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.

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).

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.

Variable Expression of the Disialoganglioside GD2 in Breast Cancer Molecular Subtypes.

The disialoganglioside GD2 is a tumor-associated antigen that may allow for the application of targeted immunotherapies (anti-GD2 antibodies, GD2 CAR T cells) in patients with neuroblastoma and other solid tumors. We retrospectively investigated GD2 expression in a breast cancer cohort, using immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays (TMAs), and its impact on survival. GD2 expression on IHC (n = 568) and IF (n = 503) was investigated in relation to subtypes and patient outcome. Overall, 50.2% of the 568 IHC-assessed samples and 69.8% of the 503 IF-assessed samples were GD2-positive. The highest proportion of GD2-positive tumors was observed in luminal tumors. Significantly fewer GD2-positive cases were detected in triple-negative breast cancer (TNBC) compared with other subtypes. The proportion of GD2-expressing tumors were significantly lower in HER2-positive breast cancer in comparison with luminal tumors on IF staining (but not IHC). GD2 expression of IHC or IF was not significantly associated with disease-free or overall survival, in either the overall cohort or in individual subtypes. However, GD2 expression can be seen in more than 50% of breast cancer cases, with the highest frequency in hormone receptor-positive tumors. With this high expression frequency, patients with GD2-positive advanced breast cancer of all subtypes may benefit from GD2-targeting immunotherapies, which are currently subject to clinical testing.

Influence of Family History of Breast or Ovarian Cancer on Pathological Complete Response and Long-Term Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

PURPOSE: In breast cancer, a pathological complete response (pCR) has been described as generally resulting in a favorable prognosis. However, there are subgroups, such as patients with a mutation in BRCA1 or BRCA2, in which the effect of pCR on the prognosis is suspected to be weaker. Patients with a family history of breast and/or ovarian cancer may therefore react differently in relation to pCR and prognosis, and this is investigated in this study. PATIENTS AND METHODS: Breast cancer patients were identified from a clinical breast cancer registry. The study subjects had been treated with neoadjuvant chemotherapy from 2001 to 2018 and their pathological and clinical information as well as medical family history were available. They were considered to have a positive family history if they had at least 1 first-degree relative with breast and/or ovarian cancer. Multivariate logistic regression analyses were performed to study the association between family history, pCR (ypT0; ypN0), and disease-free survival (DFS). RESULTS: Of 1,480 patients, 228 (15.4%) had a positive family history. The pCR rates were 24.9% in all patients, and 24.4% and 27.6% in those without/with a family history, respectively. Family history was not associated with a higher pCR rate (adjusted odds ratio [OR] 1.23; 95% confidence interval [CI] 0.85-1.76; p = 0.27) or a different disease-free survival (DFS; adjusted hazard ratio [HR] 1.15; 95% CI 0.88-1.52; p = 0.30). pCR did not affect the prognosis differently in relation to family history. CONCLUSIONS: In this retrospective analysis, family history was not associated with pCR and DFS. pCR improved survival, independently of family history.

Mammographic density and prognosis in primary breast cancer patients.

PURPOSE: Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients. METHODS: A total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status. RESULTS: After median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect. CONCLUSIONS: Although MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC.

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.

[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.

Assessment of the additional clinical potential of X-ray dark-field imaging for breast cancer in a preclinical setup.

BACKGROUND: Mammography can identify calcifications up to 50-100 µm in size as a surrogate parameter for breast cancer or ductal carcinoma in situ (DCIS). Microcalcifications measuring <50 µm are also associated with breast cancer or DCIS and are frequently not detected on mammography, although they can be detected with dark-field imaging. This study examined whether additional breast examination using X-ray dark-field imaging can increase the detection rate of calcifications. Advances in knowledge: (1) evaluation of additional modality of breast imaging; (2) specific evaluation of breast calcifications.Implications for patient care: the addition of X-ray dark-field imaging to conventional mammography could detect additional calcifications. METHODS: Talbot-Lau X-ray phase-contrast imaging and X-ray dark-field imaging were used to acquire images of breast specimens. The radiation dosage with the technique is comparable with conventional mammography. Three X-ray gratings with periods of 5-10 µm between the X-ray tube and the flat-panel detector provide three different images in a single sequence: the conventional attenuation image, differential phase image, and dark-field image. The images were read by radiologists. Radiological findings were marked and examined pathologically. The results were described in a descriptive manner. RESULTS: A total of 81 breast specimens were investigated with the two methods; 199 significant structures were processed pathologically, consisting of 123 benign and 76 malignant lesions (DCIS or invasive breast cancer). X-ray dark-field imaging identified 15 additional histologically confirmed carcinoma lesions that were visible but not declared suspicious on digital mammography alone. Another four malignant lesions that were not visible on mammography were exclusively detected with X-ray dark-field imaging. CONCLUSIONS: Adding X-ray dark-field imaging to digital mammography increases the detection rate for breast cancer and DCIS associated lesions with micrometer-sized calcifications.The use of X-ray dark-field imaging may be able to provide more accurate and detailed radiological classification of suspicious breast lesions.Adding X-ray dark-field imaging to mammography may be able to increase the detection rate and improve preoperative planning in deciding between mastectomy or breast-conserving therapy, particularly in patients with invasive lobular breast cancer.

HLA-G and HLA-F protein isoform expression in breast cancer patients receiving neoadjuvant treatment.

The immunosuppressive human leukocyte antigens HLA-G and HLA-F are expressed on trophoblast and malignant cells. Four membrane-bound and three soluble HLA-G protein isoforms have been described, which have different immunosuppressive potentials. HLA-F has three transcript variants, resulting in three different protein isoforms. The aim of this study was to evaluate the prognostic and predictive value of HLA-G and HLA-F protein isoform expression patterns in patients with breast cancer. Core biopsies were taken at diagnosis in patients with HER2+ (n = 28), luminal B-like (n = 49) and triple-negative (n = 38) breast cancers who received neoadjuvant chemotherapy. Expression levels of HLA-F and -G were correlated with the pathological complete response (pCR). Protein expression was determined by Western blot analysis, using two antibodies for each HLA, specific for different isoforms. The protein expression of HLA isoforms did not significantly differ between breast cancer subtypes. However, some initial indications were found for an association between the soluble HLA-G6 protein isoform and pCR in HER2+ breast cancer. The study provides preliminary evidence for the evaluation of HLA-G isoform expression, in particular HLA-G6, as a possible new marker for pCR in HER2+ breast cancer.

PIWI-Like 1 and PIWI-Like 2 Expression in Breast Cancer.

PIWI-like 1 and PIWI-like 2 play a role in stem cell self-renewal, and enhanced expression has been reported for several tumor entities. However, few studies have investigated PIWI-like 1 and PIWI-like 2 expressions in breast cancer subtypes regarding prognosis. Therefore, we examined protein expression in a large consecutive cohort of breast cancer patients and correlated it to breast cancer subtypes and survival outcome. PIWI-like 1 and PIWI-like 2 expressions were evaluated using immunohistochemistry in a cohort of 894 breast cancer patients, of whom 363 were eligible for further analysis. Percentage and intensity of stained tumor cells were analyzed and an immunoreactive score (IRS) was calculated. The interaction of PIWI-like 1 and PIWI-like 2 showed a prognostic effect on survival. For the combination of high PIWI-like 1 and low PIWI-like 2 expressions, adjusted hazard ratios (HRs) were significantly higher with regard to overall survival (OS) (HR 2.92; 95% confidence interval (CI) 1.24, 6.90), disease-free survival (DFS) (HR 3.27; 95% CI 1.48, 7.20), and distant disease-free survival (DDFS) (HR 7.64; 95% CI 2.35, 24.82). Both proteins were significantly associated with molecular-like and PAM50 subgroups. Combining high PIWI-like 1 and low PIWI-like 2 expressions predicted poorer prognosis and both markers were associated with aggressive molecular subtypes.

Automated volumetric radiomic analysis of breast cancer vascularization improves survival prediction in primary breast cancer.

To investigate whether automated volumetric radiomic analysis of breast cancer vascularization (VAV) can improve survival prediction in primary breast cancer. 314 consecutive patients with primary invasive breast cancer received standard clinical MRI before the initiation of treatment according to international recommendations. Diagnostic work-up, treatment, and follow-up was done at one tertiary care, academic breast-center (outcome: disease specific survival/DSS vs. disease specific death/DSD). The Nottingham Prognostic Index (NPI) was used as the reference method with which to predict survival of breast cancer. Based on the MRI scans, VAV was accomplished by commercially available, FDA-cleared software. DSD served as endpoint. Integration of VAV into the NPI gave NPIVAV. Prediction of DSD by NPIVAV compared to standard NPI alone was investigated (Cox regression, likelihood-test, predictive accuracy: Harrell's C, Kaplan Meier statistics and corresponding hazard ratios/HR, confidence intervals/CI). DSD occurred in 35 and DSS in 279 patients. Prognostication of the survival outcome by NPI (Harrell's C = 75.3%) was enhanced by VAV (NPIVAV: Harrell's C = 81.0%). Most of all, the NPIVAV identified patients with unfavourable outcome more reliably than NPI alone (hazard ratio/HR = 4.5; confidence interval/CI = 2.14-9.58; P = 0.0001). Automated volumetric radiomic analysis of breast cancer vascularization improved survival prediction in primary breast cancer. Most of all, it optimized the identification of patients at higher risk of an unfavorable outcome. Future studies should integrate MRI as a "gate keeper" in the management of breast cancer patients. Such a "gate keeper" could assist in selecting patients benefitting from more advanced diagnostic procedures (genetic profiling etc.) in order to decide whether are a more aggressive therapy (chemotherapy) is warranted.

Implementation of machine learning into clinical breast MRI: Potential for objective and accurate decision-making in suspicious breast masses.

We investigated whether the integration of machine learning (ML) into MRI interpretation can provide accurate decision rules for the management of suspicious breast masses. A total of 173 consecutive patients with suspicious breast masses upon complementary assessment (BI-RADS IV/V: n = 100/76) received standardized breast MRI prior to histological verification. MRI findings were independently assessed by two observers (R1/R2: 5 years of experience/no experience in breast MRI) using six (semi-)quantitative imaging parameters. Interobserver variability was studied by ICC (intraclass correlation coefficient). A polynomial kernel function support vector machine was trained to differentiate between benign and malignant lesions based on the six imaging parameters and patient age. Ten-fold cross-validation was applied to prevent overfitting. Overall diagnostic accuracy and decision rules (rule-out criteria) to accurately exclude malignancy were evaluated. Results were integrated into a web application and published online. Malignant lesions were present in 107 patients (60.8%). Imaging features showed excellent interobserver variability (ICC: 0.81-0.98) with variable diagnostic accuracy (AUC: 0.65-0.82). Overall performance of the ML algorithm was high (AUC = 90.1%; BI-RADS IV: AUC = 91.6%). The ML algorithm provided decision rules to accurately rule-out malignancy with a false negative rate <1% in 31.3% of the BI-RADS IV cases. Thus, integration of ML into MRI interpretation can provide objective and accurate decision rules for the management of suspicious breast masses, and could help to reduce the number of potentially unnecessary biopsies.

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.

Cost effectiveness of bilateral risk-reducing mastectomy and salpingo-oophorectomy.

BACKGROUND: Growing demand for risk-reducing surgery in individuals with inherited susceptibility to cancer leads to the question whether these procedures are cost effective for the executing hospitals. This study compared the clinical costs for bilateral risk-reducing mastectomy (BRRM) with and without different types of reconstruction, risk-reducing salpingo-oophorectomy (RRSO), and their combinations with corresponding reimbursements in the statutory health-care system in Germany. PATIENTS AND METHODS: Real total costs of care for BRRM with and without reconstruction, RRSO, and their combinations were calculated as the sum of all personnel and technical costs. These costs calculated in a German University hospital were compared with the sum of all reimbursements in the German DRG-based health-care system. RESULTS: While sole RRSO, BRRM without reconstruction, and BRRM with secondary DIEP (deep inferior epigastric perforator)-reconstruction still result in a small benefit, we even found shortfalls for the hospital with all other prophylactic operations under consideration. The calculated deficits were especially high for BRRM with implant-based breast reconstruction and for combined operations when the risk reduction is achieved with a minimum of separate operations. CONCLUSIONS: Risk-reducing surgery in BRCA-mutation carriers is frequently not cost-covering for the executing hospitals in the German health-care system. Thus, appropriate concepts are required to ensure a nationwide care.

Does higher field strength translate into better diagnostic accuracy? A prospective comparison of breast MRI at 3 and 1.5 Tesla.

OBJECTIVE: We performed a prospective monocentric study to inter-individually compare the diagnostic accuracy of breast MRI at 1.5 T and 3 T. METHODS: During a consecutive period of 12 months all 982 patients receiving breast MRI according to standard indications (problem solving, preoperative staging) were randomized to one 3 T or 1.5 T scanner both equipped with dedicated 16-channel breast coils. Protocols at 1.5 T and 3 T were optimized and in line with international recommendations. Due to restricted time slot availabilities, the randomization-key was defined as 1/10 (3 T/1.5 T). All examinations were read by two experts in breast MRI (>25 and 8 years of experience) who assigned a BI-RADS category per breast. Histopathological verification or long-term MRI follow-up (>24 months) served as standard of reference. Results were analyzed using cross tabulations, standard estimates of diagnostic accuracy, Chi-square test and Mann-Whitney U test (alpha = 5%). RESULTS: 1961 breasts were included. 1746 (89%) were imaged at 1.5 T and 215 at 3 T (11%). The 1.5 T and 3 T study cohort did not show significant differences regarding patient age (P = 0.71), results of the reference standard (P = 0.09) and indication for MRI (P = 0.53). Overall Sensitivity (94.7%), Specificity (91.4%), Accuracy (91.9%) and Negative Predictive Value (99.0%) were within the range of the literature. Pairwise comparison of Sensitivity (1,5 T/3 T: 94.1/97.9%), Specificity (91.6/%89.3%), Accuracy (92.0%/91.2%) and Negative Predictive Value (98.9%/99.3%) were without significant differences (P = 0.29-0.74). CONCLUSION: In this prospective monocentric study, we identified comparably high diagnostic accuracy for both 1.5 T and 3 T breast MRI. Both 1.5 T and 3 T are equally suited for breast imaging.

Diagnostic Accuracy of Breast Medical Tactile Examiners (MTEs): A Prospective Pilot Study.

BACKGROUND: The usefulness of clinical breast examination (CBE) in general and in breast cancer screening programs has been a matter of debate. This study investigated whether adding vision-impaired medical tactile examiners (MTEs) improves the predictiveness of CBE for suspicious lesions and analyzed the feasibility and acceptability of this approach. METHODS: The prospective study included 104 patients. Physicians and MTEs performed CBEs, and mammography and ultrasound results were used as the gold standard. Sensitivity and specificity were calculated and logistic regression models were used to compare the predictive value of CBE by physicians alone, MTEs alone, and physicians and MTEs combined. RESULTS: For CBEs by physicians alone, MTEs alone, and both combined, sensitivity was 71, 82, and 89% and specificity was 55, 45, and 35%, respectively. Using adjusted logistic regression models, the validated areas under the curve were 0.685, 0.692, and 0.710 (median bootstrapped p value (DeLong) = 0.381). CONCLUSION: The predictive value for a suspicious breast lesion in CBEs performed by MTEs in patients without prior surgery was similar to that of physician-conducted CBEs. Including MTEs in the CBE procedure in breast units thus appears feasible and could be a way of utilizing their skills.

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.

Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) - Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer.

Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Method The process of updating the S3 guideline published in 2012 was based on the adaptation of identified source guidelines. They were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and with the results of a systematic search of literature databases followed by the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point and used them to develop suggestions for recommendations and statements, which were then modified and graded in a structured consensus process procedure. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of primary, recurrent and metastatic breast cancer. Loco-regional therapies are de-escalated in the current guideline. In addition to reducing the safety margins for surgical procedures, the guideline also recommends reducing the radicality of axillary surgery. The choice and extent of systemic therapy depends on the respective tumor biology. New substances are becoming available, particularly to treat metastatic breast cancer.

Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) - Part 1 with Recommendations for the Screening, Diagnosis and Therapy of Breast Cancer.

Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Methods The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure. Recommendations Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.