Adjuvant Docetaxel in Node-Negative Breast Cancer Patients: A Randomized Trial of AGO-Breast Study Group, German Breast Group, and EORTC-Pathobiology Group.

BACKGROUND: In node-negative breast cancer (NNBC), a high risk of recurrence is determined by clinico-pathological or tumor-biological assessment. Taxanes may improve adjuvant chemotherapy. METHODS: NNBC 3-Europe, the first randomized phase-3 trial in node-negative breast cancer (BC) with tumor-biological risk assessment, recruited 4146 node-negative breast cancer patients from 2002 to 2009 in 153 centers. Risk assessment was performed by clinico-pathological factors (43%) or biomarkers (uPA/PAI-1, urokinase-type plasminogen activator/its inhibitor PAI-1). High-risk patients received six courses 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), cyclophosphamide (500 mg/m2) (FEC), or three courses FEC followed by three courses docetaxel 100 mg/m2 (FEC-Doc). Primary endpoint was disease-free survival (DFS). RESULTS: In the intent-to-treat population, 1286 patients had received FEC-Doc, and 1255 received FEC. Median follow-up was 45 months. Tumor characteristics were equally distributed; 90.6% of tested tumors had high uPA/PAI-1-concentrations. Planned courses were given in 84.4% (FEC-Doc) and 91.5% (FEC). Five-year-DFS was 93.2% (95% C.I. 91.1-94.8) with FEC-Doc and 93.7% (91.7-95.3) with FEC. Five-year-overall survival was 97.0% (95.4-98.0) for FEC-Doc and 96.6% % (94.9-97.8) for FEC. CONCLUSIONS: With adequate adjuvant chemotherapy, even high-risk node-negative breast cancer patients have an excellent prognosis. Docetaxel did not further reduce the rate of early recurrences and led to significantly more treatment discontinuations.

Gene Expression-Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial.

PURPOSE: Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT. PATIENTS AND METHODS: We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts (n = 619). RESULTS: A 20-gene classifier established in the EXPRESSION cohort using a Youden index-based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer. CONCLUSIONS: The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts.

Weaving for heart valve tissue engineering.

Weaving is a resourceful technology which offers a large selection of solutions that are readily adaptable for tissue engineering (TE) of artificial heart valves (HV). The different ways that the yarns are interlaced in this technique could be used to produce complex architectures, such as the three-layer architecture of the leaflets. Once the assembly is complete, growth of cells in the scaffold would occur in the orientation of the yarn, enabling the deposition of extra cellular matrixes proteins in an oriented manner. Weaving technology is a rapidly evolving field that, first, needs to be understood, and then explored by tissue engineers, so that it could be used to create efficient scaffolds. Similarly, the textile engineers need to gain a basic understanding of key structural and mechanical aspects of the heart valve. The aim of this review is to provide the platform for joining these two fields and to enable cooperative research efforts. Moreover, examples of woven medical products and patents as well as related publication are discussed in this review, nevertheless due to the large, and continuously growing volume of data, only the aspects strictly associated with HVTE lay in the scope of this paper.

c-met is overexpressed in type I ovarian cancer: Results of an investigative analysis in a cohort of consecutive ovarian cancer patients.

The tyrosine kinase c-met alters signaling cascades such as the BRAF-MAPK and PI3K-PKB pathways. These alterations are involved in the carcinogenesis of type I but not type II ovarian cancer (OC). Therefore, the present study investigated the patterns of c-met expression in a cohort of consecutive patients with OC. c-met expression was determined by immunohistochemical analysis. Differences in c-met overexpression among subgroups of established clinicopathological features, including age, histological subtype, tumor stage, histological grading, post-operative tumor burden and completeness of chemotherapy, were determined by χ2 test. Cox regression analyses were performed to determine the prognostic effect of c-met. Survival rates were estimated using the Kaplan-Meier method. A total of 106 patients were enrolled into the study. c-met was overexpressed in 20.8% of the entire cohort; 35.7% of patients with type I OC and 8.6% of patients with type II OC showed overexpression (P=0.001). However, c-met overexpression was not associated with any other established clinicopathological features (all P-values >0.05). Univariate Cox regression analysis showed that overexpression of c-met was associated neither with progression-free survival (PFS) nor with disease-specific survival (DSS) (P=0.835 and P=0.414, respectively). Kaplan-Meier plots also failed to demonstrate an effect of c-met on the 5-year PFS and DSS rates (P=0.938 and P=0.412, respectively). These findings support the hypotheses that the overexpression of c-met is associated with type I but not type II OC, and that overexpression of c-met does not affect the prognosis of OC.

Assessment of pelvic floor muscle contractility: digital palpation versus 2D and 3D perineal ultrasound.

PURPOSE: The aim of our study was to investigate 2D and 3D ultrasound assessment of pelvic floor muscle contractility as an objective non-invasive diagnostic tool in urogynecologic patients. METHODS: Patients from our urogynecological outpatient clinic were examined clinically by a single investigator including digital palpation as well as 2D and 3D perineal ultrasound. Muscle contractility was graded according to the modified Oxford Score and ultrasound images were saved for later analysis. Stored images were evaluated offline by another investigator blinded to all clinical data at a later stage. Bladder neck distance from pubic symphysis and symphysis-levator distance were measured in 2D at rest and during maximal pelvic floor muscle contraction. Hiatal area at the level of minimal hiatal dimensions as a 3D ultrasound parameter was measured at rest and during maximal pelvic floor muscle contraction, too. Spearman's rho was used to calculate statistical correlation between ultrasound parameters and digital assessment. RESULTS: A total of 114 patients were examined in our study. We found a significant correlation between modified Oxford Score and 2D ultrasound parameters of elongation of bladder neck length (Spearman's rho 0.292, p = 0.002) and reduction of symphysis-levator distance (Spearman's rho 0.0.301, p = 0.001), respectively. In addition, we detected a statistical significant correlation of modified Oxford Score and reduction of hiatal area in 3D ultrasound (Spearman's rho 0.458, p < 0.001), too. CONCLUSIONS: In this study, we found a significant correlation of subjective digital assessment of pelvic floor muscle strength with 2D and 3D ultrasound parameters as an objective diagnostic tool.

Management of recurrent or metastatic endometrial cancer in Germany: results of the nationwide AGO pattern of care studies from the years 2013, 2009 and 2006.

PURPOSE: The available literature on the treatment options for recurrent or metastatic endometrial cancer (EC) is full of controversies. Therefore, we explore the results of the AGO pattern of care studies from the years 2013, 2009 and 2006. METHODS: A questionnaire was developed and sent to all 682 German gynecological departments in 2013 (775 in 2009, 500 in 2006, respectively). The results of the questionnaires were compared with each other using Fisher's exact test. RESULTS: Responses were available in 40.0 % in 2013, 33.3 % in 2009 and 35.8 % in 2006. In 2013 the most preferred endocrine drug was progestin (79.8 %), followed by tamoxifen (42.8 %), aromatase inhibitor (19.8 %), fulvestrant (16.3 %) and a combination (3.9 %) (p < 0.001). 65.3, 59.8, 51.7 and 38.2 % of the participants used platinum, taxane, a combination of cytostatic drugs, anthracycline in metastatic EC, respectively (p = 0.215). 96.2, 92.7, 49.8 and 60.9 % of the participants performed an operation, radiotherapy, endocrine therapy and chemotherapy in 2013 because of a local recurrence, respectively (p < 0.001). Compared to 2009 and 2006 these rates remained stable (no p value <0.05). Because of a distant metastasis 50.4, 64.2, 78.5 and 90.8 % of the participants performed an operation, radiotherapy, endocrine therapy and chemotherapy in 2013, respectively (p < 0.001). Compared to 2009 and 2006 more participants performed an operation or radiotherapy and less an endocrine treatment. CONCLUSIONS: Whereas progestin was the favorite drug, the participants of this study did not prefer a specific cytostatic drug for metastatic EC in 2013. This might have reflected the available literature, which did not provide a real standard of care.

Adjuvant treatment decisions for patients with endometrial cancer in Germany: results of the nationwide AGO pattern of care studies from the years 2013, 2009 and 2006.

PURPOSE: In 2013, 2009 and 2006, the Arbeitsgemeinschaft Gynäkologische Onkologie evaluated the therapeutic approaches for endometrial carcinoma and the adherence to their guideline in Germany. Here, the adjuvant treatment decisions were presented. METHODS: A questionnaire was developed and sent to all 682 German gynecological departments in 2013 (775 in 2009 and 500 in 2006, respectively). The results of the questionnaires were compared with the recommendations of the guideline and with each other using Fisher's exact test. RESULTS: Responses were available in 40.0 % in 2013, 33.3 % in 2009 and 35.8 % in 2006. Participants recommended external beam radiotherapy (EBRT) in 13 out of 16 requested stages and vaginal brachytherapy (VBT) in only 10 out of 16 requested stages as suggested by the guideline. Comparing the results of 2013 with 2009, less participants used EBRT and VBT in 7 out of 16 and in 6 out of 16 requested stages, respectively. Conversely, more participants offered adjuvant chemotherapy (CT) in 2013 (90.4 %) compared to 61.9 % in 2009 (p < 0.001) and 48.8 % in 2006 (p < 0.001), respectively. However, the stage-adjusted recommendations of CT were not in line with the guideline in 11 out of 15 requested stages. In total, 77.3 % of the participants use a multiple drug schedule with a platinum and a taxane compound. CONCLUSIONS: The results suggest non-adherence to the guideline concerning the stage-adjusted use of VBT and CT in endometrial carcinoma. These findings emphasize great uncertainties and the need of more clarifying trials. Furthermore, a shift from radiotherapy toward CT is observable.

Prognostic influence of cyclooxygenase-2 protein and mRNA expression in node-negative breast cancer patients.

BACKGROUND: Cyclooxygenases (COX) play a key role in prostaglandin metabolism and are important for tumor development and progression. The aim of this study was to analyze the prognostic impact of COX-2 expression in a cohort of lymph node-negative breast cancer patients not treated in the adjuvant setting. METHODS: COX-2 expression was determined by immunohistochemistry (IHC) in tumor tissue of 193 node-negative breast cancer patients. Additionally, mRNA expression was determined in corresponding tumor samples using microarray based gene-expression data. Univariate and multivariate Cox regression analyses adjusted for age at diagnosis, tumor size, histological grade, human epithelial growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) were performed to evaluate the association of both COX-2 protein and mRNA expression with survival. Survival rates were determined by the Kaplan-Meier method. Correlations between COX-2 expression and established prognostic factors were analyzed using the Chi-square test. A potential correlation between COX-2 protein expression and COX-2 mRNA expression was assessed utilizing the Kruscal-Wallis-H-test. RESULTS: COX-2 protein expression was positive in 24.9% of the breast cancer samples. Univariate analysis showed that COX-2 protein expression was associated with shorter disease-free survival (DFS) (P = 0.0001), metastasis-free survival (MFS) (P = 0.002) as well as breast cancer specific overall survival (OS) (P = 0.043). In multivariate analysis COX-2 expression retained its significance independent of established prognostic factors for shorter DFS (P < 0.001, HR = 2.767, 95% CI = 1.563-4.901) and for inferior MFS (P = 0.002, HR = 2.7, 95% CI = 1.469-5.263) but not for OS (P = 0.096, HR = 1.929, 95% CI = 0.889-4.187). In contrast, COX-2 mRNA expression was not related to survival and failed to show a correlation with protein expression (P = 0.410). CONCLUSIONS: The present findings support the hypothesis that COX-2 protein but not mRNA expression is associated with an unfavorable outcome in node-negative breast cancer.

Prognostic influence of pre-operative C-reactive protein in node-negative breast cancer patients.

The importance of inflammation is increasingly noticed in cancer. The aim of this study was to analyze the prognostic influence of pre-operative serum C-reactive protein (CRP) in a cohort of 148 lymph node-negative breast cancer patients. The prognostic significance of CRP level for disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) was evaluated using univariate and multivariate Cox regression, also including information on age at diagnosis, tumor size, tumor grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, proliferation index (Ki67) and molecular subtype, as well as an assessment of the presence of necrosis and inflammation in the tumor tissue. Univariate analysis showed that CRP, as a continuous variable, was significantly associated with DFS (P = 0.002, hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 1.02-1.07) and OS (P = 0.036, HR= 1.03, 95% CI = 1.00-1.06), whereas a trend was observed for MFS (P = 0.111). In the multivariate analysis, CRP retained its significance for DFS (P = 0.033, HR= 1.01, 95% CI = 1.00-1.07) as well as OS (P = 0.023, HR= 1.03, 95% CI = 1.00-1.06), independent of established prognostic factors. Furthermore, large-scale gene expression analysis by Affymetrix HG-U133A arrays was performed for 72 (48.6%) patients. The correlations between serum CRP and gene expression levels in the corresponding carcinoma of the breast were assessed using Spearman's rank correlation, controlled for false-discovery rate. No significant correlation was observed between CRP level and gene expression indicative of an ongoing local inflammatory process. In summary, pre-operatively elevated CRP levels at the time of diagnosis were associated with shorter DFS and OS independent of established prognostic factors in node-negative breast cancer, supporting a possible link between inflammation and prognosis in breast cancer.

Nationwide analysis on surgical procedures for patients with endometrial cancer in Germany: results of the AGO pattern of care studies from the years 2013, 2009, and 2006.

PURPOSE: In 2013, 2009, and 2006, the Arbeitsgemeinschaft Gynäkologische Onkologie evaluated the therapeutic approaches and the adherence to their guidelines for endometrial carcinoma (EC) in Germany. Here, we present the results concerning the surgical procedures. METHODS: A questionnaire was developed and sent to 682 German gynecological departments in 2013 (775 in 2009 and 500 in 2006). The results were compared with the recommendations of the guideline and with each other. RESULTS: Responses were available in 40.0 % in 2013, 33.3 % in 2009, and 35.8 % in 2006, respectively. Pelvic lymphadenectomy (LAN) was performed in accordance with the guidelines with some exceptions in 2013, 2009, and 2006, whereas paraaortic LAN was performed in accordance with the guideline only in 2009. Histological high-risk subtypes of EC received pelvic and paraaortic LAN in 2013, 2009, and 2006 in accordance with the guidelines with small exceptions. LAN for Patients, who were postoperatively upstaged or upgraded, was not conducted in accordance with the guidelines in 2013, 2009, and 2006. In 2013, 84.6 % of the participants offered the laparoscopic approach (LSA) for hysterectomy and bilateral salpingo-oophorectomy, 63.3 % for pelvic LAN, and 49.1 % for paraaortic LAN, respectively. More participants offered the LSA in 2013 compared to 2009 and 2006 (p values <0.014). CONCLUSIONS: The paraaortic LAN, the LSA as well as the second operation on patients who had postoperatively been upstaged were not conducted in accordance with the guideline [CORRECTED]. Improvements concerning surgical treatment are possible and might lead to higher survival rates and a reduction of morbidity in patients with EC in Germany.

Efficacy of psychodynamic short-term psychotherapy for depressed breast cancer patients: study protocol for a randomized controlled trial.

BACKGROUND: There is a lack of psychotherapeutic trials of treatments of comorbid depression in cancer patients. Our study determines the efficacy of a manualized short-term psychodynamic psychotherapy and predictors of outcome by personality and quality of the therapeutic relationship. METHODS/DESIGN: Eligible breast cancer patients with comorbid depression are assigned to short-term psychodynamic psychotherapy (up to 20 + 5 sessions) or to treatment as usual (augmented by recommendation for counseling center and physician information). We plan to recruit a total of 180 patients (90 per arm) in two centers. Assessments are conducted pretreatment, after 6 (treatment termination) and 12 months (follow-up). The primary outcome measures are reduction of the depression score in the Hospital Anxiety and Depression Scale and remission of depression as assessed by means of the Structured Clinical Interview for DSM IV Disorders by independent, blinded assessors at treatment termination. Secondary outcomes refer to quality of life. DISCUSSION: We investigate the efficacy of short-term psychodynamic psychotherapy in acute care and we aim to identify predictors for acceptance and success of treatment. TRIAL REGISTRATION: ISRCTN96793588.

Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer--results from the GeparQuattro study (GBG 40).

Adjacent ductal carcinoma in situ (DCIS) is found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline-taxane-trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Fifty-nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (P = 0.033). The presence of adjacent DCIS was an independent negative predictor of pCR [odds ratio 0.42 (95% CI 0.2-0.9), P = 0.027]. Adjacent DCIS area decreased from pre-treatment to surgery (r = 0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r = 0.892) and after treatment (r = 0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (P = 0.055). HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.

Cytoplasmic poly(adenosine diphosphate-ribose) polymerase expression is predictive and prognostic in patients with breast cancer treated with neoadjuvant chemotherapy.

PURPOSE: Poly(adenosine diphosphate-ribose) polymerase (PARP) plays a key role in DNA repair and cellular stress response. Inhibitors of PARP show promising clinical activity in metastatic, triple-negative or BRCA-mutated breast cancer. PATIENTS AND METHODS: We investigated cytoplasmic PARP (cPARP) and nuclear PARP (nPARP) expression by immunohistochemistry in 638 pretreatment biopsies from patients on the GeparTrio study and evaluated its predictive and prognostic value after neoadjuvant anthracycline/taxane-based chemotherapy. RESULTS: cPARP expression was high in 23.7%, intermediate in 50.9%, and negative in 25.4% of tumors. High cPARP expression was significantly correlated with nonlobular histology (P < .001), undifferentiated grade (P < .001), positive nodal status (P = .049), and negative hormone receptor (HR) status (P < .001) but not with human epidermal growth factor receptor 2 (HER2) status. Expression was high in 35.5% of triple-negative tumors, 24.6% of HER2-positive tumors, and 18.0% of HR-positive/HER2-negative tumors (P < .001). Pathologic complete response (pCR) rates were 26.5%, 19.1%, and 8.0% in patients with high, intermediate, or negative expression, respectively (P < .001). This predictive effect was most prominent in HR-positive tumors (P = .035) or HER2-negative tumors (P < .001). High cPARP expression was a negative, but not independent, prognostic factor for disease-free survival (DFS; P = .0025) and overall survival (OS; P = .0022). cPARP expression was highly prognostic in patients without a pCR (DFS, P < .001; OS, P < .001) and in patients with HR-positive tumors (DFS, P < .001; OS, P < .001). No such correlations were found for nPARP expression. CONCLUSION: High cPARP expression correlates with aggressive tumor pattern and predicts high sensitivity to neoadjuvant taxane/anthracycline-based chemotherapy but also unfavorable long-term prognosis. As a potential target for PARP inhibitors, cPARP-positive breast cancer might become a new, clinically relevant entity.

Vacuum-assisted breast biopsy: a comparison of 11-gauge and 8-gauge needles in benign breast disease.

BACKGROUND: Minimal invasive breast biopsy is standard care for the diagnosis of suspicious breast lesions. There are different vacuum biopsy (VB) systems in use. The aim of the study was to determine the differences between the 8-gauge and the 11-gauge needle with respect to a) diagnostic reliability, b) complication rate and c) subjective perception of pain when used for vacuum-assisted breast biopsy. METHODS: Between 01/2000 and 09/2004, 923 patients at St. Josefs-Hospital Wiesbaden underwent VB using the Mammotome (Ethicon Endosurgery, Hamburg). Depending on preoperative detection, the procedure was performed under sonographic or mammographic guidance under local anaesthesia. All patients included in the study were followed up both clinically and using imaging techniques one week after the VB and a second time after a median of 41 months. Excisional biopsy on the ipsilateral breast was an exclusion criteria. Subjective pain scores were recorded on a scale of 0 - 10 (0 = no pain, 10 = unbearable pain). The mean age of the patients was 53 years (30 - 88). RESULTS: 123 patients were included in the study in total. 48 patients were biopsied with the 8-gauge needle and 75 with the 11-gauge needle. The use of the 8-gauge needle did not show any significant differences to the 11-gauge needle with regard to diagnostic reliability, complication rate and subjective perception of pain. CONCLUSION: Our data show that there are no relevant differences between the 8-gauge and 11-gauge needle when used for VB. Under sonographic guidance, the use of the 8-gauge needle is recommended for firm breast tissue due to its sharp scalpel point and especially for complete removal of benign lesions. We did not find any advantages in the use of the larger 8-gauge needle compared to the 11-gauge needle in the mammography setting. The utilisation costs of the 8-gauge needle are somewhat higher.

Neoadjuvant interstitial high-dose-rate (HDR) brachytherapy combined with systemic chemotherapy in patients with breast cancer.

BACKGROUND AND PURPOSE: This is the first study investigating neoadjuvant interstitial high-dose-rate (HDR) brachytherapy combined with chemotherapy in patients with breast cancer. The goal was to evaluate the type of surgical treatment, histopathologic response, side effects, local control, and survival. PATIENTS AND METHODS: 53 patients, who could not be treated with breast-conserving surgery due to initial tumor size (36/53) or due to an unfavorable breast-tumor ratio (17/53), were analyzed retrospectively. All but one were in an intermediate/high-risk group (St. Gallen criteria). The patients received a neoadjuvant protocol consisting of systemic chemotherapy combined with fractionated HDR brachytherapy (2 x 5 Gy/day, total dose 30 Gy). In cases, where breast-conserving surgery was performed, patients received additional external-beam radiotherapy (EBRT, 1.8 Gy/day, total dose 50.4 Gy). In patients, who underwent mastectomy but showed an initial tumor size of T3/T4 and/or more than three infiltrated lymph nodes, EBRT was also performed. RESULTS: In 30/53 patients (56.6%) breast-conserving surgery could be performed. The overall histopathologic response rate was 96.2% with a complete remission in 28.3% of patients. 49/53 patients were evaluable for follow-up. After a median of 58 months (45-72 months), one patient showed a mild fibrosis of the breast tissue, three patients had mild to moderate lymphatic edema of the arm. 6/49 (12.2%) patients died of distant metastases, 4/49 (8.2%) were alive with disease, and 39/49 (79.6%) were free from disease. Local recurrence was observed in only one case (2%) 40 months after primary therapy. After mastectomy, this patient is currently free from disease. CONCLUSION: The combination of interstitial HDR brachytherapy and chemotherapy is a well-tolerated and effective neoadjuvant treatment in patients with breast cancer. Compared to EBRT, treatment time is short. Postoperative EBRT of the whole breast -- if necessary -- is still possible after neoadjuvant brachytherapy. Even though the number of patients does not permit definite conclusions, the results are promising regarding survival and the very low rate of local recurrences.