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).

[Breast cancer in men]. / Mammakarzinom beim Mann.

Male breast cancer is an unknown field for many practitioners. Patients often see different doctors before the correct diagnosis is made - often too late. This article is intended to point out risk factors, initiation of diagnostics and therapy. In the dawning age of molecular medicine, we will also take a look at genetics.

Evaluation of automated techniques for extraction of circulating cell-free DNA for implementation in standardized high-throughput workflows.

Analysis of circulating cell-free DNA (ccfDNA) is a suitable tool for detecting somatic mutations for the purpose of making decisions on treatment, monitoring treatment response, and predicting survival. High-throughput techniques for ccfDNA extraction are essential to implementing ccfDNA testing in the clinical setting. We set out to compare two automated techniques with regard to hands-on time, ccfDNA output and integrity, and circulating mitochondrial DNA (mtDNA). CcfDNA was isolated using the EZ1&2 ccfDNA field test kit (EZ2 kit, QIAGEN) and the Maxwell RSC ccfDNA plasma kit (Maxwell kit, Promega). DNA was extracted from plasma of 30 breast cancer patients enrolled in the iMODE-B (#325_19B; 12.10.2020) study. Real-time PCR, fluorescence-based detection and automated electrophoresis were used to assess ccfDNA concentrations. The ccfDNA yield was significantly higher when extracted with the EZ2 kit. The EZ2 kit enabled the isolation of a higher proportion of short fragments and a lower proportion of long fragments, resulting in lower DNA integrity. Significantly lower mtDNA quantities were detected in the Maxwell eluate than in the EZ2 eluate. Thus, decisions on which extraction method to use should proceed on the basis of the required input for downstream applications, the anticipated fragment size and minimum hands-on time.

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.

The Randomized AMBORA Trial: Impact of Pharmacological/Pharmaceutical Care on Medication Safety and Patient-Reported Outcomes During Treatment With New Oral Anticancer Agents.

PURPOSE: Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking. METHODS: Patients were eligible for the randomized, multicenter AMBORA study, if they were newly started on any of the oral anticancer drugs approved in 2001 or later without restriction to certain tumor entities. Patients were randomly assigned to receive either standard of care (control group) or an additional, intensified clinical pharmacological/pharmaceutical care, which included medication management and structured patient counseling, over a period of 12 weeks (intervention group). Primary end points were the number of antitumor drug-related problems (ie, side effects and unresolved medication errors) and patient treatment satisfaction with the oral anticancer therapy after 12 weeks measured with the Treatment Satisfaction Questionnaire for Medication, category convenience. RESULTS: Two hundred two patients were included. Antitumor drug-related problems were significantly lower in the intervention compared with the control group (3.85 v 5.81 [mean], P < .001). Patient treatment satisfaction was higher in the intervention group (Treatment Satisfaction Questionnaire for Medication, convenience; 91.6 v 74.4 [mean], P < .001). The hazard ratio for the combined end point of severe side effects (Common Terminology Criteria for Adverse Events ≥ 3), treatment discontinuation, unscheduled hospital admission, and death was 0.48 (95% CI, 0.32 to 0.71, P < .001) in favor of the intervention group. CONCLUSION: Treatment with oral anticancer drugs is associated with a broad range of medication errors and side effects. An intensified clinical pharmacological/pharmaceutical care has considerable, positive effects on the number of medication errors, patient treatment perception, and severe side effects.

Is Reduction Mammoplasty Cost-Effective? A Cost-Utility Analysis of Surgical Treatment for Macromastia in Germany.

BACKGROUND/AIMS: Macromastia can cause physical and psychological problems. Conservative treatments such as physiotherapy and painkillers lead to substantial long-term costs, without any proven medical benefit. In contrast, surgical treatment with reduction mammoplasty leads to improvements in nearly all respects. This study analyzed the costs of reduction mammoplasty and calculated an incremental cost-utility ratio for the treatment. PATIENTS AND METHODS: The data on 76 patients who underwent reduction mammoplasty between 2008 and 2016 were collected using a two-part questionnaire (preoperative and postoperative) as well as the patients' files. Topics examined besides demographic data included physician visits, medical imaging, integrative medical procedures, remedial procedures, rehabilitation and convalescent measures, drug intake, medical aids, exercise activity, and sick leave days before and after surgery. The data were used to calculate costs per year after surgical treatment for symptomatic macromastia. Costs of surgery, including the process of obtaining insurance reimbursement and postoperative complications, were taken into account to calculate the one-time costs of reduction mammoplasty. RESULTS: The patients' quality of life and satisfaction with the breasts improve after surgery. The one-time costs of reduction mammoplasty per patient amount to EUR 5,885, and the annual costs after surgery are EUR 200. The incremental cost-utility ratio for surgical treatments shows a saving of EUR 380 per quality-adjusted life-year (QALY) gained. CONCLUSIONS: These results show that reduction mammoplasty is a treatment that not only improves a patient's quality of life but also saves money in the longer term in comparison with expensive and ineffective conservative treatment for macromastia.

Macromastia: an economic burden? A disease cost analysis based on real-world data in Germany.

PURPOSE: Symptomatic macromastia causes physical and psychological problems that can lead to restrictions in the patients' social and working lives and a reduced quality of life. Associated medical treatments also have a considerable impact on health-care costs. Several studies have assessed these costs, but the total disease costs of macromastia have never been evaluated on the basis of real-world data. METHODS: The data for 76 patients who underwent reduction mammoplasty between 2008 and 2016 were collected using a two-part questionnaire (preoperative and postoperative), as well as the patient files. Topics surveyed, besides demographic data, included physician visits, medical imaging, medical procedures, medical treatments, rehabilitation and convalescent measures, drug intake, medical aids, exercise activity, and sick leave days before surgery, to calculate the costs per year of conservative treatment of symptomatic macromastia. RESULTS: The mean time from start of symptoms to surgery was 11.82 years. The data for this group of patients with symptomatic macromastia show that costs per patient amount to €1677.55 per year. These costs include medical consultation, radiological imaging, medical treatments and procedures, physical therapy and rehabilitation, medication, special brassieres, exercise classes costs for sick leave due to problems with macromastia, and travel expenses. CONCLUSIONS: These results show that considerable health-care costs arise due to macromastia with conservative treatment. Overall, macromastia costs €1677.55 per patient/year. In particular, lost productivity due to sick days and the costs of physiotherapy are factors driving the high costs.

Discordance between Primary Breast Cancer and Ipsilateral Breast Cancer Tumor Recurrence as a Function of Distance.

BACKGROUND: Risk factors for ipsilateral breast cancer tumor recurrence (IBTR) are well established and include grading, nodal status, and receptor status. Little is known about the influence of the local distance between the primary tumor and recurrences on changes in tumor characteristics and prognosis. METHODS: In a retrospective setting, we analyzed primary breast cancers and their recurrences. Localizations of primary and recurrent breast cancer were recorded to calculate the relative distance in pixels. Analysis was performed regarding tumor characteristics, relative distance between both, and their impact on breast cancer prognosis. RESULTS: In a cohort of 142 patients with ipsilateral recurrence, no statistically significant difference could be shown in the change in tumor characteristics depending on distance. Progesterone receptor (PR) and estrogene receptor (ER) status changed in 22.7% and 14.9% of cases, respectively. human epidermal growth factor receptor 2 (ERBB2, HER2) status changed in 18.3% of cases. Survival was in accordance with the literature, with luminal-A-like tumors as best and triple negative breast cancers (TNBC) as worst prognosis. With a threshold of 162 pixels, the survival was significantly better in the group with shorter distance. CONCLUSION: Change in tumor characteristics from primary breast cancer to recurrence occurs more often in PR than ER. In contrast to other work, in this dataset, recurrences with a larger distance to the primary tumor had a worse prognosis in univariate analysis. A Cox model might indicate the possibility that this influence is independent of other risk factors.

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.

Galactography with Tomosynthesis Technique (Galactomosynthesis) - Renaissance of a Method?

INTRODUCTION: For decades, conventional galactography was the only imaging technique capable of showing the mammary ducts. Today, diagnosis is based on a multimodal concept which combines high-resolution ultrasound with magnetic resonance (MR) mammography and ductoscopy/galactoscopy and has a sensitivity and specificity of up to 95%. This study used tomosynthesis in galactography for the first time and compared the synthetic digital 2D full-field mammograms generated with this technique with the images created using the established method of ductal sonography. Both methods should be able to detect invasive breast cancers and their precursors such as ductal carcinoma in situ (DCIS) as well as being able to identify benign findings. MATERIAL AND METHODS: Five patients with pathological nipple discharge were examined using ductal sonography, contrast-enhanced 3D galactography with tomosynthesis and the synthetic digital 2D full-field mammograms generated with the latter method. Evaluation of the images created with the different imaging modalities was done by three investigators with varying levels of experience with complementary breast diagnostics (1, 5 and 15 years), and their evaluations were compared with the histological findings. RESULTS: All 3 investigators independently evaluated the images created with ductal sonography, contrast-enhanced 3D galactography with tomosynthesis, and generated synthetic digital 2D full-field mammograms. Their evaluations were compared with the histopathological assessment of the surgical specimens resected from the 5 patients. There was 1 case of invasive breast cancer, 2 cases with ductal carcinoma in situ and 2 cases with benign findings. All 3 investigators made more mistakes when they used the standard imaging technique of ductal sonography to diagnose suspicious lesions than when they used contrast-enhanced galactography with tomosynthesis and the generated synthetic digital 2D full-field mammograms. CONCLUSION: This is the first time breast tomosynthesis was used in galactography (galactomosynthesis) to create digital 3-dimensional images of suspicious findings. When used together with the generated synthetic digital 2D full-field mammograms, it could be a useful complementary procedure for the diagnosis of breast anomalies and could herald a renaissance of this method. Compared with high-resolution ductal ultrasound, the investigators achieved better results with contrast-enhanced galactography using tomosynthesis and the generated synthetic digital 2D full-field mammograms, as confirmed by histopathological findings.

Performance of Photon-Counting Breast Computed Tomography, Digital Mammography, and Digital Breast Tomosynthesis in Evaluating Breast Specimens.

RATIONALE AND OBJECTIVES: This study compared a novel photon-counting breast computed tomography (pcBCT) system with digital mammography (DM) and digital breast tomosynthesis (DBT) systems. For this reason, surgical specimens were examined with all three techniques and rated by three observers. MATERIALS AND METHODS: A total of 30 surgical specimens were investigated with DM, DBT, and pcBCT; the associated images were shown to three experienced radiologists. Findings (22 microcalcifications and 23 mass lesions) were recorded and compared to the results of the pathological examination. Sensitivity and specificity for detection of microcalcifications and lesions were calculated and displayed using receiver operating characteristic curves. RESULTS: Sensitivity for microcalcifications was 82% for DM, 70% for DBT, and 85% for pcBCT. Specificity for microcalcifications was 71% for DM, 75% for DBT, and 83% for pcBCT. Sensitivity for lesions was 45% for DM, 62% for DBT, and 65% for pcBCT. Specificity for lesions was 76% for DM, 62% for DBT, and 76% for pcBCT. CONCLUSIONS: pcBCT showed a comparable or superior performance compared to the clinically approved DM and DBT systems. Mass lesion detectability can be increased further by the use of contrast media.

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.