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The aim of this study was to evaluate the long-term efficacy of a single ultrasound-guided high-intensity focused ultrasound (US-HIFU) treatment in patients with breast fibroadenoma (FA) in terms of volume and pain reduction as well as palpation findings. From december 2013 until november 2014 27 women with a symptomatic FA were treated in one HIFU-session. Follow-up visits were performed after 7 days, 6 months and 1, 2, 3 and 5 years with clinical examination and ultrasound. One year after the procedure, a core needle biopsy of the residual lesion was offered. There was a significant volume reduction 6 months after HIFU from 1083.10 to 347.13 mm 3 (p < 0.0001) with a mean volume reduction ratio (VRR) of 61.63%. Thereafter the FAs showed a further, but no longer significant decrease in size. One patient with an initial incomplete ablation and histologically confirmed persistent vital cells after 1 year showed a strong regrowth after 3 years. Excluding this patient from analysis, the mean VRR at months 12, 24, 36, and 60 was 86.44%, 94.44%, 94.90%, and 97.85%, respectively. Before HIFU, 59.26% of the patients had pain (22.33/100 VAS) which decreased to 6.56/100 after 12 months and remained reduced over the 5 year follow up period. A decrease in palpability from 85.19 to 7.69% was observed within 24 months. A single HIFU intervention let to a substantial reduction in size, pain, and palpability with its most potential effect during the first 12 months. Subsequently, the observed effect remained stable over a 5 year follow up period. Incomplete initial treatment was associated with the risk of regrowth., (© 2024. The Author(s).)

Background: Fifteen to thirty percent of all patients with metastatic breast cancer (MBC) develop brain metastases (BCBMs). Recently, the antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have shown to be highly effective in the treatment of MBC. However, there are only limited data whether these macromolecules are also effective in patients with BCBMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BCBMs in a multicenter real-world analysis., Patients and Methods: Female patients with stable or active BCBMs who were treated with either SG or T-DXd at three breast centers in Germany before 30 June 2023 were included. As per local clinical praxis, chemotherapy efficacy was evaluated by whole-body computed tomography and cranial magnetic resonance imaging at baseline and at least every 3 months according to local standards. Growth dynamics of BCBMs were assessed by board-certified neuroradiologists., Results: Of 26 patients, with a median of 2.5 prior therapy lines in the metastatic setting (range 2-15), 12 (43%) and 16 (57%) patients received SG and T-DXd, respectively. Out of the 12 patients who received SG, 2 (17%) were subsequently treated with T-DXd. Five out of 12 (42%) and 5 out of 16 (31%) patients treated with SG and T-DXd, respectively, had active BCBMs at treatment initiation. The intracranial disease control rate was 42% [95% confidence interval (CI) 13% to 71%] for patients treated with SG and 88% (95% CI 72% to 100%) for patients treated with T-DXd. After a median follow-up of 12.7 months, median intracranial progression-free survival was 2.7 months (95% CI 1.6-10.5 months) for SG and 11.2 months (95% CI 7.5-23.7 months) for T-DXd., Conclusions: SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation of membrane-bound NKG2DLs in breast cancer has been demonstrated by immunohistochemistry. Tumor cells release NKG2DLs via proteolytic cleavage as soluble (s)NKG2DLs, which allows for effective immune escape and is associated with poor prognosis. In this study, we collected serum from 140 breast cancer (BC) and 20 ductal carcinoma in situ (DCIS) patients at the time of initial diagnosis and 20 healthy volunteers (HVs). Serum levels of sNKG2DLs were quantified through the use of ELISA and correlated with clinical data. The analyzed sNKG2DLs were low to absent in HVs and significantly higher in BC patients. For some of the ligands analyzed, higher sNKG2DLs serum levels were associated with the classification of malignant tumor (TNM) stage and grading. Low sMICA serum levels were associated with significantly longer progression-free (PFS) and overall survival (OS). In conclusion, we provide the first insights into sNKG2DLs in BC patients and suggest their potential role in tumor immune escape in breast cancer. Furthermore, our observations suggest that serum sMICA levels may serve as a prognostic parameter in the patients analyzed in this study.

Background: The surgical goals of gender reassignment surgery of the breast in female-to male transsexuals (FMT) is the aesthetic shaping of a male thoracic wall with minimal scarring, while preserving the sensitivity of the nipple-areola complex (NAC). For large and ptotic breasts, we perform a mastectomy over an inframammary access with inferior pedicled NAC under color Doppler visualization of the perforators. This paper presents the technique, including complications and assessment of quality of life, as part of a unicentric analysis., Methods: This was a retrospective analysis of 23 patients (46 mastectomies) performed between September 2014 and September 2020. The complication rate and the number of corrective surgeries were recorded for quality assessment. A semiquantitative score was used to evaluate aesthetic outcome, nipple sensitivity, quality of life, and sexuality., Results: A total of 46 mastectomies were performed in 23 patients. The patient survey showed high patient satisfaction. Loss of nipple sensitivity was observed after one mastectomy (2.17%). In 91.67% of cases, patients reported that their appearance reflected how they feel on the inside. In 75% of cases, patients reported feeling equal to other men. The overall complication rate was 10.87%. Shape correction due to persistent excess of volume was rare (2.17%, equivalent to one mastectomy)., Conclusion: Subcutaneous mastectomy with inferior nipple pedicle can be performed with a high degree of safety and satisfaction in FMT. Color Doppler-guided visualization of the perforator vessels is helpful in allowing a thin pedicle preparation, thus reducing the need for secondary surgeries to optimize the shape., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: Breast cancer patients with residual disease after neoadjuvant systemic treatment (NAST) have a worse prognosis compared with those achieving a pathologic complete response (pCR). Earlier identification of these patients might allow timely, extended neoadjuvant treatment strategies. We explored the feasibility of a vacuum-assisted biopsy (VAB) after NAST to identify patients with residual disease (ypT+ or ypN+) prior to surgery., Methods: We used data from a multicenter trial, collected at 21 study sites (NCT02948764). The trial included women with cT1-3, cN0/+ breast cancer undergoing routine post-neoadjuvant imaging (ultrasound, MRI, mammography) and VAB prior to surgery. We compared the findings of VAB and routine imaging with the histopathologic evaluation of the surgical specimen., Results: Of 398 patients, 34 patients with missing ypN status and 127 patients with luminal tumors were excluded. Among the remaining 237 patients, tumor cells in the VAB indicated a surgical non-pCR in all patients (73/73, positive predictive value [PPV] 100%), whereas PPV of routine imaging after NAST was 56.0% (75/134). Sensitivity of the VAB was 72.3% (73/101), and 74.3% for sensitivity of imaging (75/101)., Conclusion: Residual cancer found in a VAB specimen after NAST always corresponds to non-pCR. Residual cancer assumed on routine imaging after NAST corresponds to actual residual cancer in about half of patients. Response assessment by VAB is not safe for the exclusion of residual cancer. Response assessment by biopsies after NAST may allow studying the new concept of extended neoadjuvant treatment for patients with residual disease in future trials., (© 2023. The Author(s).)

Background: Breast cancer is a metabolically heterogeneous disease, and although the concept of heterogeneous cancer metabolism is known, its precise role in human breast cancer is yet to be fully elucidated., Methods: We investigated in an explorative approach a cohort of 42 primary mamma carcinoma patients with positron emission tomography/magnetic resonance imaging (PET/MR) prior to surgery, followed by histopathology and molecular diagnosis. From a subset of patients, which showed high metabolic heterogeneity based on tracer uptake and pathology classification, tumour centre and periphery specimen tissue samples were further investigated by a targeted breast cancer gene expression panel and quantitative metabolomics by nuclear magnetic resonance (NMR) spectroscopy. All data were analysed in a combinatory approach., Results: [ 18 F]FDG (2-deoxy-2-[fluorine-18]fluoro-d-glucose) tracer uptake confirmed dominance of glucose metabolism in the breast tumour centre, with lower levels in the periphery. Additionally, we observed differences in lipid and proliferation related genes between luminal A and B subtypes in the centre and periphery. Tumour periphery showed elevated acetate levels and enrichment in lipid metabolic pathways genes especially in luminal B. Furthermore, serine was increased in the periphery and higher expression of thymidylate synthase (TYMS) indicated one-carbon metabolism increased in tumour periphery. The overall metabolic activity based on [ 18 F]FDG uptake of luminal B subtype was higher than that of luminal A and the difference between the periphery and centre increased with tumour grade., Conclusion: Our analysis indicates variations in metabolism among different breast cancer subtypes and sampling locations which details the heterogeneity of the breast tumours. Correlation analysis of [ 18 F]FDG tracer uptake, transcriptome and tumour metabolites like acetate and serine facilitate the search for new candidates for metabolic tracers and permit distinguishing luminal A and B. This knowledge may help to differentiate subtypes preclinically or to provide patients guide for neoadjuvant therapy and optimised surgical protocols based on individual tumour metabolism., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

The NATALEE study showed a significant benefit in invasive disease-free survival (iDFS) for patients with HR+/HER2- early breast cancer (eBC) at intermediate and high risk of recurrence who were treated with the CDK4/6 inhibitor Ribociclib in combination with endocrine therapy (ET). This retrospective study aims to apply the NATALEE inclusion criteria to a representative real-world cohort to estimate the proportion of HR+/HER2- breast cancer patients eligible for adjuvant Ribociclib therapy. Patients who underwent full surgical treatment for eBC between January 2018 and December 2020 at two large German university breast cancer centers (University of Ulm, University of Tuebingen) were included. Descriptive statistics were used to characterize the patient population eligible for Ribociclib treatment based on the NATALEE study's inclusion criteria. Out of 2384 enrolled patients, 1738 had HR+/HER2- eBC, of whom 43% (747/1738) met the NATALEE inclusion criteria. Of note, these patients were older, received less chemotherapy and presented with less advanced tumor stages compared to the NATALEE study cohort. Additionally, compared to the NATALEE study cohort, fewer patients had lymph node involvement (72.4% vs. 88.7%). Our analysis suggests that approximately 43% of all HR+/HER2- breast cancer patients will qualify for Ribociclib treatment. Given the numerous treatment options for patients with HR+/HER2- eBC, as well as the differences between the NATALEE cohort and patients in the real-world clinical setting, future analyses will be needed to determine which patients would benefit most from adjuvant CDK4/6 inhibitor treatment.

Purpose: Disseminated tumor cells (DTCs) in the bone marrow (BM) are known to be of prognostic value for patients with early breast cancer (EBC). In addition to histopathological features, multigene expression assays, such as the commercially available 21-gene Breast Recurrence Score® assay, have been validated for evaluating prognosis and making decisions concerning adjuvant treatment in EBC. In a previous retrospective study from our group, the 21-gene assay was shown to be associated with DTC-detection. A secondary endpoint of the prospective IRMA trial was to evaluate the association between Recurrence Score® (RS) result and tumor cell dissemination in patients with EBC., Methods: DTC-status and RS result were assessed in patients with ER-positive/HER2-negative EBC with 0-3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women's Health of Tuebingen University, Germany., Results: Patients with a high RS result (≥ 26) were more frequently DTC-positive (22.6%) than patients with a low RS result (8.6%, p = 0.034). The odds for DTC-positivity increased with rising RS values (p = 0.047)., Conclusion: We therefore confirm that a high genomic risk is associated with tumor cell dissemination into the BM. Further trials are needed to investigate whether therapeutic decisions could be further individualized by combining DTC-status and prognostic gene signature testing., (© 2023. The Author(s).)

Purpose: Breast surgery is usually performed under general anesthesia. Tumescent local anesthesia (TLA) offers the possibility to anesthetize large areas with highly diluted local anesthetic., Methods: In this paper, the implementation, and experiences with TLA in the field of breast surgery are discussed., Conclusion: For carefully selected indications, breast surgery in TLA represents an alternative to ITN., (© 2023. The Author(s).)

Despite tremendous progress in deciphering breast cancer at the genomic level, the pronounced intra- and intertumoral heterogeneity remains a major obstacle to the advancement of novel and more effective treatment approaches. Frequent treatment failure and the development of treatment resistance highlight the need for patient-derived tumor models that reflect the individual tumors of breast cancer patients and allow a comprehensive analyses and parallel functional validation of individualized and therapeutically targetable vulnerabilities in protein signal transduction pathways. Here, we introduce the generation and application of breast cancer patient-derived 3D microtumors (BC-PDMs). Residual fresh tumor tissue specimens were collected from n = 102 patients diagnosed with breast cancer and subjected to BC-PDM isolation. BC-PDMs retained histopathological characteristics, and extracellular matrix (ECM) components together with key protein signaling pathway signatures of the corresponding primary tumor tissue. Accordingly, BC-PDMs reflect the inter- and intratumoral heterogeneity of breast cancer and its key signal transduction properties. DigiWest®-based protein expression profiling of identified treatment responder and non-responder BC-PDMs enabled the identification of potential resistance and sensitivity markers of individual drug treatments, including markers previously associated with treatment response and yet undescribed proteins. The combination of individualized drug testing with comprehensive protein profiling analyses of BC-PDMs may provide a valuable complement for personalized treatment stratification and response prediction for breast cancer., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Objectives: We evaluated whether lesion-to-fat ratio measured by shear wave elastography in patients with Breast Imaging Reporting and Data System (BI-RADS) 3 or 4 lesions has the potential to further refine the assessment of B-mode ultrasound alone in breast cancer diagnostics., Methods: This was a secondary analysis of an international diagnostic multicenter trial (NCT02638935). Data from 1288 women with breast lesions categorized as BI-RADS 3 and 4a-c by conventional B-mode ultrasound were analyzed, whereby the focus was placed on differentiating lesions categorized as BI-RADS 3 and BI-RADS 4a. All women underwent shear wave elastography and histopathologic evaluation functioning as reference standard. Reduction of benign biopsies as well as the number of missed malignancies after reclassification using lesion-to-fat ratio measured by shear wave elastography were evaluated., Results: Breast cancer was diagnosed in 368 (28.6%) of 1288 lesions. The assessment with conventional B-mode ultrasound resulted in 53.8% (495 of 1288) pathologically benign lesions categorized as BI-RADS 4 and therefore false positives as well as in 1.39% (6 of 431) undetected malignancies categorized as BI-RADS 3. Additional lesion-to-fat ratio in BI-RADS 4a lesions with a cutoff value of 1.85 resulted in 30.11% biopsies of benign lesions which correspond to a reduction of 44.04% of false positives., Conclusions: Adding lesion-to-fat ratio measured by shear wave elastography to conventional B-mode ultrasound in BI-RADS 4a breast lesions could help reduce the number of benign biopsies by 44.04%. At the same time, however, 1.98% of malignancies were missed, which would still be in line with American College of Radiology BI-RADS 3 definition of <2% of undetected malignancies., (© 2023 The Authors. Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

Purpose: Surgery and radiotherapy as part of breast cancer treatment can lead to lymphoedema of the upper extremities (breast cancer-related lymphoedema = BCRL) and reduce the quality of life (health-related quality of life = HRQoL). The aim of the present study was to investigate the influence of paddling in a dragon boat (PP) on HRQoL and BCRL in breast cancer survivors (BCS)., Methods: Between April and October 2017, a prospective case-control study evaluated the effects of PP compared to a control group. In the paddle group (n = 28), weekly arm circumference measurements were taken at four defined anatomic areas of the arm before and after training; in the control group (n = 70), the measurements were taken once a month. At the beginning and end of the study, questionnaires from both groups (SF 36, EORTC QLQ C30) were evaluated to understand the differences in HRQoL., Results: The paddle group started with a higher HRQoL compared to the control group. Most interesting, whether the affected or unaffected arm, whether before or after training-the arm circumference decreased over time in the paddling group. A pre-existing lymphoedema was not negatively influenced by paddling. In the paddle group, the physical health was constant over the season, while the physical health of the control group decreased significantly over time., Conclusion: PP in a dragon boat does not lead to the development or worsening of pre-existing lymphoedema due to breast cancer therapy, and seems to have a positive effect on the quality of life., (© 2022. The Author(s).)

Purpose:  In this prospective, multicenter trial we evaluated whether additional shear wave elastography (SWE) for patients with BI-RADS 3 or 4 lesions on breast ultrasound could further refine the assessment with B-mode breast ultrasound for breast cancer diagnosis., Materials and Methods:  We analyzed prospective, multicenter, international data from 1288 women with breast lesions rated by conventional 2 D B-mode ultrasound as BI-RADS 3 to 4c and undergoing 2D-SWE. After reclassification with SWE the proportion of undetected malignancies should be < 2 %. All patients underwent histopathologic evaluation (reference standard)., Results:  Histopathologic evaluation showed malignancy in 368 of 1288 lesions (28.6 %). The assessment with B-mode breast ultrasound resulted in 1.39 % (6 of 431) undetected malignancies (malignant lesions in BI-RADS 3) and 53.80 % (495 of 920) unnecessary biopsies (biopsies in benign lesions). Re-classifying BI-RADS 4a patients with a SWE cutoff of 2.55 m/s resulted in 1.98 % (11 of 556) undetected malignancies and a reduction of 24.24 % (375 vs. 495) of unnecessary biopsies., Conclusion:  A SWE value below 2.55 m/s for BI-RADS 4a lesions could be used to downstage these lesions to follow-up, and therefore reduce the number of unnecessary biopsies by 24.24 %. However, this would come at the expense of some additionally missed cancers compared to B-mode breast ultrasound (rate of undetected malignancies 1.98 %, 11 of 556, versus 1.39 %, 6 of 431) which would, however, still be in line with the ACR BI-RADS 3 definition (< 2 % of undetected malignancies)., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Breast ultrasound identifies additional carcinomas not detected in mammography but has a higher rate of false-positive findings. We evaluated whether use of intelligent multi-modal shear wave elastography (SWE) can reduce the number of unnecessary biopsies without impairing the breast cancer detection rate., Methods: We trained, tested, and validated machine learning algorithms using SWE, clinical, and patient information to classify breast masses. We used data from 857 women who underwent B-mode breast ultrasound, SWE, and subsequent histopathologic evaluation at 12 study sites in seven countries from 2016 to 2019. Algorithms were trained and tested on data from 11 of the 12 sites and externally validated using the additional site's data. We compared findings to the histopathologic evaluation and compared the diagnostic performance between B-mode breast ultrasound, traditional SWE, and intelligent multi-modal SWE., Results: In the external validation set (n = 285), intelligent multi-modal SWE showed a sensitivity of 100% (95% CI, 97.1-100%, 126 of 126), a specificity of 50.3% (95% CI, 42.3-58.3%, 80 of 159), and an area under the curve of 0.93 (95% CI, 0.90-0.96). Diagnostic performance was significantly higher compared to traditional SWE and B-mode breast ultrasound (P < 0.001). Unlike traditional SWE, positive-predictive values of intelligent multi-modal SWE were significantly higher compared to B-mode breast ultrasound. Unnecessary biopsies were reduced by 50.3% (79 versus 159, P < 0.001) without missing cancer compared to B-mode ultrasound., Conclusion: The majority of unnecessary breast biopsies might be safely avoided by using intelligent multi-modal SWE. These results may be helpful to reduce diagnostic burden for patients, providers, and healthcare systems., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

For many years, breast ultrasound has been used in addition to mammography as an important method for clarifying breast findings. However, differences in the interpretation of findings continue to be problematic 1 2. These differences decrease the diagnostic accuracy of ultrasound after detection of a finding and complicate interdisciplinary communication and the comparison of scientific studies 3. In 1999, the American College of Radiology (ACR) created a working group (International Expert Working Group) that developed a classification system for ultrasound examinations based on the established BI-RADS classification of mammographic findings under consideration of literature data 4. Due to differences in content, the German Society for Ultrasound in Medicine (DEGUM) published its own BI-RADS-analogue criteria catalog in 2006 3. In addition to the persistence of differences in content, there is also an issue with formal licensing with the current 5th edition of the ACR BI-RADS catalog, even though the content is recognized by the DEGUM as another system for describing and documenting findings. The goal of the Best Practice Guideline of the Breast Ultrasound Working Group of the DEGUM is to provide colleagues specialized in senology with a current catalog of ultrasound criteria and assessment categories as well as best practice recommendations for the various ultrasound modalities., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Breast cancer represents the most common malignancy among women in the world. Although immuno-, chemo- and radiation therapy are widely recognized as the therapeutic trifecta, new strategies in the fight against breast cancer are continually explored. The local microenvironment around the tumor plays a great role in cancer progression and invasion, representing a promising therapeutic target. CCL5 is a potent chemokine with a physiological role of immune cell attraction and has gained particular attention in R&D for breast cancer treatment. Its receptor, CCR5, is a well-known co-factor for HIV entry through the cell membrane. Interestingly, biology research is unusually unified in describing CCL5 as a pro-oncogenic factor, especially in breast cancer. In silico, in vitro and in vivo studies blocking the CCL5/CCR5 axis show cancer cells become less invasive and less malignant, and the extracellular matrices produced are less oncogenic. At present, CCR5 blocking is a mainstay of HIV treatment, but despite its promising role in cancer treatment, CCR5 blocking in breast cancer remains unperformed. This review presents the role of the CCL5/CCR5 axis and its effector mechanisms, and names the most prominent hurdles for the clinical adoption of anti-CCR5 drugs in cancer.

Wire-guided localization (WGL) is the most frequently used localization technique in non-palpable breast cancer (BC). However, low negative margin rates, patient discomfort, and the possibility of wire dislocation have been discussed as potential disadvantages, and re-operation due to positive margins may increase relapse risk. Intraoperative ultrasound (IOUS)-guided excision allows direct visualization of the lesion and the resection volume and reduces positive margins in palpable and non-palpable tumors. We performed a systematic review on IOUS in breast cancer and 2 meta-analyses of randomized clinical trials (RCTs). In non-palpable BC, 3 RCTs have shown higher negative margin rates in the IOUS arm compared to WGL. Meta-analysis confirmed a significant difference between IOUS and WGL in terms of positive margins favoring IOUS (risk ratio 4.34, p < 0.0001, I2 = 0%). 41 cohort studies including 3291 patients were identified, of which most reported higher negative margin and lower re-operation rates if IOUS was used. In palpable BC, IOUS was compared to palpation-guided excision in 3 RCTs. Meta-analysis showed significantly higher rates of positive margins in the palpation arm (risk ratio 2.84, p = 0.0047, I2 = 0%). In 13 cohort studies including 942 patients with palpable BC, negative margin rates were higher if IOUS was used, and tissue volumes were higher in palpation-guided cohorts in most studies. IOUS is a safe noninvasive technique for the localization of sonographically visible tumors that significantly improves margin rates in palpable and non-palpable BC. Surgeons should be encouraged to acquire ultrasound skills and participate in breast ultrasound training., Competing Interests: Maggie Banys-Paluchowski received study support from Mammotome, Endomag and Merit Medical., (Thieme. All rights reserved.)

Purpose: Neoadjuvant systemic treatment (NST) elicits a pathologic complete response in 40%-70% of women with breast cancer. These patients may not need surgery as all local tumor has already been eradicated by NST. However, nonsurgical approaches, including imaging or vacuum-assisted biopsy (VAB), were not able to accurately identify patients without residual cancer in the breast or axilla. We evaluated the feasibility of a machine learning algorithm (intelligent VAB) to identify exceptional responders to NST., Methods: We trained, tested, and validated a machine learning algorithm using patient, imaging, tumor, and VAB variables to detect residual cancer after NST (ypT+ or in situ or ypN+) before surgery. We used data from 318 women with cT1-3, cN0 or +, human epidermal growth factor receptor 2-positive, triple-negative, or high-proliferative Luminal B-like breast cancer who underwent VAB before surgery (ClinicalTrials.gov identifier: NCT02948764, RESPONDER trial). We used 10-fold cross-validation to train and test the algorithm, which was then externally validated using data of an independent trial (ClinicalTrials.gov identifier: NCT02575612). We compared findings with the histopathologic evaluation of the surgical specimen. We considered false-negative rate (FNR) and specificity to be the main outcomes., Results: In the development set (n = 318) and external validation set (n = 45), the intelligent VAB showed an FNR of 0.0%-5.2%, a specificity of 37.5%-40.0%, and an area under the receiver operating characteristic curve of 0.91-0.92 to detect residual cancer (ypT+ or in situ or ypN+) after NST. Spiegelhalter's Z confirmed a well-calibrated model ( z score -0.746, P = .228). FNR of the intelligent VAB was lower compared with imaging after NST, VAB alone, or combinations of both., Conclusion: An intelligent VAB algorithm can reliably exclude residual cancer after NST. The omission of breast and axillary surgery for these exceptional responders may be evaluated in future trials., Competing Interests: Geraldine RauchHonoraria: AbbVie Bettina ThomasHonoraria: Bayer/Vital (I), Boehringer Ingelheim (I), Bristol Myers Squibb (I), Medtronic (I), Pfizer (I), Daiichi Sankyo (I), Sanofi (I), St Jude Medical (I), ZOLL CMS (I)Consulting or Advisory Role: Pfizer (I), Bayer/Vital (I)Research Funding: Daiichi Sankyo (I)Patents, Royalties, Other Intellectual Property: Method and kit for assessment of sodium-channel related anti- or pro-arrhythmic potential of compounds, EU, No. EP14181787.4 (I); KCNK3-Based Gene Therapy of Cardiac Arrhythmia, EU, No. EP18793590.3 and US, 20-539-PCT-US (I); Task 1 Inhibitors for Treatment of Atrial Arrhythmias, China, 201980053974.7, US, US-2021-0308103-A1, and EU, EP2019/071858 (I) Sherko KuemmelConsulting or Advisory Role: Roche/Genentech, Genomic Health, Novartis, AstraZeneca, Amgen, Celgene, SOMATEX, Daiichi Sankyo, pfm medical, Pfizer, MSD Oncology, Lilly, SonoScape, Gilead Sciences, Seattle Genetics, AgendiaTravel, Accommodations, Expenses: Roche, Daiichi Sankyo, SonoScapeUncompensated Relationships: West German Study Group Toralf ReimerConsulting or Advisory Role: PfizerResearch Funding: Else Kröner-Fresenius-Stiftung, German Cancer AidOther Relationship: Pfizer Marc ThillHonoraria: Amgen, AstraZeneca/Daiichi Sankyo, Clovis Oncology, ClearCut Medical, Daiichi Sankyo Europe GmbH, Eisai Germany, Exact Sciences, Lilly, MSD Oncology, Novartis, Pfizer, pfm medical, Roche, Seattle Genetics, Seattle Genetics, Sysmex, Servier/PfizerConsulting or Advisory Role: Amgen, AstraZeneca, ClearCut, Clovis Oncology, Becton/Dickinson, Biom'Up, Daiichi Sankyo/Astra Zeneca, Exact Sciences, Gilead Sciences, Lilly, MSD Oncology, Neodynamics, Novartis, Pfizer, pfm medical, Pierre Fabre, Roche, Seattle Genetics, SysmexResearch Funding: Exact Sciences (Inst), Endomag (Inst)Expert Testimony: pfm medicalTravel, Accommodations, Expenses: ClearCut Medical, Roche, pfm medical, Pfizer, Lilly Jens-Uwe BlohmerHonoraria: Amgen, AstraZeneca, MSD Oncology, Novartis, Pfizer, Roche, Lilly, Gilead Sciences, Eisai Germany, Seattle Genetics, Daiichi Sankyo/Astra Zeneca, Exact Sciences, Molecular HealthConsulting or Advisory Role: Amgen, AstraZeneca, Novartis, Pfizer, RocheTravel, Accommodations, Expenses: Pfizer, Roche Wolfram MalterHonoraria: RocheConsulting or Advisory Role: PfizerTravel, Accommodations, Expenses: Celgene, Novartis Stefan PaepkeHonoraria: Grünenthal, Sysmex GmBH Deutschland, Endomag, Cambridge UK, pfm medical ag, KölnConsulting or Advisory Role: Grünenthal, Sysmex GmBH Deutschland, Endomag, Cambridge UK, pfm medical ag, Köln, Deutschland, Invitrocue Europe GmBH, Becton & DickinsonSpeakers’ Bureau: Grünenthal, Sysmex GmBH Deutschland, Endomag, Cambridge UK, pfm medical ag, Köln, Deutschland, Invitrocue Europe GmBH, Becton & Dickinson, Neodynamics, SchwedenTravel, Accommodations, Expenses: Grünenthal, Invitrocue Europe, Endomag Cambridge UK, Medtronic, Neodynamics, Novus scientific, pfm medical, Sysmex und Roche Tom DegenhardtHonoraria: PfizerConsulting or Advisory Role: Roche/GenentechResearch Funding: Pfizer (Inst)Travel, Accommodations, Expenses: Daiichi Sankyo, Tesaro Joachim RomConsulting or Advisory Role: AstraZeneca, Corza Medical, Exact Sciences, Johnson & Johnson/Janssen, LEO Pharma, Roche Pharma AG, Jörg Eickeler, Meet the Experts Academy Achim RodyHonoraria: Roche, Pfizer, Novartis, Celgen, Novartis, Exact Sciences, MSD, Pierre Fabre, Lilly, Seagen, TargosConsulting or Advisory Role: Roche, Astra Zeneca, Pfizer, Celgen, Eisai, Novartis, MSD, Hexal, Amgen, Exact Sciences, Pierre Fabre Marion van MackelenberghHonoraria: Amgen, AstraZeneca/Daiichi Sankyo, GlaxoSmithKline, Lilly, Molecular Health, Mylan, Novartis, Pfizer, Pierre Fabre, Roche, Seattle Genetics, Gilead SciencesConsulting or Advisory Role: Amgen, AstraZeneca/Daiichi Sankyo, Genomic Health, Gilead Sciences, GlaxoSmithKline, Lilly, Molecular Health, Molecular Health, Mylan, Novartis, Pfizer, Pierre Fabre, Roche, Seattle GeneticsTravel, Accommodations, Expenses: Daiichi Sankyo Europe GmbH, Lilly Maggie Banys-PaluchowskiConsulting or Advisory Role: Novartis/Pfizer, Lilly, GlaxoSmithKline, Amgen, RocheSpeakers' Bureau: Novartis/Pfizer, Lilly, Seattle Genetics, Roche, pfm medicalResearch Funding: Exact Sciences, Endomagnetics (Inst), Merit Medical Systems (Inst), Mammotome (Inst) Mattea ReinischHonoraria: Pfizer, Novartis, Lilly, Roche Pharma AG, AstraZeneca, Daiichi Sankyo, SOMATEX, Seattle Genetics, PfizerConsulting or Advisory Role: Roche Pharma AG, Daiichi Sankyo, Hexal, Lilly, Novartis, Seattle Genetics, PfizerTravel, Accommodations, Expenses: Pfizer, Celgene, Novartis Maria KarstenEmployment: AstraZeneca, Roche Michael GolattaResearch Funding: Siemens Healthineers (Inst) Joerg HeilHonoraria: Roche, Siemens Healthcare Diagnostics, Bard MedicalConsulting or Advisory Role: Roche, Siemens Healthcare DiagnosticsResearch Funding: Bard MedicalTravel, Accommodations, Expenses: CelgeneNo other potential conflicts of interest were reported.

Objectives: AI-based algorithms for medical image analysis showed comparable performance to human image readers. However, in practice, diagnoses are made using multiple imaging modalities alongside other data sources. We determined the importance of this multi-modal information and compared the diagnostic performance of routine breast cancer diagnosis to breast ultrasound interpretations by humans or AI-based algorithms., Methods: Patients were recruited as part of a multicenter trial (NCT02638935). The trial enrolled 1288 women undergoing routine breast cancer diagnosis (multi-modal imaging, demographic, and clinical information). Three physicians specialized in ultrasound diagnosis performed a second read of all ultrasound images. We used data from 11 of 12 study sites to develop two machine learning (ML) algorithms using unimodal information (ultrasound features generated by the ultrasound experts) to classify breast masses which were validated on the remaining study site. The same ML algorithms were subsequently developed and validated on multi-modal information (clinical and demographic information plus ultrasound features). We assessed performance using area under the curve (AUC)., Results: Of 1288 breast masses, 368 (28.6%) were histopathologically malignant. In the external validation set (n = 373), the performance of the two unimodal ultrasound ML algorithms (AUC 0.83 and 0.82) was commensurate with performance of the human ultrasound experts (AUC 0.82 to 0.84; p for all comparisons > 0.05). The multi-modal ultrasound ML algorithms performed significantly better (AUC 0.90 and 0.89) but were statistically inferior to routine breast cancer diagnosis (AUC 0.95, p for all comparisons ≤ 0.05)., Conclusions: The performance of humans and AI-based algorithms improves with multi-modal information., Key Points: • The performance of humans and AI-based algorithms improves with multi-modal information. • Multimodal AI-based algorithms do not necessarily outperform expert humans. • Unimodal AI-based algorithms do not represent optimal performance to classify breast masses., (© 2022. The Author(s).)

Purpose: Restriction spectrum imaging (RSI) decomposes the diffusion-weighted MRI signal into separate components of known apparent diffusion coefficients (ADCs). The number of diffusion components and optimal ADCs for RSI are organ-specific and determined empirically. The purpose of this work was to determine the RSI model for breast tissues., Methods: The diffusion-weighted MRI signal was described using a linear combination of multiple exponential components. A set of ADC values was estimated to fit voxels in cancer and control ROIs. Later, the signal contributions of each diffusion component were estimated using these fixed ADC values. Relative-fitting residuals and Bayesian information criterion were assessed. Contrast-to-noise ratio between cancer and fibroglandular tissue in RSI-derived signal contribution maps was compared to DCE imaging., Results: A total of 74 women with breast cancer were scanned at 3.0 Tesla MRI. The fitting residuals of conventional ADC and Bayesian information criterion suggest that a 3-component model improves the characterization of the diffusion signal over a biexponential model. Estimated ADCs of triexponential model were D 1,3 = 0, D 2,3 = 1.5 × 10 -3 , and D 3,3 = 10.8 × 10 -3 mm 2 /s. The RSI-derived signal contributions of the slower diffusion components were larger in tumors than in fibroglandular tissues. Further, the contrast-to-noise and specificity at 80% sensitivity of DCE and a subset of RSI-derived maps were equivalent., Conclusion: Breast diffusion-weighted MRI signal was best described using a triexponential model. Tumor conspicuity in breast RSI model is comparable to that of DCE without the use of exogenous contrast. These data may be used as differential features between healthy and malignant breast tissues., (© 2021 International Society for Magnetic Resonance in Medicine.)

Objective: We evaluated the ability of minimally invasive, image-guided vacuum-assisted biopsy (VAB) to reliably diagnose a pathologic complete response in the breast (pCR-B)., Summary Background Data: Neoadjuvant systemic treatment (NST) elicits a pathologic complete response in up to 80% of women with breast cancer. In such cases, breast surgery, the gold standard for confirming pCR-B, may be considered overtreatment., Methods: This multicenter, prospective trial enrolled 452 women presenting with initial stage 1-3 breast cancer of all biological subtypes. Fifty-four women dropped out; 398 were included in the full analysis. All participants had an imaging-confirmed partial or complete response to NST and underwent study-specific image-guided VAB before guideline-adherent breast surgery. The primary endpoint was the false-negative rate (FNR) of VAB-confirmed pCR-B., Results: Image-guided VAB alone did not detect surgically confirmed residual tumor in 37 of 208 women [FNR, 17.8%; 95% confidence interval (CI), 12.8-23.7%]. Of these 37 women, 12 (32.4%) had residual DCIS only, 20 (54.1%) had minimal residual tumor (<5 mm), and 19 of 25 (76.0%) exhibited invasive cancer cellularity of ≤10%. In 19 of the 37 cases (51.4%), the false-negative result was potentially avoidable. Exploratory analysis showed that performing VAB with the largest needle by volume (7-gauge) resulted in no false-negative results and that combining imaging and image-guided VAB into a single diagnostic test lowered the FNR to 6.2% (95% CI, 3.4%-10.5%)., Conclusions: Image-guided VAB missed residual disease more often than expected. Refinements in procedure and patient selection seem possible and necessary before omitting breast surgery., Competing Interests: The authors report no conflict of interests., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: One in eight women is diagnosed with breast cancer in the course of their life. As systematic palliative treatment has only a limited effect on survival rates, the concept of health-related quality of life (HRQoL) was developed for measurement of patient-centered outcomes. Various studies have already demonstrated the reliability of paper-based patient-reported outcome (pPRO) and electronic patient-reported outcome (ePRO) surveys and that the 2 means of assessment are equally valid., Objective: The aim of this study was to analyze the acceptance and evaluation of a tablet-based ePRO app for breast cancer patients and to examine its suitability, effort, and difficulty in the context of HRQoL and sociodemographic factors., Methods: Overall, 106 women with adjuvant or advanced breast cancer were included in a 2-center study at 2 major university hospitals in Germany. Patients were asked to answer HRQoL and PRO questionnaires both on a tablet on-site using a specific eHealth assessment website and on paper. The suitability, effort, and difficulty of the app and self-reported technical skills were also assessed. Only the results of the electronically acquired data are presented here. The results of the reliability of the pPRO data have already been published elsewhere., Results: Patients regarded the ePRO assessment as more suitable (80/106, 75.5%), less stressful (73/106, 68.9%), and less difficult (69/106, 65.1%) than pPRO. The majority of patients stated that ePRO assessment improves health care in hospitals (87/106, 82.1%). However, evaluation of ePROs depended on the level of education (P=.003) in the dimensions of effort and difficulty (regression analysis). The app was rated highly in all categories. HRQoL data and therapy setting did not show significant correlations with the app's evaluation parameters., Conclusions: The results indicate that ePRO surveys are feasible for measuring HRQoL in breast cancer patients and that those patients prefer ePRO assessment to pPRO assessment. It can also be seen that patients consider ePRO assessment to improve hospital health care. However, studies with larger numbers of patients are needed to develop apps that address the needs of patients with lower levels of education and technical skills., (©Joachim Graf, Nina Sickenberger, Katharina Brusniak, Lina Maria Matthies, Thomas M Deutsch, Elisabeth Simoes, Claudia Plappert, Lucia Keilmann, Andreas Hartkopf, Christina Barbara Walter, Markus Hahn, Tobias Engler, Stephanie Wallwiener, Florian Schuetz, Peter A Fasching, Andreas Schneeweiss, Sara Yvonne Brucker, Markus Wallwiener. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 08.02.2022.)

Background: Shear wave elastography (SWE) and strain elastography (SE) have shown promising potential in breast cancer diagnostics by evaluating the stiffness of a lesion. Combining these two techniques could further improve the diagnostic performance. We aimed to exploratorily define the cut-offs at which adding combined SWE and SE to B-mode breast ultrasound could help reclassify Breast Imaging Reporting and Data System (BI-RADS) 3-4 lesions to reduce the number of unnecessary breast biopsies., Methods: We report the secondary results of a prospective, multicentre, international trial (NCT02638935). The trial enrolled 1288 women with BI-RADS 3 to 4c breast masses on conventional B-mode breast ultrasound. All patients underwent SWE and SE (index test) and histopathologic evaluation (reference standard). Reduction of unnecessary biopsies (biopsies in benign lesions) and missed malignancies after recategorising with SWE and SE were the outcome measures., Results: On performing histopathologic evaluation, 368 of 1288 breast masses were malignant. Following the routine B-mode breast ultrasound assessment, 53.80% (495 of 920 patients) underwent an unnecessary biopsy. After recategorising BI-RADS 4a lesions (SWE cut-off ≥3.70 m/s, SE cut-off ≥1.0), 34.78% (320 of 920 patients) underwent an unnecessary biopsy corresponding to a 35.35% (320 versus 495) reduction of unnecessary biopsies. Malignancies in the new BI-RADS 3 cohort were missed in 1.96% (12 of 612 patients)., Conclusion: Adding combined SWE and SE to routine B-mode breast ultrasound to recategorise BI-RADS 4a patients could help reduce the number of unnecessary biopsies in breast diagnostics by about 35% while keeping the rate of undetected malignancies below the 2% ACR BI-RADS 3 definition., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC., Experimental Design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients., Results: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06-1.43, p = 0.006), 1.30 (95% CI: 1.12-1.52, p < 0.001) and 1.30 (95% CI: 1.08-1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68-2.16; p = 0.512)., Conclusions: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ADH, FAT and SYB report a grant from Exact Sciences. TNF received personal fees from AstraZeneca, Novartis, Roche, Pfizer, Esai, Tesaro, Teva, Celgene, Daichi Sankyo, MSD, Menarini. PAF reports grants from Cepheid, Novartis and Biontech, personal fees from Novartis, Roche, Pfizer, Celgene, Daiichi-Sankyo, TEVA, Astra Zeneca, Merck Sharp & Dohme, Myelo Therapeutics, Macrogenics, Eisai, Puma and Lilly. CAK is a member of the SAB of HiberCell, New York. All other authors declare no potential conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Diffusion-weighted MRI (DW-MRI) is a contrast-free modality that has demonstrated ability to discriminate between predefined benign and malignant breast lesions. However, how well DW-MRI discriminates cancer from all other breast tissue voxels in a clinical setting is unknown. Here we explore the voxelwise ability to distinguish cancer from healthy breast tissue using signal contributions from the newly developed three-component multi-b-value DW-MRI model., Experimental Design: Patients with pathology-proven breast cancer from two datasets ( n = 81 and n = 25) underwent multi-b-value DW-MRI. The three-component signal contributions C 1 and C 2 and their product, C 1 C 2 , and signal fractions F 1 , F 2 , and F 1 F 2 were compared with the image defined on maximum b-value ( DWI max ), conventional apparent diffusion coefficient ( ADC ), and apparent diffusion kurtosis ( K app ). The ability to discriminate between cancer and healthy breast tissue was assessed by the false-positive rate given a sensitivity of 80% (FPR 80 ) and ROC AUC., Results: Mean FPR 80 for both datasets was 0.016 [95% confidence interval (CI), 0.008-0.024] for C 1 C 2 , 0.136 (95% CI, 0.092-0.180) for C 1 , 0.068 (95% CI, 0.049-0.087) for C 2 , 0.462 (95% CI, 0.425-0.499) for F 1 F 2 , 0.832 (95% CI, 0.797-0.868) for F 1 , 0.176 (95% CI, 0.150-0.203) for F 2 , 0.159 (95% CI, 0.114-0.204) for DWI max , 0.731 (95% CI, 0.692-0.770) for ADC , and 0.684 (95% CI, 0.660-0.709) for K app . Mean ROC AUC for C 1 C 2 was 0.984 (95% CI, 0.977-0.991)., Conclusions: The C 1 C 2 parameter of the three-component model yields a clinically useful discrimination between cancer and healthy breast tissue, superior to other DW-MRI methods and obliviating predefining lesions. This novel DW-MRI method may serve as noncontrast alternative to standard-of-care dynamic contrast-enhanced MRI., (©2020 American Association for Cancer Research.)

Background: Interventional methods of the breast serve as percutaneous minimally invasive diagnostic tools in case of suspicious findings in the breast or axilla. Further indications are lesion localization and the minimally invasive therapeutic approach., Objectives: Aim of this paper is to give an overview of the existing methods, their indications and the imaging techniques for guidance. On the basis of the most recent publications, clinical management is described.

Purpose: Postoperative seromas are a problem in the surgical treatment of breast cancer. The aim of the study was to evaluate whether the lysine-urethane-based tissue adhesive TissuGlu ® without drainage is equal/ non-inferior to standard mastecomy with drainage., Methods: The study was designed as a prospective, randomized, multicentre non-inferiority study comparing the use of TissuGlu ® without drainage with standard wound care with a drain insertion in ablative breast procedures. The number of clinical interventions, quality of life and wound complications were followed-up for 90 days in both groups., Results: Although the statistical power was not reached, twice as many clinical interventions were performed in the TissuGlu ® group than in the drainage group, especially aspirations of clinically relevant seromas (p = 0.014). The TissuGlu ® group produced overall less wound fluid, but developed a clinically relevant seroma (100% vs. 63%) which made an intervention necessary. Less hospitalisation time was observed in the TissuGlu ® group, but the complication rate was higher. There was no significant difference in regards to postoperative pain. In summary the non-inferiority of TissuGlu ® compared to standard drainage couldn't be reached., Discussion: The present evaluation shows no advantage of the tissue adhesive TissuGlu ® in terms of seroma formation and frequency of intervention compared to a standard drainage for mastectomies, but the shorter inpatient stay certainly has a positive effect on the quality of life.

Background/aim: The study aimed at investigating the correlation between ductoscopic and histopathological findings and clarify whether the former allow for accurate prediction of malignancy., Patients and Methods: The prospective national multi-center study covered a sample of 224 patients with pathologic nipple discharge. A total of 214 patients underwent ductoscopy with subsequent extirpation of the mammary duct. The ductoscopic findings were categorized according to shape, number, color and surface structure of lesions and vascularity and compared to the histological results and analyses., Results: Ductoscopy revealed lesions in 134 of 214 patients (62.2%). The criteria "multiple versus solitary lesion" differed significantly between malignant and benign lesions. All other criteria were not statistically significant. Malignant tumors were more frequently presented as multiple lesions, benign lesions or masses as solitary lesions (80% vs. 24.8%; p=0.018)., Conclusion: The ductoscopic criterion "solitary vs. multiple lesion" appears to have a low diagnostic prediction of malignancy or benignity., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Data on the optimal treatment strategy for patients undergoing neoadjuvant therapy (NAT) who initially presented with metastatic nodes and convert to node-negative disease (cN+ → ycN0) are limited. Since NAT leads to axillary downstaging in 20-60% of patients, the question arises whether these patients might be offered less-invasive procedures than axillary dissection, such as sentinel node biopsy or targeted removal of lymph nodes marked before therapy., Methods: We performed a systematic review of clinical studies on the use of axillary ultrasound for prediction of response to NAT and ultrasound-guided marking of metastatic nodes for targeted axillary dissection., Results: The sensitivity of ultrasound for prediction of residual node metastasis was higher than that of clinical examination and MRI/PET in most studies; specificity ranged in large trials from 37 to 92%. The diagnostic performance of ultrasound after NAT seems to be associated with tumor subtype: the positive predictive value was highest in luminal, the negative in triple-negative tumors. Several trials evaluated the usefulness of ultrasound for targeted axillary dissection. Before NAT, nodes were most commonly marked using ultrasound-guided clip placement, followed by ultrasound-guided placement of a radioactive seed. After chemotherapy, the clip was detected on ultrasound in 72-83% of patients; a comparison of sonographic visibility of different clips is lacking. Detection rate after radioactive seed placement was ca. 97%., Conclusion: In conclusion, ultrasound improves prediction of axillary response to treatment in comparison to physical examination and serves as a reliable guiding tool for marking of target lymph nodes before the start of treatment. High quality and standardization of the examination is crucial for selection of patients for less-invasive surgery.

In the case of female breast cancer, a breast-conserving excision is often desirable. This surgery is based on preoperatively gathered MRI, mammography, and sonography images. These images are recorded in multiple patient positions, e. g., 2D mammography images in standing position with a compressed breast and 3D MRI images in prone position. In contrast, the surgery happens in supine or beach chair position. Due to these different perspectives and the flexible, thus challenging, breast tissue, the excision puts high demands on the physician. Therefore, this publication presents a novel eight-step excision support workflow that can be used to include information captured preoperatively through medical imaging based on a finite element (FE) model. In addition, an indoor positioning system is integrated in the workflow in order to track surgical devices and the sonography transducer during surgery. The preoperative part of the navigation system-supported workflow is outlined exemplarily based on first experimental results including 3D scans of a patient in different patient positions and her MRI images. Graphical Abstract Finite Element model based navigation system supported workflow for breast tumor excision is based on eight steps and allows inclusion of information from medical images recorded in multiple patient positions.

In case of female breast cancer, a breast conserving excision is often necessary. For this purpose, information from multiple medical imaging techniques have to be combined. Sonography imaging is essential for dense breast tissue and the only medical imaging technique available during surgery. During sonography of the outer breast quadrants the woman is usually in contralateral posterior oblique position, being in supine orientation while holding her ipsilateral arm over the head. Thus, these images cannot be directly registered with MRI or mammography images because these imaging technologies are performed in other patient positions with hands on the side of the body. Thus, we present a novel Finite Element approach how to enable a sonography image registration by showing the first time how to transfer the supine position with the arm straight on side into a supine position with the ipsilateral arm over the head which can be used to include information from MRI or mammography images. This approach is shown and validated with 3D scanner breast surface data as proof of concept. When comparing the simulation result with a 3D surface scan in supine orientation with the arm over the head, a mean surface distance error of 1.57 mm is achieved.

Purpose:  Breast-conserving therapy is associated with a risk of tumor-involved margins. For intraoperative orientation, non- palpable or indistinctly palpable lesions are wire-marked prior to surgery. Ultrasound-guided surgery has the potential to reduce the number of tumor-involved margins. In the MAC 001 trial we evaluated ultrasound-guided breast-conserving surgery compared to wire-guided surgery with regard to free tumor margins, duration of surgery and resection volume., Materials and Methods:  In this randomized, prospective, single-center controlled trial, patients with ductal invasive breast cancer were recruited for either ultrasound-guided or wire localization surgery. Primary outcomes were tumor-free resection margins, the reoperation rate and the resection volume in each group. The results were analyzed by intention to treat. The trial was registered under ClinicalTrials.gov NCT02222675., Results:  56 patients were assessed, and 47 patients were evaluated in the trial. 93 % (25/27) of the patients in the ultrasound arm had an R0 reoperation compared to 65 % (13/20) in the wire localization control arm. This result was statistically significant (p = 0.026). No statistical difference was found for the resection volume or the duration of surgery between the two arms. No major complication was seen in either arm., Conclusion:  Ultrasound-assisted breast surgery significantly increases the possibility of tumor-free margins and therefore reduces the risk of reoperations. Breast surgeons should be trained in ultrasound and ultrasound should be available in every breast surgery operating room., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Rationale and Objectives: Ductal carcinoma in situ (DCIS) hinders imaging detection due to multifocal appearance and discontinuous growth. Preoperative determination of its extent is therefore challenging. Aim of this study was to investigate the additional benefit of breast magnetic resonance imaging (MRI) to mammography (MG) in the diagnosis of DCIS according to size and grading., Materials and Methods: Retrospective analysis of 295 patients with biopsy-proven, pure DCIS. Mean patient age was 57.0 years (27-87 years). All patients obtained MG. Additional MRI was performed in 41.7% (123/295). Mammographic breast density, background parenchymal enhancement (BPE), tumor size and grading were analysed. Tumor size on MG and MRI were compared to histopathological size of the surgical specimen., Results: Mean tumor size was 39.6 mm. DCIS was occult on MG in 24.4% (30/123) and on MRI in 1.6% (2/123). Size was underestimated by 4.6 mm (mean) mammographically. DCIS was high grade in 54.5% (67/123), intermediate grade in 40.7% (50/123) and low grade in 4.9% (6/123). MG was exact regarding tumor size in low grade DCIS, underestimated intermediate grade DCIS by 1 mm (median) and high grade DCIS by 10.5 mm. MRI overestimated low grade DCIS by 1 mm (median), was exact regarding intermediate grade DCIS and underestimated high grade DCIS by 1 mm. BPE did not influence tumor detection and measurement., Conclusion: MRI outperforms MG in the detection and size estimation of DCIS and can reduce positive margin rates., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: Oncoplastic breast-conserving surgery has been part of clinical routine for several years without an internationally accepted nomenclature, standardization or a systematic evaluation of single surgical procedures., Methods: We carried out a structured survey of breast surgeons (n = 50) during the annual meeting of the German Society for Senology in Berlin 2017. In the run-up to the event, 10 questions were determined and released for an anonymous survey during the consensus meeting., Results: Most surgeons participating in the consensus meeting had an expertise of more than 200 oncologic breast surgeries in the last 3 years and approved the need of a higher rate of standardization in oncoplastic techniques. From the oncological standpoint, oncoplastic surgery is considered safe with a comparable rate of compilations as seen in conventional breast-conserving procedures. Most surgeons approve that using oncoplastic surgery, higher rates of breast conservation and improved aesthetic results can be accomplished. The majority of the participants would endorse a more systematic review of subjective aesthetic results in clinical routine., Conclusions: A higher degree in standardization of oncoplastic breast surgery is required for surgical-technical, educational, and scientific reasons as well as for a more differentiated monetary compensation of the surgical procedures. This process has already been started.

Purpose: To prospectively investigate the role of re-irradiation (re-RT) combined with hyperthermia (HT) in a contemporary cohort of patients affected by recurrent breast cancer (RBC)., Methods: Within the prospective registry HT03, patients with resected RBC and previous irradiation were included. Re-RT was applied to the recurrence region with doses of 50-50.4 Gy, with a boost up to 60-60.4 Gy to the microscopically or macroscopically positive resection margins (R1/R2) region. Concurrent HT was performed at 40-42 ℃. Primary endpoint was LC. Acute and late toxicity, overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) were also evaluated., Results: 20 patients and 21 RBC were analyzed. Median re-RT dose was 50.4 Gy and a median of 11 HT fractions were applied. Re-RT+HT was well tolerated, with three patients who experienced a grade (G) 3 acute skin toxicity and no cases of ≥G3 late toxicity. With a median follow up of 24.7 months, two local relapses occurred. Ten patients experienced regional and/or distant disease progression. Five patients died, four of them from breast cancer. PFS was favorable in patients treated with re-RT+HT for the first recurrence with doses of 60 Gy. A trend towards better CSS was found in patients with negative or close margins and after doses of 60 Gy., Conclusion: Full-dose re-RT+HT for RBC is well tolerated, provides good LC, and seems to be more effective when applied at the time of the first relapse and after doses of 60 Gy. The registry will be continued for validation in a larger cohort and with longer follow-up.

Alcohol consumption has consistently been shown to increase breast cancer (BC) risk. This association may be modified by single nucleotide polymorphisms (SNPs) in alcohol dehydrogenase (ADH) isoenzymes ADH1B and ADH1C. The Netherlands Cohort Study comprises 62 573 women, aged 55-69 years at baseline (1986). Follow-up for postmenopausal BC for 20.3 years was available. Genotyping of six tag SNPs in ADH1B and ADH1C was performed on DNA from toenails. A case-cohort approach was used for analysis (complete data available for nsubcohort = 1301; ncases = 1630). Cox regression models for postmenopausal BC were applied to determine marginal effects of alcohol intake and SNPs using a dominant genetic model, as well as multiplicative interaction of the two. Results were also obtained for subtypes by estrogen receptor (ER) and progesterone receptor (PR) status. Multiple testing was adjusted for by applying the false discovery rate (FDR). Alcohol intake (categorical) increased the risk of postmenopausal BC (Ptrend = 0.031). Trends for ER and PR subgroups followed a similar pattern. Continuous modeling of alcohol resulted in a hazard rate ratio (HR) for overall postmenopausal BC of 1.09 (95% confidence interval: 1.01-1.19) per 10 g/day of alcohol. SNPs were not associated with BC risk. No effect modification of the alcohol-BC association by SNP genotype was seen after FDR correction in overall BC and ER/PR subgroups. In conclusion, alcohol consumption was shown to increase the risk of postmenopausal BC. This association was not significantly modified by common SNPs in ADH1B and ADH1C, neither in overall BC nor in hormone receptor-defined subtypes.

Purpose:  The aim was to obtain an overview of the hygiene measures undertaken during ultrasound guided core cut biopsies of the breast by experts certified by the German Society for Ultrasound in Medicine in order to derive recommendations for clinical routine, taking into account the available literature and the lack of evidence based guidelines., Materials and Methods:  A survey was conducted with all members of the levels I to III of the breast ultrasound working group of the German Society for Ultrasound in Medicine. The estimation of the risk of infection after a core cut biopsy of the breast was asked for as well as the hygiene measures undertaken in practice to avoid infection., Results:  The risk of infection after a core cut biopsy of the breast was estimated to be one per thousand (median value). The most commonly performed hygiene measures were a spray, wipe, spray desinfection (98.1 %) and the use of sterile gloves (54.7 %)., Conclusion:  Due to the very low risk of infection we recommend the routine use of gloves and an adequate skin disinfection. Contact of the transducer or of an unsterile contact medium with the biopsy needle is considered highly unlikely und should be avoided., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background The limited sensitivity of mammography in case of a high breast density often produces unclear or false-positive findings, so-called BI-RADS 3 lesions, which have to be followed up to prove benignity. Digital breast tomosynthesis (DBT) was developed to reduce such summation effects. Purpose To evaluate the influence of an additional DBT on the management of mammographic BI-RADS 3 findings and whether DBT can decrease the time to definitive diagnosis or not. Material and Methods We analyzed 87 patients with a mammographic non-calcified BI-RADS 3 lesion who underwent an additional DBT of the affected breast. A follow-up two-dimensional (2D) examination or a histological result of the lesion had to be available. The images were analyzed especially for the BI-RADS category and incremental diagnostic accuracy. Moreover, the inter-reader reliability and the radiation dose were evaluated. Results The BI-RADS category has been changed by the addition of DBT: 57.1% were assessed as BI-RADS 1 or 2, 4.6% as BI-RADS 4, and only 38.3% remained as BI-RADS 3. The intraclass correlation coefficient for the three readers showed a good agreement for inter-reader reliability. No false-negative examination was found in the follow-ups. Nine lesions were biopsied (seven benign, two malignant). Both malignant lesions were suspicious in the DBT (BI-RADS 4). A significant higher glandular dose was necessary for the DBT. Conclusion DBT has the potential to reduce the recall-rate of BI-RADS 3 lesions and to find and diagnose malignant lesions earlier than 2D mammography alone.

Background: Approximately 10% of all MRI-guided vacuum-assisted breast biopsies (MR-VAB) are histologically classified as B3 lesions. In most of these cases surgical excision is recommended. The aim of our study was to evaluate the malignancy rates of different B3 lesions which are visible on MRI to allow a lesion-adapted recommendation of further procedure., Methods: Retrospective analysis of 572 consecutive MR-VAB was performed. Inclusion criteria were a representative (=successful) MR-VAB, histologic diagnosis of a B3 lesion and either the existence of a definite histology after surgical excision or proof of stability or regression of the lesion on follow-up MRI. Malignancy rates were evaluated for different histologies of B3 lesions. Lesion size and lesion morphology (mass/non-mass enhancement) on MRI were correlated with malignancy., Results: Of all MR-VAB 43 lesions fulfilled the inclusion criteria. The malignancy rate of those B3 lesions was 23.3% (10/43). The highest malignancy rate was found in atypical ductal hyperplasia (ADH) lesions (50.0%; 4/8), 33.3% (2/6) in flat epithelial atypia (FEA), 28.6% (2/7) in lobular intraepithelial neoplasia (LIN) and 12.5% (2/16) in papillary lesions (PL). All 6 complex sclerosing lesions were benign. Mass findings were significantly more frequently malignant (31.3%, 10/32; p < 0.05) than non-mass findings (0/11). Small lesions measuring 5-10 mm were most often malignant (35.0%; 7/20). All large lesions (> 20 mm) were not malignant (0/10). Intermediate sized lesions (11-20 mm) turned out to be malignant in 23.1% (3/13)., Conclusions: The malignancy rate of B3 lesions which were diagnosed after MR-VAB was 23.3%. ADH, FEA and LIN showed considerable malignancy rates (50%, 33% and 29%) and should therefore undergo surgical excision. None of the cases, which were diagnosed as radial scars, non-mass enhancement or larger lesions (> 20 mm) were malignant. Here, a follow-up MRI seems to be advisable to avoid unnecessary operations., Trial Registration: Retrospective study design, waived by the IRB.

Background: Neoadjuvant chemotherapy (NACT) is a standard approach of the multidisciplinary treatment of breast cancer. Depending on the biological subtype a pathological complete response in the breast (bpCR) can be achieved in up to 60% of the patients. However, only limited accuracy can be reached when using imaging for prediction of bpCR prior to surgery. Due to this diagnostic uncertainty, surgery after NACT is considered to be obligatory for all patients in order to either completely remove residual disease or to diagnose a bpCR histologically. The purpose of this trial is to evaluate the accuracy of a vacuum-assisted biopsy (VAB) to diagnose a bpCR after NACT prior to surgery., Methods: This study is a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial. The study will take place at 21 trial sites in Germany. Six hundred female patients with breast cancer after completed NACT showing at least a partial response to NACT treatment will be enrolled. A vacuum-assisted biopsy (VAB) guided either by ultrasound or mammography will be performed followed by histopathological evaluation of the VAB specimen before standard, guideline-adherent breast surgery. The study is designed to prove that the false negative rate of the VAB is below 10%., Discussion: As a bpCR is becoming a more frequent result after NACT, the question arises whether breast surgery is therapeutically necessary in such cases. To study this subject further, it will be crucial to develop a reliable test to diagnose a bpCR without surgery. During the study we anticipate possible problems in patient recruitment as the VAB intervention does not provide participating patients with any personal benefit. Hence, a proficient informed consent discussion with the patient and a detailed explanation of the study aim will be crucial for patient recruitment. Another critical issue is the histopathological VAB evaluation of a non-tumorous specimen as this may have been taken either from the former tumor region (bpCR) or outside of the (former) tumor region (non-representative VAB, sampling error)., Trial Registration: The trial has been registered at clinicaltrials.gov with the identifier NCT02948764 on October 28, 2016 and at the German Clinical Trials Register ( DRKS00011761 ) on February 20, 2017. The date of enrolment of the first participant to the trial was on March 8, 2017.

Purpose: Pregnancy-associated breast cancer (PABC) is considered the second most common malignancy affecting pregnancy. The limited knowledge as to long-term survival is nonuniform. This retrospective study aims to contribute by a follow-up of pregnancies of breast cancer patients treated at a single university centre with focus on maternal long-term survival in relation to time point of diagnosis (before, during, and after pregnancy)., Methods: Data of 25 patients were reviewed for the period between 2000 and 2009 in relation to their neonatal and maternal outcome parameters as well as their maternal breast cancer outcomes by assessing maternal mortality at annual intervals up to a maximum of 10 years follow-up., Results: Median age at diagnosis was 33 years. Maternal survival rate of the total collective came to 76% after 5 years and to 68% after 10 years. The newborns were healthy, 22% of them presented with a 1'Apgar score 5-7. Preterm delivery occurred in 53%. PABC significantly affected maternal survival compared to the national breast cancer cohort at 5 years and barely significantly at 10 years, with highly significant (p < 0.003) to significant (p < 0.01) effects at 5 and 10 years, respectively, for PABC diagnosed during and after pregnancy., Conclusions: The present findings on survival rates suggest that maternal medical assessment at the beginning of and during further course of pregnancy should include a scrutinized thorough breast examination. Conveying/delivering special competences to monitor these high-risk pregnancies at the interface of oncological care should be considered an obligatory part of academic medical education, obstetrical training and interprofessional midwifery education.

Background Contrast-enhanced spectral mammography (CESM) is a novel breast imaging technique providing comparable diagnostic accuracy to breast magnetic resonance imaging (MRI). Purpose To show that CESM in patients with MRI contraindications is feasible, accurate, and useful as a problem-solving tool, and to highlight its limitations. Material and Methods A total of 118 patients with MRI contraindications were examined by CESM. Histology was obtained in 94 lesions and used as gold standard for diagnostic accuracy calculations. Imaging data were reviewed retrospectively for feasibility, accuracy, and technical problems. The diagnostic yield of CESM as a problem-solving tool and for therapy response evaluation was reviewed separately. Results CESM was more accurate than mammography (MG) for lesion categorization (r = 0.731, P < 0.0001 vs. r = 0.279, P = 0.006) and for lesion size estimation (r = 0.738 vs. r = 0.689, P < 0.0001). Negative predictive value of CESM was significantly higher than of MG (85.71% vs. 30.77%, P < 0.0001). When used for problem-solving, CESM changed patient management in 2/8 (25%) cases. Superposition artifacts and timing problems affected diagnostic utility in 3/118 (2.5%) patients. Conclusion CESM is a feasible and accurate alternative for patients with MRI contraindications, but it is necessary to be aware of the method's technical limitations.

Background/aim: Only 30-50% of patients with sentinel lymph node (SLN) metastases present with further axillary lymph node metastases. Therefore, up to 70% of patients with positive SLN are overtreated by axillary dissection (AD) and may suffer from complications such as sensory disturbances or lymphedema. According to the current S3 guidelines, AD can be avoided in patients with a T1/T2 tumor if breast-conserving surgery with subsequent tangential irradiation is performed and no more than two SLNs are affected. Additionally, use of nomograms, that predict the probability of non-sentinel lymph node (NSLN) metastases, is recommended. Therefore, models for the prediction of NSLN metastases in our defined population were constructed and compared with the published nomograms., Patients and Methods: In a retrospective study, 2,146 primary breast cancer patients, who underwent SLN biopsy at the University Women's Hospital in Tuebingen, were evaluated by dividing the patient group in a training and validation collective (TC or VC). Using the SLN-positive TC patients, three models for the prediction of the likelihood of NSLN metastases were adapted and were then validated using the SLN-positive VC patients. In addition, the predictive power of nomograms from Memorial Sloan Kettering Cancer Center (MSKCC), Stanford, and the Cambridge model were compared with regard to our patient collective., Results: A total of 2,146 patients were included in the study. Of these, 470 patients had positive SLN, 295 consisted the training collective and 175 consisted the validation collective. In a regression model, three variants - with 11, 6 and 2 variables - were developed for the prediction of NSLN metastases in our defined population and compared to the most frequently used nomograms. Our variants with 11 and with 6 variables were proven to be a particularly suitable model and showed similarly good results as the published MSKCC nomogram., Conclusion: Our developed nomograms may be used as a prediction tool for NSLN metastases after positive SLN., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Pathological complete response (pCR) is a common endpoint in neoadjuvant chemotherapy (NACT) of primary breast cancer patients (PBC), but does not address the systemic prevalence of minimal residual disease. In this study, we compared pCR with the detection of circulating (CTC) and disseminated tumor cells (DTC) following NACT, as well as their impact on survival., Methods: Patients with PBC receiving NACT and consecutive surgery were eligible for this study. CTCs were detected using the CellSearch ® system and DTCs were determined using immunocytochemistry (cytokeratin staining with the A45-B/B3 antibody). pCR was defined as ypT0/ypTis and ypN0., Results: 58 patients were included in the analysis with a median follow-up of 30 months. Of these, 5 (9%) presented with CTCs and 36 (62%) with DTCs. 16 patients (28%) achieved a pCR. No significant correlation between CTCs, DTCs and pCR and no statistically significant impact on disease free (DFS) or overall survival (OS) was apparent., Conclusions: Both CTCs and DTCs are detectable after NACT. As we could not show a significant relationship between CTC detection, DTC detection and pCR, all three methods may provide independent information regarding treatment response. Since we were unable to show a significant impact on survival, larger prospective studies that include CTCs and DTCs are needed. These trials should include the molecular characterization of primary tumor tissue, CTCs and DTCs to determine whether these cells are independent subpopulations of malignant cell clones.

Purpose: The impact of preoperative MRI on re-excisions and mastectomy rate is discussed controversially in the literature. Aim of this study was to evaluate the effect of preoperative breast MRI on the surgical procedure and rate of repeated surgeries., Material and Methods: A total of 991 consecutive patients in the years 2009 and 2010 with 1036 primary breast cancers were retrospectively analyzed. Sixty percent (599 patients with 626 cancers) received preoperative breast MRI. Planned surgical procedures before and after MRI and numbers of repeated surgeries in patients with (MR+ ) and without preoperative MRI (MR-) were compared., Results: The result of preoperative MRI changed the surgical procedure in 25% (157/626) of the cases. In 81% (127/157), MRI was beneficial for the patients, as otherwise occult carcinomas were removed (n=122) or further biopsy could be prevented (n=5). Mastectomy rates did not differ between MR+ and MR- group (39% vs. 39%). On multiple regression analysis, the MR+ group had a lower chance for repeated surgery (p<0.05)., Conclusion: Preoperative MRI could lower the chance for repeated surgery in patients with primary breast cancer. The rate of mastectomy did not differ between patients undergoing preoperative MRI and those who did not., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Retrospective analysis of breast cancer imaging methods is a common tool for evaluating the effectiveness of ultrasound and mammography regarding ductal carcinoma in situ (DCIS). No large number subpopulation of pure DCIS has been reported. It is however known that mammography and ultrasound underestimate tumor dimension with increasing tumor size. We aimed to quantify this discrepancy., Materials and Methods: This retrospective analysis reviewed the ultrasound and mammography data from 173 patients with DCIS at the University of Cologne - Department of Gynecology and Obstetrics between the years 2007 and 2010. Of these 173 patients, 34 fulfilled the DCIS analysis requirements and were evaluated in this study., Results: Overall, ultrasound underestimated tumor size 79.4% of the time, while overestimating only 20.6% of the time. Mammography underestimated tumor size in 50%, overestimated in 38.2%, correctly estimating in 11.8%. Over and underestimation distributions differed drastically above and a cut-off point of ≤2 cm actual tumor size, with a significant shift toward severe underestimation by both methods above a tumor size of 2 cm. DCIS misestimation was defined as the absolute value of the difference between actual tumor size and pre-surgical measurement by an imaging method. Mean DCIS size misestimation (actual tumor size ≤2 cm) was 3 mm for ultrasound and 6.2 mm for mammography., Conclusion: We support previous findings that ultrasound and mammography lose accuracy with increasing tumor size. Nonetheless, ultrasound may be more useful in estimation of DCIS size for tumors ≤2 cm than previously expected., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To obtain consensus recommendations for the standardization of oncoplastic breast conserving surgery (OPS) from an international panel of experts in breast surgery including delegates from the German, Austrian and Swiss societies of senology., Methods: A total of 52 questions were addressed by electronic voting. The panel's recommendations were put into context with current evidence and the report was circled in an iterative open email process until consensus was obtained., Results: The panelists considered OPS safe and effective for improving aesthetic outcomes and broadening the indication for breast conserving surgery (BCS) towards larger tumors. A slim majority believed that OPS reduces the rate of positive margins; however, there was consensus that OPS is associated with an increased risk of complications compared to conventional BCS. The panel strongly endorsed patient-reported outcomes measurement, and recommended selected scales of the Breast-Q™-Breast Conserving Therapy Module for that purpose. The Clough bi-level classification was recommended for standard use in clinical practice for indicating, planning and performing OPS, and the Hoffmann classification for surgical reports and billing purposes. Mastopexy and reduction mammoplasty were the only two recognized OPS procedure categories supported by a majority of the panel. Finally, the experts unanimously supported the statement that every OPS procedure should be tailored to each individual patient., Conclusions: When implemented into clinical practice, the panel recommendations may improve safety and effectiveness of OPS. The attendees agreed that there is a need for prospective multicenter studies to optimize patient selection and for standardized criteria to qualify and accredit OPS training centers.

Objectives: Analysing the influence of additional carcinoma in situ (CIS) and background parenchymal enhancement (BPE) in preoperative MRI on repeated surgeries in patients with invasive lobular carcinoma (ILC) of the breast., Methods: Retrospective analysis of 106 patients (mean age 58.6±9.9years) with 108 ILC. Preoperative tumour size as assessed by MRI, mammography and sonography was recorded and compared to histopathology. In contrast-enhanced MRI, the degree of BPE was categorised by two readers. The influence of additionally detected CIS and BPE on the rate of repeated surgeries was analysed., Results: Additional CIS was present in 45.4% of the cases (49/108). The degree of BPE was minimal or mild in 80% of the cases and moderate or marked in 20% of the cases. In 17 cases (15.7%) at least one repeated surgery was performed. In n=15 of these cases, repeated surgery was performed after BCT (n=9 re-excisions, n=6 conversions to mastectomy), in n=2 cases after initial mastectomy. The initial surgical procedure (p=0.008) and additional CIS (p=0.046) significantly influenced the rate of repeated surgeries, while tumour size, patient age and BPE did not (p=ns)., Conclusions: Additional CIS was associated with a higher rate of repeated surgeries, whereas BPE had no influence., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Differential diagnosis and therapy of heterogeneous breast tumors poses a major clinical challenge. To address the need for a comprehensive, noninvasive strategy to define the molecular and functional profiles of tumors in vivo, we investigated a novel combination of metabolic PET and diffusion-weighted (DW)-MRI in the polyoma virus middle T antigen transgenic mouse model of breast cancer. The implementation of a voxelwise analysis for the clustering of intra- and intertumoral heterogeneity in this model resulted in a multiparametric profile based on [(18)F]Fluorodeoxyglucose ([(18)F]FDG)-PET and DW-MRI, which identified three distinct tumor phenotypes in vivo, including solid acinar, and solid nodular malignancies as well as cystic hyperplasia. To evaluate the feasibility of this approach for clinical use, we examined estrogen receptor-positive and progesterone receptor-positive breast tumors from five patient cases using DW-MRI and [(18)F]FDG-PET in a simultaneous PET/MRI system. The postsurgical in vivo PET/MRI data were correlated to whole-slide histology using the latter traditional diagnostic standard to define phenotype. By this approach, we showed how molecular, structural (microscopic, anatomic), and functional information could be simultaneously obtained noninvasively to identify precancerous and malignant subtypes within heterogeneous tumors. Combined with an automatized analysis, our results suggest that multiparametric molecular and functional imaging may be capable of providing comprehensive tumor profiling for noninvasive cancer diagnostics. Cancer Res; 76(18); 5512-22. ©2016 AACR., (©2016 American Association for Cancer Research.)

Objectives: To correlate the decrease in background parenchymal enhancement (BPE) and tumour response measured with MRI in breast cancer patients treated with neoadjuvant chemotherapy (NAC)., Methods: One hundred and forty-six MRI examinations of 73 patients with 80 biopsy-proven breast cancers who underwent breast MRI before and after NAC were retrospectively analysed. All images were reviewed by two blinded readers, who classified BPE into categories (BEC; 1 = minimal, 2 = mild, 3 = moderate, 4 = marked) before and after NAC. Histopathological and morphological tumour responses were analysed and compared., Results: The distribution of BEC 1/2/3/4 was 25/46/18/11 % before and 78/20/2/0 % after NAC. On average, BPE decreased by 0.87 BEC. Cohen's kappa showed substantial agreement (k = 0.73-0.77) before and moderate agreement (k = 0.43-0.60) after NAC and moderate agreement (k = 0.62-0.60) concerning the change in BEC. Correlating the change in BPE with tumour response, the average decrease in BEC was 1.3 in cases of complete remission, 0.83 in cases with partial response, 0.85 in cases with stable disease and 0.40 in cases with progressive disease. Correlation analysis showed a significant correlation between the decrease in BEC and tumour response (r = -0.24, p = 0.03)., Conclusions: BPE decreased by, on average, 0.87 BEC following NAC for breast cancer. The degree of BPE reduction seemed to correlate with tumour response., Key Points: • BPE decreases by an average of 0.87 categories under neoadjuvant chemotherapy. • The reduction of BPE following neoadjuvant chemotherapy correlates with the tumour response. • The classification of the BPE shows good agreement among trained readers.