Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project.

INTRODUCTION: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved. METHODS AND ANALYSIS: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance. ETHICS AND DISSEMINATION: Ethical approval for the consensus process will be obtained from the Queen's University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely. REGISTRATION: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854).

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.).

National long-term patient-reported outcomes following mastectomy with or without breast reconstruction: The Swedish Breast Reconstruction Outcome Study Part 2 (SweBRO 2).

BACKGROUND: The Swedish Breast Reconstruction Outcome Study (SweBRO) initiative is a nationwide study with the primary aim of assessing long-term outcomes after mastectomy with and without breast reconstruction (BR). The current part (SweBRO 2) is designed to evaluate health-related quality of life (HRQoL), with the hypothesis that BR has a positive impact on patient-reported HRQoL in the long-term. METHODS: Women who underwent mastectomy in Sweden in 2000, 2005, or 2010 and were alive at the time of the survey were identified through the National Breast Cancer Registry. Eligible participants received formal invitation letters to take part in a survey evaluating their HRQoL at 5 , 10, or 15 years post-mastectomy. The EORTC QLQ-C30, EORTC QLQ-BR23, and EQ-5D-3L questionnaires were employed. RESULTS: Of 2904 respondents (50% of 5853 invited), 895 (31%) had received BR. Among them, 516 (58%) were reconstructed with implants and 281 (31%) with autologous tissue. Women with BR scored significantly better in the EORCT QLQ-C30 physical functioning domain (mean 90 versus 81 points), fatigue (mean 21 versus 25), and dyspnoea (mean 16 versus 22) compared to non-reconstructed women. The EORTC QLQ-BR23 revealed that women with BR experienced favourable sexual functioning compared with non-reconstructed women (mean 26 versus 14). The EQ-5D-3L visual analogue scale score was similar between groups. CONCLUSION: The current study underscores the benefits of BR for long-term well-being, for example, in terms of physical and sexual functioning. These underline the importance of informing women undergoing mastectomy about BR alternatives and its potential benefits in enhancing long-term well-being.

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.

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).

Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial.

INTRODUCTION: Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence. METHODS AND ANALYSIS: In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5 years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5 percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included. ETHICS AND DISSEMINATION: The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05634889.

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.

Uncertainties and controversies in axillary management of patients with breast cancer.

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register.

Localization Techniques for Non-Palpable Breast Lesions: Current Status, Knowledge Gaps, and Rationale for the MELODY Study (EUBREAST-4/iBRA-NET, NCT 05559411).

BACKGROUND: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. METHODS: We performed a systematic review on localization techniques for non-palpable breast cancer. RESULTS: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons' and radiologists' attitudes towards these techniques. CONCLUSIONS: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.

EBCC-13 manifesto: Balancing pros and cons for contralateral prophylactic mastectomy.

After a diagnosis of unilateral breast cancer, increasing numbers of patients are requesting contralateral prophylactic mastectomy (CPM), the surgical removal of the healthy breast after diagnosis of unilateral breast cancer. It is important for the community of breast cancer specialists to provide meaningful guidance to women considering CPM. This manifesto discusses the issues and challenges of CPM and provides recommendations to improve oncological, surgical, physical and psychological outcomes for women presenting with unilateral breast cancer: (1) Communicate best available risks in manageable timeframes to prioritise actions; better risk stratification and implementation of risk-assessment tools combining family history, genetic and genomic information, and treatment and prognosis of the first breast cancer are required; (2) Reserve CPM for specific situations; in women not at high risk of contralateral breast cancer (CBC), ipsilateral breast-conserving surgery is the recommended option; (3) Encourage patients at low or intermediate risk of CBC to delay decisions on CPM until treatment for the primary cancer is complete, to focus on treating the existing disease first; (4) Provide patients with personalised information about the risk:benefit balance of CPM in manageable timeframes; (5) Ensure patients have an informed understanding of the competing risks for CBC and that there is a realistic plan for the patient; (6) Ensure patients understand the short- and long-term physical effects of CPM; (7) In patients considering CPM, offer psychological and surgical counselling before surgery; anxiety alone is not an indication for CPM; (8) Eliminate inequality between countries in reimbursement strategies; CPM should be reimbursed if it is considered a reasonable option resulting from multidisciplinary tumour board assessment; (9) Treat breast cancer patients at specialist breast units providing the entire patient-centred pathway.

Axillary staging in node-positive breast cancer converting to node negativity through neoadjuvant chemotherapy: Current evidence and perspectives.

PURPOSE: Over the recent years, axillary staging of initially node-positive breast cancer patients converting to clinical node negativity after neoadjuvant chemotherapy has seen rapid changes. This narrative review aims to give a contemporary overview over published evidence and clinical practice, and thus provide some guidance to the surgical community in the process of re-evaluating and re-shaping surgical practice. METHODS: The search strategy aimed at finding relevant studies. Only articles in English were considered. RESULTS: The introduction of modern techniques offer more precise staging surgery and thus hopefully reduced arm morbidity. Clinical practice has however diverged both within countries and internationally. While some countries have adapted de-escalated axillary staging techniques such as targeted axillary dissection, targeted lymph node biopsy or sentinel lymph node biopsy, others continue to recommend a full axillary lymph node dissection. With the implementation of new techniques, many questions arise, regarding aspects of oncological safety, technical performance, budget and practicality, patient selection and indications for different levels of axillary staging procedures. CONCLUSIONS: There is a growing body of evidence on de-escalation of axillary surgery in the setting of cN+ → ycN0 breast cancer treated with neoadjuvant chemotherapy. However, standards differ between countries and future studies are necessary to fully assess the optimal strategy for these patients.

Medical and surgical postoperative complications after breast conservation versus mastectomy in older women with breast cancer: Swedish population-based register study of 34 139 women.

BACKGROUND: Mastectomy rates in breast cancer are higher in older patients. The aim was to compare postoperative complication rates after breast-conserving surgery (BCS) to mastectomy in women aged 70-79 and older than 80 years versus those aged 50-69 years, and to evaluate survival effects. METHODS: This population-based cohort included women aged 50 years and older with invasive breast cancer T1-3 N0-3 M0 operated on in Sweden 2008-2017. Major surgical and medical 30-day postoperative complications were assessed in adjusted logistic regression models. Overall survival was assessed in Cox models adjusted for clinical confounders, socio-economics, and comorbidity. RESULTS: Of 34 139 women, 8372 (24.5 per cent) were aged 70-79 years, 3928 (11.5 per cent) were 80 years of age or older, and 21 839 (64.0 per cent) were aged 50-69 years. Major surgical postoperative complications did not differ between age groups receiving equivalent surgery (BCS: 2.1 per cent and 2.0 per cent versus 2.1 per cent (P = 0.90); mastectomy: 4.6 per cent and 5.1 per cent versus 4.6 per cent (P = 0.49)). Major medical postoperative complications were higher in women aged >70 years than in women aged 50-69 years (BCS: 1.0 per cent and 2.3 per cent versus 0.4 per cent (P < 0.001); mastectomy: 3.1 per cent and 6.2 per cent versus 1.1 per cent (P < 0.001)), which persisted after adjustments. In women treated by mastectomy, major medical and surgical postoperative complications were associated with worse overall survival in all but the middle age group. CONCLUSION: Mastectomy has higher medical and surgical postoperative complication rates than BCS. Major medical postoperative complications increase significantly with age. Major postoperative complications are associated with worse survival after mastectomy, which should be used with caution in older women.

In breast cancer, either a bit of the breast or the whole breast is removed. Older women more often have their whole breast removed. Such larger surgery may have a higher risk of complications. Complications after surgery can lower the chances of survival. The aim of this project was to find out whether older age comes with more complications after breast surgery. The authors also wanted to know whether this has an effect on survival. This work used information on women aged 50 years and older operated on for breast cancer in Sweden from 2008 to 2017. Major surgical and medical complications after breast surgery were compared in three different age groups. In addition, death of any cause was analysed. Of 34 139 women, 8372 were 70­79 years old and 3928 were aged 80 years or older. These older women were compared to 21 839 women who were 50­69 years old. Major surgical complications did not increase with age. However, medical complications were more common in older women. Removing the whole breast gave more complications than removing only part of the breast. In women aged 80 years or older who had their whole breast removed, complications after surgery increased the risk of death. This was true even when considering how severe the cancer was, how it was treated, and also what kind of socio-economic background and afflictions other than breast cancer the women had. Therefore, removal of the whole breast should be done with caution in older women.

Current trends in diagnostic and therapeutic management of the axilla in breast cancer patients receiving neoadjuvant therapy: results of the German-wide NOGGO MONITOR 24 survey.

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.

Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: Trial protocol of the randomized Neo-ACT trial.

INTRODUCTION: In early breast cancer, neoadjuvant chemotherapy (NACT) is increasingly used. The proof of efficacy is pathologically complete response (pCR), i.e. the absence of invasive tumour in breast and lymph nodes at surgery. Today, pCR is a common endpoint in pharmaceutical trials since it is significantly associated with survival especially in triple-negative and HER2-positive subtypes. Apart from the mitigation of treatment-related toxicity and symptoms, physical exercise mediates anti-tumoral systemic effects associated with tumour regression in preclinical and clinical models. The aim of Neo-ACT is to test the hypothesis that physical exercise can improve pCR rates in breast cancer patients receiving NACT. METHOD: The Neo-ACT trial is a prospective clinical trial, randomising T1-3N0-2 breast cancer patients planned for NACT to either a home-based physical exercise intervention supported by a mobile application or routine care. The primary endpoint is pCR; secondary endpoints are patient-reported quality of life, toxicity-related outcomes, and oncological outcomes such as Residual Cancer Burden, objective radiological tumour response, as well as overall, breast cancer-specific and disease-free survival at 2, 5 and 10 years. The intervention consists of a combination of high-intensity interval and resistance training of progressing intensity, and includes at least 150 min of moderate to vigorous physical activity per week, inclusive of two weekly 60-min exercise sessions. In order to show an improvement in pCR of 10%, a total of 712 participants need to be included in the analysis. The Neo-ACT has been registered at clinicaltrials.gov on January 11, 2022 (NCT05184582). EXPECTED RESULTS: If Neo-ACT can prove the oncological efficacy of physical exercise, implementation of training programmes into NACT schedules will be pursued. The use of a digitally led exercise intervention aims to test the potential of such a strategy for use in rural areas and areas of limited resources.

Effectiveness of Single vs Multiple Doses of Prophylactic Intravenous Antibiotics in Implant-Based Breast Reconstruction: A Randomized Clinical Trial.

Importance: Multiple-dose antibiotic prophylaxis is widely used to prevent infection after implant-based breast reconstruction despite the lack of high-level evidence regarding its clinical benefit. Objective: To determine whether multiple-dose antibiotic prophylaxis is superior to single-dose antibiotic prophylaxis in preventing surgical site infection (SSI) after implant-based breast reconstruction. Design, Setting, and Participants: This prospective, multicenter, randomized clinical superiority trial was conducted at 7 hospitals (8 departments) in Sweden from April 25, 2013, to October 31, 2018. Eligible participants were women aged 18 years or older who were planned to undergo immediate or delayed implant-based breast reconstruction. Follow-up time was 12 months. Data analysis was performed from May to October 2021. Interventions: Multiple-dose intravenous antibiotic prophylaxis extending over 24 hours following surgery, compared with single-dose intravenous antibiotic. The first-choice drug was cloxacillin (2 g per dose). Clindamycin was used (600 mg per dose) for patients with penicillin allergy. Main Outcomes and Measures: The primary outcome was SSI leading to surgical removal of the implant within 6 months after surgery. Secondary outcomes were the rate of SSIs necessitating readmission and administration of intravenous antibiotics, and clinically suspected SSIs not necessitating readmission but oral antibiotics. Results: A total of 711 women were assessed for eligibility, and 698 were randomized (345 to single-dose and 353 to multiple-dose antibiotics). The median (range) age was 47 (19-78) years for those in the multiple-dose group and 46 (25-76) years for those in the single-dose group. The median (range) body mass index was 23 (18-38) for the single-dose group and 23 (17-37) for the multiple-dose group. Within 6 months of follow-up, 30 patients (4.3%) had their implant removed because of SSI. Readmission for intravenous antibiotics because of SSI occurred in 47 patients (7.0%), and 190 women (27.7%) received oral antibiotics because of clinically suspected SSI. There was no significant difference between the randomization groups for the primary outcome implant removal (odds ratio [OR], 1.26; 95% CI, 0.69-2.65; P = .53), or for the secondary outcomes readmission for intravenous antibiotics (OR, 1.18; 95% CI, 0.65-2.15; P = .58) and prescription of oral antibiotics (OR, 0.72; 95% CI, 0.51-1.02; P = .07). Adverse events associated with antibiotic treatment were more common in the multiple-dose group than in the single-dose group (16.4% [58 patients] vs 10.7% [37 patients]; OR, 1.64; 95% CI, 1.05-2.55; P = .03). Conclusions and Relevance: The findings of this randomized clinical trial suggest that multiple-dose antibiotic prophylaxis is not superior to a single-dose regimen in preventing SSI and implant removal after implant-based breast reconstruction but comes with a higher risk of adverse events associated with antibiotic treatment. Trial Registration: EudraCT 2012-004878-26.

Long-term outcomes of implant-based immediate breast reconstruction with and without radiotherapy: a population-based study.

BACKGROUND: Radiotherapy (RT) is a risk factor for impaired outcomes after implant-based immediate breast reconstruction (IBR). Large studies including long-term follow-up are relatively scarce. The purpose of this analysis was to assess long-term effects of RT in implant-based IBR, distinguishing between implant removal because of postoperative complications versus patient preference. METHODS: This population-based cohort study included all patients with breast cancer who underwent implant-based IBR in Stockholm between 2005 and 2015. Data were collected through national registers and medical charts. The main endpoint was implant removal owing to postoperative complications (wound breakdown, infection, bleeding) or patient preference (dissatisfaction, pain, capsular contracture), with or without conversion to autologous reconstruction. RESULTS: Some 1749 implant-based IBRs in 1687 women were included. Median follow-up was 72 (range 1-198) months. Reconstructions were divided according to receipt of RT: No RT (n = 856, 48.9 per cent), adjuvant RT (n = 749, 42.8 per cent), and previous RT (n = 144, 8.2 per cent). Implant removal occurred after 266 reconstructions (15.2 per cent); 68 (7.9 per cent) in the no RT, 158 (21.1 per cent) in the adjuvant RT, and 40 (27.8 per cent) in the previous RT group. Implant removal was because of postoperative complications in 152 instances (57.1 per cent) and was most common in the first 3 years. This was especially observed in the previous RT group, where 15 of 23 implant removals occurred during the first 6 months. Implant removal owing to patient preference (114 of 266, 42.9 per cent) became more common with increasing follow-up. CONCLUSION: Implant removal after implant-based IBR is significantly associated with RT. The reason for implant removal shifts over time from postoperative complications to patient preference.

Irradiation of the chest wall after breast removal and implant placement (reconstruction) increases the risk of complications. These may lead to removal of the implant. Some women then choose a new breast reconstruction without an implant. The aim of this project was to find out how much irradiation affects complications after breast reconstruction using implants. This work used information on women who had a breast reconstruction with implants in Stockholm, Sweden, from 2005 to 2015. The main focus was on removal of the implant. This could be due to complications or patient preference. Implant removal could be with or without a new breast reconstruction. Of 1749 reconstructed breasts in 1687 women, 266 implants were removed. This was most often because of a complication, especially in the first years after surgery, but nearly as often due to patient wish. Implant removal owing to patient wish occurred later. Irradiation was a major factor increasing the risk of implant removal, together with, for example, smoking and obesity.

Major surgical postoperative complications and survival in breast cancer: Swedish population-based register study in 57 152 women.

BACKGROUND: Postoperative complications may activate prometastatic systemic pathways through tissue damage, wound healing, infection, and inflammation. Postoperative complications are associated with inferior survival in several types of cancer. The aim was to determine the association between postoperative complications and survival in breast cancer. METHODS: This population-based cohort included women operated for T1-3 N0-3 M0 invasive breast cancer in Sweden from 2008 to 2017. Only major surgical postoperative complications leading to readmission and/or reoperation within 30 days were considered. Main outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Prospectively collected nationwide register data were used. Multivariable Cox models were adjusted for clinical and socioeconomic confounders and co-morbidity. RESULTS: Among 57 152 women, major surgical postoperative complications were registered for 1854 patients. Median follow-up was 6.22 (0.09-11.70) years. Overall, 9163 patients died, and 3472 died from breast cancer. Major surgical postoperative complications were more common after mastectomy with or without immediate reconstruction (7.3 and 4.3 per cent respectively) than after breast-conserving surgery (2.3 per cent). Unadjusted 5-year OS and BCSS rates were 82.6 (95 per cent c.i. 80.8 to 84.5) and 92.1 (90.8 to 93.5) per cent respectively for women with a major surgical postoperative complication, and 88.8 (88.6 to 89.1) and 95.0 (94.8 to 95.2) per cent for those without a complication (P < 0.001). After adjustment, all-cause and breast cancer mortality rates remained higher after a major surgical postoperative complication (OS: HR 1.32, 95 per cent c.i. 1.15 to 1.51; BCSS: HR 1.31, 1.04 to 1.65). After stratification for type of breast surgery, this association remained significant only for women who had mastectomy without reconstruction (OS: HR 1.41, 1.20 to 1.66; BCSS: HR 1.36, 1.03 to 1.79). CONCLUSION: Major surgical postoperative complications are associated with inferior survival, especially after mastectomy. These results underline the importance of surgical de-escalation.

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.