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.).

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.

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.

Designing clinical trials based on modern imaging and metastasis-directed treatments in patients with oligometastatic breast cancer: a consensus recommendation from the EORTC Imaging and Breast Cancer Groups.

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed.

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).

Current clinical practice in the management of phyllodes tumors of the breast: an international cross-sectional study among surgeons and oncologists.

PURPOSE: Phyllodes tumors of the breast are rare fibroepithelial lesions that are classified as benign, borderline or malignant. There is little consensus on best practice for the work-up, management, and follow-up of patients with phyllodes tumors of the breast, and evidence-based guidelines are lacking. METHODS: We conducted a cross-sectional survey of surgeons and oncologists with the aim to describe current clinical practice in the management of phyllodes tumors. The survey was constructed in REDCap and distributed between July 2021 and February 2022 through international collaborators in sixteen countries across four continents. RESULTS: A total of 419 responses were collected and analyzed. The majority of respondents were experienced and worked in a university hospital. Most agreed to recommend a tumor-free excision margin for benign tumors, increasing margins for borderline and malignant tumors. The multidisciplinary team meeting plays a major role in the treatment plan and follow-up. The vast majority did not consider axillary surgery. There were mixed opinions on adjuvant treatment, with a trend towards more liberal regiments in patients with locally advanced tumors. Most respondents preferred a five-year follow-up period for all phyllodes tumor types. CONCLUSIONS: This study shows considerable variation in clinical practice managing phyllodes tumors. This suggests the potential for overtreatment of many patients and the need for education and further research targeting appropriate surgical margins, follow-up time and a multidisciplinary approach. There is a need to develop guidelines that recognize the heterogeneity of phyllodes tumors.

Axillary surgery after neoadjuvant therapy in initially node-positive breast cancer: international EUBREAST survey.

BACKGROUND: There is no consensus on axillary management after neoadjuvant therapy (NAT) in patients with clinically node-positive (cN+) breast cancer. To investigate current clinical practice, an international survey was conducted among breast surgeons and radiation oncologists. The aim of the first part of the survey was to provide a snapshot of international discrepancies regarding axillary surgery in this context. METHODS: The European Breast Cancer Research Association of Surgical Trialists (EUBREAST) developed a web-based survey containing 39 questions describing clinical scenarios in the setting of axillary management in patients with cN1 disease converting to ycN0 after NAT. The survey was then distributed to breast surgeons and radiation oncologists via 14 breast cancer societies between April and October 2021. RESULTS: Responses from 349 physicians in 45 countries were recorded. The most common post-NAT axillary surgery in patients with cN1 disease converting to ycN0 was targeted axillary dissection (54.2 per cent), followed by sentinel lymph node biopsy (SLNB) alone (20.9 per cent), level 1-2 axillary lymph node dissection (ALND) (18.4 per cent), level 1-3 ALND (4 per cent), and targeted lymph node biopsy (2.5 per cent). For SLNB alone, dual tracers were most commonly used (62.3 per cent). Management varied widely in patients with ambiguous axillary status before initiation of treatment or a residual metastatic burden in the axilla after NAT. In patients with ycN+ tumours, ALND was the preferred surgical approach for 66.8 per cent of respondents. CONCLUSION: These results highlight the wide heterogeneity in surgical approaches to the axilla after NAT. To standardize the guidelines, further data from clinical research are urgently needed, which underlines the importance of the ongoing AXSANA (EUBREAST-3) study.

De-epithelialized Skin Flaps to Minimize Complications in Large Breast Reconstruction: A Tailored Approach.

ABSTRACT: Mastectomy and immediate reconstruction may be challenging in patients with large breasts, especially when significant ptosis is also present. Skin-reducing mastectomy (SRM) is usually indicated in these cases, although with increased morbidity. The aims of the study were to introduce 2 modifications of the classic technique and to incorporate them in the management algorithm to improve the outcomes.Twenty patients fulfilling the criteria for SRM underwent mastectomy and reconstruction either with the "classic SRM" (8 patients) or with 1 of the 2 modifications described here: modification A "vertical limb bridging" (for patients with very large breasts, 2 patients) and modification B "dual coverage" (for patients with moderate breasts, 10 patients). All reconstructions were performed using a slow progressive expansion of the implant. Herein, we describe the techniques along with the proposed indications for each one of them.There was no reconstruction failure, and all patients were satisfied with the final results. There were 2 cases with T junction, lateral skin flap partial ischemia managed with delayed revision of the wound on the fifth postoperative day to allow less skin excision. One patient (smoker) developed severe lower pole cellulitis, which was managed conservatively. Finally, 1 patient who underwent radiotherapy developed a late infected seroma, which was managed successfully with drainage and antibiotics. Overall, there was good lower pole projection even with the dual-coverage modification.Skin-reducing mastectomy can be tailored according to individual patient anatomy, and the high reported complication rate associated with this technique can be minimized using certain surgical modifications, tissue expanders with progressive inflation, and good patient selection.

How breast cancer treatments affect the quality of life of women with non-metastatic breast cancer one year after surgical treatment: a cross-sectional study in Greece.

BACKGROUND: The continuously increasing survivorship of female breast cancer makes the monitoring and improvement of patients' quality of life ever so important. While globally there is a growing body of research on health-related quality of life 1 year after surgical treatment for non-metastatic breast cancer, up-to-date information regarding Greek patients is scarce. OBJECTIVE: To measure the level of QoL of non-metastatic BC survivors in Greece 1 year after surgery. METHODS: A sample of 200 female breast cancer survivors aged 18 to 75, who followed up as outpatients in five public hospitals were included in this cross-sectional study. All recruited patients agreed to participate in the study (100% response rate). Quality of life data were collected through the EORTC QLQ-C30 as well as BR23 questionnaires. RESULTS: Cronbach's alpha for all scales of the two questionnaires was from 0.551 to 0.936 indicating very good reliability. According to the Multiple Linear Regression, older patients showed a lower future perspective (p = .031), with those living in rural areas, which was associated with more financial difficulties (p = .001). Women with tertiary education and those who had been hospitalized in a university hospital recorded better on global health status (p = .003 and .000 respectively). Patients who underwent chemotherapy reported better scores in the emotional function sub-scale (p = .025). Women with reconstruction and at least one complication appeared to have significantly better scores in future perspective and social function (p = .005, .002 respectively). CONCLUSIONS: Breast cancer survivors were found to have an overall good quality of life, functioning/symptoms scores and were satisfied with the provided care.

Health-related quality of life of young women with breast cancer. Review of the literature.

PURPOSE: The purpose of the present article was to investigate the health related quality of life (QoL) of young women with breast cancer. METHODS: For the purposes of this article, we reviewed the literature via the electronic databases Pubmed, Scopus and Google Scholar. Key words used were breast cancer, young women, health related quality of life, and quality of life. RESULTS: Young women reported fatigue, pain in the breast and hand problems with lymphedema as the most frequent physical effects of treatment. Other physical problems were the not periodic and painful menses, vaginal dryness and loss of libido. Many young women had depressive symptoms such as depressed mood, helplessness, hopelessness, sleep loss, psychomotor retardation and disorders of appetite. There were often concerns about the health monitoring and self-image, while they were anxious if they will have a baby in the future or if they can nurture the existing ones. Many problems arose in the career of young women. They faced discrimination in the labor supply and/or layoff because they were considered unable to do their job effectively. In addition, they reported isolation problems and feeling different from other women of similar age. CONCLUSIONS: Young women consider that their healthrelated QoL is worse compared with older women. Young women worry about their future, with particular reference to their role as mothers and especially to children-bearing. The free screening and non-exclusion of young women is particularly important for breast cancer prevention and women's well-being.

Microwave versus saline-linked radiofrequency (Aquamantys) assisted liver resection in a porcine liver resection model. A safety and feasibility pilot study.

PURPOSE: The aim of this study was to compare the feasibility, efficacy and safety of microwave ablation and saline-linked radiofrequency (Aquamantys) in liver resection. METHODS: Sixteen domestic pigs (8 per group) underwent thermoablations. Group A consisted of 8 pigs in which microwave left lateral liver resection was performed. Group B consisted of 8 pigs which underwent left lateral liver resection by the Aquamantys system. After 28 days of close follow-up, the animals were sacrificed in order to study the macroscopic and microscopic findings of each intervention on the liver edge. RESULTS: An average of 47.13 min was enough for the entire operation to take place using Aquamantys, whereas an average of 59.13 min was needed in the microwave liver resection group. Mean blood loss was 40 ml (range 5-85) with Aquamantys whereas mean blood loss was 72.37 ml (range 42-100) using microwave. Postoperative complications rates were extremely low in both groups. There was no intra- or postoperative mortality. CONCLUSIONS: Our study demonstrated that left lateral liver resection using Aquamantys system is technically feasible in the porcine model and proved to be highly effective and a safer hemostatic method compared to microwave ablation.

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.

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.

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.

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy.

AIM: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. METHODS: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. RESULTS: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. CONCLUSIONS: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR.

False Negativity of Targeted Axillary Dissection in Breast Cancer.

INTRODUCTION: Targeted axillary dissection (TAD) has been proposed as an alternative method for the staging of patients with node-positive breast cancer who undergo neoadjuvant chemotherapy. However, not much is known yet about the false-negative rate (FNR) of the method and the subsequent risk of underestimation of residual axillary disease. METHODS: This study reviews published articles with calculations of false negativity of TAD and potential factors that may influence it. RESULTS: The FNR of TAD is usually reported as being <10%, but this calculation is usually based on small study populations. Lower FNR is a common finding along with lower N status, while not enough data are available yet for greater axillary involvement. When a marked node is revealed to be a sentinel lymph node (SLN) at surgery after neoadjuvant chemotherapy (NAC), this seems to be another factor that contributes to reliable TAD. With regard to the methods used to mark the positive node before chemotherapy and retrieval at surgery, there is no clear advantage of one over the other. The availability of relevant resources, the costs, and local legislation must all be taken into account for the selection of the optimal strategy. CONCLUSION: Although still in its early days, the FNR of TAD can be low, at least in patients with relatively little axillary involvement and when the marked node is the SLN. All reported methods of lymph node marking seem reliable.

The value of the intraoperative assessment of the SLN via frozen section in the post Z0011 era.

INTRODUCTION: Sentinel node (SN) assessment via frozen section (FS) has declined since the publication of Z0011 which modified the management of a specific group of patients with positive SN. The risk of misleading the surgeons to a preventable ALND and the cost are among the main factors for that. The aim of our study is to assess the value of FS in the post Z0011. MATERIAL AND METHODS: 244 patients out of 434 were eligible for an upfront SLNB. Based on the final histology and the clinical data we selected the eligible for breast conserving surgery patients (55.4%). 78 patients had positive SN and 26 of them fulfilled the criteria of Z0011. We assessed the false negative findings, the impact on the management and the indications and value of FS in the post Z0011 era. RESULTS: Overall, there were 12 FN cases out of which 7 were macrometastases (8.97%). Only in one case there were > 2 positive LN and 3 patients needed mastectomy. The remaining cases fulfilled the criteria of Z0011 and needed no further surgery hence in 96.1% of the cases the axillary status was correctly assessed via FS and the reoperation rate was 1.2%. On the contrary, if FS was not used, at least 21.3% of the patents would have needed reoperation based on the today's guidelines. DISCUSSION: We believe FS is still valuable and may spare a significant percentage of patients from a second operation (SNB) without leading to axillary overtreatment if used wisely.

Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study.

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).

Delayed Breast Cellulitis following Surgery for Breast Cancer: A Literature Review.

BACKGROUND: Delayed breast cellulitis (DBC) is a relatively rare complication following breast-conserving surgery. It is often challenging to distinguish DBC from other clinical conditions such as postoperative infection, inflammatory reaction following radiation, and recurrent inflammatory carcinoma. The definition of DBC, diagnostic approach, and treatment are not well established in the literature. METHODS: We performed a literature search with the keywords 'Delayed breast cellulitis' and 'Breast conservation therapy cellulitis', without limitations to the dates or the article types, in the PubMed database. Information about the number of cases with DBC, the age of the patients, the interval between the onset of symptoms and the time of surgery or radiotherapy, and the type and outcome of DBC treatment were reviewed and tabulated. RESULTS: We identified only 5 papers that were absolutely related to our subject, reflecting the fact that 'delayed breast cellulitis' is a fairly unknown term and the condition is rather underreported. Although most agree that DBC is primarily an aseptic inflammatory process, bacterial growth may contribute to its development or recurrence. Obesity, breast size, location of the breast tumor, removal of the axillary lymph nodes, and connective tissue disorders are considered as risk factors. There is no clear evidence on how DBC should be best managed. Antibiotic treatment is controversial, and many authors suggest anti-inflammatory agents or sole observation. Prevention of lymph stasis and its consequences with massage and skin care may be helpful. Despite the fact that malignancy is rare, in cases where the condition persists for more than 4 months, a core biopsy should be performed to rule out recurrent or second primary carcinoma. CONCLUSION: The correct diagnostic approach is essential as it provides patients with reassurance, minimizes anxiety, and prevents unnecessary medical investigations, treatments, and costs.