German Adjuvant Intergroup Node-positive Study (GAIN): a phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients.

BACKGROUND: Dose-dense (dd) regimens are one of the preferred options for the adjuvant treatment of breast cancer patients with intermediate to high risk. The German Adjuvant Intergroup Node-positive trial aimed at optimizing intense dd (idd) strategies by evaluating drug combinations and the addition of capecitabine. PATIENTS AND METHODS: Women (aged 18 years and biologically <65 years) with histologically involved axillary lymph nodes were randomly assigned to receive three courses each of epirubicin (E) 150 mg/m2, paclitaxel (P) 225 mg/m2 and cyclophosphamide (C) 2500 mg/m2 (reduced to 2000 mg/m2 after recruitment of 1200 patients) q2w intravenously (i.v.) (iddEPC-regimen) or ddEC (E 112.5 mg/m2 + C 600 mg/m2, i.v. q2w for 4 cycles) followed by paclitaxel weekly (Pw 67.5 mg/m2 i.v. q8d for 10 weeks) plus capecitabine (X 2000 mg/m2 p.o. days 1-14, q22 for 4 cycles) (ddEC-PwX-regimen). Further randomization assigned patients to ibandronate for 2 years versus observation and to pegfilgrastim day 2 versus 4. RESULTS: From June 2004 to August 2008, 2994 patients were randomized to either iddEPC (N = 1498), or ddEC-PwX (N = 1496) and started treatment. Median age was 50 years; pN1 (37.8%), pN2 (35.3%); pN3 (26.9%); 46.4% were G3 tumors; 76.9% hormone receptor-positive and 22% HER2-positive. After a median follow-up of 74 months, 645 events and 383 deaths were recorded. Hematological adverse events grades 3-4 were more common with iddEPC (P < 0.001), nonhematological with ddEC-PwX (P = 0.04), even if the toxicity profile of the two regimens was different. At 5 years, estimated disease-free survival rates for ddEC-PwX and iddEPC were 81.7% [95% confidence interval (CI) 79.5-83.6] versus 80.2% (95% CI 78.0-82.2). Hazard ratio (HR)=0.95 (95% CI 0.81-1.11, log-rank P = 0.49). Five-year overall survival rates were 89.4% for ddEC-PwX (95% CI 87.7-91.0) and 89.0% for iddEPC (95% CI 87.2-90.6), HR = 0.85 (95% CI 0.69-1.04, log-rank P = 0.10). CONCLUSION: Adding capecitabine to ddEC-Pw did not improve outcome in comparison to iddEPC but increased toxicity and should not be recommended for further use.

Efficacy and patient satisfaction of breast conserving therapy for central breast cancer by the B technique.

PURPOSE: To evaluate the oncologic safety and cosmetic results after breast cancer surgery for central breast cancer by the B technique. METHODS: Seventy women with operable breast cancer located in the central portion of the breast that had received resection surgery with the B technique were recruited. The primary outcome was the oncological safety, quantified as rate of positive resection margins and the cosmetic outcome evaluated by postsurgical self-assessment of the cosmetic outcome via questionnaire. The median follow-up period was 61.4 months (range 7.9-142.6 months). RESULTS: With one exception all patients had T1-2 tumors less than 5 cm in diameter. Most patients had invasive ductal breast cancers (57.1 %), followed by ductal carcinoma-in situ (27.1 %) and invasive lobular breast cancers (8.6 %). The incidence of positive resection margins was 17.1 %. No local tumor recurrence occurred during follow-up; one patient had distant metastases. In total, 80 % of the patients reported that the cosmetic results met or exceeded their expectations. CONCLUSIONS: The B technique is a safe breast conservation surgery for the excision of tumors located in the central portion of the breast and yields a high rate of satisfactory cosmetic results.

Comparative study of surgical margins and cosmetic outcome in lumpectomy versus segmental resection in breast cancer.

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.

Non-pegylated liposomal doxorubicin and docetaxel in metastatic breast cancer: final results of a phase II trial.

BACKGROUND: Non-pegylated liposomal doxorubicin (NPLD) has demonstrated equivalent antitumor activity to conventional doxorubicin and a significantly lower risk of cardiotoxicity when given as single agent or in combination with cyclophosphamide, but there is limited experience with the combination of NPLD and taxanes. This phase II study was performed to evaluate the efficacy and safety of the NPLD and docetaxel in patients with metastatic breast cancer. PATIENTS AND METHODS: A total of 51 patients were treated with NPLD (60 mg/m(2)) and docetaxel (75 mg/m(2)) in 3-weeks intervals for up to eight cycles. RESULTS: The overall response rate was 50% and 78% of patients derived a clinical benefit. Median time to progression and overall survival were 10.0 months (95% CI, 6.9-13.1 months) and 25 months (95% CI, 22.1-29.8 months), respectively. Median duration of response was 12.0 months (95% CI 7.1-16.9). The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents and of anthracycline/taxane combinations. There were no symptomatic cardiac averse events and mild asymptomatic LVEF changes were reported in five patients. CONCLUSIONS: The combination of NPLD and docetaxel is well tolerated and has high antitumour activity in MBC patients.

[Minimal invasive transvaginal right hemicolectomy: report of the first complex NOS (natural orifice surgery) bowels operation using a hybrid approach]. / Minimalinvasive transvaginale Hemikolektomie rechts: Bericht über die erste komplexe NOS (Natural Orifice Surgery)Darmoperation in Hybridtechnik.

BACKGROUND: Laparoscopic surgery has dramatically changed abdominal surgery by reducing the risk of wound infections, incisional hernias and adhesions. The surgical concept using natural orifices (NOS) may be even less traumatic and so less invasive. PATIENT AND METHODS: This operation was performed in a 66-year-old woman with an adenoma in the ascending colon. Through a 5 mm incision at the umbilicus a pneumoperitoneum was created and a trocar inserted. For the operation a 12 mm trocar and a curved grasper have been inserted in the posterior fornix of the vagina. Because of adhesions an additional 5 mm trocar was necessary. Through this incision the laparoscopic right hemicolectomy with an intracorporal anastomosis was performed. RESULTS: The histology showed an adenoma with 21 lymph nodes. The removal of the specimen through the vagina was without any difficulties. The postoperative course was regular. CONCLUSIONS: This operation is to our knowledge the first right hemicolectomy as a NOS/NOTES-operation in a human patient. It shows that with rigid instruments even complex procedures through natural orifices are feasible.

Quality of care of VLBW neonates: relationship between unit volume and outcome is different between metropolitan and rural regions.

BACKGROUND: Recent studies from predominantly rural areas in Germany show that neonatal outcome of very low birth weight (VLBW) neonates is (on average) inferior with lower NICU (neonatal intensive care unit) volume. However, there are no data available which show that study results of one specific region can be transferred to other areas with possibly different medical infrastructure and needs. AIM: It was investigated whether a systematic difference of treatment quality between smaller (1000-2000 births/year; < or =20 neonatal beds) vs. larger neonatal centres in Berlin (>3000 births/year; >20 neonatal beds) exists. Furthermore, the results are compared to data from a rural region in order to discuss transferability between regions. METHODS: Retrospectively, completely, and for the first time, the data of all centres which treat VLBW neonates (< or =1500 g birth weight) in the city-state of Berlin, Germany, from the years 2003/2004 were reviewed. RESULTS: Our study showed no difference in the treatment quality of smaller vs. larger neonatal units in Berlin. This result differs from those of a study in Baden-Württemberg, a predominantly rural state, with different medical infrastructure than Berlin. CONCLUSION: The present study suggests that regional investigations on the infrastructure vs. treatment outcome are not transferable between areas. Patient volume/unit appears inadequate for predicting the future treatment quality of neonatal departments. Direct quality indicators are stable for the assessed departments and should be preferably used to organize medical infrastructure.

Significant changes in circulating plasma levels of IGF1 and IGFBP3 after conventional or dose-intensified adjuvant treatment of breast cancer patients with one to three positive lymph nodes.

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.

Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy for node-positive breast cancer.

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.

Primary chemotherapy with gemcitabine as prolonged infusion, non-pegylated liposomal doxorubicin and docetaxel in patients with early breast cancer: final results of a phase II trial.

BACKGROUND: Combinations of anthracyclines, taxanes and gemcitabine have shown high activity in breast cancer. This trial was designed to evaluate a modified combination regimen as primary chemotherapy. Non-pegylated liposomal doxorubicin (NPLD) was used instead of conventional doxorubicin to improve cardiac safety. Gemcitabine was given 72 h after NPLD and docetaxel as a prolonged infusion over 4 h in order to optimize synergistic effects and accumulation of active metabolites. PATIENTS AND METHODS: Forty-four patients with histologically confirmed stage II or III breast cancer were treated with NPLD (60 mg/m(2)) and docetaxel (75 mg/m(2)) on day 1 and gemcitabine as 4-h infusion (350 mg/m(2)) on day 4. Treatment was repeated every 3 weeks for a maximum of six cycles. All patients received prophylactically recombinant granulocyte colony-stimulating factor. Patients with axillary lymph node involvement after primary chemotherapy received adjuvant treatment with cyclophosphamide, methotrexate and fluorouracil. RESULTS: The clinical response rate was 80%, and complete remissions of the primary tumor occurred in 10 patients (25%). Breast conservation surgery was performed in 19 out of 20 patients (95%) with an initial tumor size of less than 3 cm and in 14 patients (70%) with a tumor size

Primary chemotherapy with doxorubicin and paclitaxel in patients with early breast cancer: final results of a multicenter phase II study.

PURPOSE: To assess the efficacy and safety of primary systemic treatment with doxorubicin and paclitaxel in patients with early breast cancer. PATIENTS AND METHODS: Forty patients with newly diagnosed, histologically confirmed breast cancer (T2, N0-1, M0) received primary chemotherapy with doxorubicin (60 mg/m2) and paclitaxel (200 mg/m2) in 3-week intervals for up to four courses. RESULTS: A total of 151 cycles were administered. The clinical response rate as assessed by sonographic measurement was 70%, and complete remissions of the primary tumor occurred in two patients. Eight patients (20%) had histologically confirmed complete responses. Predominant toxicity was myelosuppression with grade 3/4 neutropenia in 70% of patients. Non-hematological toxicity was generally moderate. Grade 4 non-hematological toxicities were not observed and grade 3 toxicity was reported with alopecia (98%) and stomatitis (10%). CONCLUSIONS: The combination of doxorubicin and paclitaxel is safe and highly active in patients with early breast cancer. The evaluated schedule is suitable for phase III studies.

Adjuvant treatment of breast cancer patients with 1-3 positive lymph nodes: vinorelbine plus epirubicin; vinorelbine plus epirubicin sequential followed up by paclitaxel; epirubicin plus cyclophosphamide; epirubicin plus cyclophosphamide sequential followed up by paclitaxel. A phase II study.

PURPOSE: The efficacy of anthracyclin-containing adjuvant chemotherapy of node-positive breast cancer can be further improved by adding sequential paclitaxel (T). There is also clinical evidence that replacing cyclophosphamide (C) with vinorelbin (V) might further reduce toxicity. In order to assess the safety of these options, we initiated a clinical cohort study of epirubicin/cyclophoshamide and epirubicin/vinorelbine with or without sequential paclitaxel. METHOD: Patients with node-positive (1-3) breast cancer were assigned to open-label epirubicin/vinorelbine (EV), epirubicin/vino-relbine and sequential paclitaxel (EV/T), epirubicin/cyclophosphamide (EC) or epirubicin/cyclophosphamide plus sequential paclitaxel (EC/T) therapy. RESULTS: Fifty four outpatients received a total of 304 chemotherapy cycles. There were significant differences in grade III/IV anemia only between the EV/T and EC/T groups, in favor of the EC/T group (P=0.002). CONCLUSIONS: The safety of paclitaxel is not impaired when given sequentially after administration of the two anthracyclin-containing regimens. The exchange of cyclophosphamide against vinorelbine leads to deteriorating safety of the EC/T regimen.

Gemcitabine combined with cisplatin as first-line treatment in patients 60 years or older with epithelial ovarian cancer: a phase II study.

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.

A phase II study of topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first-line chemotherapy.

BACKGROUND: Second-line chemotherapy for patients with ovarian cancer who failed platinum and paclitaxel treatment remains a therapeutic challenge. We investigated the toxicity profile and therapeutic efficacy of a novel combination regimen, topotecan plus gemcitabine, in a clinical phase II study. PATIENTS AND METHODS: Women with relapsed epithelial ovarian cancer after platinum and paclitaxel treatment were eligible to participate in this trial. Topotecan was given at an initial dose of 0.5 mg/m(2) daily (days 1-5), combined with gemcitabine 800 mg/m(2) and 600 mg/m(2) on days 1 and 8, respectively. Precluding good tolerability, this protocol facilitated subsequent dose increases of topotecan up to 1.0 mg/m(2). The primary objective was to determine the dose-limiting toxicity, whereas secondary objectives comprised measurable and CA-125 response rates, disease-free and overall survival. RESULTS: The twenty-one patients (median age 57 years, range 37-70 years) who were allocated to this trial received a total of 94 courses of chemotherapy. Median follow-up was 20.5 months. Topotecan dosage could be escalated to 0.75 mg/m(2) in nine patients and 1 mg/m(2) in another two patients. Dose reduction was not necessary in any case. There were no episodes of neutropenic fever, sepsis or chemotherapy-related fatalities. Only one patient developed CTC grade 4 leukopenia after the first treatment cycle, whereas three patients showed grade 3/4 anaemia. Five patients experienced thrombocytopenia grade 4 without clinical sequelae. Non-hematological toxicities were mild and rare. Eleven patients could be evaluated for clinical tumour response, with three complete, and four partial remissions. Two patients each had stable and progressive diseases. The median progression-free survival rate was 8.8 months [95% confidence interval (CI) 6.3-13.4 months]. The median overall survival rate was 21.1 months (95% CI 14.8-22.1 months). CONCLUSIONS: Topotecan combined with gemcitabine has a favourable toxicity profile and encouraging efficacy in patients with recurrent ovarian cancer.

[Adjuvant chemotherapy of cervix carcinoma--results of a phase II study]. / Die adjuvante Chemotherapie des Zervixkarzinoms-Ergebnisse einer Phase II-Studie.

OBJECTIVE: Therapies involving a radical operation and radiation treatment for cervical carcinoma in stages I and II are not sufficiently effective in patient subgroups with high risk for recurrence. In recent publications, patients with high risk cervical cancer had with adjuvant simultaneous radio-chemotherapy a better disease free and overall survival but a higher toxicity compared with patients received an adjuvant radiotherapy alone. MATERIAL AND METHODS: 34 patients with at least 2 risk factors for recurrence of cervical cancer were treated with adjuvant chemotherapy after radical hysterectomy. The protocol consisted of 3 cycles of ifosfamide 1.6 g/m2 (d 1-3) and carboplatin (AUC 4, d1) every three weeks. For cell protection 21 patients received amifostine 740 mg/m2 d1-3; this was followed by standard radiation therapy (50.4 Gy percutaneous and high-dose-rate-after-loading for 21 patients, 2 x 5 Gy). The dose determination of the substances and their toxicity were investigated. RESULTS: Patient (p) data: Median age 43 years (range: 25-70); pT1b-2a: n = 22; pT2b: n = 12; pN1: n = 28; pN0: n = 6; G3: n = 10; adeno- and adenosquamous carcinoma: n = 9, G3: n = 10, R1-resection: n = 5. 70.6% of these high-risk patients were disease-free after a median observation time of 40 (18-62) months. Median number of cycles of chemotherapy: 2.8. There was no more dose escalation than carboplatin according to AUC 4 possible. Hematologic toxicity (CTC grading, % of 96 documented cycles): anemia-grade 3-4: 30; -grade 1-2: 10.4; leukopenia-grade 3-4: 13, -grade 1-2: 21.7; alopecia-grade 3: all p.; cerebral neurotoxicity-grade 3-4: 8.3, -grade 1-2; 17.7; diarrhea under radiotherapy-grade 3-4: 2 p., -grade 1-2: 6 p. CONCLUSION: This combined sequential adjuvant therapy was effective and had an acceptable level of toxicity. A phase III study comparing adjuvant sequential chemo-radiotherapy with and without Erythropoeitin to counteract the negative effects of anemia started in Germany in 1999 and had randomized now about 270 patients.

Intraductal component in invasive breast cancer: analysis of 250 resected surgical specimens.

The presence of an intraductal component together with an invasive carcinoma is known to be associated with a higher rate of local recurrence. The results of reviewing 250 resected surgical specimens from patients with breast cancer are reported. Two-hundred and fifty mastectomy specimens of invasive breast cancer were retrospectively analysed in order to determine intraductal components within the primary tumour as well as additional foci. In addition to the invasive carcinoma, a ductal carcinoma in situ (DCIS) of varying extent was identified in 127 instances. The intraductal components were marginal in 27.6% of the cases, extensive in 61.4%, and predominant in 11.0%. In addition, 21 patients had isolated DCIS only. Such in situ components were more frequently found in the age group younger than 41 years and in premenopausal patients. Seventeen percent of carcinomas associated with an intraductal component were multicentric in location as opposed to only 5% of the breast lesions without an intraductal component. The highest proportion of residual tumour was seen in poorly differentiated invasive carcinomas with DCIS. Intraductal carcinomas with intraductal component tended to have a higher incidence of a positive surgical margin. Small carcinomas with an extensive in situ component require careful surgical management in order to achieve a tumour-free margin.

[Dose intensified adjuvant chemotherapy in high risk breast carcinoma with 4-9 positive lymph nodes]. / Dosisintensivierte adjuvante Chemotherapie beim Hochrisikomammakarzinom mit 4-9 positiven Lymphknoten.

OBJECTIVE: Taxanes and anthracyclines represent the two most active groups of agents for the treatment of breast cancer. We evaluated this combination in patients with more than 3 positive lymph nodes in an adjuvant, dose-intensive, sequential therapy in comparison with the standard chemotherapy regimen epirubicin/cyclophosphamide in relation to toxicities. MATERIAL AND METHODS: Since 9/96 127 patients with 4-9/over 9 positive lymph nodes have been recruited from 21 participating centers in an ongoing trial. 67 patients were prospectively randomised for first-line chemotherapy to treatment group A (epirubicin 90 mg/m2-paclitaxel 175 mg/m2; 4 cycles bi-weekly, supported by G-CSF 5 micrograms/kg day 5-13 and 3 sequential cycles of CMF 600/40/600 mg/m2 at 2-weeks interval) and 60 patients to treatment group B (epirubicin 90 mg/m2-cyclophosphamide 600 mg/m2, 4 cycles tri-weekly, and 3 sequential cycles of CMF 600/40/600 mg/m2 at 3-weeks interval). RESULTS: Preliminary safety and toxicity data are evaluable for 679 cycles. Data about response rate and disease-free-survival and overall survival will be delivered later. For the hematological toxicity the main grade 3 and 4 adverse events for A vs. B were: leucopenia 9.8% vs. 8.4%, febrile neutropenia 1.6% vs. 0.8%--anemia (< 5.9 mmol/l), 0.4% vs. 0.2%--thrombopenia 0% vs. 0%. Non-hematological toxicity occurred more frequently in group A (grade 2, 3, 4):--neuropathy 4.4% vs. 0%,--nausea/emesis 27.8% vs. 19.3%,--fatigue 14.6% vs. 3.4% and mucositis 2.8% vs. 0.3%.

Detection of BRCA1 and BRCA2 mutations in breast cancer families by a comprehensive two-stage screening procedure.

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.

[Treatment of vaginal atresia by a cecum transplantation after radical operation for cervical cancer and postoperative radiotherapy]. / Behandlung einer atretischen Scheide nach Radikaloperation und postoperativer Radiatio mittels Coecum-Ersatz-Plastik.

Case report is given about treatment of atretic vagina after radical operation of cervical cancer and postoperative radiation. Neovagina was created with coecum. Good plastic results with uncomplicated cohabitation were reached. This method is recommended in cases with actinic lesions of vagina.

Dose- intensified, preoperative and adjuvant chemotherapy in patients with T3- and T4- breast cancer: toxicity, clinical and pathological remission.

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.

[Case report of squamous epithelial cancer of the female breast]. / Kasuistischer Beitrag zum Plattenepithelkarzinom der weiblichen Brustdrüse.

A report its given about one case of squamous cell cancer of female breast. The authors analyse the therapeutic management and prognostic factors of this disease.