Use of an Additional Diagnostic Work-up Following a Treatment Recommendation from the Preoperative Conference of the Mammography Screening Units.

Objective: If a focus of suspicion is classified as being B 3-5 by a punch biopsy as part of a mammography screening, a recommendation for further action to be taken will be given in the preoperative conference of the screening unit. As part of this investigation, these treatment recommendations were compared with the final therapeutic approach taken at a certified breast centre. Furthermore, it was investigated whether and which additional examinations were performed on patients, depending on compliance with the recommended treatment. Material and Method: The data from 272 breast cancer patients from the years 2007, 2008 and 2009 was analysed. The patients took part in the screening programmes of four screening units in the German mammography screening programme, in one federal state. In addition, the data from each patient from one screening unit was analysed in two further federal states. Results: In total, the most recently conducted intervention deviated from the treatment recommendation from the preoperative conference in the screening unit in 77 out of 272 patients (28.3 %). Of these, there were 50 recommendations for open biopsy which ultimately resulted in breast-conserving surgery, which is not to be evaluated as an error, as the bioptic result was supplemented by the open biopsy. Additional examinations were performed in patients with deviating treatment recommendation in 39 cases (50.6 %) and in patients without deviating treatment recommendation in 66 cases (34.0 %). The additional examinations carried out included additional punch biopsies (most frequent) and MRI scans, but also additional ultrasounds or a mammography. Conclusions: Additional examinations lead to a change in treatment in a higher percentage of patients in comparison with the initial screening including assessment. An exact reexamination of the findings obtained in the screening is therefore preoperatively necessary in order to guarantee optimum treatment.

Impact of magnification views on the characterization of microcalcifications in digital mammography.

PURPOSE: To evaluate the additional benefit of true geometric (air-gap) magnification views for the characterization of microcalcifications in digital mammography. MATERIALS AND METHODS: After ethical approval, we retrospectively reviewed patient records to identify 100 patients with suspicious microcalcifications (35 malignant, 65 benign) who had a standard digital mammography and an additional digital magnification view in the same projection within three months. All images were obtained using an amorphous silicon-based full-field digital system (Senographe 2000 D, GE Healthcare, Chalfont St. Giles, UK). Images were independently analyzed by six board-certified radiologists. The probability of malignancy was estimated using first standard contact mammography alone (MG) and then mammography in combination with the magnification view (MG+MAG) using a modified Breast Imaging Reporting and Data System (BI-RADS) classification system and a percentage scale. Results were compared using receiver operating characteristic (ROC) analysis. In addition, readers assessed the subjective visibility of the calcifications. RESULTS: For all six readers combined, the area under the curve (AUC) was 0.664 ±â€Š0.052 for MG and 0.813 ±â€Š0.042 for MG + MAG, resulting in a statistically significant improvement of 0.148 ±â€Š0.120. Each reader had a higher AUC for MG + MAG than MG, with the improvement being statistically significant in four of the six readers. In 76.34 % of the cases, MG + MAG resulted in better visibility of calcifications compared with mammography alone. In 33 % slightly more and in 39 % significantly more calcifications were found. CONCLUSION: Even in digital mammography with the option of using electronic magnification (zoom) at the viewing workstation, true geometric (air-gap) magnification views remain important for the visibility and correct classification of microcalcifications and for the assessment of their extent.

Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size.

OBJECTIVES: To compare mammography (MG), contrast-enhanced spectral mammography (CESM), and magnetic resonance imaging (MRI) in the detection and size estimation of histologically proven breast cancers using postoperative histology as the gold standard. METHODS: After ethical approval, 80 women with newly diagnosed breast cancer underwent MG, CESM, and MRI examinations. CESM was reviewed by an independent experienced radiologist, and the maximum dimension of suspicious lesions was measured. For MG and MRI, routine clinical reports of breast specialists, with judgment based on the BI-RADS lexicon, were used. Results of each imaging technique were correlated to define the index cancer. Fifty-nine cases could be compared to postoperative histology for size estimation. RESULTS: Breast cancer was visible in 66/80 MG, 80/80 CESM, and 77/79 MRI examinations. Average lesion largest dimension was 27.31 mm (SD 22.18) in MG, 31.62 mm (SD 24.41) in CESM, and 27.72 mm (SD 21.51) in MRI versus 32.51 mm (SD 29.03) in postoperative histology. No significant difference was found between lesion size measurement on MRI and CESM compared with histopathology. CONCLUSION: Our initial results show a better sensitivity of CESM and MRI in breast cancer detection than MG and a good correlation with postoperative histology in size assessment. KEY POINTS: • Contrast-enhanced spectral mammography (CESM) is slowly being introduced into clinical practice. • Access to breast MRI is limited by availability and lack of reimbursement. • Initial results show a better sensitivity of CESM and MRI than conventional mammography. • CESM showed a good correlation with postoperative histology in size assessment. • Contrast-enhanced spectral mammography offers promise, seemingly providing information comparable to MRI.

[Compliance of patients concerning recommended radiotherapy in breast cancer : Association with recurrence, age, and hormonal therapy]. / Compliance der Patientinnen in Bezug zur empfohlenen Strahlentherapie beim Mammakarzinom : Zusammenhang mit Rezidiv, Alter und Hormontherapie.

BACKGROUND AND PURPOSE: In this study, we investigated how often guidelines for radiation therapy in patients with breast cancer are not complied with, which patient group is mostly affected, and how this influences local recurrence. PATIENTS AND METHODS: All patients (n = 1,903) diagnosed between November 2003 and December 2008 with primary invasive or intraductal breast cancer in the interdisciplinary breast center of the Charité Hospital Berlin were included and followed for a median 2.18 years. RESULTS: Patients who, in contrast to the recommendation of the interdisciplinary tumor board, did not undergo postoperative radiation experienced a fivefold higher local recurrence rate (p < 0.0005), corresponding to a 5-year locoregional recurrence-free survival of 74.5% in this group. The 5-year locoregional recurrence-free survival of patients following the recommendations was 93.3%. Guideline compliance was dependent on age of patients, acceptance of adjuvant hormonal treatment or chemotherapy, and increased diameter of the primary tumor. Multiple logistic regression analysis showed an association between compliance and age or hormonal therapy. CONCLUSION: In order to avoid local recurrence patients should be motivated to comply with guideline driven therapy. Since a higher number of local recurrences is observed in health services research compared to clinical research, studies on the value of adjuvant treatment following local recurrence should be performed.

[Quality rating of follow-up examinations conducted on breast cancer patients]. / Wertigkeit der routinemässig erfassten Nachsorgedaten bei Brustkrebspatientinnen.

For breast centre certification, follow-up care data have to be presented, although the further treatment is carried out outside of the hospital. An analysis of 2062 patients with their first operation (breast cancer and carcinoma in situ) occurring between 1.1.1984 and 31.12.1998 has been conducted. The tracking of follow-up results ended on 1.7.2007. The survival of breast cancer patients appears to be superior in the pure clinical register than with cross-linking with additional registers (Epidemiological Cancer Register and registration of address office). The outcome of this is that the completed feedback of the cases of death (Cancer Register) and of living patients (registration of address office) increases the qualitative statement. The compliance with the data security laws may be ensured by pseudo-anonymisation.

Radiation therapy and tamoxifen after breast-conserving surgery: updated results of a 2 x 2 randomised clinical trial in patients with low risk of recurrence.

To study the role of radiotherapy and tamoxifen after breast-conserving surgery (BCS) in patients with a favourable prognosis, a clinical trial was initiated by the German Breast Cancer Study Group (GBSG-V). Between 1991 and 1998, 361 patients (pT 1pN0M0, aged 45-75 years, receptor positive, grades I and II) were randomised to radiotherapy (yes/no) and tamoxifen for 2 years (yes/no) in a 2 x 2-factorial design; the exclusion of seven centres (14 patients) left 347 patients for the analysis. First results after a median follow-up of 5.9 years were published. Herein we present updated results after a median follow-up of about 10 years. Hundred and eleven events concerning event-free survival (EFS) have been observed. Since a strong interactive effect between radiotherapy and tamoxifen has been established, the results are presented in terms of the treatment effects for all four treatment groups separately. Mainly due to the presence of local recurrences, the event rate was much higher in the group with BCS only than in the other three groups. No significant difference could be established between the four treatment groups for distant disease-free survival rates (DDFS). Updated results give further evidence that even in patients with a favourable prognosis, the avoidance of radiotherapy and tamoxifen after BCS increases the rate of local recurrences substantially. Rates are about three times higher in the BCS only group. For the two outcomes EFS and DDFS, no important difference could be seen between the three groups with an additional treatment. However, because of the limited sample size with corresponding low power the strength of evidence for such a comparison is weak.

Co-expression and prognostic value of gross cystic disease fluid protein 15 and mammaglobin in primary breast cancer.

Gross cystic disease fluid protein (GCDFP-15) and mammaglobin are both widely used and accepted markers for epithelia of breast origin. We aimed to evaluate their relation of expression on parallel whole tissue sections in primary breast cancer by immunohistochemistry and also to correlate it with clinico-pathological parameters including patient survival. Primary breast carcinomas from 165 patients with a mean clinical follow-up of 73 months were immunostained using commercially available antibodies against GCDFP-15 and mammaglobin. An immunoreactive score (IRS) was calculated based on the cytoplasmic staining intensity and the number of cells stained. Cytoplasmic expression of GCDFP-15 and mammaglobin was observed in 73.3% and 72.1% of invasive breast carcinomas respectively. 91.8% of breast cancer cases expressed at least one of both markers. Both markers strongly correlated with each other and were significantly associated with lower tumour grading. Additionally, GCDFP-15 negativity was significantly associated with shortened disease-free survival times in univariate and multivariate analyses. We demonstrated the strong correlation of GCDFP-15 and mammaglobin with each other and showed that only very few primary breast cancers are completely negative for both markers. The significantly longer disease free survival times for patients with GCDFP-15 positive tumours clearly warrants further study.

Real-time elastography--an advanced method of ultrasound: First results in 108 patients with breast lesions.

OBJECTIVES: To evaluate whether real-time elastography, a new, non-invasive method for the diagnosis of breast cancer, improves the differentiation and characterization of benign and malignant breast lesions. METHODS: Real-time elastography was carried out in 108 potential breast tumor patients with cytologically or histologically confirmed focal breast lesions (59 benign, 49 malignant; median age, 53.9 years; range, 16-84 years). Tumor and healthy tissue were differentiated by measurement of elasticity based on the correlation between tissue properties and elasticity modulus. Evaluation was performed using the three-dimensional (3D) finite element method, in which the information is color-coded and superimposed on the B-mode ultrasound image. A second observer evaluated the elastography images, in order to improve the objectivity of the method. The results of B-mode scan and elastography were compared with those of histology and previous sonographic findings. Sensitivities and specificities were calculated, taking histology as the gold standard. RESULTS: B-mode ultrasound had a sensitivity of 91.8% and a specificity of 78%, compared with sensitivities of 77.6% and 79.6% and specificities of 91.5% and 84.7%, respectively, for the two observers evaluating elastography. Agreement between B-mode ultrasound and elastography was good, yielding a weighted kappa of 0.67. CONCLUSIONS: Our initial clinical results suggest that real-time elastography improves the specificity of breast lesion diagnosis and is a promising new approach for the diagnosis of breast cancer. Elastography provides additional information for differentiating malignant BI-RADS (breast imaging reporting and data system) category IV lesions.

Cytoplasmic overexpression of ALCAM is prognostic of disease progression in breast cancer.

BACKGROUND: Activated leucocyte cell adhesion molecule (ALCAM, CD166) is a cell surface member of the immunoglobulin superfamily. ALCAM expression has prognostic relevance in prostate and colon cancer. OBJECTIVE: To evaluate ALCAM protein expression in breast cancer by immunohistochemistry and to correlate expression levels with clinicopathological data. METHODS: 162 primary breast carcinomas with a mean clinical follow up time of 53 months were immunostained using a monoclonal ALCAM antibody. The staining was evaluated as an immunoreactive score (IRS) and grouped into low v high for both membranous and cytoplasmic staining. RESULTS: Intraductal and invasive carcinomas showed a higher ALCAM expression (median IRS 4 and 6 respectively) than normal breast tissue (IRS 2). In univariate survival analyses a significant association of high cytoplasmic ALCAM expression with shortened patient disease-free survival (mean (SD) five year non-progression rate, 69.4 (4.6)% v 49.4 (11.1)%, p = 0.0142) was found. In multivariate analyses of disease-free survival times, high cytoplasmic ALCAM expression (relative risk (RR) = 2.086, p = 0.026) and nodal status (RR = 2.246, p = 0.035) were significantly associated with earlier disease progression, whereas tumour grading (RR = 1.6, p = 0.052) was of borderline significance. CONCLUSIONS: The data suggest that strong cytoplasmic ALCAM expression in primary breast cancer, as detected by immunohistochemistry, might be a new marker for a more aggressive breast cancer biology.

Expression of human Kallikrein 14 (KLK14) in breast cancer is associated with higher tumour grades and positive nodal status.

Human kallikrein 14 (KLK14) is a steroid hormone-regulated member of the tissue kallikrein family of serine proteases, for which a prognostic and diagnostic value in breast cancer has been suggested. To further characterise the value of KLK14 as a breast tumour marker, we have carefully analysed KLK14 expression in normal breast tissue and breast cancer both on the RNA level by real-time RT-PCR (n = 39), and on the protein level (n = 127) using a KLK14-specific antibody for immunohistochemistry. We correlated KLK14 protein expression data with available clinico-pathological parameters (mean follow-up time was 55 months) including patient prognosis. KLK14 RNA expression as quantified by real-time RT-PCR was significantly more abundant in breast tumours compared to normal breast tissue (P = 0.027), an issue that had not been clarified recently. Concordantly with the RNA data, cytoplasmic KLK14 protein expression was significantly higher in invasive breast carcinomas compared to normal breast tissues (P = 0.003). Furthermore, KLK14 protein expression was associated with higher tumour grade (P = 0.041) and positive nodal status (P = 0.045) but was not significantly associated with shortened disease-free or overall patient survival time in univariate analyses. We conclude that KLK14 is clearly overexpressed in breast cancer in comparison to normal breast tissues and is positively associated with conventional parameters of tumour aggressiveness, but due to a missing association with survival times, the use of KLK14 immunohistochemistry as a prognostic marker in breast cancer is questionable.

[Diagnosis and treatment of breast cancer]. / Diagnostik und Therapie des Mammakarzinoms.

Today, the treatment of breast cancer should be carried out in interdisciplinary centers. Preoperative diagnosis comprises clinical examination, mammography, ultrasound, and possibly magnetic resonance imaging. To exclude metastases, X-ray of the thorax, ultrasound examination of the abdomen (liver), and skeletal scintigraphy have to be performed. Preoperatively, the possibility of primary systemic therapy to reduce the size of the tumor can be investigated in order to increase the likelihood of surgery preserving the breast, the goal in at least 70% of cases and which always requires radiation therapy. Histopathological investigation to confirm the R0 resection must always be carried out. In the case of intraductal components, the tumor-free periphery must be larger. Systemic therapy is based on risk groups and comprises hormonal therapy, chemotherapy, and immune (antibody) therapy. Follow-up should focus in particular on determining whether relapse has occurred or contralateral breast carcinoma has developed.

[Wound infection and infection-promoting factors in breast cancer surgery -- a prospective multicenter study on quality control]. / Wundinfektionen und sie begünstigende Faktoren im Rahmen der Mammakarzinomchirurgie -- prospektive Multizenterstudie zur Qualitätssicherung.

INTRODUCTION: The quality of treatment of cancer of the female breast is reflected not only in such parameters as local recurrence rate and survival times, but also in the development of surgical complications. Within the framework of a study investigating the performance and quality assurance in surgical treatment of breast cancer, therefore, the wound infection rate (WIR) and factors influencing it were analysed in a large patient population. METHODS: In the period between 1.1.2000 and 31.12.2000, 84 surgical departments participated in a prospective multicenter study to investigate primary surgery for breast cancer. A total of 1 416 patients were recruited to the study, the organization and conduction of which was in the hands of the former surgical department 1 of the University of Leipzig under the patronage of the East German Working Group for Performance and Quality Control in Surgery in cooperation with the An Institute for Quality Control in Operative Medicine of the Otto-von-Guericke University in Magdeburg. In addition to parameters characterizing patients, tumors and diagnostic work-up, we also analysed the surgical treatment and its possible complications with the aid of a questionnaire. The definition of wound infection was based on the criteria of the "Hospital Infection Control Practice Advisory Committee". RESULTS: The overall WIR was 4.5 % (n = 65). 21 (32 %) of the wound infections (WI) were diagnosed exclusively on a clinical basis without establishing the responsible pathogens. In 44 (68 %) of the WI, a search for the pathogen was undertaken which in 3 cases (7 %) was negative, and in 41 cases (93 %) positive. 118 (8.3 %) of the patients received perioperative antibiotic cover. The following parameters were found to have a significant influence on WIR: local drainage, blood transfusion, the time lapse between biopsy and definitive surgery, and the size of the primary tumor. DISCUSSION: Some of the above factors (transfusion, time lapse, drainage) can be influenced by the therapist. The wound infection rate is a marker for treatment quality.

Radiation therapy after breast-conserving surgery; first results of a randomised clinical trial in patients with low risk of recurrence.

To study the role of radiotherapy and tamoxifen after breast-conserving surgery (BCS) in patients with a favourable prognosis, a clinical trial was initiated by the German Breast Cancer Study Group. Between 1991 and 1998, 361 patients (pT1pN0M0, aged 45-75 years, receptor positive, grade I-II) were randomised to radiotherapy (yes/no) and tamoxifen for 2 years (yes/no) in a 2x2 factorial design; the exclusion of seven centres (14 patients) left 347 patients in the analysis. After a median follow-up of 5.9 years, 77 events concerning event-free survival have been observed. Since a strong interactive effect between radiotherapy and tamoxifen has been established, the results are presented in terms of the treatment effects for all four treatment groups separately. Mainly due to the presence of local recurrences, the event rate was about three times higher in the group with BCS only than in the other three groups. No difference could be established between the four treatment groups for distant disease-free survival rates. It is concluded that even in patients with a favourable prognosis, the avoidance of radiotherapy and tamoxifen after BCS increases the rate of local recurrences substantially.

[Preoperative MRT of the breast in invasive lobular carcinoma in comparison with invasive ductal carcinoma]. / Präoperative MRT der Brust beim invasiv-lobulären im Vergleich zum invasiv-duktalen Karzinom.

PURPOSE: To evaluate the role of preoperative MRI of the breast in invasive lobular carcinoma (ILC) compared to invasive ductal carcinoma (IDC). MATERIALS AND METHODS: For one year, all patients transferred by the hospital's gynecologic outpatient service for suspicious findings in routine mammography and/or ultrasound (conventional modalities = CM) underwent preoperative MRI of the breast. Retrospective analysis of the histologic findings identified 17 patients with ILC. These were compared with 30 proven IDC patients, chosen by random. The MRI findings of these 2 patient groups were compared with regard to the detection of additional lesions. The average number of additional lesions detected by MRI was compared for significant differences between both groups using the T-test for paired samples. RESULTS: In the 17 patients with ILC, conventional modalities (CM) identified 21malignant lesions whereas MRI detected a total of 30 lesions. At least one additional lesion was detected by MRI in 7 of the 17 patients with ILC. In the 30 patients with IDC, on the other hand, MRI detected an additional lesion in three instances only. In one patient of the ILC group, MRI identified an additional lesion in the contralateral breast that had escaped detection by CM. No additional contralateral lesion was detected by MRI in any of the IDC patients. Benefit of MRI in ILC-Group: The mean numbers of detected malignant lesions differed significantly between diagnosis by MRI and CM in the ILC group (1.77 carcinomas per patient with MRI versus 1.24 with conventional modalities, T-test, p = 0.0078). Benefit of MRI in IDC-Group: although it was possible to find 1.27 carcinomas vs. 1.17 carcinomas per patient in the IDC-Group, this benefit was not statistical significant (T-test, p = 0.0831). CONCLUSION: Preoperative MRI detects multiple additional lesions compared to the ones already known by CM. The higher incidence of multiple lesions in ILC compared to IDC and the difficult diagnosis of ILC in CM might be the reason for the fact that preoperative MRI is particularly useful in patients with ILC.

[Sentinel node biopsy in breast cancer]. / Wächterlymphknotenbiopsie beim Mammakarzinom.

The international consensus conference from St. Gallen concerning the treatment of early breast cancer concluded in 2003, that sentinel node biopsy was now accepted as method allowing axillary staging in breast cancer. This procedure may avoid complete lymph node dissection in appropriate cases. Since numerous questions associated with the technique are still not defined and the procedure itself is not yet standardized, the German Society of Senology defined the conditions for the routine clinical use of sentinel node biopsy in an interdisciplinary consensus meeting.

[Prospective multicenter study for quality management of breast cancer surgery]. / Prospektive Multizenterstudie zur Qualitätssicherung der Chirurgie des Mammakarzinoms.

Over the last 10 years a dramatic decrease became apparent in primary treatment of breast cancer in general surgical departments. A prospective 1-year observational study involving 84 surgical departments was carried out to describe the current therapeutic situation. A total of 1,416 patients undergoing primary surgical treatment for mammary carcinoma were recorded, and their data evaluated. 68.9% of the carcinomas were treated in departments with an annual case load for this disease of more than 20 operations, with 50% of them being operated on in 8 departments with a case load of 40-100 procedures per year. 94.4% of the carcinomas were confirmed histologically, and in 91% of the patients surgery was performed in curative intention. The rate of breast-preserving procedures was 40%, and breast amputations accounted for 60%. An analysis of the data allowed an evaluation of this specific patient group in the surgical departments. Deficits in terms of management quality are identified.

Use of iodine-based contrast media in digital full-field mammography--initial experience.

AIM: To investigate the use of iodine-based contrast media in digital full-field mammography. METHODS: After performing initial phantom studies, seven patients underwent digital mammography (Senographe 2000D, GE Medical Systems, Milwaukee, USA) using a specially filtered beam before as well as 60, 120, and 180 seconds after injection of 80 ml of iodine contrast medium (Ultravist 370, Schering AG, Germany). The precontrast mammograms were then subtracted from the postcontrast mammograms and the resulting images compared with a contrast-enhanced dynamic MRI study, performed on all women. RESULTS: Contrast medium accumulation within the tumors was visualized with a good quality in all cases. The conditions under which successful contrast-enhanced digital mammography can be performed were determined in phantom studies. CONCLUSIONS: Contrast-enhanced digital mammography has a potential for improving the visualization of breast tumors in mammography using special beam filtering, adjusted x-ray parameters, proper timing, and suitable subtraction software.

[Comparing the visualization of microcalcifications with direct magnification in digital full-field mammography vs. film-screen mammography]. / Vergleich der Visualisierung von Mikroverkalkungen durch Vergrösserungsaufnahmen in digitaler Vollfeldmammographie und konventioneller Mammographie.

PURPOSE: To evaluate the conspicuity of microcalcifications in magnified mammographic views of preparations obtained with full field digital mammography (FFDM), film-screen mammography (FSM), and the DIMA technique. MATERIAL AND METHODS: Twelve preparations were examined by FFDM and FSM using 1.8 x magnification and DIMA using 7 x magnification. Parameter settings were identical for all three techniques. The number of visible microcalcifications was then determined for each modality by three radiologists. As far as possible, all preparations were X-rayed at 22 kV and 10 mAS. RESULTS: Altogether 9705 calcifications were counted (DIMA: 1609/1542/1534; FFDM: 1020/753/881; FSM: 901/643/822). The total number of microcalcifications identified with the DIMA technique was 4685 as compared to 2654 with FFDM and 2366 with FSM. The calcifications counted with FFDM and FSM thus corresponded to 56.6 % and 50.5 %, respectively, of those identified with DIMA. The differences between the groups were statistically significant (F-Test, p < 0.05). CONCLUSION: Significantly more calcifications are identified when magnified mammographic views of preparations containing microcalcifications are obtained with the DIMA technique compared to FFDM or FSM. FFDM depicts markedly more calcifications than FSM. This means one should increase spatial resolution. Digital mammography offers the potential for improved visualization of microcalcifications with advanced applications.