Surgical staging procedures of the axilla in initially clinically node-positive (cN +) breast cancer patients receiving neoadjuvant chemotherapy (NACT) vary across countries. Different procedures such as axillary lymph node dissection, sentinel lymph node biopsy, target lymph node biopsy and targeted axillary dissection are currently in use. To date, data on radar reflectors as a non-wire and non-radioactive technique for marking target lymph nodes are limited. The present study aims at examining the detection rate, the rate of lost markers, and magnetic resonance imaging artifacts after TLN marking using a radar reflector before NACT in the largest available cohort of breast cancer patients enrolled in the international prospective AXSANA study. AXSANA (EUBREAST-03) is an international prospective cohort study including cN + patients managed with different surgical axillary staging techniques after NACT. Eligible patients have cT1-4c cN + breast cancer and receive neoadjuvant chemotherapy. Patients are followed up for 5 years. In the present subgroup analysis, only patients with a TLN marked by a radar reflector were included. A TLN was marked by radar reflector insertion in 158 patients prior to NACT. Of these, 136 had final surgery results available at the time of analysis, and in 135 out of these 136 patients, localization of TLN was attempted. All radar markers were successfully removed. While lymphoid tissue corresponding to the TLN was identified in 132 patients (97.8

Prognostic markers in routine clinical management of breast cancer are often assessed using RNA-based multi-gene panels that depend on fluctuating tumor purity. Multiplex fluorescence immunohistochemistry (mfIHC) holds the potential for an improved risk assessment. To enable automated prognosis marker detection (i.e., progesterone receptor [PR], estrogen receptor [ER], androgen receptor [AR], GATA3, TROP2, HER2, PD-L1, Ki67, TOP2A), a framework for automated breast cancer identification was developed and validated involving thirteen different artificial intelligence analysis steps and an algorithm for cell distance analysis using 11+1-marker-BLEACH&STAIN-mfIHC staining in 1404 invasive breast cancers of no special type (NST). The framework for automated breast cancer detection discriminated normal glands from malignant glands with an accuracy of 98.4%. This approach identified that five (PR, ER, AR, GATA3, PD-L1) of nine biomarkers were associated with prolonged overall survival (p ≤ 0.0095 each) and two of these (PR, AR) were found to be independent risk factors in multivariate analysis (p ≤ 0.0151 each). The combined assessment of PR-ER-AR-GATA3-PD-L1 as a five-marker prognosis score showed strong prognostic relevance (p < 0.0001) and was an independent risk factor in multivariate analysis (p = 0.0034). Automated breast cancer detection in combination with an artificial intelligence-based analysis of mfIHC enables a rapid and reliable analysis of multiple prognostic parameters. The strict limitation of the analysis to malignant cells excludes the impact of fluctuating tumor purity on assay precision.

To study the extent of heterogeneity of mesothelin overexpression in primary ovarian cancers and their peritoneal and lymph node metastases, a tissue microarray (TMA) was constructed from multiple sites of 220 ovarian cancers and analyzed by immunohistochemistry. One tissue core each was taken from up to 18 different tumor blocks per cancer, resulting in a total of 2460 tissue spots from 423 tumor sites (188 primary cancers, 162 peritoneal carcinosis, and 73 lymph node metastases). Positive mesothelin expression was found in 2041 of the 2342 (87%) arrayed tissue spots and in 372 of the 392 (95%) tumor sites that were interpretable for mesothelin immunohistochemistry. Intratumoral heterogeneity was found in 23% of 168 primary cancer sites interpretable for mesothelin and decreased to 12% in 154 peritoneal carcinosis and to 6% in 71 lymph node metastases (P<0.0001). Heterogeneity between the primary tumor and matched peritoneal carcinosis was found in 16% of 102 cancers with interpretable mesothelin results. In these cancers, the mesothelin status switched from positive in the primary tumor to negative in the peritoneal carcinosis (3 cancers) in or vice versa (2 cancers), or a mixture of positive and negative peritoneal carcinoses was found (11 cancers). No such switch was seen between the mesothelin-interpretable primary tumors and their nodal metastases of 59 cancers, and only 1 mesothelin-positive tumor had a mixture of positive and negative lymph node metastases. In conclusion, mesothelin expression is frequent and highly homogeneous in ovarian cancer.

Purpose The use of autologous tissues is considered gold standard for patients undergoing breast reconstruction and is the preferred method in the post-radiation setting. Although the latissimus dorsi flap (LDF) has been replaced by abdominal flaps as technique of choice, it remains a valuable option in several specific clinical situations and its use has been regaining popularity in recent years. In this work, we present an 18-year retrospective analysis of a single-institution single-surgeon experience with LDF-based reconstruction with focus on early complications and reconstructive failures. Methods Hospital records of all patients undergoing breast surgery for any reason in the Certified Breast Cancer Center, Regio Klinikum Pinneberg, Germany between April, 1st 2005 and October, 31st 2022 were reviewed. 142 consecutive LDF-based reconstructive procedures were identified. Detailed information was gathered on patient characteristics, treatment-related factors, and complications. Results One hundred forty patients (139 female, 1 male) received 142 LDF-based surgeries. The flap was used mainly for immediate breast reconstruction with or without implant (83% of patients), followed by defect coverage after removal of a large tumor (7%), implant-to-flap conversion with or without placement of a new implant (6%), and delayed post-mastectomy reconstruction (4%). The use of LDF decreased between 2005 and 2020 (2005: 17, 2006: 13, 2007: 14, 2008: 16, 2009: 5, 2010: 9, 2011: 8, 2012: 3, 2013: 10, 2014: 8, 2015: 8, 2016: 7, 2017: 7, 2018: 4, 2019: 4, 2020: 2, 2021: 6, 2022: 4). Surgery was performed for invasive breast cancer in 78%, ductal carcinoma in situ in 20% and other reasons such as genetic mutation in 1% of patients. Ipsilateral radiation therapy was received by 12% of patients prior to LDF surgery and by 37% after the surgery. 25% of patients were smokers. The median duration of surgery, including all procedures conducted simultaneously such as e.g., mastectomy, axillary surgery, or implant placement, was 117 min (range 56–205). Patients stayed in the hospital for a median of 7 days (range 2–23 days). The most common complication was seroma (26%), followed by wound dehiscence (8%), surgical site infection (7%), partial skin and/or nipple necrosis of any size (7%) and hematoma requiring surgical evacuation (2%). 19% of all patients required seroma aspiration or drainage, mostly at the donor site and performed under ultrasound guidance in the ambulatory setting. Flap loss due to necrosis occurred in 2% of patients. Conclusions Latissimus dorsi flap is a well-established surgical technique commonly used for immediate breast reconstruction as well as defect coverage in locally advanced breast cancer. To the best of our knowledge, this is one of the largest single-surgeon analyses of early complications in patients receiving LDF. As expected, seroma was the most common complication observed in nearly one third of patients and requiring a therapeutic intervention in every fifth patient. Serious adverse events occurred rarely, and flap loss rate was very low.

Background: Mesothelin is a glycosylphosphatidylinositol-anchored cell surface protein of widely unknown function that may play a role in tumor growth control. Because mesothelin is overexpressed in a variety of human cancer types including ovarian cancers, it represents an attractive target for novel therapies employing adaptive T-cell transfer in these tumors. However, tumor heterogeneity is a challenge for targeted therapies. Methods: To study the extent of heterogeneity of mesothelin overexpression in primary ovarian cancers and their peritoneal and lymph node metastases, a tissue microarray (TMA) was constructed from multiple sites of 220 ovarian cancers and analyzed by immunohistochemistry. One tissue core each was taken from up to 18 different tumor blocks per cancer, resulting in a total of 2,460 tissue spots from 423 tumor sites (188 primary cancers, 162 peritoneal carcinosis and 73 lymph node metastases). Results: Positive mesothelin expression was found in 2,041 of the 2,342 (87%) arrayed tissue spots and in 372 of the 392 (95%) tumor sites that were interpretable for mesothelin immunohistochemistry. Intratumoral heterogeneity was found in 23% of 168 primary cancer sites interpretable for mesothelin and decreased to 12% in 154 peritoneal carcinosis and to 6% in 71 lymph node metastases (p<0.0001). Heterogeneity between the primary tumor and matched peritoneal carcinosis was found in 16% of 102 cancers with interpretable mesothelin results. In these cancers, the mesothelin status switched from positive in the primary tumor to negative in the peritoneal carcinosis (3 cancers) in or vice versa (2 cancers), or a mixture of positive and negative peritoneal carcinoses was found (11 cancers). No such switch was seen between the mesothelin-interpretable primary tumors and their nodal metastases of 59 cancers, and only one mesothelin-positive tumor had a mixture of positive and negative lymph node metastases. Conclusions: Our data demonstrate that mesothelin expression is frequent and highly homogeneous in ovarian cancer and prompt for future anti-mesothelin therapy studies in this tumor type. Citation Format: Sören Weidemann, Natalia Gorbokon, Maximilian Lennartz, Claudia Hube-Magg, Christoph Fraune, Christian Bernreuther, Till Clauditz, Frank Jacobsen, Kristina Jansen, Barbara Schmalfeldt, Linn Wölber, Peter Paluchowski, Enikö Berkes, Uwe Heilenkötter, Guido Sauter, Ria Uhlig, Waldemar Wilczak, Stefan Steurer, Ronald Simon, Till Krech, Andreas Marx, Eike Burandt. High homogeneity of mesothelin expressionin primary and metastatic ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3303.

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.

The 'twinkle' or 'twinkling' artifact represents a phenomenon observed using color Doppler ultrasound that leads to a rapid alternation of color in and immediately behind an echogenic and highly reflective object. It occurs during sonographic examination of kidney stones, and has been also described in clips used for marking breast and axillary lesions.

Circulating tumor cells (CTCs) have emerged as a promising new biomarker in breast cancer and various settings in which liquid biopsy may improve diagnostics are currently under discussion. In patients with metastatic disease, high CTC counts have been shown to predict poor prognosis with level I evidence. Persistence of elevated CTC numbers after begin of systemic treatment is associated with higher risk of progression. This review discusses current evidence on the clinical use of CTC diagnostics in metastatic breast cancer.

Zusammenfassung Drahtlokalisation 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.

Purpose In the last 2 decades, the optimal management of the axilla in breast cancer patients receiving neoadjuvant chemotherapy (NACT) has been one of the most frequently discussed topics. Little is known about the attitudes of surgeons/radiologists towards new developments such as targeted axillary dissection. Therefore, the NOGGO conducted a survey to evaluate the current approach to axillary management. Methods A standardized digital questionnaire was sent out to > 200 departments in Germany between 7/2021 and 5/2022. The survey was supported by EUBREAST. Results In total, 116 physicians completed the survey. In cN0 patients scheduled to receive NACT, 89% of respondents recommended sentinel lymph node biopsy (SLNB) after NACT. In case of ypN1mi(sn), 44% advised no further therapy, while 31% proposed ALND and 25% axillary irradiation. 64% of respondents recommended a minimally invasive axillary biopsy to cN + patients. TAD was used at the departments of 82% of respondents and was offered to all cN + patients converting to ycN0 by 57% and only to selected patients, usually based on the number of suspicious nodes at time of presentation, by 43%. The most common marking technique was a clip/coil. 67% estimated that the detection rate of their marker was very good or good. Conclusion This survey shows a heterogenous approach towards axillary management in the neoadjuvant setting in Germany. Most respondents follow current guidelines. Since only two-thirds of respondents experienced the detection rate of the marker used at their department as (very) good, future studies should focus on the comparative evaluation of different marking techniques.

Zusammenfassung Einleitung Das optimale axilläre Stagingverfahren für initial nodal positive MammakarzinompatientInnen nach neoadjuvanter Chemotherapie (NACT) ist bislang unklar. Die AXSANA-Studie wird mit dem Ziel durchgeführt, die verschiedenen operativen Stagingtechniken hinsichtlich ihres onkologischen Outcomes und der Lebensqualität prospektiv miteinander zu vergleichen. Über die aktuelle klinische Praxis in Deutschland ist wenig bekannt. Material und Methoden Die Daten der von Juni 2020 bis März 2022 an deutschen Studienzentren in die AXSANA-Studie aufgenommenen PatientInnen wurden analysiert. Ergebnisse Im Untersuchungszeitraum wurden 1135 PatientInnen an 143 Studienstandorten rekrutiert. Bei 22 % der PatientInnen fanden sich initial mehr als 3 suspekte Lymphknoten. In 64 % der Fälle wurde der Target-Lymphknoten (TLN) markiert. Dabei erfolgte die Markierung bei 83 % der PatientInnen mit Clips/Coils, bei je 8 % mit magnetischen Seeds oder Kohlenstoffsuspension und bei 1 % mit einem Radarmarker. Bei jeweils 48 % der PatientInnen wurde nach NACT eine Targeted Axillary Dissection (TAD) oder eine axilläre Lymphonodektomie (ALND) geplant, bei 2 % eine alleinige Sentinel-Lymphknoten-Biopsie (SLNB). Klinisch wurde der Nodalstatus nach NACT in 65 % der Fälle als unauffällig beurteilt. Bei 65 % der Frauen wurde der histologische Lymphknotenstatus durch die Palpation und bei 69 % der PatientInnen durch die Sonografie korrekt erfasst. Schlussfolgerung An den deutschen AXSANA-Studienzentren werden derzeit die TAD und die ALND als häufigste operative Stagingverfahren nach NACT bei primär nodal positiven MammakarzinompatientInnen durchgeführt, wobei die Markierung des TLN vor NACT mit verschiedenen Markern erfolgt. Aufgrund der ungenügenden Genauigkeit der klinischen Beurteilung des axillären Lymphknotenstatus nach NACT sollte kritisch hinterfragt werden, ob eine Axilladissektion nach NACT auf der Grundlage einer alleinigen klinischen Bewertung des Nodalstatus erfolgen sollte.

Introduction To date, the optimal axillary staging procedure for initially node-positive breast carcinoma patients after neo-adjuvant chemotherapy ( NACT) has been unclear. The aim of the AXSANA study is to prospectively compare different surgical staging techniques with respect to the oncological outcome and quality of life for the patients. Little is known about current clinical practice in Germany. Material and Methods In this paper we analyzed data from patients enrolled in the AXSANA study at German study sites from June 2020 to March 2022. Results During the period under investigation, 1135 patients were recruited at 143 study sites. More than three suspicious lymph nodes were initially found in 22% of patients. The target lymph node (TLN) was marked in 64% of cases. This was done with clips/coils in 83% of patients, with magnetic seeds or carbon suspension in 8% each, and with a radar marker in 1% of patients. After NACT, targeted axillary dissection (TAD) or axillary lymphadenectomy (ALND) were each planned in 48% of patients, and sentinel lymph node biopsy alone (SLNB) in 2%. Clinically, the nodal status after NACT was found to be unremarkable in 65% of cases. Histological lymph node status was correctly assessed by palpation in 65% of patients and by sonography in 69% of patients. Conclusion At the German AXSANA study sites, TAD and ALND are currently used as the most common surgical staging procedures after NACT in initially node-positive breast cancer patients. The TLN is marked with various markers prior to NACT. Given the inadequate accuracy of clinical assessment of axillary lymph node status after NACT, it should be questioned whether axillary dissection after NACT should be performed based on clinical assessment of nodal status alone.

Background Deletions involving the long arm of chromosome 6 have been reported to occur in breast cancer, but little is known about the clinical relevance of this alteration. Methods We made use of a pre-existing tissue microarray with 2197 breast cancers and employed a 6q15/centromere 6 dual-labeling probe for fluorescence in situ (FISH) analysis Results Heterozygous 6q15 deletions were found in 202 (18%) of 1099 interpretable cancers, including 19% of 804 cancers of no special type (NST), 3% of 29 lobular cancers, 7% of 41 cribriform cancers, and 28% of 18 cancers with papillary features. Homozygous deletions were not detected. In the largest subset of NST tumors, 6q15 deletions were significantly linked to advanced tumor stage and high grade ( p < 0.0001 each). 6q deletions were also associated with estrogen receptor negativity ( p = 0.0182), high Ki67 proliferation index ( p < 0.0001), amplifications of HER2 ( p = 0.0159), CCND1 ( p = 0.0069), and cMYC ( p = 0.0411), as well as deletions of PTEN ( p = 0.0003), 8p21 ( p < 0.0001), and 9p21 ( p = 0.0179). However, 6q15 deletion was unrelated to patient survival in all cancers, in NST cancers, or in subsets of cancers defined by the presence or absence of lymph-node metastases. Conclusion Our data demonstrate that 6q deletion is a frequent event in breast cancer that is statistically linked to unfavorable tumor phenotype and features of genomic instability. The absence of any prognostic impact argues against a clinical applicability of 6q15 deletion testing in breast cancer patients.

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).

Hintergrund. Während die Indikation zur (neo-)adjuvanten Chemotherapie bei tripelnegativem und/oder HER2-positivem Mammakarzinom in der Regel klar zu stellen ist, wird bei luminalen Tumoren nach wie vor nach prädiktiven Markern gesucht, um die Frage der Notwendigkeit einer Chemotherapie individuell beantworten zu können. Hier kann das Hinzuziehen eines Genexpressionsprofils, insbesondere bei intermediärem klinischem Rückfallrisiko, hilfreich und für die Therapieentscheidung wegweisend sein. Nach den Daten der TAILORx-Studie konnte diese Fragestellung für nodal-negative Frauen im prospektiven, randomisierten Setting weitgehend geklärt werden [1]. Allerdings blieb das Vorgehen bei Patientinnen mit moderatem Nodalbefall (1–3 befallene Lymphknoten) weiterhin unklar. Gleichzeitig zeigten die Ergebnisse anderer Untersuchungen, z.B. der Plan-B-Studie, dass bei vielen Frauenmit luminalen Tumoren trotz des Nodalbefalls auf eine Chemotherapie verzichtet werden kann. Vor diesem Hintergrund wurden die auf dem diesjährigen San Antonio Breast Cancer Symposium präsentierten Ergebnisse der prospektiven, randomisierten RxPONDER-Studie besonders aufmerksam erwartet.

Mucin 5AC (MUC5AC) is a secreted gel-forming mucin which is expressed by mucus producing cells of several organs but can also be found in cancer cells of the ovary, pancreas, and gastrointestinal tract. This study aimed to characterize the expression of MUC5AC and its potential prognostic implications in different ovarian cancer subtypes. MUC5AC expression was analyzed by immunohistochemistry on a tissue microarray containing 603 ovarian cancers. MUC5AC was commonly expressed in mucinous (27/36; 75%) and endometrioid (12/39; 31%) carcinomas, whereas malignant mixed Mullerian tumors (2/27; 7%), high-grade serous (20/373; 5%) and clear cell carcinomas (1/28; 4%) were only rarely MUC5AC positive and also showed lower expression levels. MUC5AC positive endometroid carcinomas and high-grade serous carcinomas lacked lymph node metastases (p = 0.0495 and p = 0.0216) suggesting a more favorable prognosis. Deficient mismatch repair (dMMR), associated with a favorable prognosis in different cancer types, was found in 4/39 (10%) MUC5AC positive cancers but in only 5/375 (1%) of MUC5AC negative cancers (p = 0.0052). In subgroup analyses MUC5AC positive endometroid carcinomas more frequently showed dMMR (4/10; 40%) as opposed to MUC5AC negative endometroid carcinomas (3/23; 13%; p = 0.0932). In summary, the results of our study show that MUC5AC expression is associated with mucinous and endometrioid ovarian carcinomas, lack of nodal metastases and dMMR. MUC5AC expressing ovarian cancers should be evaluated for dMMR.

Abstract Introduction To date, the optimal axillary staging procedure for initially node-positive breast carcinoma patients after neoadjuvant chemotherapy (NACT) has been unclear. The aim of the AXSANA study is to prospectively compare different surgical staging techniques with respect to the oncological outcome and quality of life for the patients. Little is known about current clinical practice in Germany. Material and Methods In this paper we analyzed data from patients enrolled in the AXSANA study at German study sites from June 2020 to March 2022. Results During the period under investigation, 1135 patients were recruited at 143 study sites. More than three suspicious lymph nodes were initially found in 22% of patients. The target lymph node (TLN) was marked in 64% of cases. This was done with clips/coils in 83% of patients, with magnetic seeds or carbon suspension in 8% each, and with a radar marker in 1% of patients. After NACT, targeted axillary dissection (TAD) or axillary lymphadenectomy (ALND) were each planned in 48% of patients, and sentinel lymph node biopsy alone (SLNB) in 2%. Clinically, the nodal status after NACT was found to be unremarkable in 65% of cases. Histological lymph node status was correctly assessed by palpation in 65% of patients and by sonography in 69% of patients. Conclusion At the German AXSANA study sites, TAD and ALND are currently used as the most common surgical staging procedures after NACT in initially node-positive breast cancer patients. The TLN is marked with various markers prior to NACT. Given the inadequate accuracy of clinical assessment of axillary lymph node status after NACT, it should be questioned whether axillary dissection after NACT should be performed based on clinical assessment of nodal status alone. Zusammenfassung Einleitung Das optimale axilläre Stagingverfahren für initial nodal positive MammakarzinompatientInnen nach neoadjuvanter Chemotherapie (NACT) ist bislang unklar. Die AXSANA-Studie wird mit dem Ziel durchgeführt, die verschiedenen operativen Stagingtechniken hinsichtlich ihres onkologischen Outcomes und der Lebensqualität prospektiv miteinander zu vergleichen. Über die aktuelle klinische Praxis in Deutschland ist wenig bekannt. Material und Methoden Die Daten der von Juni 2020 bis März 2022 an deutschen Studienzentren in die AXSANA-Studie aufgenommenen PatientInnen wurden analysiert. Ergebnisse Im Untersuchungszeitraum wurden 1135 PatientInnen an 143 Studienstandorten rekrutiert. Bei 22% der PatientInnen fanden sich initial mehr als 3 suspekte Lymphknoten. In 64% der Fälle wurde der Target-Lymphknoten (TLN) markiert. Dabei erfolgte die Markierung bei 83% der PatientInnen mit Clips/Coils, bei je 8% mit magnetischen Seeds oder Kohlenstoffsuspension und bei 1% mit einem Radarmarker. Bei jeweils 48% der PatientInnen wurde nach NACT eine Targeted Axillary Dissection (TAD) oder eine axilläre Lymphonodektomie (ALND) geplant, bei 2% eine alleinige Sentinel-Lymphknoten-Biopsie (SLNB). Klinisch wurde der Nodalstatus nach NACT in 65% der Fälle als unauffällig beurteilt. Bei 65% der Frauen wurde der histologische Lymphknotenstatus durch die Palpation und bei 69% der PatientInnen durch die Sonografie korrekt erfasst. Schlussfolgerung An den deutschen AXSANA-Studienzentren werden derzeit die TAD und die ALND als häufigste operative Stagingverfahren nach NACT bei primär nodal positiven MammakarzinompatientInnen durchgeführt, wobei die Markierung des TLN vor NACT mit verschiedenen Markern erfolgt. Aufgrund der ungenügenden Genauigkeit der klinischen Beurteilung des axillären Lymphknotenstatus nach NACT sollte kritisch hinterfragt werden, ob eine Axilladissektion nach NACT auf der Grundlage einer alleinigen klinischen Bewertung des Nodalstatus erfolgen sollte.

Mitochondria are relevant for cancer initiation and progression. Antibodies against mitochondrially encoded cytochrome c oxidase II (MTCO2), targeting a mitochondria specific epitope, can be used to quantitate the mitochondria content of tumor cells. The present study evaluated the impact of the cellular mitochondrial content on the prognosis of patients with breast cancer using immunohistochemical analysis on 2,197 arrayed breast cancer specimens. Results were compared with histological tumor parameters, patient overall survival, tumor cell proliferation using Ki67 labeling index (Ki67LI) and various other molecular features. Tumor cells exhibited stronger MTCO2 expression than normal breast epithelial cells. MTCO2 immunostaining was largely absent in normal breast epithelium, but was observed in 71.9% of 1,797 analyzable cancer specimens, including 34.6% tumors with weak expression, 22.3% with moderate expression and 15.0% with strong expression. High MTCO2 expression was significantly associated with advanced tumor stage, high Bloom-Richardson-Elston/Nottingham (BRE) grade, nodal metastasis and shorter overall survival (P<0.0001 each). In multivariate analysis, MTCO2 expression did not provide prognostic information independent of BRE grade, pathological tumor and pathological lymph node status. Additionally, significant associations were observed for high MTCO2 expression and various molecular features, including high Ki67LI, amplifications of HER2, MYC, CCND1 and MDM2, deletions of PTEN, 8p21 and 9p, low estrogen receptor expression (P<0.0001 each) and progesterone receptor expression (P<0.0001). The present study demonstrated that high MTCO2 expression was strongly associated with a poor prognosis and unfavorable phenotypical and molecular tumor features in patients with breast cancer. This suggests that the mitochondrial content may have a pivotal role in breast cancer progression.