Axillary clearance and chemotherapy rates in ER+HER2- breast cancer: secondary analysis of the SENOMAC trial.

Background: Randomized trials have shown that axillary clearance (AC) can safely be omitted in patients with sentinel lymph node-positive breast cancer. At the same time, de-escalation of chemotherapy in postmenopausal patients with ER+HER2- breast cancer may depend on detailed axillary nodal stage. The aim of this pre-specified secondary analysis of the SENOMAC trial was to investigate whether the choice of axillary staging affected the proportion of patients receiving adjuvant chemotherapy, and recurrence-free survival (RFS). Methods: Proportion receiving adjuvant chemotherapy was calculated according to AC or sentinel lymph node biopsy (SLNB) only, menopausal status, and region of inclusion, for 2168 patients with clinically node-negative ER+HER2- breast cancer and 1-2 sentinel lymph node macrometastases included in the SENOMAC trial. Findings: In premenopausal patients, 514 out of 615 patients (83.6%) received adjuvant chemotherapy with no significant difference between randomization arms. In postmenopausal patients, the proportion receiving chemotherapy varied considerably by region and country (36.0-82.4%). In Denmark, where 194 out of 539 postmenopausal patients (36.0%) received adjuvant chemotherapy, rates differed significantly between the AC and the SLNB only arm (41.3% vs 31.4%, p = 0.019). After a median follow-up of 44.88 months for Danish postmenopausal patients, no significant difference was seen in 5-year RFS, which was 91% (85.6%-96.6%) for the SLNB only and 90.9% (86.3%-95.6%) for the AC arm (p = 0.42). Interpretation: When omitting axillary clearance, and thus reducing the risk of long-term arm morbidity, potential under-treatment of postmenopausal patients with ER+HER2- breast cancer may require the development of new predictive and imaging tools. Funding: Swedish Research Council, Swedish Cancer Society, Nordic Cancer Union, Swedish Breast Cancer Association.

Idiopathic Granulomatous Mastitis as a Benign Condition Mimicking Inflammatory Breast Cancer: Current Status, Knowledge Gaps and Rationale for the GRAMAREG Study (EUBREAST-15).

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition often mistaken for inflammatory breast cancer and, therefore, requires a biopsy for accurate diagnosis. Although not cancerous, IGM can cause emotional distress because of severe pain and ensuing breast deformity. Differentiating IGM from other breast inflammations caused by infections is essential. IGM mostly affects premenopausal women and is potentially associated with recent pregnancies and breastfeeding. The risk factors, including smoking and contraceptive use, have inconsistent associations. Steroid responses suggest an autoimmune component, though specific markers are lacking. METHODS: We performed a narrative review on potential risk factors, diagnostics, and therapy of IGM. RESULTS: Diagnostics and clinical management of IGM are challenging. The treatment options include NSAIDs, steroids, surgery, antibiotics, immunosuppressants, prolactin suppressants, and observation, each with varying effectiveness and side effects. CONCLUSIONS: Current IGM treatment evidence is limited, based on case reports and small series. There is no consensus on the optimal management strategy for this disease. The GRAMAREG study by the EUBREAST Study Group aims to collect comprehensive data on IGM to improve diagnostic and treatment guidelines. By enrolling patients with confirmed IGM, the study seeks to develop evidence-based recommendations, enhancing patient care and understanding of this condition.

Prediction of High Nodal Burden in Patients With Sentinel Node-Positive Luminal ERBB2-Negative Breast Cancer.

Importance: In patients with clinically node-negative (cN0) breast cancer and 1 or 2 sentinel lymph node (SLN) macrometastases, omitting completion axillary lymph node dissection (CALND) is standard. High nodal burden (≥4 axillary nodal metastases) is an indication for intensified treatment in luminal breast cancer; hence, abstaining from CALND may result in undertreatment. Objective: To develop a prediction model for high nodal burden in luminal ERBB2-negative breast cancer (all histologic types and lobular breast cancer separately) without CALND. Design, Setting, and Participants: The prospective Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases (SENOMAC) trial randomized patients 1:1 to CALND or its omission from January 2015 to December 2021 among adult patients with cN0 T1-T3 breast cancer and 1 or 2 SLN macrometastases across 5 European countries. The cohort was randomly split into training (80%) and test (20%) sets, with equal proportions of high nodal burden. Prediction models were developed by multivariable logistic regression in the complete luminal ERBB2-negative cohort and a lobular breast cancer subgroup. Nomograms were constructed. The present diagnostic/prognostic study presents the results of a prespecified secondary analysis of the SENOMAC trial. Herein, only patients with luminal ERBB2-negative tumors assigned to CALND were selected. Data analysis for this article took place from June 2023 to April 2024. Exposure: Predictors of high nodal burden. Main Outcomes and Measures: High nodal burden was defined as ≥4 axillary nodal metastases. The luminal prediction model was evaluated regarding discrimination and calibration. Results: Of 1010 patients (median [range] age, 61 [34-90] years; 1006 [99.6%] female and 4 [0.4%] male), 138 (13.7%) had a high nodal burden and 212 (21.0%) had lobular breast cancer. The model in the training set (n = 804) included number of SLN macrometastases, presence of SLN micrometastases, SLN ratio, presence of SLN extracapsular extension, and tumor size (not included in lobular subgroup). Upon validation in the test set (n = 201), the area under the receiver operating characteristic curve (AUC) was 0.74 (95% CI, 0.62-0.85) and the calibration was satisfactory. At a sensitivity threshold of ≥80%, all but 5 low-risk patients were correctly classified corresponding to a negative predictive value of 94%. The prediction model for the lobular subgroup reached an AUC of 0.74 (95% CI, 0.66-0.83). Conclusions and Relevance: The predictive models and nomograms may facilitate systemic treatment decisions without exposing patients to the risk of arm morbidity due to CALND. External validation is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02240472.

Completion axillary lymph node dissection for the identification of pN2-3 status as an indication for adjuvant CDK4/6 inhibitor treatment: a post-hoc analysis of the randomised, phase 3 SENOMAC trial.

BACKGROUND: In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1-2, grade 1-2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2-3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial. METHODS: In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1-T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1-2, histological grade 1-2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing. FINDINGS: Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND and 903 (53%) had a sentinel lymph node biopsy only. Median age at randomisation was 62 years (IQR 52-71), 1699 (>99%) of 1705 patients were female, and six (<1%) were male. Among 1342 patients who responded to questionnaires, after a median follow-up of 45·2 months (IQR 25·6-59·8; data cutoff Nov 17, 2023), patient-reported severe or very severe impairment of physical arm function was reported in 84 (13%) of 634 patients who had cALND versus 30 (4%) of 708 who had sentinel lymph node biopsy only (χ2 test p<0·0001). To avoid one invasive disease-free survival event at 5 years with adjuvant abemaciclib, cALND would need to be performed in 104 patients, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery. INTERPRETATION: As a method to potentially identify an indication for abemaciclib, and subsequently avoid invasive disease-free survival events at 5 years with 2 years of adjuvant abemaciclib, cALND carries a substantial risk of severe or very severe arm morbidity and so cALND should be discouraged for this purpose. FUNDING: Swedish Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Breast Cancer Association.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2024.

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer. Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024. Results and Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2024.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2024 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer.

Quality assessment of radiotherapy in the prospective randomized SENOMAC trial.

BACKGROUND AND PURPOSE: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. MATERIALS AND METHODS: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1-2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015-2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail. RESULTS: CRF-data and RT plans agreed in 99.3 % (breast/chest wall) and in 96.6 % of patients (regional RT). Congruence for whether level I was an intended RT target was lower (78 %). In accordance with Danish national guidelines, level I was more often an intended target in the SLN biopsy only arm (N = 334/611, 55 %,) than in the cALND arm (N = 174/565, 31 %,). When an intended target, level I received prescribed dose to 100 % (IQR 98-100 %) of the volume. However, even when not an intended target, full dose was delivered to > 80 % of level I (IQR 75-90 %). The intentional inclusion of level I in the target volume more than doubled the dose received by ≥ 50 % of the humeral head. CONCLUSION: Congruence between CRF data and RT plans was excellent. Level I received a high dose coverage even when not intentionally included in the target. Including level I in target significantly increased dose to the humeral head.

Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases.

BACKGROUND: Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups. METHODS: We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44. RESULTS: Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy-only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy-only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin. CONCLUSIONS: The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).

Breast-conserving surgery is not associated with increased local recurrence in patients with early-stage node-negative triple-negative breast cancer treated with neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is routinely used for patients with triple-negative breast cancer (TNBC). Upfront breast-conserving therapy (BCT) consisting of breast-conserving surgery (BCS) and adjuvant radiotherapy (RT) has been shown to be associated with improved outcome in patients with early TNBC as compared to mastectomy. METHODS: We identified 2632 patients with early TNBC from the German Breast Group meta-database. Patients with cT1-2 cN0 and ypN0, available surgery and follow-up data were enrolled. Data of 1074 patients from 8 prospective NACT trials were available. Endpoints of interest were locoregional recurrence as first site of relapse (LRR), disease-free survival (DFS) and overall survival (OS). We performed univariate and multivariate Fine-Gray analysis and Cox regression models. RESULTS: After a median follow-up of 64 months, there were 94 (8.8%) locoregional events as first site of relapse. Absence of pathologic complete response (pCR) was associated with increased LRR upon uni- and multivariate analysis (hazard ratio [HR] = 2.28; p < 0.001 and HR = 2.22; p = 0.001). Type of surgery was not associated with LRR. Patients in the BCS-group had better DFS and OS (DFS: HR = 0.47; p < 0.001 and OS: HR = 0.40; p < 0.001). BCS was associated with improved DFS and OS upon multivariate analysis (DFS: HR = 0.51; p < 0.001; and OS HR = 0.43; p < 0.001), whereas absence of pCR was associated with worse DFS and OS (DFS: HR = 2.43; p < 0.001; and OS: HR = 3.15; p < 0.001). CONCLUSIONS: In this retrospective analysis of patients with early stage node-negative TNBC treated with NACT, BCS was not associated with an increased risk of LRR but with superior DFS and OS.

Targeted axillary dissection: worldwide variations in clinical practice.

PURPOSE: Targeted axillary dissection (TAD) for the axillary staging of clinically node-positive (cN +) breast cancer patients converting to clinically node negative post neoadjuvant chemotherapy (NAC), has gained popularity due to its minimal false negative rate and low arm morbidity. The aim of this study is to shed more light on the variation in the clinical practice globally in terms of indications and perceived limitations of TAD. METHODS: A panel of expert breast surgeons constructed a structured questionnaire comprising of 18 questions and asked surgeons worldwide for their opinions and routine practice on TAD. The questionnaire was electronically distributed and answers were collected between May 1st and August 1st 2022. RESULTS: Responses included 137 entries from 36 countries. Of them, 73.7% consider TAD for cN + patients planned to receive NAC. Among them, the greatest number of respondents (45%) perform the procedure for tumours up to T3, whereas 27% regardless of T-stage. The majority (42%) perform TAD on patients with 1-3 positive nodes and only 30% consider TAD when matted nodes are present. HER2 positive and Triple Negative subtypes are more likely to undergo TAD than Luminal A and B (86%, 79.1%, 39.5%, and 62.8%, respectively). Maximum acceptable lymph node burden is median 3 nodes for any subtype with a tendency to accept more positive nodes for Triple Negative. CONCLUSION: This study demonstrates the differences in current practice regarding TAD as well as the fact that the biology of the tumour heavily affects the method of axillary staging.

Fatigue and quality of life during neoadjuvant chemotherapy of early breast cancer: a prospective multicenter cohort study.

BACKGROUND: Few measurements of fatigue and quality of life have been performed during neoadjuvant chemotherapy of early breast cancer. This study evaluates fatigue and quality of life experienced by early breast cancer patients during neoadjuvant chemotherapy and their association with different clinical parameters. METHODS: Fifty-four stage I-III patients' responses to the Multidimensional Fatigue Inventory (MFI) and to the Functional Assessment of Cancer Therapy-Breast (FACT-B) were analyzed by a linear covariance pattern model. Chemotherapy regimen, age, baseline fatigue level, body-mass-index and cancer stage were added to the model to estimate their impact on both outcomes. RESULTS: All fatigue dimensions worsened in clinically relevant levels. Physical fatigue worsened the most, mental fatigue the least. For quality of life, physical and functional well-being worsened the most. Only emotional well-being improved during chemotherapy. Physical well-being worsened more during standard than during dose-dense chemotherapy, and more during anthracycline than during taxane cycles. Age, body-mass-index and cancer stage had no impact. The higher the fatigue levels at baseline, the less they worsened during chemotherapy. CONCLUSIONS: Further actions to reduce fatigue and improve quality of life during neoadjuvant chemotherapy of early breast cancer are needed. Focus should be laid on the physical dimension. Future research should also investigate the impact of different chemotherapy sequences and densities on fatigue and quality of life. STUDY REGISTRATION: The study was registered in the German Clinical Trials Register in May 2019 (DRKS00016761).

Locoregional Therapy: From Mastectomy to Reconstruction, Targeted Surgery, and Ultra-Hypofractionated Radiotherapy.

Background: The past 3 decades have seen an unprecedented shift toward treatment de-escalation in surgical therapy of breast cancer. Summary: Radical mastectomy has been replaced by breast-conserving and oncoplastic approaches in most patients, and full axillary lymph node dissection by less radical staging procedures, such as sentinel lymph node biopsy and targeted axillary dissection. Further, attempts have been made to spare healthy tissue while increasing the probability of removing the tumor with clear margins, thus improving cosmetic results and minimizing the risk of local recurrence. In this context, modern probe-guided localization techniques have been introduced to guide surgical excision. This progress was accompanied by the development of targeted systemic therapies. At the same time, radiotherapy for breast cancer has undergone significant changes. The use of hypofractionation has decreased the typical length of a treatment course from 5-6 weeks to 1-3 weeks. Partial breast irradiation is now a valid option for de-escalation in patients with low-risk features. Axillary radiotherapy achieves similar recurrence rates and decreases the risk of lymphedema in patients with limited sentinel node involvement. Key Messages: Taken together, these advances are important steps toward individualization of locoregional management strategies. This highlights the importance of interdisciplinary approaches for de-escalation of locoregional therapies.

AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2023.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2023 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer (mBC).

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2023.

Background: Each year the interdisciplinary Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), German Gynecological Oncology Group Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer. Summary: The updated evidence-based treatment recommendation for early and metastatic breast cancer has been released in March 2023. Key Messages: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

Deep learning to predict breast cancer sentinel lymph node status on INSEMA histological images.

BACKGROUND: Sentinel lymph node (SLN) status is a clinically important prognostic biomarker in breast cancer and is used to guide therapy, especially for hormone receptor-positive, HER2-negative cases. However, invasive lymph node staging is increasingly omitted before therapy, and studies such as the randomised Intergroup Sentinel Mamma (INSEMA) trial address the potential for further de-escalation of axillary surgery. Therefore, it would be helpful to accurately predict the pretherapeutic sentinel status using medical images. METHODS: Using a ResNet 50 architecture pretrained on ImageNet and a previously successful strategy, we trained deep learning (DL)-based image analysis algorithms to predict sentinel status on hematoxylin/eosin-stained images of predominantly luminal, primary breast tumours from the INSEMA trial and three additional, independent cohorts (The Cancer Genome Atlas (TCGA) and cohorts from the University hospitals of Mannheim and Regensburg), and compared their performance with that of a logistic regression using clinical data only. Performance on an INSEMA hold-out set was investigated in a blinded manner. RESULTS: None of the generated image analysis algorithms yielded significantly better than random areas under the receiver operating characteristic curves on the test sets, including the hold-out test set from INSEMA. In contrast, the logistic regression fitted on the Mannheim cohort retained a better than random performance on INSEMA and Regensburg. Including the image analysis model output in the logistic regression did not improve performance further on INSEMA. CONCLUSIONS: Employing DL-based image analysis on histological slides, we could not predict SLN status for unseen cases in the INSEMA trial and other predominantly luminal cohorts.

Applicability of magnetic seeds for target lymph node biopsy after neoadjuvant chemotherapy in initially node-positive breast cancer patients: data from the AXSANA study.

PURPOSE: Currently, various techniques are available to mark and selectively remove initially suspicious axillary lymph nodes (target lymph nodes, TLNs) in breast cancer patients receiving neoadjuvant chemotherapy (NACT). To date, limited data are available on whether the use of magnetic seeds (MS) is suitable for localizing TLNs. This study aimed to investigate the feasibility of MS in patients undergoing target lymph node biopsy (TLNB) or targeted axillary dissection (TAD) after NACT. METHODS: Prospective data from the ongoing multicentric AXSANA study were extracted from selected patients in whom the TLN had been marked with an MS before NACT and who were enrolled from June 2020 to June 2023. The endpoints of the analysis were the detection rate, the rate of lost markers, and the potential impairment on magnetic resonance imaging (MRI) assessment. RESULTS: In 187 patients from 27 study sites in seven countries, MS were placed into the TLN before NACT. In 151 of these, post-NACT surgery had been completed at the time of analysis. In 146 patients (96.0%), a TLN could successfully be detected. In three patients, the seed was removed but no lymphoid tissue was detected on histopathology. The rate of lost markers was 1.2% (2 out of 164 MS). In 15 out of 151 patients (9.9%), MRI assessment was reported to be compromised by MS placement. CONCLUSION: MS show excellent applicability for TLNB/TAD when inserted before NACT with a high DR and a low rate of lost markers. Axillary MS can impair MRI assessment of the breast. TRIAL REGISTRATION NUMBER: NCT04373655 (date of registration May 4, 2020).

The Lucerne Toolbox 2 to optimise axillary management for early breast cancer: a multidisciplinary expert consensus.

Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the "Lucerne Toolbox", a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients' journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%-74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema.

Systemic Therapy of Premenopausal Patients with Early Stage Hormone Receptor-Positive, HER2-Negative Breast Cancer - Controversies and Standards in Healthcare.

In patients with existing ovarian function, there are some special aspects to adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive, HER2-negative (HR pos./HER2 neg.) breast cancer. Treatment options include tamoxifen with or without a GnRH analog, and aromatase inhibitors with a GnRH analog. Furthermore, ovarian function is affected by previous chemotherapy. Both aromatase inhibitors (+GnRH analogs) and GnRH analogs in combination with tamoxifen are supposed to be indicated for patients at increased risk of recurrence. However, national and international guidelines and therapy recommendations do not provide a clear definition of intermediate or high risk; as a result, therapy decisions are often made for each patient on an individual basis. This is also reflected in the considerable variability at national and international levels, e.g., with regard to the use of aromatase inhibitors + GnRH analogs. This review summarizes the data on completed studies (e.g., SOFT, TEXT, EBCTCG meta-analyses) and the current multigene testing studies (TailorX, RxPonder, ADAPT), discusses the rationale for current studies (e.g., CLEAR-B), and looks ahead to future questions.

Elderly and Patients with Large Breast Volume Have an Increased Risk of Seroma Formation after Mastectomy-Results of the SerMa Pilot Study.

The collective of the SerMa pilot study included 100 cases of primary breast cancer or Carcinoma in situ who had undergone a mastectomy procedure with or without reconstruction of the breast using an implant or expander at Augsburg University Hospital between 12/2019 and 12/2022. The study aimed to investigate possible causes of seroma formation; reported here are the clinicopathological correlations between seroma formation and tumor biology and surgical procedures. Seroma occurred significantly more often in patients with older age (median patient age in cases with seroma was 73 years vs. 52 years without seroma; p < 0.001). In addition, patients with larger mastectomy specimen were significantly more likely to develop seroma (median ablation weight in cases with seroma 580 g vs. 330 g without seroma; p < 0.001). Other significant parameters for seroma formation were BMI (p = 0.005), grading (p = 0.015) and tumor size (p = 0.036). In addition, with insertion of implant or expander, a seroma occurred significantly less frequently (p < 0.001). In a binary logistic regression, age in particular was confirmed as a significant risk factor. In contrast, tumor biological characteristics, number of lymph nodes removed or affected showed no significant effect on seroma formation. The present study shows the need for patient education about the development of seroma in particular in older patients and patients with large breast volumes within the preoperative surgical clarification. These clinicopathological data support the previously published results hypothesizing that seroma formation is related to autoimmune/inflammatory processes and will be tested on a larger collective in the planned international multicenter SerMa study.