BRCA2 mutations by adapting the 5' nuclease assay to heterozygote screening. For stage 2 screening, we applied the conformation sensitive gel electrophoresis (CSGE) method by adapting this technique to automated heteroduplex analysis of BRCA1 and BRCA2 using fragment scanning on an ABI 377 sequencing device. Of the 120 patients with a family history of breast and ovarian cancer who took part in this study so far, 45 entered stage 1 testing. Disease-associated mutations were detected in 6 patients by stage 1 testing (13%). For these patients, the final result was available within 10 days. Mutation 300T-->G was found in 2 patients. One patient with mutation 3036delACAA in BRCA2 reported only 1 sister with a multifocal bilateral breast cancer. New disease-associated mutations were detected in 2 of the 114 patients who entered the stage 2 test (1.7%). Of particular interest was 1 patient who was diagnosed with a medullary breast carcinoma at age 39 and who had no family history of breast cancer. We conclude that pre-screening by 5' nuclease assay for the mutations most frequently seen in a given population represents a relatively effective first line of analysis. Subsequent detailed analysis by fluorescence conformation sensitive gel electrophoresis (F-CSGE) and fragment sequencing is a sensitive alternative to full nucleotide sequencing., (Copyright 2000 Wiley-Liss, Inc.)

Objective: The aim of the study was to investigate a dose-intensified, preoperative chemotherapy with 3 cycles (cy) of epirubicin 60 mg/m2, ifosfamide 5 g/m2 with mesna 5 g/m2, biweekly with G-CSF 5 micrograms/kg (filgrastim), in terms of toxicity, clinical and pathological remission rates and changes of immunohistochemical characteristics (ER, PR, c-erbB2, p53) during chemotherapy of inoperable patients (pt) with poor prognosis (locally advanced (LABC, 9 pt), inflammatory breast cancer (IBC, 12 pt) and M0., Patients and Methods: Following preoperative chemotherapy (63 cy) and mastectomy patients received adjuvant 3 cy of epirubicin 60 mg/m2 and paclitaxel 175 mg/m2 (biweekly) with G-CSF (54 cy), and subsequently radiation of the thoracic wall and tamoxifen 20 mg/day., Results: Primary toxicity (T): grade 3 alopecia (21 pt), grade 3-4 leucopenia (7 cy), grade 1-2 leucopenia (26 cy), grade 1-2 anemia (61 cy), grade 1-2 neurocortical T (13 cy), grade 1-2 neurosensory T (7 cy), grade 1 cardiac toxicity (1 pt). ORR: 65% (CR: 0 pt, PR: 13 pt, NC: 8 pt). The grades of histological regression were: 0: 14 pt, 1: 6 pt, 2: 0 pt, 3: 1 pt. No significant correlation was observed between the clinical response and the histological regression (Fischer's exact test). The immunohistochemical expression of tumor characteristics did not change significantly during preoperative chemotherapy (Wilcoxon test). 81% of the pt were disease-free after a median follow-up of 20 months (7-26)., Conclusion: This therapy is safe, feasible and effective, both as primary and adjuvant chemotherapy in women with LABC and IBC.