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.

Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression.

Breast cancers are either primarily resistant to chemotherapy (intrinsic resistance), or respond to chemotherapy but later recur with a multidrug-resistant phenotype because of overexpression of the multidrug transporter P-glycoprotein. The MDR1 gene encoding P-glycoprotein may be transcriptionally regulated by a Y-box transcription factor. We now report that, in multidrug-resistant MCF-7 breast cancer cells, nuclear localization of YB-1 is associated with MDR-1 gene expression. In drug-sensitive MCF-7 cells, however, YB-1 was localized to the cytoplasm. Regulated overexpression of YB-1 in drug-sensitive diploid breast epithelial cells induced MDR-1 gene expression and multidrug resistance. In 27 out of 27 untreated primary breast cancers, YB-1 protein was expressed in the cytoplasm although it was undetectable in normal breast tissue of these patients. In a subgroup of tumors (9/27), however, YB-1 was also localized to the nucleus and, in these cases, high levels of P-glycoprotein were present. These results show that in a subset of untreated primary breast cancers, nuclear localization of YB-1 protein is associated with intrinsic multidrug resistance. Our data show that YB-1 has an important role in controlling MDR1 gene transcription and this finding provides a basis for the analysis of molecular mechanisms responsible for intrinsic multidrug resistance in human breast cancer.

[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.

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.

A defined chromosome 6q fragment (at D6S310) harbors a putative tumor suppressor gene for breast cancer.

Recent evidence obtained by cytogenetic and molecular studies indicates that in breast cancer chromosome 6q is often affected by genetic changes suggesting the existence of putative tumor suppressor genes (TSGs). However the function of gene(s) on this chromosome in breast cancer suppression is not understood. To substantiate further the presence of breast cancer related TSGs at 6q and to define their location, we first performed microcell-mediated transfer of chromosome 6 to CAL51 breast cancer cells for studying possible suppression of malignant phenotype and secondly, we analysed DNAs from 46 primary breast cancers for loss of constitutive heterozygosity (LOH) using 24 poly-morphic microsatellite markers. The chromosome transfer resulted in loss of tumorigenicity and reversion of other neoplastic properties of the microcell hybrids. Polymorphism analysis of single hybrids revealed that they harbored only a small donor chromosome fragment defined by the marker D6S310 (6q23.3-q25) and flanked by D6S292 and D6S311. The LOH data suggest that four tumor suppressor gene loci mapped to the central and distal portion of 6q may be independently deleted in breast cancer. One of these regions corresponds to the region identified by chromosome transfer.

[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.

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.

[Intraoperative digital radiography for diagnosis of nonpalpable breast lesions]. / Digitale intraoperative Präparate-radiographie bei diagnostischen Exzisionen nicht palpabler Läsionen der Brust.

PURPOSE: A procedure for performing intraoperative digital radiography of diagnostic breast specimens directly in the operating suite with teleradiologic assessment by a radiologist is presented. The efficiency of this procedure is compared with that of conventional magnification mammography performed in the radiology department. MATERIAL AND METHODS: Thirty-six specimen radiographs obtained by conventional magnification mammography were compared with 38 intraoperative digital magnification radiographs (DIMA Soft P42 prototype, Feinfocus Inc., Garbsen). The radiographs were assessed for lesion conspicuity and time savings for the surgeon, anesthesiologist, and radiologist. RESULTS: The new procedure identified all 38 labeled pathological lesions, and the conventional technique likewise had a detection rate of 100% (36/36). The new technique resulted in considerable time savings for the surgeon and the radiologist. The duration of surgery was shorter and the time interval from removal of the specimen to reporting of the results was reduced from about 23 min to about 13 min. A single radiograph was sufficient for complete visualization of the specimen in all cases. CONCLUSION: Digital intraoperative specimen radiography considerably reduces the time of surgery depending on the local conditions and is highly accurate in locating a suspicious area within the tissue.

[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.

[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.

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.

[Automated mammary sonography and mammography: the differentiation of benign and malignant breast lesions]. / Automatisierte Mammasonographie und Mammographie: Differenzierung benigner und maligner Mammaläsionen.

PURPOSE: A prospective study on the differentiation of breast lesions was carried out using experimental combination schemes of mammography and automatic sonography. MATERIALS AND METHODS: X-ray mammograms and a B image from automatic sonography of 39 malignant and 41 benign lesions as well as 40 cases without lesions were separately examined by four experienced diagnosticians. The observers differentiated the findings mammographically and by measurement in the B images. RESULTS: For two examiners the combination of mammography and automatic sonography gave with regard to the differentiation of breast lesions an improvement in sensitivity of 3 or 5% and in specificity of 31 and 18%, respectively, as compared to mammography alone while for the other two examiners an improved specificity of 21 and 36%, respectively, was accompanied by an 8 and 10% decrease in sensitivity as compared to mammography alone. CONCLUSIONS: The differentiating criteria from automatic sonography and mammography can, in principle, be used to evaluate the dignity of breast lesions. However, an optimization is necessary since the improvement in specificity does not compensate the loss in sensitivity.

[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.

[Evaluation of neoadjuvant therapy in breast carcinoma]. / Bilanz der neoadjuvanten Therapie beim Mammacarcinom.

For 20 years preoperative chemotherapy has been the treatment of choice in inflammatory breast cancer. Adjuvant chemotherapy does not show any advantages over neoadjuvant systemic chemotherapy in terms of survival of patients with breast cancer. Reduction of the size of the tumor enables the surgeon to perform more breast-conserving surgery, but the long-term results for breast tumor to recur in these patients are not yet available. At our hospital, a tumor larger than 30 mm is an indication for mastectomy. In general, only 20.6% of all patients are suitable for neoadjuvant chemotherapy. Patients with lobular carcinoma or with tumors with an extensive ductal carcinoma in situ part will not benefit from such therapy. Tumor remission following neoadjuvant chemotherapy is of prognostic relevance. The rapid therapeutic effect of neoadjuvant therapy allows short-term evaluation of this treatment.

[Three-dimensional breast biopsy and surgery]. / Dreidimensionale Mammabiopsie und Chirurgie.

For the histological verification of suspicious non-palpable small breast tumors, the three-dimensional breast biopsy applied as cylindrical extirpation using the ABBI system is the optimal solution at present. Because of the possibility of performing mammography during the operation, errors of localization can be corrected and incorrect incisions avoided. Taking the three radiomorphologically leading symptoms into consideration--suspicious microcalcification, focal shadow and structural irregularity--it can be stated that the digital mammography of the ABBI system is more sensitive than the conventional one for detecting microcalcification, but focal shadow and structural irregularity are detected less well by digital technique. These structures should be preoperatively marked by using sonography. After the complete removal of suspicious microcalcification checked by digital mammography during the operation, residual tumor might be found in a second excision when histologically invasive or intraductal tumor terminations reach the excision margin (R1 resection). Thirteen invasive and 8 intraductal carcinomas were found in 80 cases of cylindrical extirpation using the ABBI system. In 7 procedures carried out to exclude an in-breast recurrence, 3 intraductal carcinomas and 1 invasive carcinoma were observed. In 8 of 12 invasive carcinomas and in 1 of 5 intraductal carcinomas, breast-conserving therapy was indicated. Two cases of invasive carcinoma fulfilled the criteria applied (minimal tumor-free margin > 2 mm, no extensive intraductal component) to use the ABBI cylinder as lumpectomy without a second excision to follow.

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.

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.