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Introduction: The goal of breast conserving surgery (BCS) for early breast cancer (EBC) is to remove the tumor in toto and preserving as much of the normal breast tissue as possible. In 20-50% of cases a re-excision is necessary because of involved margins. Repeat surgeries are not only a burden to patients physically but also psychologically and can delay recommended adjuvant therapies. Accurate determination of tumor margins during surgery is therefore a critical need. Breast cancer tissue produces significantly higher amounts of VEGF-A than healthy tissue. VEGF-A stimulates tumor angiogenesis and is therefore a target for molecular imaging techniques. The fluorescence imaging agent bevacizumab-IRDye800CW (Beva800) is a conjugate of bevacizumab and IRDye800CW and binds specifically to VEGF-A. Beva800 provides a potentially efficacious approach to imaging specimen and cavity margins during BCS. We are presenting a phase II study that combined Beva800 with the SurgVision Explorer Air camera for intraoperative margin assessment during BCS for EBC. Methods: MARGIN II is a multicenter open-label single arm prospective clinical trial aimed at evaluating Beva800 for assessment of tumor margins in women with EBC scheduled for BCS. The study was a within-patient comparison of positive tumor margin rates using BCS standard of care margin assessment compared to intraoperative assessment with 4.5 mg Beva800 and fluorescence imaging with the SurgVision Explorer Air camera. All patients received an i.-v. bolus injection of 4.5 mg of Beva800 three days before surgery. The fluorescent signal was visualized during surgery using NIR fluorescence imaging (700–1000 nm). Standard of care margin assessment was defined as visual inspection, palpation and, in cases of pre-operative wire marking, specimen sonography or mammography. Beva800 efficacy was determined as the number of patients in which a pathology-confirmed positive margin was identified by fluorescence-guided surgery using Beva800 but not by standard of care BCS. Results: 49 patients were included in 5 centers. 4 training cases were only included in the safety analysis, 45 patients were evaluable for the efficacy analysis. 8 patients (17.8%) had involved margins after standard of care BCS, 4 of which were detected by molecular fluorescence intraoperatively resulting in the reduction of patients with positive margins by 50% (95% CI: 15.7%, 84.3%). 4 patients (8.9%; 95% CI: 2.5%, 21.1%) needed a re-excision because of involved margins. In 27 patients (60.0%) the additional molecular fluorescence guided cavity shaving did not change the resection status from positive to negative (false positive). Adverse events were reported by 16 of 49 patients (32.7%), but only 3 (6.1%) were related to Beva800 (syncope, hot flush, hypertensive crisis). One patient experienced a treatment related SAE (hypertensive crisis). No anti-Beva800 antibodies were detected. Conclusion: In our analysis the rate of necessary second operations was reduced by 50% using Beva800 and the SurgVision Explorer Air camera. The safety analysis confirmed the positive safety profile of Beva800 found in previous studies. Molecular fluorescence-guided surgery may have the potential to change the practice of breast conserving surgery by reducing unnecessary re-excisions. Future studies will have to address the high false positive rates. Citation Format: Hans-Christian Kolberg, Carmen Röhm, Angrit Stachs, Florian Schütz, Jens-Uwe Blohmer, Sarah Wetzig, Steffi Hartmann, Jörg Heil, Markus Hahn. MOLECULAR FLUORESCENCE-GUIDED SURGERY USING BEVA800 FOR THE ASSESSMENT OF TUMOR MARGINS DURING BREAST CONSERVING SURGERY OF PATIENTS WITH PRIMARY BREAST CANCER (MARGIN-II) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-01.

ZusammenfassungDrahtlokalisation stellt die am häufigsten verwendete Lokalisationsmethode bei nicht palpablen Mammakarzinomen dar. Zu potenziellen Nachteilen der Technik gehören eine niedrige Rate an R0-Resektionen, die Invasivität und das Risiko der Drahtdislokation. Des Weiteren ist die Notwendigkeit einer Re-Operation mit einem erhöhten Rezidivrisiko assoziiert. Intraoperative Sonografie (IOUS) erlaubt eine direkte Visualisierung der Läsion und des Resektionsvolumens und reduziert die Rate an positiven Rändern bei palpablen und nicht palpablen Tumoren. Wir führten ein systematisches Review der Studien zur IOUS durch. Die randomisierten Studien wurden in 2 Metaanalysen ausgewertet. In nicht palpablen Mammakarzinomen zeigten 3 randomisierte Studien höhere R0- Resektionsraten im IOUS-Arm, verglichen mit Drahtlokalisation. Der signifikante Unterschied konnte in der Metaanalyse bestätigt werden (Risk Ratio 4,34, p < 0,0001, I2 = 0 %). Die meisten der 41 Kohortenstudien mit 3291 Patientinnen zeigten höhere R0-Resektionsraten und niedrigere Nachresektionsraten bei Verwendung von IOUS. Eine Metaanalyse von 3 randomisierten Studien bei palpablem Mammakarzinom zeigte signifikant höhere Raten an positiven Rändern im Palpations-Arm (Risk Ratio 2,84, p=0,0047, I2=0%). In 13 Kohortenstudien mit 942 Patientinnen mit palpablem Mammakarzinom, waren die R0-Resektionsraten meist höher und die Gewebsvolumina niedriger bei Verwendung von IOUS. IOUS ist eine sichere nicht invasive Technik zur Lokalisation von sonografisch sichtbaren Tumoren und verbessert R0-Resektionsraten bei palpablem und nicht palpablem Mammakarzinom. Sonografische Weiterbildung für Brustoperateure erscheint empfehlenswert.

ZusammenfassungDie Mammasonografie hat sich seit vielen Jahren neben der Mammografie als wichtige Methode zur Abklärung von Brustbefunden etabliert. Problematisch bleiben jedoch Unterschiede in der Interpretation von Befunden 1 2. Dies vermindert die diagnostische Treffsicherheit der Sonografie nach Detektion eines Befundes, erschwert die interdisziplinäre Kommunikation und den Vergleich von wissenschaftlichen Arbeiten 3. Das American College of Radiology (ACR) hatte 1999 eine Arbeitsgruppe gebildet (International Expert Working Group), die auf der Basis der langjährig etablierten BI-RADS-Klassifizierung von mammografischen Befunden und unter Berücksichtigung von Literaturdaten eine ähnliche Einteilung für die Ultraschalluntersuchung erarbeitet hatte 4. Aufgrund inhaltlicher Unterschiede hatte die DEGUM bereits 2006 einen eigenen BI-RADS-analogen Kriterienkatalog publiziert 3. Die aktuelle 5. Edition des ACR-BI-RADS-Katalogs offenbart neben diesen weiterhin bestehenden inhaltlichen Unterschieden zudem das Problem der formalen Lizenzierung, wird aber inhaltlich von der DEGUM als weiteres Befundbeschreibungs- und Dokumentationssystem anerkannt.Der Arbeitskreis Mammasonografie der DEGUM beabsichtigt mit der „Best Practice Guideline“, den senologisch tätigen Kolleginnen und Kollegen einen aktuellen Dignitätskriterien- und Befundungskatalog sowie „Best Practice“-Empfehlungen zu den verschiedenen Modalitäten an die Hand zu geben.

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 key endpoint of the prospective IRMA trial was to evaluate the association between Recurrence Score® (RS) result and tumor cell dissemination in patients with EBC. 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. 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). 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.

ZusammenfassungDie Mammasonografie hat sich seit vielen Jahren neben der Mammografie als wichtige Methode zur Abklärung von Brustbefunden etabliert.Der Arbeitskreis Mammasonografie der DEGUM beabsichtigt mit der „Best Practice Guideline“ den senologisch tätigen Kolleginnen und Kollegen neben dem in Teil I publizierten aktuellen Dignitätskriterien- und Befundungskatalog in dem vorliegenden Teil II die additiven und fakultativen Anwendungsmodalitäten zur Abklärung von Brustbefunden zu beschreiben und dazu DEGUM-Empfehlungen zu äußern, um die Differenzialdiagnose von unklaren Läsionen zu erleichtern.Die vorliegende „Best Practice Guideline“ hat sich zum Ziel gesetzt, den Anforderungen zur Qualitätssicherung und der Gewährleistung einer qualitätskontrollierten Durchführung der Mammasonografie nachzukommen. Die wichtigsten Aspekte der Qualitätssicherung werden in diesem Teil II der Best Practice Guideline erläutert.

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 [18F]Fluorodeoxyglucose ([18F]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 [18F]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.

Detailed description of mean and max value analysis of ADC and [18F]FDG data of tumors of tg(PyV-mT) mice.

Mean (blue) and maximal (red) ADC and [18F]FDG uptake values of the same representative 8 tumors: VOIs were drawn on the basis of the T2-weighted TSE MRI data, and transferred to the appropriate PET and ADC data. The mean and max values were determined. The comparison between mean or maximal values between the tumors revealed different trends.

Supplemental Table I is a list of abbreviations, Supplemental Table II contains the classification parameters for the different phenotypes in the mouse model and Supplemental Table III contains a summary of clinical data correlating image-derived and histology-derived tumor volumes.

More detailed description of ex-vivo procedures of mouse tumor samples

Background Dendritic cells (DC), the most potent professional antigen presenting cells capable of effective cross-presentation, have been demonstrated to license T helper cells to induce antitumor immunity in solid tumors. Specific DC subtypes are recruited to the injured brain by microglial chemokines, locally adapting to distinct transcriptional profiles. In isocitrate dehydrogenase (IDH) type 1 mutant gliomas, monocyte-derived macrophages have recently been shown to display an attenuated intratumoral antigen presentation capacity as consequence of the local accumulation of the oncometabolite R-2-hydroxyglutarate. The functionality and the contribution of DC to the IDH-mutant tumor microenvironment (TME) remains unclear. Methods Frequencies and intratumoral phenotypes of human DC in IDH-wildtype (IDHwt) and -mutant high-grade gliomas are comparatively assessed by transcriptomic and proteomic profiling. DC functionality is investigated in experimental murine glioblastomas expressing the model antigen ovalbumin. Single-cell sequencing-based pseudotime analyses and spectral flow cytometric analyses are used to profile DC states longitudinally. Results DC are present in primary and recurrent high-grade gliomas and interact with other immune cell types within the TME. In murine glioblastomas, we find an IDH-status-associated major histocompatibility class I-restricted cross-presentation of tumor antigens by DC specifically in the tumor but not in meninges or secondary lymphoid organs of tumor-bearing animals. In single-cell sequencing-based pseudotime and longitudinal spectral flow cytometric analyses, we demonstrate an IDH-status-dependent differential, exclusively microenvironmental education of DC. Conclusions Glioma-associated DCs are relevantly abundant in human IDHwt and mutant tumors. Glioma IDH mutations result in specifically educated, dysfunctional DCs via paracrine reprogramming of infiltrating monocytes, providing the basis for combinatorial immunotherapy concepts against IDH mutant gliomas.

Background: Breast ultrasound identifies additional carcinomas not detected in mammography, but has a higher rate of false-positive findings which result in more unnecessary breast biopsies. Shear-Wave Elastography (SWE), an ultrasound technique used to quantify the stiffness of a lesion, showed promising results to improve the diagnostic performance of B-mode breast ultrasound but also to miss some cancers. As the stiffness of a lesion is found to be influenced by individual patient characteristics, incorporation of lesion stiffness in more individualized assessments may be key to the problem of reducing unnecessary breast biopsies without impairing the breast cancer detection rate. Thus, in this study, we evaluated whether an intelligent algorithm incorporating traditional SWE values as well as other patient and clinical variables (hereafter “intelligent SWE”) could reduce the number of unnecessary breast biopsies without impairing the breast cancer detection rate compared to traditional SWE and B-mode breast ultrasound for patients with suspicious breast lesions. Methods: We trained, tested, and validated machine learning algorithms using patient, clinical, ultrasound, and SWE information to classify breast masses. We used international, multicenter data from 857 women with BI-RADS 4 breast masses at 12 study sites in 7 countries. Patients underwent B-mode breast ultrasound, SWE, and subsequent histopathologic evaluation. 10-fold cross-validation was used to train and test the algorithms on data from 11 of the 12 sites which were further validated using the additional site’s data. The results of B-mode breast ultrasound, traditional SWE, and intelligent SWE were compared to the gold standard of histopathologic evaluation. We calculated sensitivity, specificity, and AUROC and used McNemar tests to test for significant differences in diagnostic performance. Results: The mean age was 49.5 years (SD 16.3) and 42.2% breast masses (n=362 of 857) were found to be malignant as confirmed by histopathology. In the external validation set (n=285), traditional SWE showed a significantly higher diagnostic performance compared to B-mode breast ultrasound (P < 0.001), whereas intelligent SWE outperformed both B-mode breast ultrasound and traditional SWE (P < 0.001). The neural network algorithm showed a significantly higher diagnostic performance compared to the Logistic Regression with Elastic Net Penalty (P = 0.004). The neural network algorithm achieved a sensitivity of 100% (95% CI 97.1 to 100%, 126 of 126) and a specificity of 50.3% (95% CI 42.3 to 58.3%, 80 of 159); the number of unnecessary biopsies were reduced by 50.3% (79 vs. 159) without missing any cancer compared to B-mode breast ultrasound. Model-agnostic variable importance plots to provide insights into the model predictions showed that the three most important variables for intelligent SWE were patient age followed by Shear-Wave velocity and orientation of the lesion (parallel vs. not parallel) in B-mode ultrasound. Conclusion: This is the first evidence which suggests that the majority of false-positive breast biopsies could be safely avoided by using intelligent SWE without impairing breast cancer detection rates. These results may be helpful in their ability to reduce treatment burden for patients, providers, and healthcare systems. Trial registration: NCT02638935. Funding: Siemens Medical Solutions USA, Inc Diagnostic Performance ComparisonB-mode Breast UltrasoundTraditional Shear-Wave ElastographyIntelligent Shear-Wave Elastography – Logistic Regression with Elastic Net PenaltyIntelligent Shear-Wave Elastography – neural networkAUROC – value (95% CI)–0.84 (0.79-0.89)0.93 (0.90-0.95)0.93 (0.90-0.96)Sensitivity – % (95% CI); no.100% (97.1-100%); 126 of 12697.6% (93.2-99.5%); 123 of 126100% (97.1-100%); 126 of 126100% (97.1-100%); 126 of 126Specificity – % (95% CI); no.0% (0.0-2.3%); 0 of 15923.9% (17.5-31.3%); 38 of 15936.5% (29.0-44.5%); 58 of 15950.3% (42.3-58.3%); 80 of 159Negative predictive value – % (95% CI); no.–92.7% (80.1-98.5%); 38 of 41100% (93.8-100%); 58 of 58100% (95.5-100%); 80 of 80Positive predictive value – % (95% CI); no.44.2% (38.4-50.2); 126 of 28550.4% (44.0-56.8%); 123 of 24455.5% (48.8-62.1%); 126 of 22761.5% (54.4-68.2%); 126 of 205 Citation Format: André Pfob, Chris Sidey-Gibbons, Richard G. Barr, Volker Duda, Zaher Alwafai, Corinne Balleyguier, Dirk-André Clevert, Sarah Fastner, Christina Gomez, Manuela Goncalo, Ines Gruber, Markus Hahn, André Hennigs, Chi Ho, Panagiotis Kapetas, Sheng-Chieh Lu, Juliane Nees, Ralf Ohlinger, Fabian Riedel, Matthieu Rutten, Benedikt Schaefgen, Anne Stieber, Riku Togawa, Mitsuhiro Tozaki, Sebastian Wojcinski, Cai Xu, Geraldine Rauch, Joerg Heil, Michael Golatta. Intelligent shear-wave elastography to reduce unnecessary biopsies in breast cancer diagnosis (INSPiRED 002): An international, multicenter analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD11-05.

Simple Summary Most breast cancers are small and can be treated using breast-conserving surgery. Since these tumors are non-palpable, they require a localization step that helps the surgeon to decide which tissue needs to be removed. The oldest localization technique is a guidewire placed into the tumor before surgery, usually using ultrasound or mammography. Afterwards, the surgeon removes the tissue around the wire tip. However, this technique has several disadvantages: It can cause the patient discomfort, requires a radiologist or another professional specialized in breast diagnostics to perform the procedure shortly before surgery, and 15-20% of patients need a second surgery to completely remove the tumor. Therefore, new techniques have been developed but most of them have not yet been examined in large, prospective, multicenter studies. In this review, we discuss all available techniques and present the MELODY study that will investigate their safety, with a focus on patient, surgeon, and radiologist preference. Background: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. Methods: We performed a systematic review on localization techniques for non-palpable breast cancer. Results: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons\" and radiologists\" attitudes towards these techniques. Conclusions: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.

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.

Background ABP 980 is a biosimilar antibody to reference trastuzumab (RTZ). Aim of the following study is to confirm the similarity of ABP 980 and RTZ in terms of clinical efficacy and safety in patients with HER2-positive early breast cancer (EBC) undergoing neoadjuvant trastuzumab-containing chemotherapy in a clinical real-world situation that also includes patients receiving pertuzumab. Methods Patients with HER2-positive EBC, who were treated from 12/2010 to 03/2020 at the Department of Women’s Health at Tuebingen University Hospital, Germany, with at least four cycles of neoadjuvant chemotherapy (+/− pertuzumab) in combination with ABP 980 or RTZ were included in a retrospective analysis. For efficacy analysis patients achieving a pathologic complete remission (pCR = no invasive tumor in breast and lymph nodes) were compared. Safety was evaluated by comparing the number of patients with a decrease in left ventricular function (LVEF) of > 10%. Results 124 patients were included of whom 46 (37.1%) have received ABP 980 and 77 (62.9%) were treated with RTZ. A pCR was found in 77 patients (62.1%). For patients treated with ABP 980 as compared to RTZ, there was no significant difference regarding efficacy (pCR-rates of 60.9% versus 62.8%, p = 0.829) or cardiac safety (LVEF decline in 6.5% versus 2.6%, p = 0.274). Conclusion Similarity of ABP 980 as compared to RTZ was confirmed in a real-world situation, including a large proportion of patients that have also received pertuzumab treatment.

Zusammenfassung Einleitung Multigen-Assays werden zunehmend als Entscheidungshilfe für eine Chemotherapie beim Mammakarzinom verwendet. Wir stellen hier den 21-Gen-Recurrence-Score (RS) von Patientinnen mit Brustkrebs vor, die routinemäßig in Deutschland untersucht wurden. Patientinnen und Methoden 4695 Patientinnen mit hormonrezeptorpositivem und HER2-negativem Brustkrebs im Frühstadium (pT1–3, pN0–1, M0) wurden einer retrospektiven Analyse unterzogen. Bei diesen Patientinnen wurde in Deutschland zwischen November 2015 und Juli 2018 der Genexpressionstest Oncotype DX zur Ermittlung des Recurrence-Scores durchgeführt. Die Klassifikation der RS-Gruppen erfolgte gemäß der TAILORx Studie (RS: 0–10; 11–25; 26–100). Ergebnisse Von diesen Patientinnen wurden 21 % in die niedrige RS-Gruppe, 63 % in die mittlere RS-Gruppe, und 15 % in die hohe RS-Gruppe eingeteilt. 1772 (81 %) von 2175 Patientinnen im Alter von über 50 Jahren und ohne Lymphknotenbefall wurden entweder in die niedrige oder die mittlere RS-Gruppe eingeteilt. Der Prozentsatz an Patientinnen mit einem niedrigen oder mittleren RS betrug 90 % bei Patientinnen ohne Lymphknotenbefall (1284 von 1432 Patientinnen), 79 % bei Patientinnen mit einem hohen (≥ 20 %) Ki-67-Wert (1829 von 2310 Patientinnen), 86 % bzw. 70 % bei Patientinnen mit G2- bzw. G3-Tumoren (3244 von 3762 Patientinnen bzw. 368 von 522 Patientinnen), 88 % bei Patientinnen mit einem Tumordurchmesser von > 5 cm (140 von 159 Patientinnen) und 82 % bei Patientinnen ohne Lymphknotenbefall, aber mit einem hohen klinischen Risiko (1110 von 1352). Schlussfolgerung Die Verteilung des 21-Gens RS bei deutschen Patientinnen, die in der klinischen Routinepraxis getestet wurden, deutet darauf hin, dass gemäß den Ergebnissen der TAILORx-Studie die Chemotherapie bei den meisten dieser Patientinnen keinen Nutzen hat.

Zusammenfassung Einleitung Narbige Verengungen und ein Volumendefizit im Bereich der Axilla können zu einem anhaltenden Lymphödem führen und zählen zu den häufigsten Nebenwirkungen nach einer Brustkrebstherapie im Achselbereich. Ziel dieser Arbeit ist die Vorstellung einer Operationstechnik zur Reduzierung von Lymphödemen mithilfe eines Turn-Over Flaps. Material und Methoden Zwischen Oktober 2016 und Mai 2018 wurden 5 Patientinnen mit einem Lymphödem Grad 2 nach Mammakarzinomtherapie mit dieser neuen Methode behandelt. Dabei erfolgte die vollständige Entfernung der kompromittierenden Narbenstränge der Axilla, gefolgt von einer Reaugmentation der Axilla mittels Turn-Over Flap. Danach wurde bei allen Patientinnen eine Brustrekonstruktion mit einer an die thorakodorsalen Gefäße angeschlossenen Fernlappenplastik durchgeführt. Prä- und postoperativ wurden der Umfang beider Arme, die Lebensqualität und die Schmerzen gemessen. Ergebnisse Im Durchschnitt sanken die Schmerzen im ipsilateralen Arm von 6 auf 1 auf der numerischen Schmerzskala, und die Lebensqualität verbesserte sich merklich (2,8 vs. 7,0). Es zeigte sich eine deutliche Verringerung des Lymphödems, vor allem im Oberarm. Komplikationen wie sekundäre Blutungen, Infektionen oder Lappenverlust sind nicht aufgetreten. Schlussfolgerung Eine vollständige Entfernung der nach Brustkrebsbehandlungen entstandenen Vernarbungen im Bereich der Axilla und eine Reaugmentation der Axilla mittels Turn-Over Flap führten zu einer Verringerung des ipsilateralen Lymphödems und zu einer Verbesserung der Schmerzen und der Lebensqualität. Wir deuten dieses Outcome als Ergebnis der physiologischen Ausrichtung der Lymphgefäße und eines lymphknotenhaltigen Transpositionslappens. Die Reaugmentation der Axilla mittels Turn-Over Flap könnte eine wirksame, nicht mikrochirurgische Alternative zur Lymphknotentransplantation darstellen.

Patients with hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer (eBC) with a high risk of relapse often undergo adjuvant chemotherapy. However, only a few patients will gain benefit from chemotherapy. Since classical tumor characteristics (grade, tumor size, lymph node involvement, and Ki67) are of limited value to predict chemotherapy efficacy, multigene expression assays such as the Oncotype DXThe RS result was assessed in patients with HR+/HER2- unilateral eBC with 0-3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women's Health of Tuebingen University, Germany. Therapy recommendations without knowledge of the RS result were compared to therapy recommendations with awareness of the RS result.In total, 245 patients underwent RS assessment. Without knowledge of the RS result, 92/245 patients (37.6%) would have been advised to receive chemotherapy. After RS assessment, 56/245 patients (22.9%) were advised to undergo chemotherapy. Chemotherapy was waived in 47/92 patients (51.1%) that were initially recommended to receive it. Chemotherapy was added in 11/153 patients (7.2%) that were recommended to not receive it initially.Using the RS result to guide adjuvant treatment decisions in HR+/HER2- breast cancer led to a substantial reduction of chemotherapy. In view of the results achieved in prospective studies, the RS result is among other risk-factors suitable for the individualization of adjuvant systemic therapy.