Correlation of RANK and RANKL with mammographic density in primary breast cancer patients.

PURPOSE: The receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) have been shown to promote proliferation of the breast and breast carcinogenesis. The objective of this analysis was to investigate whether tumor-specific RANK and RANKL expression in patients with primary breast cancer is associated with high percentage mammographic density (PMD), which is a known breast cancer risk factor. METHODS: Immunohistochemical staining of RANK and RANKL was performed in tissue microarrays (TMAs) from primary breast cancer samples of the Bavarian Breast Cancer Cases and Controls (BBCC) study. For RANK and RANKL expression, histochemical scores (H scores) with a cut-off value of > 0 vs 0 were established. PMD was measured in the contralateral, non-diseased breast. Linear regression models with PMD as outcome were calculated using common predictors of PMD (age at breast cancer diagnosis, body mass index (BMI) and parity) and RANK and RANKL H scores. Additionally, Spearman rank correlations (ρ) between PMD and RANK and RANKL H score were performed. RESULTS: In the final cohort of 412 patients, breast cancer-specific RANK and RANKL expression was not associated with PMD (P = 0.68). There was no correlation between PMD and RANK H score (Spearman's ρ = 0.01, P = 0.87) or RANKL H score (Spearman's ρ = 0.04, P = 0.41). RANK expression was highest in triple-negative tumors, followed by HER2-positive, luminal B-like and luminal A-like tumors, while no subtype-specific expression of RANKL was found. CONCLUSION: Results do not provide evidence for an association of RANK and RANKL expression in primary breast cancer with PMD.

[Fusion of mammography and ultrasonography]. / Fusion von Mammographie und Ultraschall.

STANDARD RADIOLOGICAL PROCEDURES: Currently, the combination of mammography and sonography is the gold standard in breast diagnostics. If there are any uncertainties, further examinations such as breast magnetic resonance imaging (MRI) and, in studies, computer tomographic procedures can be used. These investigations are carried out separately. METHODICAL INNOVATION: The combination of different imaging techniques in fusion devices promises a significant improvement in breast diagnostics. Advantages of the new imaging technique include the simultaneous acquisition of different image modalities with a fixed breast, which allows better spatial localization of the region of interest (ROI). This can also reduce the time and investigator effort and compensate for the weaknesses of one imaging technique with the strengths of a second imaging technique. The current state of research and the history of the fusion of ultrasound and mammography in breast diagnostics are summarized.

Breast MRI in the era of diffusion weighted imaging: do we still need signal-intensity time curves?

OBJECTIVE: Dynamic contrast-enhanced imaging of the initial (IP) and delayed phase (DP) is an integral part of any clinical breast MRI protocol. Furthermore, DWI is increasingly used as an add-on sequence by the breast-imaging community. We investigated whether DWI could be used as a substitute DP. MATERIAL AND METHODS: One hundred thirty-two consecutive patients with equivocal or suspicious findings at ultrasound and/or mammography received a full diagnostic breast MRI according to international recommendations. Histopathological verification served as reference standard. We evaluated three sections of the MRI protocol: IP, DP, and apparent diffusion coefficient (ADC) maps derived from DWI. Circular ROIs (regions of interest, mean size 5-10 mm2) were drawn into the enhancing parts of the lesion (first postcontrast). ROIs were transferred to the corresponding location on ADC maps and IP and DP images. Mean ROI values were investigated signal intensity (SI): (1) Initial-phase enhancement = (SI(IP) - SI(precontrast))/SI(precontrast); (2) Delayed-phase enhancement = (SI(DP) - SI(IP))/SI(IP); (3) ADC. Multiparametric combinations were computed using logistic regression analysis: (1) IP+: Initial-phase enhancement and ADC; (2) Curve: Initial-phase enhancement and delayed-phase enhancement; (3) Curve+: Curve and ADC. The diagnostic performances of these feature combinations to diagnose malignancy were compared by the area under the receiver-operating characteristics curve (AUC). RESULTS: One hundred thirty-two patients (age: mean = 57.1 years, range 23-83 years) with 145 lesions were included (malignant/benign 101/44). IP+ (AUC = 0.877) outperformed Curve (AUC = 0.788, p = 0.03). Curve+ was not superior to IP+ (p = 1). CONCLUSION: DWI could substitute DP. Because DWI is typically used as an add-on to IP and DP, our results might help to abbreviate and to simplify current practice of breast MRI. KEY POINTS: • DWI provides similar but superior diagnostic information for diagnosis of malignancy in enhancing breast lesions compared to DP. • Adding DP to DWI does not provide incremental information to distinguish benign from malignant lesions. • DWI could substitute DP. As DWI is typically used as an add-on to IP and DP, our findings might help to abbreviate and to simplify current breast MRI practice.

Efficacy of neoadjuvant pertuzumab in addition to chemotherapy and trastuzumab in routine clinical treatment of patients with primary breast cancer: a multicentric analysis.

PURPOSE: Neoadjuvant combination treatment with chemotherapy (CTX), trastuzumab (TZM), and pertuzumab (PTZ) has been shown to result in higher pathological complete response rates (pCR) in comparison with treatment with chemotherapy and trastuzumab (CTX/TZM). This analysis was aimed at real-world validation of these results from prospective randomized trials. METHODS: In a retrospective analysis conducted in the PRAEGNANT network, patients were eligible for inclusion if they had either received neoadjuvant therapy with CTX/TZM or chemotherapy, trastuzumab, and pertuzumab (CTX/TZM/PTZ) and subsequently underwent surgery for their primary breast cancer. The effect of the two neoadjuvant regimens on pCR in addition to commonly applicable predictors of pCR was analyzed in 300 patients from three study sites, using logistic regression analyses with treatment arm, age, clinical tumor stage, grading, and hormone receptor status as predictors. RESULTS: pCR with complete disappearance of all tumor cells was seen in 30.2% (n = 58) of patients treated with CTX/TZM and in 52.8% (n = 57) of those treated with CTX/TZM/PTZ. CTX/TZM/PTZ was positively associated with pCR (adjusted odds ratio 2.44; 95% CI 1.49-4.02). Mastectomy rates were not influenced by the therapy. CONCLUSIONS: The results of clinical trials were confirmed in this dataset of patients who were treated outside of clinical trials in everyday routine work. pCR rates can be improved by 20% with pertuzumab in routine clinical use.

Prediction of pathological complete response and prognosis in patients with neoadjuvant treatment for triple-negative breast cancer.

BACKGROUND: It has been reported that pathological complete response is an important surrogate marker for disease-free survival and overall survival in patients with triple-negative breast cancer. This study investigates predictors of the response to neoadjuvant platinum-based or anthracycline-based treatment, and of the prognosis, in patients with triple-negative breast cancer. METHODS: A total of 121 patients with triple-negative breast cancer received neoadjuvant treatment with either platinum or anthracycline between 2008 and 2013. Pathological complete response was assessed relative to different treatments using logistic regression models with age, clinical tumor stage, grading, and Ki-67 as predictors and interaction terms, to obtain adjusted and subgroup-specific results. The impact of the pathological complete response rate on disease-free survival and overall survival was also analyzed. RESULTS: The pathological complete response rate was higher after platinum/taxane treatment compared with anthracycline/taxane (50.0% vs. 41.8%), but this was not significant in the adjusted analysis (OR 1.44; 95% CI, 0.68 to 3.09). A high histological grade (G3) was a predictor for higher pathological complete response in platinum-based therapy (OR 2.27; 95% CI, 1.00 to 5.30). The effect of neoadjuvant chemotherapy on pathological complete response was significantly different for G1-2 vs. G3 (Pinteraction = 0.013), and additional subgroup-specific differences were noted. Pathological complete response was a predictor for improved disease-free survival and overall survival in both treatment groups, with and without platinum chemotherapy. CONCLUSIONS: This retrospective study of patients with triple-negative breast cancer adds to the evidence that the treatment effect of platinum may be greatest particularly in G3 tumors. In addition, the effect of pathological complete response on the prognosis does not depend on the treatment used.

Initial clinical results with a fusion prototype for mammography and three-dimensional ultrasound with a standard mammography system and a standard ultrasound probe.

BACKGROUND: Combinations *Equal contributors. of different imaging techniques in fusion devices appear to be associated with improvements in diagnostic assessment. PURPOSE: The aim of this study was to test the feasibility of using an automated standard three-dimensional (3D) ultrasound (US) device fused with standard mammography for the first time in breast cancer patients. MATERIAL AND METHODS: Digital mammograms and 3D automated US images were obtained in 23 patients with highly suspicious breast lesions. A recently developed fusion machine consisting of an ABVS 3D US transducer from an Acuson S2000 machine and a conventional Mammomat Inspiration device (both Siemens Healthcare GmbH, Erlangen, Germany) were used for the purpose. The feasibility of the examinations, imaging coverage, and patients' experience of the procedure were examined. RESULTS: In 15 out of 19 patients, the region of interest (ROI) with the tumor marked in the mammogram was visible on US. The examination was experienced positively by the patients, with no unexpected pain or injury. The examination was time-saving and well tolerated. CONCLUSION: In conclusion, we have shown initial clinical feasibility of an US/radiography fusion prototype with good localization and evaluation of the ROIs. The combined examination was well tolerated. The simultaneous evaluation with mammography and US imaging may be able to improve detection and reduce examiner-related variability.

Association between mammographic density and pregnancies relative to age and BMI: a breast cancer case-only analysis.

PURPOSE: Percentage mammographic density (PMD) is a major risk factor for breast cancer (BC). It is strongly associated with body mass index (BMI) and age, which are themselves risk factors for breast cancer. This analysis investigated the association between the number of full-term pregnancies and PMD in different subgroups relative to age and BMI. METHODS: Patients were identified in the breast cancer database of the University Breast Center for Franconia. A total of 2410 patients were identified, for whom information on parity, age, and BMI, and a mammogram from the time of first diagnosis were available for assessing PMD. Linear regression analyses were conducted to investigate the influence on PMD of the number of full-term pregnancies (FTPs), age, BMI, and interaction terms between them. RESULTS: As in previous studies, age, number of FTPs, and BMI were found to be associated with PMD in the expected direction. However, including the respective interaction terms improved the prediction of PMD even further. Specifically, the association between PMD and the number of FTPs differed in young patients under the age of 45 (mean decrease of 0.37 PMD units per pregnancy) from the association in older age groups (mean decrease between 2.29 and 2.39 PMD units). BMI did not alter the association between PMD and the number of FTPs. CONCLUSIONS: The effect of pregnancies on mammographic density does not appear to become apparent before the age of menopause. The mechanism that drives the effect of pregnancies on mammographic density appears to be counter-regulated by other influences on mammographic density in younger patients.

Semi-automated delineation of breast cancer tumors and subsequent materialization using three-dimensional printing (rapid prototyping).

OBJECTIVE: Three-dimensional (3D) printing has become widely available, and a few cases of its use in clinical practice have been described. The aim of this study was to explore facilities for the semi-automated delineation of breast cancer tumors and to assess the feasibility of 3D printing of breast cancer tumors. METHODS: In a case series of five patients, different 3D imaging methods-magnetic resonance imaging (MRI), digital breast tomosynthesis (DBT), and 3D ultrasound-were used to capture 3D data for breast cancer tumors. The volumes of the breast tumors were calculated to assess the comparability of the breast tumor models, and the MRI information was used to render models on a commercially available 3D printer to materialize the tumors. RESULTS: The tumor volumes calculated from the different 3D methods appeared to be comparable. Tumor models with volumes between 325 mm3 and 7,770 mm3 were printed and compared with the models rendered from MRI. The materialization of the tumors reflected the computer models of them. CONCLUSION: 3D printing (rapid prototyping) appears to be feasible. Scenarios for the clinical use of the technology might include presenting the model to the surgeon to provide a better understanding of the tumor's spatial characteristics in the breast, in order to improve decision-making in relation to neoadjuvant chemotherapy or surgical approaches. J. Surg. Oncol. 2017;115:238-242. © 2016 Wiley Periodicals, Inc.

Differentiation of ductal carcinoma in situ versus fibrocystic changes by magnetic resonance imaging: are there pathognomonic imaging features?

Background In breast magnetic resonance imaging (MRI), the diagnosis of ductal carcinoma in situ (DCIS) remains controversial; the most challenging cause of false-positive DCIS diagnosis is fibrocystic changes (FC). Purpose To search for typical and pathognomonic patterns of DCIS and FC using a standard clinical MRI protocol. Material and Methods Consecutive patients scheduled for breast MRI (standardized protocols @ 1.5T: dynamic-T1-GRE before/after Gd-DTPA [0.1 mmol/kg body weight (BW)]; T1-TSE), with subsequent pathological sampling, were investigated. Sixteen MRI descriptors were prospectively assessed by two experienced radiologists in consensus (blinded to pathology) and explored in patients with DCIS (n = 77) or FC (n = 219). Univariate and multivariate statistics were performed to identify the accuracy of descriptors (alone, combined). Furthermore, pathognomonic descriptor-combinations with an accuracy of 100% were explored (χ2 statistics; decision trees). Results Six breast MRI descriptors significantly differentiated DCIS from FC ( Pcorrected < 0.05; odds ratio < 7.9). Pathognomonic imaging features were present in 33.8% (n = 100) of all cases allowing the identification of 42.9% of FC (n = 94). Conclusion Pathognomonic patterns of DCIS and FC were frequently observed in a standard clinical MRI protocol. Such imaging patterns could decrease the false-positive rate of breast MRI and hence might help to decrease the number of unnecessary biopsies in this clinically challenging subgroup.

Mammographic density is the main correlate of tumors detected on ultrasound but not on mammography.

Although mammography screening programs do not include ultrasound examinations, some diagnostic units do provide women with both mammography and ultrasonography. This article is concerned with estimating the risk of a breast cancer patient diagnosed in a hospital-based mammography unit having a tumor that is visible on ultrasound but not on mammography. A total of 1,399 women with invasive breast cancer from a hospital-based diagnostic mammography unit were included in this retrospective study. For inclusion, mammograms from the time of the primary diagnosis had to be available for computer-assisted assessment of percentage mammographic density (PMD), as well as Breast Imaging Reporting and Data System (BIRADS) assessment of mammography. In addition, ultrasound findings were available for the complete cohort as part of routine diagnostic procedures, regardless of any patient or imaging characteristics. Logistic regression analyses were conducted to identify predictors of mammography failure, defined as BIRADS assessment 1 or 2. The probability that the visibility of a tumor might be masked at diagnosis was estimated using a regression model with the identified predictors. Tumors were only visible on ultrasound in 107 cases (7.6%). PMD was the strongest predictor for mammography failure, but age, body mass index and previous breast surgery also influenced the risk, independently of the PMD. Risk probabilities ranged from 1% for a defined low-risk group up to 40% for a high-risk group. These findings might help identify women who should be offered ultrasound examinations in addition to mammography.

Fine needle aspiration cytology of lymph nodes in breast cancer follow-up is a feasible alternative to watchful waiting and to histology.

BACKGROUND: Early detection of loco-regional breast cancer recurrence improves patients' overall survival, as treatment can be initiated or active treatment can be changed. If a suspicious lymph node is diagnosed during a follow-up exam, surgical excision is often performed. The aim of this study was to evaluate the diagnostic performance of the minor invasive ultrasound-guided fine-needle aspiration cytology (FNAC) in sonomorphologically suspicious lymph nodes in breast cancer follow-up. METHODS: Between April 2010 and November 2012, we performed ultrasound-guided FNAC in 38 sonographically suspicious lymph nodes of 37 breast cancer follow-up patients. Cytological specimens were evaluated if the sample material was sufficient for diagnosis and if they contained cancer cells. Patients with negative cytology were followed up clinically and sonographically. To evaluate the diagnostic performance we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for physical examination, the different sonomorphological malignancy criteria and FNAC. RESULTS: In 36/38 (94.7 %) lymph nodes, the pathologist had enough material to establish a final diagnosis; in 2/38 (5.3 %) lymph nodes, the probe material was non-evaluable during cytology, these 2 were excluded from further statistical evaluation. Cytology revealed malignancy in 21 lymph nodes and showed no evidence for malignancy in 15 lymph nodes. There was no evidence for malignant disease in follow-up exams in the 15 cytologically benign lymph nodes with an average follow-up time of 3 years. The diagnostic performances of physical examination and FNAC were: Sensitivity 52/100 %, specificity 88/100 %, PPV 85/100 %, NPV 60/100 %, respectively. CONCLUSIONS: Our preliminary results show that FNAC is a safe and fast diagnostic approach for the evaluation of suspicious lymph nodes in the follow-up of patients with breast cancer and, thus, together with follow-up represents a feasible alternative to surgery.

FemZone trial: a randomized phase II trial comparing neoadjuvant letrozole and zoledronic acid with letrozole in primary breast cancer patients.

BACKGROUND: The objective of this prospectively randomized phase II trial (Trial registration: EUCTR2004-004007-37-DE) was to compare the clinical response of primary breast cancer patients to neoadjuvant therapy with letrozole alone (LET) or letrozole and zoledronic acid (LET + ZOL). METHODS: Patients were randomly assigned to receive either LET 2.5 mg/day (n = 79) or the combination of LET 2.5 mg/day and a total of seven infusions of ZOL 4 mg every 4 weeks (n = 89) for 6 months. Primary endpoint was clinical response rate as assessed by mammogram readings. The study was terminated prematurely due to insufficient recruitment. We report here on an exploratory analysis of this data. RESULTS: Central assessment of tumor sizes during the treatment period was available for 131 patients (66 LET, 65 LET + ZOL). Clinical responses (complete or partial) were seen in 54.5% (95% CI: 41.8-66.9) of the patients in the LET arm and 69.2% (95% CI: 56.6-80.1) of those in the LET + ZOL arm (P = 0.106). A multivariate model showed an OR of 1.72 (95% CI: 0.83-3.59) for the experimental arm. CONCLUSION: No increase in the clinical response rate was observed with the addition of ZOL to a neoadjuvant treatment regimen with LET. However a trend towards a better reponse in the LET + ZOL arm could be observed. This trend is consistent with previous studies that have investigated the addition of ZOL to chemotherapy, and it may support the evidence for a direct antitumor action of zoledronic acid.

Financing of certified centers: a willingness-to-pay analysis.

INTRODUCTION: Although care in certified breast centers is now established throughout Germany, numerous services are still not being reimbursed. This also affects other centers involved in the specialty of gynecology such as gynecological cancer centers, perinatal centers, and endometriosis centers. Although a certified center is entitled to charge additional fees, these are in most cases not reimbursed. Calculation of additional costs is limited by the fact that data from the Institute for the Hospital Reimbursement System (Institut für das Entgeltsystem im Krankenhaus, InEK) do not reflect interdisciplinary services and procedures. For decision-makers, society's willingness to pay is an important factor in guiding decisions on the basis of social priorities. A hypothetical maximum willingness to pay can be calculated using a willingness-to-pay analysis, making it possible to identify deficiencies in the arbitrary setting of health budgets at the macro-level. MATERIALS AND METHODS: In a multicenter study conducted between November 2009 and December 2010, 2,469 patients at a university hospital and at a non-university hospital were asked about the extent of their awareness of certified centers, the influence of centers on hospital presentation, and about personal attitudes toward quality-oriented reimbursement. A subjective assessment of possible additional charges was calculated using a willingness-to-pay analysis. RESULTS: In the overall group, 53.4 % of the patients were aware of what a certified center is and 27.4 % had specific information (obstetrics 40.0/32.3 %; mastology 66.8/23.2 %; gynecological oncology 54.7/27.3 %; P < 0.001). For 43.8 %, a certified center was one reason or the major reason for presentation (obstetrics 26.2 %; mastology 66.8 %; gynecological oncology 46.6 %; P < 0.001). A total of 72.6 % were in favor of quality-oriented reimbursement and 69.7 % were in favor of an additional charge for a certified center amounting to €538.56 (mastology €643.65, obstetrics €474.67, gynecological oncology €532.47). In all, 33.9 % would accept an increase in health-insurance fees (averaging 0.3865 %), and 28.3 % were in favor of reduced remuneration for non-certified centers. CONCLUSIONS: The existence of certified centers is being increasingly recognized by patients. Additional charges for certified centers are generally supported. There is therefore a clear demand for them-from patients as well. This may be useful when negotiations are being conducted.

Predicting mammographic density with linear ultrasound transducers.

BACKGROUND: High mammographic density (MD) is a risk factor for the development of breast cancer (BC). Changes in MD are influenced by multiple factors such as age, BMI, number of full-term pregnancies and lactating periods. To learn more about MD, it is important to establish non-radiation-based, alternative examination methods to mammography such as ultrasound assessments. METHODS: We analyzed data from 168 patients who underwent standard-of-care mammography and performed additional ultrasound assessment of the breast using a high-frequency (12 MHz) linear probe of the VOLUSON® 730 Expert system (GE Medical Systems Kretztechnik GmbH & Co OHG, Austria). Gray level bins were calculated from ultrasound images to characterize mammographic density. Percentage mammographic density (PMD) was predicted by gray level bins using various regression models. RESULTS: Gray level bins and PMD correlated to a certain extent. Spearman's ρ ranged from - 0.18 to 0.32. The random forest model turned out to be the most accurate prediction model (cross-validated R2, 0.255). Overall, ultrasound images from the VOLUSON® 730 Expert device in this study showed limited predictive power for PMD when correlated with the corresponding mammograms. CONCLUSIONS: In our present work, no reliable prediction of PMD using ultrasound imaging could be observed. As previous studies showed a reasonable correlation, predictive power seems to be highly dependent on the device used. Identifying feasible non-radiation imaging methods of the breast and their predictive power remains an important topic and warrants further evaluation. Trial registration 325-19 B (Ethics Committee of the medical faculty at Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany).

Characterizing mammographic images by using generic texture features.

INTRODUCTION: Although mammographic density is an established risk factor for breast cancer, its use is limited in clinical practice because of a lack of automated and standardized measurement methods. The aims of this study were to evaluate a variety of automated texture features in mammograms as risk factors for breast cancer and to compare them with the percentage mammographic density (PMD) by using a case-control study design. METHODS: A case-control study including 864 cases and 418 controls was analyzed automatically. Four hundred seventy features were explored as possible risk factors for breast cancer. These included statistical features, moment-based features, spectral-energy features, and form-based features. An elaborate variable selection process using logistic regression analyses was performed to identify those features that were associated with case-control status. In addition, PMD was assessed and included in the regression model. RESULTS: Of the 470 image-analysis features explored, 46 remained in the final logistic regression model. An area under the curve of 0.79, with an odds ratio per standard deviation change of 2.88 (95% CI, 2.28 to 3.65), was obtained with validation data. Adding the PMD did not improve the final model. CONCLUSIONS: Using texture features to predict the risk of breast cancer appears feasible. PMD did not show any additional value in this study. With regard to the features assessed, most of the analysis tools appeared to reflect mammographic density, although some features did not correlate with PMD. It remains to be investigated in larger case-control studies whether these features can contribute to increased prediction accuracy.

Association of mammographic density with hormone receptors in invasive breast cancers: results from a case-only study.

For many breast cancer (BC) risk factors, there is growing evidence concerning molecular subtypes for which the risk factor is specific. With regard to mammographic density (MD), there are inconsistent data concerning its association with estrogen receptor (ER) and progesterone receptor (PR) expression. The aim of our study was to analyze the association between ER and PR expression and MD. In our case-only study, data on BC risk factors, hormone receptor expression and MD were available for 2,410 patients with incident BC. MD was assessed as percent MD (PMD) using a semiautomated method by two readers for every patient. The association of ER/PR and PMD was studied with multifactorial analyses of covariance with PMD as the target variable and including well-known factors that are also associated with MD, such as age, parity, use of hormone replacement therapy, and body mass index (BMI). In addition to the commonly known associations between PMD and age, parity, BMI and hormone replacement therapy, a significant inverse association was found between PMD and ER expression levels. Patients with ER-negative tumors had an average PMD of 38%, whereas patients with high ER expression had a PMD of 35%. A statistical trend toward a positive association between PMD and PR expression was also seen. PMD appears to be inversely associated with ER expression and may correlate positively with PR expression. These effects were independent of other risk factors such as age, BMI, parity, and hormone replacement therapy, possibly suggesting other pathways that mediate this effect.

Association of mammographic density with the proliferation marker Ki-67 in a cohort of patients with invasive breast cancer.

There is growing evidence that certain breast cancer (BC) risk factors specifically increase the risk for specific molecular tumor subtypes. Different molecular subtypes of BC can partly be described by analyzing proliferation in tumors. Very few data are available regarding the association of mammographic density (MD), as a BC risk factor, with proliferation. The aim of this study was to analyze the association between Ki-67 expression in BCs and MD. In this case-only study, data on BC risk factors, hormone receptor expression, and MD were available for 1,975 patients with incident BC. MD was assessed as percentage mammographic density (PMD) using a semiautomated method by two readers for every patient. The association of the Ki-67 proliferation index and PMD was studied using multifactorial analyses of covariance (ANCOVA), with PMD as the target variable and including well-known factors that are also associated with MD such as age, parity, use of hormone replacement therapy (HRT), and body mass index (BMI). There were no significant differences in PMD between women with BC who had low and high Ki-67 values (P = 0.31). However, there were relevant differences in women with low BMI (P = 0.07), and in women using postmenopausal HRT (P = 0.06) as well as in women with low PR values (P = 0.07). In these subgroups, the Ki-67 expression index increased with decreasing PMD. Likewise PMD is correlated with BMI, parity status, and menopausal status stronger in patients with low proliferating tumors, and with progesterone receptor expression in patients with high proliferating tumors. MD correlates inversely with Ki-67 proliferation in BC tumors only in some subgroups of BC patients, defined by commonly known BC risk factors that are usually associated with MD as well.

Evaluation of a Wireless Localization System for Nonpalpable Breast Lesions - Feasibility and Cost-effectiveness in Everyday Clinical Routine.

BACKGROUND/AIM: Smaller, earlier-stage breast tumors are being found in breast cancer screening, and neoadjuvant chemotherapy is the gold standard when chemotherapy is indicated. Precise marking and localization of the tumor are thus becoming increasingly important. Wire-free localization techniques are under investigation in order to reduce presurgical radiography, pain, the risk of wire dislocation, and allow scheduling flexibility for patients and surgery departments. PATIENTS AND METHODS: This single-center observational study from June 2020 to October 2021 included 15 patients with mammographically or sonographically detected nonpalpable breast lesions. Radiofrequency identification (RFID) tags were placed preoperatively under ultrasound or radiologic guidance to localize lesions for planned surgery. All patients underwent breast conservation surgery, including one bilateral and one targeted axillary dissection. RESULTS: Histology identified two benign and 13 malignant lesions, including three ductal carcinomas in situ and 11 invasive breast cancers. Placement, control radiography, and handling of the RFID tag were feasible in everyday routine for different radiologists and surgeons and managed cost-effectively. All of the RFID tags were found in the specimen radiographs. CONCLUSION: The feasibility and cost-effectiveness of this non-wire localization method were demonstrated in this rather small cohort of patients. Further studies including larger numbers of patients are needed to confirm the method's accuracy.

Assessment of breast cancer tumour size using six different methods.

OBJECTIVES: Tumour size estimates using mammography (MG), conventional ultrasound (US), compound imaging (CI) and real-time elastography (RTE) were compared with histopathological specimen sizes. METHODS: The largest diameters of 97 malignant breast lesions were measured. Two US and CI measurements were made: US1/CI1 (hypoechoic nucleus only) and US2/CI2 (hypoechoic nucleus plus hyperechoic halo). Measurements were compared with histopathological tumour sizes using linear regression and Bland-Altman plots. RESULTS: Size prediction was best with ultrasound (US/CI/RTE: R (2) 0.31-0.36); mammography was poorer (R(2) = 0.19). The most accurate method was US2, while US1 and CI1 were poorest. Bland-Altman plots showed better size estimation with US2, CI2 and RTE, with low variation, while mammography showed greatest variability. Smaller tumours were better assessed than larger ones. CI2 and US2 performed best for ductal tumours and RTE for lobular cancers. Tumour size prediction accuracy did not correlate significantly with breast density, but on MG tumours were more difficult to detect in high-density tissue. CONCLUSIONS: The size of ductal tumours is best predicted with US2 and CI2, while for lobular cancers RTE is best. Hyperechoic tumour surroundings should be included in US and CI measurements and RTE used as an additional technique in the clinical staging process.

Images Are Data: A Breast Imaging Perspective on a Contemporary Paradigm.

BACKGROUND: Considering radiological examinations not as mere images, but as a source of data, has become the key paradigm in the diagnostic imaging field. This change of perspective is particularly popular in breast imaging. It allows breast radiologists to apply algorithms derived from computer science, to realize innovative clinical applications, and to refine already established methods. In this context, the terminology "imaging biomarker", "radiomics", and "artificial intelligence" are of pivotal importance. These methods promise noninvasive, low-cost (e. g., in comparison to multigene arrays), and workflow-friendly (automated, only one examination, instantaneous results, etc.) delivery of clinically relevant information. METHODS AND RESULTS: This paper is designed as a narrative review on the previously mentioned paradigm. The focus is on key concepts in breast imaging and important buzzwords are explained. For all areas of breast imaging, exemplary studies and potential clinical use cases are discussed. CONCLUSION: Considering radiological examination as a source of data may optimize patient management by guiding individualized breast cancer diagnosis and oncologic treatment in the age of precision medicine. KEY POINTS: · In conventional breast imaging, examinations are interpreted based on patterns perceivable by visual inspection.. · The radiomics paradigm treats breast images as a source of data, containing information beyond what is visible to our eyes.. · This results in radiomic signatures that may be considered as imaging biomarkers, as they provide diagnostic, predictive, and prognostic information.. · Radiomics derived imaging biomarkers may be used to individualize breast cancer treatment in the era of precision medicine.. · The concept and key research of radiomics in the field of breast imaging will be discussed in this narrative review.. CITATION FORMAT: · Dietzel M, Clauser P, Kapetas P et al. Images Are Data: A Breast Imaging Perspective on a Contemporary Paradigm. Fortschr Röntgenstr 2021; 193: 898 - 908.