Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023.

The 18th St Gallen International Breast Cancer Conference held in March 2023, in Vienna, Austria, assessed significant new findings for local and systemic therapies for early breast cancer with a focus on the evaluation of multimodal treatment options. The emergence of more effective, innovative agents in both the preoperative (primary or neoadjuvant) and post-operative (adjuvant) settings has underscored the pivotal role of a multidisciplinary approach in treatment decision making, particularly when selecting systemic therapy for an individual patient. The importance of multidisciplinary discussions regarding the clinical benefits of interventions was explicitly emphasized by the consensus panel as an integral part of developing an optimal treatment plan with the 'right' degree of intensity and duration. The panelists focused on controversies surrounding the management of common ductal/no special type and lobular breast cancer histology, which account for the vast majority of breast tumors. The expert opinion of the panelists was based on interpretations of available data, as well as current practices in their professional environments, personal and socioeconomic factors affecting patients, and cognizant of varying reimbursement and accessibility constraints around the world. The panelists strongly advocated patient participation in well-designed clinical studies whenever feasible. With these considerations in mind, the St Gallen Consensus Conference aims to offer guidance to clinicians regarding appropriate treatments for early-stage breast cancer and assist in balancing the realistic trade-offs between treatment benefit and toxicity, enabling patients and clinicians to make well-informed choices through a shared decision-making process.

ESMO Expert Consensus Statements on the management of breast cancer during pregnancy (PrBC).

The management of breast cancer during pregnancy (PrBC) is a relatively rare indication and an area where no or little evidence is available since randomized controlled trials cannot be conducted. In general, advances related to breast cancer (BC) treatment outside pregnancy cannot always be translated to PrBC, because both the interests of the mother and of the unborn should be considered. Evidence remains limited and/or conflicting in some specific areas where the optimal approach remains controversial. In 2022, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process on this topic to gain insights from a multidisciplinary group of experts and develop statements on controversial topics that cannot be adequately addressed in the current evidence-based ESMO Clinical Practice Guideline. The aim of this consensus-building process was to discuss controversial issues relating to the management of patients with PrBC. The virtual meeting included a multidisciplinary panel of 24 leading experts from 13 countries and was chaired by S. Loibl and F. Amant. All experts were allocated to one of four different working groups. Each working group covered a specific subject area with two chairs appointed: Planning, preparation and execution of the consensus process was conducted according to the ESMO standard operating procedures.

ESO-ESMO fifth international consensus guidelines for breast cancer in young women (BCY5).

We dedicate this manuscript in memory of a dear friend and colleague Bella Kaufman. The fifth International Consensus Symposium for Breast Cancer in Young Women (BCY5) took place virtually in October 2020, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY4 with incorporation of new evidence to inform the guidelines. Areas of research priorities as well as specificities in different geographic and minority populations were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.

The 17th St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID-19 pandemic. More than 3300 participants took part in this important bi-annual critical review of the 'state of the art' in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix 1) from all continents discussed and commented on the previously elaborated consensus questions, as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's conference was 'Customizing local and systemic therapies.' A well-organized program of pre-recorded symposia, live panel discussions and real-time panel voting results drew a worldwide audience of thousands, reflecting the far-reaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early-stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response before surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response.

ESO-ESMO 4th International Consensus Guidelines for Breast Cancer in Young Women (BCY4).

The 4th International Consensus Conference for Breast Cancer in Young Women (BCY4) took place in October 2018, in Lugano, Switzerland, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY3 with incorporation of new evidence to inform the guidelines. Areas of research priorities were also identified. This article summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019.

BACKGROUND: The 16th St. Gallen International Breast Cancer Conference 2019 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. DESIGN: Treatments were assessed in light of their intensity, duration and side-effects, estimating the magnitude of clinical benefit according to stage and biology of the disease. The Panel acknowledged that for many patients, the impact of adjuvant therapy or the adherence to specific guidelines may have modest impact on the risk of breast cancer recurrence or overall survival. For that reason, the Panel explicitly encouraged clinicians and patients to routinely discuss the magnitude of benefit for interventions as part of the development of the treatment plan. RESULTS: The guidelines focus on common ductal and lobular breast cancer histologies arising in generally healthy women. Special breast cancer histologies may need different considerations, as do individual patients with other substantial health considerations. The panelists' opinions reflect different interpretation of available data and expert opinion where is lack of evidence and sociocultural factors in their environment such as availability of and access to medical service, economic resources and reimbursement issues. Panelists encourage patient participation in well-designed clinical studies whenever available. CONCLUSIONS: With these caveats in mind, the St. Gallen Consensus Conference seeks to provide guidance to clinicians on appropriate treatments for early-stage breast cancer and guidance for weighing the realistic tradeoffs between treatment and toxicity so that patients and clinical teams can make well-informed decisions on the basis of an honest reckoning of the magnitude of clinical benefit.

Gynecologic cancers in pregnancy: guidelines based on a third international consensus meeting.

We aimed to provide comprehensive protocols and promote effective management of pregnant women with gynecological cancers. New insights and more experience have been gained since the previous guidelines were published in 2014. Members of the International Network on Cancer, Infertility and Pregnancy (INCIP), in collaboration with other international experts, reviewed existing literature on their respective areas of expertise. Summaries were subsequently merged into a manuscript that served as a basis for discussion during the consensus meeting. Treatment of gynecological cancers during pregnancy is attainable if management is achieved by collaboration of a multidisciplinary team of health care providers. This allows further optimization of maternal treatment, while considering fetal development and providing psychological support and long-term follow-up of the infants. Nonionizing imaging procedures are preferred diagnostic procedures, but limited ionizing imaging methods can be allowed if indispensable for treatment plans. In contrast to other cancers, standard surgery for gynecological cancers often needs to be adapted according to cancer type and gestational age. Most standard regimens of chemotherapy can be administered after 14 weeks gestational age but are not recommended beyond 35 weeks. C-section is recommended for most cervical and vulvar cancers, whereas vaginal delivery is allowed in most ovarian cancers. Breast-feeding should be avoided with ongoing chemotherapeutic, endocrine or targeted treatment. More studies that focus on the long-term toxic effects of gynecologic cancer treatments are needed to provide a full understanding of their fetal impact. In particular, data on targeted therapies that are becoming standard of care in certain gynecological malignancies is still limited. Furthermore, more studies aimed at the definition of the exact prognosis of patients after antenatal cancer treatment are warranted. Participation in existing registries (www.cancerinpregnancy.org) and the creation of national tumor boards with multidisciplinary teams of care providers (supplementary Box S1, available at Annals of Oncology online) is encouraged.

Discrepancies between biomarkers of primary breast cancer and subsequent brain metastases: an international multicenter study.

PURPOSE: Discordances between the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), expression between primary breast tumors and their subsequent brain metastases (BM) were investigated in breast cancer patients. METHODS: We collected retrospective data from 11 institutions in 8 countries in a predefined-standardized format. Receptor status (positive or negative) was determined according to institutional guidelines (immunohistochemically and/or fluorescence in situ hybridization). The study was subject to each institution's ethical research committee. RESULTS: A total of 167 breast cancer patients with BM were included. 25 patients out of 129 with a complete receptor information from both primary tumor and BM (ER, PR, HER2) available, had a change in receptor status: 7 of 26 (27%) ER/PR-positive/HER2-negative primaries (3 gained HER2; 4 lost expression of ER/PR); 10 of 31 (32%) ER/PR-positive/HER2-positive primaries (4 lost ER/PR only; 3 lost HER2 only; 3 lost both ER/PR and HER2); one of 33 (3%) ER/PR-negative receptor/HER2-positive primaries (gained ER); and 7 of 39 (18%) triple-negative primaries (5 gained ER/PR and 2 gained HER2). CONCLUSIONS: The majority of breast cancer patients with BM in this series had primary HER2-enriched tumors, followed by those with a triple-negative profile. One out of 5 patients had a receptor discrepancy between the primary tumor and subsequent BM. Therefore, we advise receptor status assessment of BM in all breast cancer patients with available histology as it may have significant implications for therapy.

Lack of beneficial effects of low-dose radiation therapy on hand osteoarthritis symptoms and inflammation: a randomised, blinded, sham-controlled trial.

OBJECTIVES: Low-dose radiation therapy (LDRT) is widely used as treatment for osteoarthritis (OA) in some countries, while relatively unknown in others. Systematic literature review displayed a lack of high-level evidence for beneficial effects in clinical practice. The aim was to assess the efficacy of LDRT on symptoms and inflammation in hand OA patients in a randomised, blinded, sham-controlled trial, using validated outcome measures. DESIGN: Hand OA patients, ≥50 years, with pain ≥5 (scale 0-10) and non-responding to conservative therapy were included and randomised 1:1 to receive LDRT (6 × 1 Gy in 2 weeks) or sham (6 × 0 Gy in 2 weeks). Primary outcome was the proportion of OMERACT-OARSI responders, 3 months post-intervention. Secondary outcomes were pain and functioning (Australian/Canadian Hand Osteoarthritis Index; AUSCAN), quality of life (Short Form Health Survey; SF36) and inflammatory outcomes: erythrocyte sedimentation rate and C-reactive protein serum levels, effusion, synovial thickening and power Doppler signal on ultrasound (range 0-3). RESULTS: Fifty-six patients were included. After 3 months, no significant difference in responders was observed between groups (LDRT: 8 (29%); sham: 10 (36%); difference -7% (95%CI -31-17%)). Also, differences in clinical and inflammatory outcomes between groups were small and not significant. CONCLUSIONS: We were unable to demonstrate a substantial beneficial effect of LDRT on symptoms and inflammation in patients with hand OA, compared to sham treatment. Although a small effect can not be excluded, a treatment effect exceeding 20% is very unlikely, given the confidence interval. Therefore, in the absence of other high-level evidence, we advise against the use LDRT as treatment for patients with hand OA. CLINICAL TRIAL REGISTRATION NUMBER: NTR4574 (Dutch Trial Register).

Nationwide population-based study of trends and regional variation in breast-conserving treatment for breast cancer.

BACKGROUND: Landmark trials have shown breast-conserving surgery (BCS) combined with radiotherapy to be as safe as mastectomy in breast cancer treatment. This population-based study aimed to evaluate trends in BCS from 1989 to 2015 in nine geographical regions in the Netherlands. METHODS: All women diagnosed between 1989 and 2015 with primary T1-2 N0-1 breast cancer, treated with BCS or mastectomy, were identified from the Netherlands Cancer Registry. Crude and case mix-adjusted rates of BCS were evaluated and compared between nine Dutch regions for two time intervals: 1989-2002 and 2003-2015. The annual percentage change in BCS per region over time was assessed by means of Joinpoint regression analyses. Explanatory variables associated with the choice of initial surgery were evaluated using multivariable logistic regression. RESULTS: A total of 202 934 patients were included, 82 200 treated in 1989-2002 and 120 734 in 2003-2015. During 1989-2002, the mean rate of BCS was 50·6 per cent, varying significantly from 39·0 to 71·7 per cent between the nine regions. For most regions, a marked rise in BCS was observed between 2002 and 2003. During 2003-2015, the mean rate of BCS increased to 67·4 per cent, but still varied significantly between regions from 58·5 to 75·5 per cent. A significant variation remained after case-mix correction. CONCLUSION: This large nationwide study showed that the use of BCS increased from 1989 to 2015 in the Netherlands. After adjustment for explanatory variables, a large variation still existed between the nine regions. This regional variation underlines the need for implementation of a uniform treatment and decision-making strategy.

Incidence of second tumors after treatment with or without radiation for rectal cancer.

Background: The aim of this study was to analyze the association between radiation therapy (RT) for rectal cancer and the development of second tumors. Patients and methods: Data on all surgically treated non-metastatic primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from the Netherlands population-based cancer registry. Fine and Gray's competing risk model was used for estimation of the cumulative incidence of second tumors. Multivariable analysis was conducted using Cox regression. Results: The cohort consisted of 29 027 patients of which 15 467 patients had undergone RT. Median follow-up was 7.7 years (range 0-27). Among all 4398 patients who were diagnosed with a second primary tumor, 1030 had one or more pelvic tumors. The standardized incidence risk for any second tumor was 1.16 (95% confidence interval [CI] 1.12-1.19), resulting in 27.7/10 000 excess cancer cases per year in patients treated for rectal cancer compared with the general population. RT reduced the cumulative incidence of second pelvic tumors compared with patients who did not receive RT (subhazard ratio [SHR] 0.77, CI 0.68-0.88). Second prostate tumors were less common in patients who received RT (SHR 0.54, CI 0.46-0.64), gynecological tumors were more frequently observed in patients who received RT (SHR 1.49, CI 1.11-2.00). Conclusions: Patients with previous rectal cancer had a marginally increased risk of a second tumor compared with the general population. Gynecological tumors occurred more often in females who received RT, but this did not result in an overall increased risk for a second cancer. RT even seemed to have a protective effect on the development of other second pelvic tumors, pre-dominantly for prostate cancer. These findings are highly important and can contribute to improved patient counseling.

Patterns and predictors of first and subsequent recurrence in women with early breast cancer.

PURPOSE: Little is known about the occurrence, timing and prognostic factors for first and also subsequent local (LR), regional (RR) or distant (DM) breast cancer recurrence. As current follow-up is still consensus-based, more information on the patterns and predictors of subsequent recurrences can inform more personalized follow-up decisions. METHODS: Women diagnosed with stage I-III invasive breast cancer who were treated with curative intent were selected from the Netherlands Cancer Registry (N = 9342). Extended Cox regression was used to model the hazard of recurrence over ten years of follow-up for not only site-specific first, but also subsequent recurrences after LR or RR. RESULTS: In total, 362 patients had LR, 148 RR and 1343 DM as first recurrence. The risk of first recurrence was highest during the second year post-diagnosis (3.9%; 95% CI 3.5-4.3) with similar patterns for LR, RR and DM. Young age (<40), tumour size >2 cm, tumour grade II/III, positive lymph nodes, multifocality and no chemotherapy were prognostic factors for first recurrence. The risk of developing a second recurrence after LR or RR (N = 176) was significantly higher after RR than after LR (50 vs 29%; p < 0.001). After a second LR or RR, more than half of the women were diagnosed with a third recurrence. CONCLUSIONS: Although the risk of subsequent recurrence is high, absolute incidence remains low. Also, almost half the second recurrences are detected in the first year after previous recurrence and more than 80% are DM. This suggests that more intensive follow-up for early detection subsequent recurrence is not likely to be (cost-)effective.

Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

BACKGROUND: Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. METHODS: The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. DISCUSSION: If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. TRIAL REGISTRATION: The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

Breast-conserving therapy versus mastectomy in T1-2N2 stage breast cancer: a population-based study on 10-year overall, relative, and distant metastasis-free survival in 3071 patients.

PURPOSE: Our previous study demonstrated breast-conserving surgery with radiation therapy (BCT) to be at least equivalent to mastectomy in T1-2N0-1 breast cancer. Yet, 10-year survival rates after BCT and mastectomy with radiation therapy (MAST) in T1-2N2 breast cancer specifically have not been examined. Our study aimed to determine 10-year overall (OS), relative (RS), and distant metastasis-free survival (DMFS) in T1-2N2 breast cancer after BCT and MAST, stratified for T category. METHODS: All women diagnosed with primary invasive T1-2N2 breast cancer in 2000-2004, treated with BCT or MAST, both with axillary dissection and RT, were selected from the Netherlands Cancer Registry. Ten-year OS and DMFS were estimated using multivariable Cox regression. Excess mortality ratios (EMR) were calculated to estimate RS, using life tables of the general population. OS and RS were determined on the whole cohort, and DMFS on the 2003 cohort with completed follow-up. Missing data were imputed. RESULTS: Of 3071 patients, 1055 (34.4 %) received BCT and 2016 (65.7 %) MAST. BCT and MAST showed equal 10-year OS and RS. After stratification, BCT was significantly associated with improved 10-year OS [HRadjusted 0.82 (95 % CI 0.71-0.96)] and RS (EMRadjusted 0.81 (95 % CI 0.67-0.97]) in T2N2, but not in T1N2. Ten-year DMFS was equal for both treatments [HRadjusted 0.87 (95 % CI 0.64-1.18)] in the 2003 cohort (n = 594), which was representative for the full cohort. CONCLUSION: BCT showed at least equal 10-year OS, RS, and DMFS compared to MAST. These results confirm that BCT is a good treatment option in T1-2N2 breast cancer.

Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey.

BACKGROUND: Predicting outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is an area of uncertainty. It influences the decision-making for regional nodal irradiation (RNI). The aim of the NORA (NOdal RAdiotherapy) survey was to examine the patterns of RNI. METHODS: A web-questionnaire, including several clinical scenarios, was distributed to 88 EORTC-affiliated centers. Responses were received between July 2013 and January 2014. RESULTS: A total of 84 responses were analyzed. While three-dimensional (3D) radiotherapy (RT) planning is carried out in 81 (96%) centers, nodal areas are delineated in only 51 (61%) centers. Only 14 (17%) centers routinely link internal mammary chain (IMC) and supraclavicular node (SCN) RT indications. In patients undergoing total mastectomy (TM) with ALND, SCN-RT is recommend by 5 (6%), 53 (63%) and 51 (61%) centers for patients with pN0(i+), pN(mi) and pN1, respectively. Extra-capsular extension (ECE) is the main factor influencing decision-making RNI after breast conserving surgery (BCS) and TM. After primary systemic therapy (PST), 49 (58%) centers take into account nodal fibrotic changes in ypN0 patients for RNI indications. In ypN0 patients with inner/central tumors, 23 (27%) centers indicate SCN-RT and IMC-RT. In ypN1 patients, SCN-RT is delivered by less than half of the centers in patients with ypN(i+) and ypN(mi). Twenty-one (25%) of the centers recommend ALN-RT in patients with ypN(mi) or 1-2N+ after ALND. Seventy-five (90%) centers state that age is not considered a limiting factor for RNI. CONCLUSION: The NORA survey is unique in evaluating the impact of SLNB/ALND status on adjuvant RNI decision-making and volumes after BCS/TM with or without PST. ALN-RT is often indicated in pN1 patients, particularly in the case of ECE. Besides the ongoing NSABP-B51/RTOG and ALLIANCE trials, NORA could help to design future specific RNI trials in the SLNB era without ALND in patients receiving or not PST.

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.

The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial (BOOG 2013-07).

BACKGROUND: Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013-07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy. DESIGN: This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up. DISCUSSION: We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival. TRIAL REGISTRATION: The BOOG 2013-07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682 .