Influence of migrant background on patient preference and expectations in breast and gynecological malignancies (NOGGO-expression V study): results of a prospective multicentre study in 606 patients in Germany.

BACKGROUND: An effective cross-cultural doctor-patient communication is vital for health literacy and patient compliance. Building a good relationship with medical staff is also relevant for the treatment decision-making process for cancer patients. Studies about the role of a specific migrant background regarding patient preferences and expectations are lacking. We therefore conducted a multicentre prospective survey to explore the needs and preferences of patients with a migrant background (PMB) suffering from gynecological malignancies and breast cancer to evaluate the quality of doctor-patient communication and cancer management compared to non-migrants (NM). METHODS: This multicentre survey recruited patients with primary or recurrence of breast, ovarian, peritoneal, or fallopian tube cancer. The patients either filled out a paper form, participated via an online survey, or were interviewed by trained staff. A 58-item questionnaire was primarily developed in German and then translated into three different languages to reach non-German-speaking patients. RESULTS: A total of 606 patients were included in the study: 54.1% (328) were interviewed directly, 9.1% (55) participated via an online survey, and 36.8% (223) used the paper print version. More than one quarter, 27.4% (166) of the participants, had a migrant background. The majority of migrants and NM were highly satisfied with the communication with their doctors. First-generation migrants (FGM) and patients with breast cancer were less often informed about participation in clinical trials (p < 0.05) and 24.5% of them suggested the help of an interpreter to improve the medical consultation. Second and third-generation migrants (SGM and TGM) experienced more fatigue and nausea than expected. CONCLUSIONS: Our results allow the hypothesis that training medical staff in intercultural competence and using disease-related patient information in different languages can improve best supportive care management and quality of life in cancer patients with migrant status.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study.

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1-5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5-10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information.

Bilateral gonadal cysts and late diagnosis of androgen insensitivity syndrome treated by laparoscopic gonadectomy.

Background. Complete androgen insensitivity syndrome is a rare syndrome in which the uterus is absent and testes rather than ovaries are present. Patients usually visit a gynecologist due to primary amenorrhea. Case. A forty-eight-year-old woman with lower abdominal pain and anamnesis of uterus agenesis was operated on due to bilateral cystic masses. A 5 × 3 × 1.2 cm left adnexal cyst revealed the presence of a serous cyst with a hypoplastic ductus deferens. A smaller cyst of the right adnexa revealed immature testis tissue with Leydig-cell hyperplasia. After karyotype and hormonal examinations, laparoscopic gonadectomy was performed. Conclusion. Attention should be paid in all cyst-removing operations in cases of uterus agenesis, due to the high incidence of malignancy. Not of less importance is the issue of informing the patient in the most appropriate way.

[Metastatic breast cancer: options for metastasectomy]. / Das metastasierte Mammakarzinom -- Möglichkeiten einer operativen Therapie.

Usually, the therapy of metastatic breast cancer consists of chemotherapy or endocrine therapy, because even in the case of isolated metastases in one organ, diffuse tumor cell dissemination exists, so that local surgical treatment does not seem sensible. Particurlarly in patients with hepatic or pulmonary metastases the indication for hepatic or pulmonary metastasectomy should be individualized, as hepatic or pulmonary metastases usually develop during a phase of disease, when extrahepatic or -pulmonary metastases also can be detected. Only in patients with long disease-free interval, with isolated hepatic or pulmonary metastases, and the possibility of R0-resection is hepatic or pulmonary metastasectomy a therapeutic option in selected cases.

[Treatment of breast cancer patients with brain metastases]. / Behandlung von zerebralen Metastasen beim Mammakarzinom.

Treatment of patients with brain metastases is based on an interdisciplinary approach. It is essential to perform a differenciated indication for procedures with consideration of all therapeutical options like modalities of radiotherapy, surgery and oncology. In the case of multiple brain metastases the whole brain radiotherapy is the standard of treatment, while in case of a single or solitary brain metastasis surgical procedures followed by radiotherapy should be preferred.

Microcalcifications of the breast: how does radiologic classification correlate with histology?

PURPOSE: To assess the correlation between the pre-biopsy classification of microcalcifications and the underlying histology. MATERIAL AND METHODS: Using the morphology and distribution patterns according to the Breast Imaging-Reporting and Data System (BI-RADS) lexicon, the microcalcifications of 199 lesions in 163 consecutive patients scheduled to undergo 11 G vacuum core biopsy were classified within the BI-RADS categories. The correlation between BI-RADS assessment categories 3, 4, and 5 and the final histological results was statistically evaluated with the chi2 test. The diagnostic indices were calculated. RESULTS: The prospectively classified BI-RADS 3/4/5 findings revealed a malignant histology in 5.9%/17.6%/90.9% of all lesions, respectively. The relationship between BIRADS categories 3, 4, and 5 and histology was statistically highly significant (P<0.0001). The sensitivity, specificity, positive and negative predictive values were 95.7%/21.2%,/37.8%/94.3%, respectively. CONCLUSION: The BI-RADS lexicon describes microcalcifications of the breast and provides diagnostic categories that lead to standardized biopsy recommendations. Nevertheless, how to link description to classification of microcalcifications is still a difficult diagnostic task. The evaluation of microcalcifications as proposed in this article may help to set standards in the clinical routine and in the comparability of scientific data.

Skin-sparing mastectomy and immediate breast reconstruction: incidence of recurrence in patients with invasive breast cancer.

The aim of this study was to investigate whether skin-sparing mastectomy (SSM), which is gaining increasing importance and gives well-accepted cosmetic results, provides adequate treatment of the patients' oncologic disease. From 1995 to 2003, 60 patients diagnosed with invasive breast cancer were treated with SSM and complete axillary dissection. All patients underwent immediate breast reconstruction after primary surgery. Patients were treated either with a latissimus dorsi flap or with a transversus rectus abdominis myocutaneous flap. Depending on the intraoperative analysis of frozen sections, 14 patients were treated with preservation of the nipple-areola complex. During a median follow-up of 52 months (4-92 months), four local recurrences (6.6%) occurred. One patient was also found to have contralateral breast carcinoma. Three patients developed distant metastases, and two patients died of their disease a mean of 18 months after primary therapy. Factors associated with local recurrence were tumor size, poor tumor differentiation, and positive node involvement. SSM followed by immediate breast reconstruction is an alternative to modified radical mastectomy in a subset of patients with invasive breast cancer. The risk of local recurrence is low and is associated with such factors as tumor stage, poor tumor differentiation, and node-positive disease. This procedure does not increase the risk of distant metastases, which is comparable to that after other surgical approaches.

[Clinical value of mammography, ultrasound and MR imaging during the first year after breast conserving therapy of breast cancer]. / Klinischer Stellenwert bildgebender Verfahren im ersten Jahr nach brusterhaltender Therapie des Mammakarzinoms.

PURPOSE: To compare the accuracy of lesion detection and characterization and to determine the agreement of observers, methods and timing of mammography (MX), ultrasound (US) and MR imaging (MRI) during the first year after breast conserving therapy. MATERIALS AND METHODS: The study included 20 patients diagnosed with breast cancer of stages equal or inferior to T2 N1bi M0 after breast conserving therapy and subsequent radiotherapy. Patients with any history of breast diseases in the affected or contralateral breast were excluded. Patients were examined before and at 3, 6 and 12 months after adjuvant radiotherapy with MX, US and dynamic MR mammography. Additional US and MRI were performed 3 months after radiotherapy. All 220 examinations were retrospectively read in a randomized order by two independent readers, blinded for the results of the other examinations. The outcome after 2.5 years of follow-up was used as gold standard. Histological examination was available in one case. Lesion detection and specificity were assessed including kappa values for different reliabilities between observers, timing and methods. The kappa values were used to characterize the degree of agreement as follows: > 0.8 very good; 0.6 - 0.8 good; 0.4 - 0.6 fair; 0.2 - 0.4 minimal; and < 0.2 negligible. RESULTS: Based on the interpretation of all available findings (clinical examination, MX, US, MRT and histology in one case), 20 patients observed for a mean period of 2.5 years had no evidence of intramammary recurrence. Therefore the sensitivity of the various methods could not be assessed. The reading of certainly no lesion was given by MRI in 43 %, by MX in 30 % and by US in 5 % of all examinations (p < 0.05). True negative findings were observed by MRI in 94.4 %, by MX in 90.4 % and by US in 82.5 %. Reliability between observers, timing and imaging methods was 0.496, 0.411, and 0.215 for lesion detection and 0.303, 0.282, and 0.030 for lesion characterization. CONCLUSION: Within the first year after breast conserving therapy, MRI was the most confident method for the exclusion of lesions and presented the highest true negative rate. The assessment of dignity of a particular lesion was difficult by all imaging methods, reflected by the weak agreement between observers, methods and timing. The difference between times of readings were marginal in the first year after therapy. Agreement between the different diagnostics methods was minimal to negligible.

Sentinel node identification and intraoperative lymphatic mapping. First results of a pilot study in patients with endometrial cancer.

INTRODUCTION: To minimize the surgical morbidity after lymphadenectomy, sentinel node biopsy (SLNB) has become fundamental in the management of different malignancies. We decided to evaluate sentinel lymph node (SNL) biopsies also in patients with endometrial cancer undergoing hysterectomy with lymphadenectomy. METHODS: In the setting of a prospective study we developed a technique for sentinel node biopsy of ten patients with histologically confirmed endometrial cancer. Prior to surgery 99m Tc Nanocol was injected in the peritumoral region by hysteroscopy. Six hours later lymphoscintigraphy was performed to identify the draining lymph nodes. During surgery we first detected the sentinel lymph node by a hand-held gamma tracer and then removed it. Surgery was completed by the standard therapy of total hysterectomy, bilateral salpingo-oophorectomy and pelvic and/or para-aortic lymphadenectomy. RESULTS: Scintigraphic identification was possible in eight out of ten patients. Intraoperative identification of sentinel lymph nodes was possible in seven out of eight patients. In five patients we found the sentinel lymph nodes in the pelvic region while the other two patients had bilateral sentinel nodes in the pelvic and para-aortic region. Histologically confirmed microscopic tumor metastases of the SLNs and para-aortic lymph nodes were only found in one case. The sentinel lymph nodes from the other six patients were free of tumor and accurately reflected the pathological status. CONCLUSION: The identification of sentinel lymph nodes in endometrial cancer is a practical and safe method. In order to improve this technique as a standard procedure for staging of endometrial cancer further studies with a larger number of patients have to be done.

Changes in vascular endothelial growth factor (VEGF) after chemoendocrine therapy in breast cancer.

PURPOSE: Angiogenesis has been proposed as a possible target for anticancer treatment, either by inhibition of the production of angiogenic factors or by inhibition of endothelial cell proliferation. The impact of preoperative chemoendocrine therapy is unknown in the regulation of angiogenic factors, but recent reports suggest that anticancer drugs have antiangiogenic activity. METHODS: The expression of two angiogenic factors VEGF and Angiopoetin-1 were quantified at different concentrations of doxorubicin, docetaxel, tamoxifen, exemestane and letrozol on MCF-7 and T47D cells. RESULTS: Low-drug concentrations led to increased VEGF-A gene transcription whereas high (10-fold increased) drug concentrations suppressed gene expression. A similar cell reaction was observed for VEGF protein with a smaller variety in the extent of modulation. Incubation of MCF-7 cells to different drugs showed a similar dose-dependent modulation of Angiopoietin-1 gene expression with enhancement at low-drug concentrations. CONCLUSION: Treatment of breast cancer cells following a preoperative protocol showed a dose-dependent expression of VEGF and Angiopoetin-1. Only high-drug concentrations were followed by a decreased secretion of both factors whereas low concentrations induced up-regulation of VEGF and Angiopoietin 1.

[Stereotactic vacuum-assisted breast biopsy--success, histologic accuracy, patient acceptance and optimizing the BI-RADSTM-correlated indication]. / Stereotaktische Vakuumbiopsie mammographisch detektierter Läsionen - Erfolg, histologische Sicherheit, Patientenakzeptanz und BI-RADS trade mark -korrelierte Indikationsoptimierung.

PURPOSE: To evaluate success, histologic accuracy, patient acceptance and BI-RADS TM-correlated malignancy rate of stereotactic vacuum-assisted breast biopsies in order to optimize the indication. MATERIALS AND METHODS: In 132 patients with mammographically detected breast lesions 166 stereotactic vacuum- assisted 11 gauge core biopsies were performed. All lesions were classified according to the BI-RADS TM categories of the ACR. Removal of the lesion was radiographically assessed as complete, representative or not representative. Patient acceptance was evaluated. RESULTS: Of the 166 lesions, 54 (32.5 %) lesions were judged completely removed, 110 (66.3 %) representatively removed and 2 (1.2 %) not representatively removed. Malignancy was found in 38 (22.9 %) lesions. The rate of malignancy increased from 6.3 % (2/32) for BI-RADS TM category 3 to 16.7 % (19/114) for BI-RADS TM category 4 and increased further to 85 % (17/20) for BI-RADS TM category 5 (p < 0.001). The histology of a sufficient vacuum-assisted biopsy was underestimated in 6 (15 %) of the 40 lesions that were subsequently excised surgically. Most patients (98.5 %; 130/132) stated they would undergo a vacuum-assisted biopsy again. CONCLUSION: Vacuum-assisted breast biopsy is accurate, has a justifiable rate of histologic underestimation and is well accepted by patients. Patients with BI-RADS TM category 4 microcalcification benefit the most. Lesions of BI-RADS TM category 3 and BI-RADS TM category 5 should be biopsied only under special circumstances (family risk of breast cancer; assessment of lesions extension).

Large-core needle biopsy for diagnosis and treatment of breast lesions.

PURPOSE: Large-core needle biopsy (LCNB) has become a more widely used technique in the evaluation of breast lesions. This study was undertaken to access the accuracy of percutaneous LCNB on breast lesions and the impact on further proceeding. METHODS: A retrospective review of imaging-guided LCNB of 159 breast lesions was done. 143 LCNB were taken with ultrasound guided automated spring gun biopsy and 16 stereotactic-guided with vacuum-assisted biopsy device. Histology and morphobiological parameters were compared with subsequent material from surgery. RESULTS: In 113 core biopsies (71%), an infiltrating breast cancer was diagnosed, 5 biopsies (3%) yielded in-situ/atypical lesions and a benign lesion was shown in 38 cases (24%). In 3 cases, insufficient/necrotic material was obtained. 108 patients underwent subsequent surgery. In 100/108 cases (93%), histology on LCNB and surgery was identical. LCNB was false negative in 5 core biopsies (5%). Immunhistochemical stains of hormone receptors, bcl-2, c-erbB-2, p53 and MIB-1 was comparable on LCNB and on surgical material. Based on the results of LCNB, 17/113 patients (15%) with infiltrating carcinoma were primarily treated with hormones or with neoadjuvant therapy. 32/38 patients (84%) with benign lesions were followed up by imaging control. CONCLUSIONS: In patients with benign lesions on imaging, open biopsies can be avoided by LCNB. In patients with biopsy proven carcinoma, therapy planning is improved. The addition of morphobiological parameters allows early individual treatment.

[Quantitative assessment of therapy related effects after breast conserving therapy with dynamic MRI of the breast]. / Quantitative Erfassung von Gewebsveränderungen der Mamma nach brusterhaltender Therapie mit der dynamischen MR-Mammographie *

PURPOSE: To quantify therapy related effects after breast conservation therapy (BCT) with dynamic MRI of the breast. METHODS: Twenty patients (median age 51 years) with breast conserving tumor excision were included. Contrast enhanced dynamic MRI was performed before and 3, 6 and 12 months after adjuvant radiation therapy (RT) with a total dose of 50.0 to 50.4 Gy. The following sequences were applied: axial fat-suppressed T(2)-weighted; coronal contrast enhanced 3D spoiled gradient-echo (first measurement prior to the administration of 0.16 mmol/kg Gd-DTPA, six repetitive measurements); sagittal T(1)-weighted Flash3D. Enhancement data were obtained using a computer software with automated segmentation of regions of interest (ROIs). After defining ROIs for skin, parenchyma and pectoral muscle of each breast the early enhancement after the first post contrast measurement (E(1)) and the slope of enhancement between the second and last postcontrast measurement (SE(2-L)) were calculated. The edema was quantified by assessing the signal intensities (SI) in the T(2)-weighted images. The thickness of the skin was measured in the sagittal T(1)-weighted images. RESULTS: Three months after RT statistically significant increases between 51 and 179 % of the SI and E(1) quotients were detected for all tissues compared to the examinations prior to RT. Six months after RT the skin still presented a by 102 % significantly higher E(1) quotient, and a by 140 % significantly increased SI quotient. No significant differences for SI and E(1) quotients could be observed 12 months after RT compared to the examinations prior to RT. A significant increase of the SE(2-L) difference for the skin from 0.0225 to 0.0691 and 0.0665 was found 3 and 6 months after RT, respectively. No significant differences between the initial MR examination and the follow-up examinations 3, 6 and 12 months could be detected for the SE(2-L) differences of the parenchyma. CONCLUSION: Early therapy related effects after BCT can be exactly quantified with dynamic MRI using an automated ROI-segmentation and whole breast analysis software. Both edema formation and early enhancement show peaks 3 months after RT, and after 12 months there is no statistically significant difference compared with baseline.

[Clinical experience with large-core needle biopsies of the breast and evaluation of histopathology]. / Klinische Erfahrungen mit perkutanen Biopsien der Brust und deren histologische Beurteilung.

OBJECTIVE: Interventional techniques allow a microinvasive diagnostic of breast lesions. We examined the reliability of large core needle biopsies for histologic diagnosis on breast lesions. MATERIAL AND METHODS: 143 ultrasound guided automated spring gun biopsies and 16 stereotactic guided vacuum-assisted device biopsies were analyzed. Indications included confirmation of malign or benign lesions and diagnosis of suspicious lesions. RESULTS: In 113 biopsies (71%) an invasive breast carcinoma was diagnosed, in 5 biopsies (3%) in situ/atypical lesions were seen and 38 cases (24%) showed benign lesions. Based on the bioptic results, 108 patients underwent subsequent surgery. An identical histology was seen in 100/108 patients (93%), 5 biopsies were false negative (5%) and 3 specimens yielded necrotic/insufficient material. The immunohistochemical results of percutaneous biopsies and surgical specimens were comparable. 17 out of 113 patients (15%) with biopsy proven carcinoma were treated with neoadjuvant therapy. 32/38 patients with benign lesions were follow-up clinically. CONCLUSION: Ultrasound- or stereotactic guided percutaneous biopsies are methods to confirm histological diagnosis. Based on the biopsy results the, number of surgical excisions can be reduced and treatment of biopsy proven carcinoma can be improved by individual presurgical planing.

Stage III and oestrogen receptor negativity are associated with poor prognosis after adjuvant high-dose therapy in high-risk breast cancer.

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage II/III breast cancer. There were 71 patients with more than nine tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7.5 g m(-2)) and epirubicin (120 mg m(-2)) was given, and PBSC were harvested during G-CSF-supported leucocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose, 12,000 mg m(-2)), carboplatin (900 mg m(-2)) and epirubicin (180 mg m(-2)). Patients were autografted with a median number of 3.7 x 10(6) CD34+ cells kg(-1) (range, 1.9-26.5 x 10(6)) resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-one patients relapsed between 3 and 30 months following the last cycle of high-dose therapy (median, 11 months). The probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stage II disease had a significantly better probability of disease-free survival (74%) in comparison to patients with stage III disease (36%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (70%) compared to patients with receptor-negative ones (40%). Bone marrow samples collected from 52 patients after high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour cell-positive samples did not change in comparison to that observed before high-dose therapy (65% vs 71%), but a decrease in the incidence and concentration of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse and for those in remission, which argues against a prognostic significance of isolated tumour cells in bone marrow. In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy, including the addition of non-cross resistant drugs or immunological approaches such as the use of antibodies against HER-2/NEU, may be envisaged for patients with stage III disease and hormone receptor-negative tumours.

Efficacy and toxicity of sequential high-dose therapy with peripheral blood stem cell support in patients with high-risk breast cancer.

Patients with high-risk breast cancer may benefit from dose-escalated chemotherapy. We studied toxicity and therapeutic efficacy of sequential high-dose therapy consisting of two cycles of ifosfamide 12,000 mg/m2, carboplatin 900 mg/m2, and epirubicin 180 mg/m2 (ICE) with peripheral blood stem cell support. Ninety-one patients with advanced breast cancer were included. Fifty-one patients with stage II/III disease and 10 or more tumor-positive axillary lymph nodes received high-dose therapy as adjuvant treatment; the remaining 40 patients were treated for metastatic disease. Peripheral blood stem cells were collected following granulocyte colony-stimulating factor-supported induction chemotherapy. In 68 patients, induction chemotherapy included two cycles of ifosfamide 7,500 mg/m2 and epirubicin 120 mg/m2, while 23 patients received one cycle of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 135 mg/m2, ifosfamide 6,000 mg/m2, and epirubicin 90 mg/m2. One hundred ninety-two cycles of ICE were supported with a median of 3.5 x 10(6) CD34+ cells/kg body weight (range, 1.7 to 38 x 10(6) CD34+ cells/kg body weight), which resulted in rapid hematologic reconstitution with recovery times, for a median neutrophil count of 0.5 x 10(9)/L of 13 days (range, 6 to 20 days) and for a median platelet count greater than 20 x 10(9)L of 9 days (range, 5 to 24 days). Seven patients received only one cycle of ICE because of progressive disease (in two patients with metastatic disease), central nervous system toxicity (one patient), cardiac toxicity (one patient), severe enterocolitis (one patient), development of human leukocyte antigen antibodies (one patient), and wish to withdraw from the study (one patient). Seventeen patients with metastatic disease received an additional high-dose cycle consisting of the non-cross-resistant agents thiotepa 600 mg/m2, etoposide 1,500 mg/m2, and paclitaxel 165 mg/m2. In patients treated adjuvantly, the probability of disease-free survival was 64% at 47 months, which compares favorably with results of conventional treatment protocols, with a 47% event-free probability at the same time period. The probability of progression-free survival in patients with metastatic disease was 18% at 44 months. In conclusion, sequential high-dose therapy with peripheral blood stem cell support in patients with high-risk breast cancer can be administered safely and offers a potential benefit in the adjuvant setting.

[Prognostic significance of plasminogen activator inhibitor-1 (PAI-1) in primary breast carcinoma]. / Prognostische Bedeutung des Plasminogenaktivator Inhibitor-1 (PAI-1) beim primären Mammakarzinom.

The plasminogen activator system plays a key role in the proteolysis of malignant tumours. In 155 patients with primary breast cancer levels from PAI-1 and uPA were measured in cytosol with monoclonal antibodies and by an enzyme-linked immunosorbent assay. 35 tumour tissue samples form benign breast were also examined. Malignant tumours contain higher levels of PAI-1 (8.6 ng/mg) than benign tumours (1.28 ng/mg) (p < 0.01). Also the median level of uPA was significantly higher (p < 0.01) in malignant tissue (2.38 ng/mg) in comparison to benign disease (0.54 ng/mg). No correlation was found between the proteases and the classical prognostic parameters like axillary lymph node involvement, tumour size and menopausal status. However, a significant correlation (p < 0.01) was found in tumours with lymphangiosis carcinomatosa, negative hormone receptors, grade III tumour cells and high S-phase fractions (> 5%). After a median follow-up of 46 months we found that high levels of PAI-1 correlated with short DFS (p = 0.0005) and OAS (p = 0.003). However, in the Cox multivariate regression analysis only PAI-1 was significantly independent for OAS and could therefore give additional information. We conclude that levels from PAI-1 antigen measured in cytosol of primary breast cancer is an independent prognostic parameter to identify patients with high and low risk for relapse and for individualised treatment.