[Interdisciplinary Diagnosis and Treatment of Deep Infiltrating Endometriosis]. / Interdisziplinäre Diagnostik und Therapie der tief infiltrierenden Endometriose.

Endometriosis is the second most common benign female genital disease after uterine myoma. This review discusses the interdisciplinary approach to the treatment of deep infiltrating endometriosis. Endometriosis has been defined as the presence of endometrial glands and stroma outside the internal epithelial lining of the cavum uteri. As a consequence, endometriosis can cause a wide range of symptoms such as chronic pelvic pain, subfertility, dysmenorrhea, deep dyspareunia, cyclical bowel or bladder symptoms (e.g., dyschezia, bloating, constipation, rectal bleeding, diarrhoea and hematuria), abnormal menstrual bleeding, chronic fatigue or low back pain. Approx. 50 % of teenagers and up to 32 % of women of reproductive age, operated for chronic pelvic pain or dysmenorrhoea, suffer from endometriosis. The time interval between the first unspecific symptoms and the medical diagnosis of endometriosis is about 7 years. This is caused not only by the non-specific nature of the symptoms but also by the frequent lack of awareness on the part of the cooperating disciplines with which the patients have first contact. As the pathogenesis of endometriosis is not clearly understood, a causal treatment is still impossible. Treatment options include expectant management, analgesia, hormonal medical therapy, surgical intervention and the combination of medical treatment before and/or after surgery. The correct treatment for each patient should take into account the severity of the disease and whether the patient desires to have children. The treatment should be as radical as necessary and as minimal as possible. The recurrence rate among treated patients lies between 5 and > 60 % and is very much dependent on the integrated management and surgical skills of the respective hospital. Consequently, to optimise the individual patient's treatment, a high degree of interdisciplinary cooperation in diagnosis and treatment is crucial and should, especially in the case of deep infiltrating endometriosis, be undertaken in appropriate centres.

Impact of radical operative treatment on the quality of life in women with vulvar cancer--a retrospective study.

OBJECTIVES: For patients undergoing vulva surgery the quality of life (QoL) is generally accepted as an important outcome parameter in addition to long-term survival, mortality and complication rates. Less radical operative treatment can reduce morbidity and thereby improve quality of life. This study focuses on outcome in terms of QoL in patients comparing wide local excision (WLE) with radical vulvectomy and waiver of lymphonodectomy (LNE) with inguinofemoral lymphonodectomy. METHODS: In a retrospective single-center study from 2000 to 2010, 199 patients underwent surgery for vulvar cancer. To assess QoL, the EORTC QLQ-C30 and a tumor-specific module questionnaire were sent to all patients in the follow-up period. RESULTS: Women who underwent WLE have a superior QoL with regard to global health status and physical, role, emotional and cognitive functioning than those who underwent radical vulvectomy. Less radical surgery also implies less fatigue, nausea/vomiting, pain, insomnia, appetite loss, diarrhea and financial difficulties. After radical vulvectomy 89% of patients have sexual complications. CONCLUSION: Radical operative treatment, such as radical vulvectomy, causes deterioration in the QoL of these patients. An individualized, less radical surgery must be the aim in the treatment of vulvar cancer.

Surgical impact of new treatments in breast cancer.

Local treatment of breast cancer with tumor-free surgical margins is the standard procedure in the treatment of T1 and small T2 breast cancers. Surgery is followed by radiation therapy, and adjuvant systemic therapy is offered depending on primary tumor characteristics, such as tumor size, grade of differentiation, number of involved axillary lymph nodes, the status of estrogen (ER) and progesterone (PR) receptors, and the expression of the human epidermal growth factor 2 (HER2) receptor. Although this approach implies a higher risk of ipsilateral breast tumor recurrence, the total risk of recurrence is low (1% per year), with rates of overall survival similar to that after radical procedures. The most peripheral part of epithelial tumors, the tumor margin, is the part which is most likely to remain in loco after surgical resection. Thus, understanding the biology of the invasion front is important as these tumor cells have been reported to lose epithelial properties, such as cohesiveness and keratin expression, and to acquire features of mesenchymal cells. The parallel appearance of tumor cells in different states of cell dedifferentiation implicates a dynamic equilibrium that is determined by the induction of epithelial-mesenchymal transition (EMT). EMT has been suggested to be of prime importance for tissue and vessel invasion. Furthermore, features of EMT are associated with the activity of tumor stem cells (TSC). TSC exist in breast cancer and their appearance varies depending on the used marker profile. Consequently, intratumoral heterogeneity is reflected by the grade of EMT activation. A specific function at the invasion front is hypothesized but has not yet been proven. Nevertheless, the molecular differentiation between the tumor center and the invasion front enhances the importance of tumor-free surgical margins.

Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer.

BACKGROUND: The progesterone-receptor (PR) antagonists onapristone (type I) and mifepristone (type II) showed modest activity in hormone-receptor-positive breast cancer; however, onapristone in particular was associated with hepatotoxicity. Lonaprisan is a novel, type III PR antagonist that was well tolerated in phase I studies. PATIENTS AND METHODS: This randomized, open-label, phase II study evaluated the efficacy and tolerability of lonaprisan as second-line endocrine therapy in postmenopausal women with stage IV, PR-positive, HER2-negative, metastatic breast cancer. RESULTS: Patients received once-daily lonaprisan 25 mg (n = 34) or 100 mg (n = 34). The primary objective was not met (≥ 35% clinical benefit rate: complete/partial responses at any time until month 6 or stable disease [SD] for ≥ 6 months from start of treatment). There were no complete/partial responses. In the 25 mg and 100 mg groups, 6 of 29 patients (21%) and 2 of 29 patients (7%), respectively, had SD ≥ 6 months. Overall, 61 of 68 patients (90%) had ≥ 1 adverse event (AE), the most frequent (≥ 10% overall) being fatigue, hot flush, dyspnoea, nausea, asthenia, headache, constipation, vomiting, and decreased appetite; 33 patients had serious AEs. CONCLUSION: Lonaprisan showed limited efficacy as second-line endocrine therapy in postmenopausal women with PR-positive metastatic breast cancer.

Interventional bleeding, hematoma and scar-formation after vacuum-biopsy under stereotactic guidance: Mammotome(®)-system 11 g/8 g vs. ATEC(®)-system 12 g/9 g.

PURPOSE: To evaluate prospectively the correlation of scar-formations after vacuum-assisted biopsy with different systems and needle-sizes and interventional bleeding/post-interventional hematoma. METHODS AND MATERIALS: Between 01/2008 and 12/2009, 479 patients underwent vacuum-assisted biopsy under stereotactic-guidance, using the Mammotome(®)-system with 11/8-gauge and ATEC(®)-system with 12/9-gauge, whereas in 178 cases with representative benign histology no surgical-biopsy after vacuum-assisted biopsy was performed and at least a 2-plane-follow-up-mammogram after 6 month post-vacuum-assisted biopsy was available. Bleeding during intervention, hematoma post-intervention and scar-tissue was scored as minimal and moderate/severe. Statistical analysis included Chi-Square-trend-test, p-value <0.05 was considered to be significant. RESULTS: Significantly more bleedings and post-interventional hematomas for 8-gauge-Mammotome(®)-system vs. 11-gauge-Mammotome(®)-system (41.9% vs. 8.4%, p<0.001/35.5% vs. 16.7%, p=0.029), no significant-differences for the ATEC(®)-systems 9-gauge vs. 12-gauge (26.9% vs. 29.7%, p=0.799/42.3% vs. 43.2%, p=0.596). 11-gauge-Mammotome(®)-system vs. ATEC(®)-12-gauge-system revealed significantly less bleedings/hematomas (8.4% vs. 29.7%, p=0.015/16.7% vs. 43.2%, p=0.001), no significant differences for the large-systems (p=0.135/p=0.352). Follow-up of Mammotome(®)-11/8-gauge-system system has shown 13.1/16.1% minimal scar-formation and 1.2/3.2% moderate/severe scars, whereas ATEC(®)-12/9-gauge-system has shown 10.8/3.8% minimal scar-formation and 0/11.5% moderate/severe scars, no significant differences. No significant difference was found when comparing Mammotome(®)-11/8-g-systems vs. ATEC(®)-12/9-g-systems (p=0.609/p=0.823). There was also no correlation between risk of scar-formation after occurrence of bleeding or hematoma with any examined VAB-system or any needle size in this study (p=0.800). CONCLUSION: Using larger needle-sizes significantly (Mammotome(®))/not significant for ATEC(®)) more interventional bleedings and post-interventional hematomas were detected, only a tendency concerning scar-formation.

The sequential use of endocrine treatment for advanced breast cancer: where are we?

BACKGROUND: Hormone receptor-positive advanced breast cancer is an increasing health burden. Although endocrine therapies are recognised as the most beneficial treatments for patients with hormone receptor-positive advanced breast cancer, the optimal sequence of these agents is currently undetermined. METHODS: We reviewed the available data on randomised controlled trials (RCTs) of endocrine therapies in this treatment setting with particular focus on RCTs reported over the last 15 years that were designed based on power calculations on primary end points. RESULTS: In this paper, data are reviewed in postmenopausal patients for the use of tamoxifen, aromatase inhibitors and fulvestrant. We also consider the available data on endocrine crossover studies and endocrine therapy in combination with chemotherapy or growth factor therapies. Treatment options for premenopausal patients and those with estrogen receptor-/human epidermal growth factor receptor 2-positive tumours are also evaluated. CONCLUSION: We present the level of evidence available for each endocrine agent based on its efficacy in advanced breast cancer and a diagram of possible treatment pathways.

Rare Benign Entities of the Breast - Myoid Hamartoma and Capillary Hemangioma.

Hamartomas can occur in different areas of the breast, but they are rarely found in the breast. Myoid hamartomas with smooth muscle cells of the type described here are particularly unusual. The pathogenesis of this benign entity with its tendency to growth and recurrence is not clear. Excision is the therapy of choice. Capillary hemangiomas are rare vascular malformations of the breast which, in contrast to cavernous hemangiomas, usually remain clinically occult. It is important to differentiate these benign findings from malignant angiosarcoma. The possible heterogeneities between myoid hamartoma and capillary hemangioma using current breast imaging methods for the differential diagnosis (high-resolution ultrasound, duplex sonography, shear wave elastography, digital mammography, minimally invasive intervention) are discussed together with an overview of the literature.

Randomised phase II trial of gemcitabine plus vinorelbine vs gemcitabine plus cisplatin vs gemcitabine plus capecitabine in patients with pretreated metastatic breast cancer.

BACKGROUND: An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory. METHODS: Anthracycline-pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m(-2) plus vinorelbin 25 mg m(-2) on days 1+8 (GemVin), or plus cisplatin 30 mg m(-2) on days 1+8 (GemCis), or plus capecitabine 650 mg m(-2) b.i.d. orally days 1-14 (GemCap), q3w. The primary end point was response rate. RESULTS: A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia ≥grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand-foot syndrome in 2.0% of the GemCap patients (per patient analysis). CONCLUSIONS: This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer.

Breast ultrasound elastography--results of 193 breast lesions in a prospective study with histopathologic correlation.

PURPOSE: To evaluate the diagnostic performance of ultrasound elastography in breast masses. MATERIAL AND METHODS: 193 lesions (129 benign, 64 malignant) were analyzed with the EUB 8500 Logos-ultrasonic-unit (Hitachi Medical, Japan) and a linear-array-transducer of 7.5-13-MHz. Standard of reference was cytology (FNAfine needle aspiration) or histology (core biopsy). The elastic-score was classified according to a 6-point colour-scale (Ueno classification; 1-3 = benign, 4-5 = malignant). Conventional B-mode ultrasound (US) findings were classified according to the BI-RADS classification. Statistical analysis included sensitivity, specificity, ROC-analysis and kappa-values for intra-/interobserver reliability. RESULTS: The mean score for elasticity was 4.1 ± 0.9 for malignant lesions, and 2.1 ± 1.0 for benign lesions (p < 0.001). With a best cut-off point between elasticity scores 3 and 4, sensitivity was 96.9%, and specificity 76%. Setting a best cut-off point for conventional US between BI-RADS 4 and 5, sensitivity was 57.8%, and specificity 96.1%. Elastography provided higher sensitivity and lower specificity than conventional US, but two lesions with elasticity score 1 were false negative, whereas no lesion scored BI-RADS 1-3 were false negative. ROC-curve was 0.884 for elastography, and 0.820 for conventional US (p < 0.001). Weighted kappa-values for intra-/interobserver reliability were 0.784/0.634 for BI-RADS classification, and 0.720/0.561 for elasticity scores. CONCLUSION: In our study setting, elastography does not have the potential to replace conventional B-mode US for the detection of breast cancer, but may complement conventional US to improve the diagnostic performance.

Heterogeneous expression of serine protease inhibitor maspin in ovarian cancer.

UNLABELLED: Ovarian cancer (OC) is a disease with poor prognosis, and molecular markers are needed to improve understanding of disease progression and resultant treatment. Only limited data concerning the expression of maspin, a serine protease inhibitor, in ovarian cancer (OC) are available. This study investigates the prognostic value of maspin expression (ME) in various OC cell lines and clinical tissue specimens from OC patients. PATIENTS AND METHODS: Tumour purified mouse anti-human maspin monoclonal antibody was applied to tissue specimens from 87 OC patients. ME was recorded by an immunoreactive score, which was correlated with grading, stage, histopathological subtypes and overall survival. Additionally ME was evaluated in established ovarian cancer cell lines (HEY, SKOV3, OVCAR3/8) and paclitaxel- and docetaxel-resistant HEY cells by QRT-PCR. RESULTS: There was significant correlation between cytoplasmatic ME and overall survival (p<0.05). OC patients with high levels of ME had a median survival of 28 vs. 57 months for those with low levels. Significant differential ME was detected between benign, borderline ovarian lesions and OC, as well as among different tumour gradings. Normal ovarian epithelial cells expressed less maspin than ovarian cancer cells as measured by QRT-PCR. Docetaxel- and paclitaxel-resistant ovarian cell lines showed an even higher level of ME, suggesting an unfavourable role of ME in OC cell lines. CONCLUSION: Maspin is expressed differentially in OC, and low expression levels of maspin are correlated with a longer survival.

Influence of additional breast ultrasound on cancer detection in a cohort study for quality assurance in breast diagnosis--analysis of 102,577 diagnostic procedures.

PURPOSE: To determine the value of a breast ultrasound (US) examination in addition to mammography in cases of American College of Radiology (ACR) tissue pattern III and IV in symptomatic women and women at risk. MATERIALS AND METHODS: A prospective cohort was initiated between 2001 and 2005 with a total of 59,514 patients and 102,744 mammograms. Documentation was available for 102,557 diagnostic procedures. Breast US was indicated in all women with ACR III and IV in addition to a suspicious clinical examination and in cases of masses and focal asymmetries in mammography. RESULTS: In total, 62,006 additional USs were performed, in which 116 mammographically and clinically occult breast cancers were diagnosed (detection rate: 1.9/1,000 examinations), while mammography alone (40,551 examinations) revealed 903 cancers (22.3/1,000). Of all 1,019 breast cancer findings, 12.8% were detected because of the combination of mammography and US. In the group with ACR III/IV, 15.9% of cancers were found by supplemental US compared with mammography alone. CONCLUSION: The addition of US to mammography vs. mammography alone resulted in a significant (P < 0.01) increase in breast cancer detection rate.

Hospital treatment - Is it affordable? A structured cost analysis of vaginal deliveries and planned caesarean sections.

INTRODUCTION: The analysis of cost effectiveness in hospitals is as difficult as treating the patients properly. We are yet not able to answer the simple question of what costs are caused by a certain diagnosis and its treatment during an average hospital stay. METHODS: To answer some issues of the global problem of cost effectiveness during hospitalisation, we analysed the costs and the cost structure of a normal obstetrical hospital stay during an uncomplicated vaginal delivery and a planned caesarean section. Cost data was collected and summarized from the patients file, the hospital's computer system gathering all cost centres, known material expenses and expenses of non obstetrical medical services. RESULTS: For vaginal deliveries/planned caesareans we can calculate with a surplus of about 83Euro/1432Euro. About 45% of the summarized costs are calculated on a reliable database. DISCUSSION: The introduction of the DRG based clearing system in Germany has aggravated the discussion on cost effectiveness. Our meticulous work-up of expenses excluded personal precautionary costs and personnel costs of documentation because no tools are described to depict such costs. If we would add these costs to the known expenses of our study, we strongly suspect that hospital treatment of vaginal deliveries or planned caesarean sections is not cost effective.

Randomized trial of high-dose adjuvant chemotherapy with autologous hematopoietic stem-cell support versus standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: overall survival after 6 years of follow-up.

Investigation of high-dose chemotherapy (HD-CT) compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and >/=10 axillary lymph nodes. From November 1993 to September 2000, 307 patients were randomized to receive after four cycles of epirubicin (90 mg/m(2)), cyclophosphamide (600 mg/m(2)) i.v. (every 21 days) and either HD-CT of cyclophosphamide (1500 mg/m(2)), thiotepa (150 mg/m(2)) and mitoxantrone (10 mg/m(2)) i.v. for four consecutive days followed by stem cell transplantation or a SD-CT of three cycles CMF (cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), 5-fluorouracil 600 mg/m(2), i.v. on day 1 and 8, respectively, every 28 days). After a median follow-up of 6.1 years, 166 events with respect to event-free survival (EFS) (SD-CT: 91, HD-CT: 75) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0.80 [95% confidence interval (0.59, 1.08)], P = 0.15. The trend to a superiority of HD-CT as compared with SD-CT with respect to EFS seems to be more pronounced in premenopausal patients as compared with postmenopausal patients and in patients with tumor grade 3 as compared with patients with tumor grade 1/2. With a follow-up of 6 years, there was a trend in favor of HD-CT with respect to EFS not being significant. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients who might benefit from HD-CT.

Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel.

Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.

Comparison of c-DNA microarray analysis of gene expression between eutopic endometrium and ectopic endometrium (endometriosis).

PROBLEM: As recent studies have suggested abnormalities in the regulation of specific genes in the development of endometriosis, we investigated differentially expressed genes in endometriosis compared to endometrium. METHOD OF STUDY: Gene expression profiles using the Atlas microarray were performed in endometriotic tissue and endometrium. Nine of the 13 genes of endometriotic tissue showed an up-regulation in relation to endometrium and four of the 13 genes a down-regulation. RESULTS: Of the 1176 genes on the Atlas Human 1,2 array, only 13 differentially expressed identical genes were detected after repeating the gene analysis three times. CONCLUSION: According to our c-DNA analysis some differentially expressed genes may be involved in the pathogenesis of endometriosis. An imbalance in the genes responsible for the reproductive process may lead to a decrease in embryo implantation in patients with endometriosis.

Factors associated with one step surgery in case of non-palpable breast cancer.

PURPOSE: To examine factors associated with one step surgery in case of non-palpable breast cancer. MATERIALS AND METHODS: Clinical data of 152 consecutively diagnosed patients with breast cancer were analyzed retrospectively. Preoperative diagnostic findings were divided in subgroups: mammographically visible mass/microcalcifications/sonographically visible mass/sonographically visible architectural distortion. Correlation between tumor-size, radiologic tumor morphology, quality of localization and number of operation was evulated. For localization exact wire position was defined less than 3mm apart from the lesion. RESULTS: One hundred and thirty-six patients attempted breast conservation and underwent preoperative tumor localization. Fourteen of 16 patients had mastectomy without preoperative localization. Average tumor size was 12mm for one-operation, and 17mm for re-operation. Significant correlation (p<0.001) was found between one operation and masses visible in mammograms (55/62 (89%) patients) or sonography (53/64 (83%) patients). Significant correlation was found (p<0.001) between more re-operation and microcalcifications in mammograms (33/89 (37% patients). In 123/138 (89%) cases wire position was central, in 15/138 (11%) cases distance was maximally 10mm. No significant correlation was found between number of operation and wire position. Re-operation was required in 38 cases. CONCLUSION: Mammographically or sonographically visible mass, small size of tumors, preoperative percutaneous biopsy and exact preoperative localization are important for a single step procedure for definite surgical treatment, that we found in 74% of the patients.

Proof of partial imbalances 6q and 11q due to maternal complex balanced translocation analyzed by microdissection of multicolor labeled chromosomes (FISH-MD) in a patient with Dandy-Walker variant.

We report on a family in which a daughter is described with mental retardation, as well as malformations of the heart, and of the brain (Dandy-Walker variant). The patient's phenotype suggests a chromosomal rearrangement. However, her karyotype was unremarkable by conventional cytogenetic analysis. In order to detect chromosome rearrangements overseen by this method, the subtelomere regions of suspicious chromosomes were verified by fluorescence in situ hybridization (FISH). A rearranged derivative chromosome 6 was identified. Further examinations by FISH-microdissection (FISH-MD) revealed a maternal complex balanced translocation. The patient inherited the derivative chromosome 6 from her mother and therefore carries a partial monosomy 6q26-->qter and a partial trisomy 11q23.3-->qter.

Trends in endocrine therapy and chemotherapy for early breast cancer: a focus on the premenopausal patient.

PURPOSE: The majority of breast cancers are diagnosed at an early stage, and treatment is focused on cure and prolonging disease-free survival. Local therapy (surgery and/or radiation treatment) is standard, along with systemic adjuvant therapy that may effectively prevent or delay relapse and death in early-stage disease. In premenopausal women, adjuvant therapeutic approaches include combination cytotoxic chemotherapy and endocrine therapy. Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) was the established chemotherapy regimen; however, newer regimens have more recently been introduced that may offer some benefit over CMF including anthracycline-containing regimens [e.g. cyclophosphamide, epirubicin and 5-fluorouracil (CEF)], and taxane-containing regimens. For women with oestrogen receptor (ER)-positive disease, a second option is endocrine therapy that aims to suppress mitogenic oestrogen signalling. Until recently, 5 years of tamoxifen was regarded as the standard adjuvant endocrine treatment in ER-positive disease. Ovarian ablation is also effective in premenopausal women, and can be achieved by surgery, radiotherapy, or via the use of a luteinising hormone-releasing hormone analogue such as goserelin. Combining tamoxifen and goserelin treatment provides more effective oestrogen blockade than either drug alone. However, as the third-generation aromatase inhibitors (AIs) have demonstrated improved efficacy over tamoxifen in postmenopausal women with early and advanced disease, combination treatment with goserelin plus an AI may provide optimal oestrogen blockade in premenopausal patients. CONCLUSIONS: This review assesses the relative merits of chemotherapeutic and endocrine approaches for the treatment of early breast cancer, and summarises relevant ongoing clinical trials, with an emphasis on the premenopausal setting.

The impact of electrical charge on the viability and physiology of dendritic cells.

The use of electrical charge for electroporation or electrofusion is widely applied to customize dendritic cells (DC) and their immunological properties as anticancer vaccines. The aim of this study was to evaluate the influence of various electrical field strengths on the recovery, viability and physiology of DC. Immature DC were transferred into low-conductive medium and electrically charged within a range of 0-1500 V/cm. Viability was assessed by Trypan Blue dye exclusion or staining with impermeant nucleic acid stains and fluorescence-activated cell sorter analysis. Additionally, apoptosis was determined by flow cytometry after staining with Annexin-V, endocytosis by uptake of fluorescein isothiocyanate-dextran and metabolic activity by a standardized fluorescent live/dead assay. There was a strong correlation between the electrical field strength and the viability and physiology of DC. Field strengths > or =1000 V/cm significantly impaired viability, metabolism and endocytotic activity. Dual fluorescence with 7-7-amino-actinomycin D and Annexin-V demonstrated that loss of viability was predominantly due to necrosis rather than apoptosis. Field strengths < or =500 V/cm allowed to maintain good cell viability and recovery of DC and did not cause alterations of metabolism and endocytosis. Therefore, the frequently used amplification of field strengths to improve the efficacy of electroporation and electrofusion requires critical re-evaluation.