Health-related quality of life (HRQoL) after different axillary treatments in women with breast cancer: a 1-year longitudinal cohort study.

PURPOSE: As life expectancy continues to rise, post-treatment health-related quality of life (HRQoL) of breast cancer patients becomes increasingly important. This study examined the one-year longitudinal relation between axillary treatments and physical, psychosocial, and sexual wellbeing and arm symptoms. METHODS: Women diagnosed with breast cancer who received different axillary treatments being axilla preserving surgery (APS) with or without axillary radiotherapy or full axillary lymph node dissection (ALND) with or without axillary radiotherapy were included. HRQoL was assessed at baseline, 6- and 12-months postoperatively using the BREAST-Q and the European Organization for Research and Treatment of Cancer QoL Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Mixed regression models were constructed to assess the impact of axillary treatment on HRQoL. HRQoL at baseline was compared to HRQoL at 6- and at 12-months postoperatively. RESULTS: In total, 552 patients were included in the mixed regressions models. Except for ALND with axillary radiotherapy, no significant differences in physical and psychosocial wellbeing were found. Physical wellbeing decreased significantly between baseline and 6- and 12-months postoperatively (p < 0.001, p = 0.035) and psychosocial wellbeing decreased significantly between baseline and 12 months postoperatively (p = 0.028) for ALND with axillary radiotherapy compared to APS alone. Arm symptoms increased significantly between baseline and 6 months and between baseline and 12 months postoperatively for APS with radiotherapy (12.71, 13.73) and for ALND with radiotherapy (13.93, 16.14), with the lowest increase in arm symptoms for ALND without radiotherapy (6.85, 7.66), compared to APS alone (p < 0.05). CONCLUSION: Physical and psychosocial wellbeing decreased significantly for ALND with radiotherapy compared to APS alone. Shared decision making and expectation management pre-treatment could be strengthened by discussing arm symptoms per axillary treatment with the patient.

Treatment of the axila in breast cancer surgery: Systematic review of its impact on survival. / Estado actual del tratamiento de la axila en la cirugía primaria del cáncer de mama: Revisión sistemática de su impacto en la supervivencia.

Sentinel lymph node biopsy and ACOSOG-Z0011 criteria have modified axillary treatment in breast cancer surgery. We performed a systematic review of studies assessing the impact of axillary treatment on survival. The search showed 6891 potentially eligible items. Of them, 23 clinical trials and 12 meta-analyses published between 1980 and 2017 met the study criteria. The review revealed that axillary lymph node dissection (ALND) can be omitted in patients pN0 and pN1mic, without compromising survival. In patients pN1 it is proposed not to treat the axilla or replace ALND for axillary radiotherapy. The main limitations of this study are the inclusion of old tests that do not use therapeutic targets and lack of risk categorization of relapse. In conclusion, axillary treatment can be avoided in patients without metastatic involvement or micrometastases in the sentinel lymph node. However, there is no evidence to make a recommendation of axillary treatment in N1 patients, so individualized analysis of patient risk factors is needed.

Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II). / Radioterapia axilar en la cirugía conservadora del cáncer de mama en estadio temprano (estadio I y II).

INTRODUCTION: Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. METHODS: Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. RESULTS: A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. CONCLUSION: The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors.

[Sentinel node biopsy and axillary clearence in early breast cancer--An algorithm with explanations and queries]. / Orszemnyirokcsomó-biopszia és axillaris blokkdissectio korai emlorákban--Algoritmus magyarázatokkal, nyitott kérdésekkel.

The introduction of sentinel lymph node biopsy in early breast cancer patients has substantially changed the approach to axillary management traditionally consisting of lymph node dissection. It has also rendered it more sophisticated. Several factors influence the decision on whether a patient should be offered sentinel lymph node biopsy or axillary lymph node dissection after the biopsy or instead of it. The potential options have been combined into an algorithm, of which each step is explained with the most important evidences in support or against summarized.

Radiotherapy Trends and Variations in Invasive Non-metastatic Breast Cancer Treatment in the Netherlands: A Nationwide Overview From 2008 to 2019.

AIMS: This nationwide study provides an overview of trends and variations in radiotherapy use as part of multimodal treatment of invasive non-metastatic breast cancer in the Netherlands in 2008-2019. MATERIALS AND METHODS: Women with invasive non-metastatic breast cancer were selected from the population-based Netherlands Cancer Registry. Treatments trends were presented over time. Factors associated with (1) boost irradiation in breast-conserving therapy and (2) regional radiotherapy instead of axillary lymph node dissection (ALND) in N+ disease were identified using multilevel logistic regression analyses. RESULTS: Radiotherapy use increased from 61% (2008) to 70% (2016), caused by breast-conserving therapy instead of mastectomy, increased post-mastectomy radiotherapy, and increased regional radiotherapy (32% in 2011 to 61% in 2019) instead of ALND in N+ disease. Omission of radiotherapy after breast-conserving surgery (BCS) in 2016-2019 (4-9%, respectively), mainly in elderly, decreased overall radiotherapy use to 67%. Radiotherapy treatment was further de-escalated by decreased boost irradiation in breast-conserving therapy (66% in 2011 to 37% in 2019) and partial (1% in 2011 to 6% in 2019) instead of whole breast irradiation following BCS. Boost irradiation was associated with high-risk features: younger age (OR>75 vs <50:0.04, 95%CI:0.03-0.05), higher grade (OR grade III vs I:11.46, 95%CI:9.90-13.26) and residual disease (OR focal residual vs R0-resection:28.08, 95%CI:23.07-34.17). Variation across the country was found for both boost irradiation use (OR South vs North:0.58, 95%CI:0.49-0.68), and regional radiotherapy instead of ALND (OR Southwest vs North:0.55, 95%CI:0.37-0.80). CONCLUSION: Overall radiotherapy use increased in 2008-2016, while a decreasing trend was observed after 2016, caused by post-BCS radiotherapy omission. Boost irradiation in breast-conserving therapy became omitted in low-risk patients, and regional radiotherapy use increased as an alternative for ALND in N+ disease.

Reevaluating Axillary Lymph Node Dissection in Total Mastectomy for Low Axillary Burden Breast Cancer: Insights from a Meta-Analysis including the SINODAR-ONE Trial.

Complete axillary lymph node dissection (cALND) was previously the standard of care for breast cancer (BC) patients with axillary node disease or macro-metastases found via sentinel lymph node biopsy (SLNB). However, due to significant morbidity, contemporary management now considers a more selective approach, influenced by studies like ACOSOG Z0011. This trial showed that cALND could be omitted without compromising local control or survival in patients with low axillary nodal disease burden undergoing breast-conserving therapy, radiotherapy, and systemic therapy. The relevance of this approach for women with low axillary nodal burden undergoing total mastectomy (TM) remained unclear. A PubMed search up to September 2023 identified 147 relevant studies, with 6 meeting the inclusion criteria, involving 4184 patients with BC and low-volume axillary disease (1-3 positive lymph nodes) undergoing TM. Postmastectomy radiotherapy receipt was similar in both groups. After a mean 7.2-year follow-up, both the pooled results and the meta-analysis revealed no significant differences in overall survival. The combined analysis of the published studies, including the subgroup analysis of the SINODAR-One trial, indicates no survival advantage for cALND over SLNB in T1-T2 breast cancer patients with 1-3 positive sentinel lymph nodes (pN1) undergoing mastectomy. This suggests that, following a multidisciplinary evaluation, cALND can be safely omitted. However, the impact of other patient, tumor, and treatment factors on survival requires consideration and therefore further prospective trials are needed for conclusive validation.

Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial).

Introduction: Breast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects. Methods and analyses: This multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival. Discussion: This study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity. Ethics and dissemination: The Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results. Trial registration: ClinicalTrials.gov, identifier number NCT04889924.

The role of irradiation in the management of the axilla in early breast cancer patients.

The need for axillary radiotherapy in patients with invasive breast cancer (IBC) has been a topic of great debate in the last decade. Management of the axilla has evolved significantly over the past four decades with a trend towards de-escalation of surgical interventions and the aim of reducing morbidity and enhancing QOL without compromising long-term oncology outcomes. This review article will address the role of axillary irradiation with a focus on the omission of completion axillary lymph node dissection in selected patients with sentinel lymph node (SLN) positive early breast cancer (EBC) with reference to current guidelines based on evidence to date.

De-escalating Locoregional Therapy for Axillary Micrometastases in Breast Cancer: How Much is Too Much?

BACKGROUND: The applicability of modern prospective data on adjuvant radiotherapy (RT) fields in patients with micrometastases is limited because many trials occurred prior to routine measurement of nodal metastasis size and modern sentinel lymph node evaluation techniques. We aimed to determine prognostic factors for patients with micrometastases and evaluate the impact of adjuvant RT on disease outcomes. PATIENTS AND METHODS: Patients diagnosed with pathologic T1-T3 N1mi breast cancers between 2004-2015 were identified. Cox proportional hazards methods were used to determine characteristics predictive of locoregional recurrence (LRR). Tumor and treatment-specific factors were further evaluated using log-rank statistics to compare rates of LRR-free survival. RESULTS: This analysis included 156 patients. On multivariable analysis, grade 3 histology (HR 10.84, 95% CI 2.72-43.21) and adjuvant RT (HR 0.22, 95% CI 0.06-0.81) were independent predictors of LRR. Among patients with grade 1-2 histology, 5-year LRR-free survival was 98.8% in patients who received adjuvant RT versus 100% in patients who did not receive adjuvant RT (P = .82). Among patients with grade 3 histology, 5-year LRR-free survival was 90.1% in patients who received adjuvant RT versus 53.0% in patients who did not receive adjuvant RT (P = .025), and 100% in patients receiving comprehensive nodal irradiation versus 76.7% in patients receiving whole breast irradiation or no RT (P = .045). CONCLUSION: Patients with grade 3 micrometastases are at substantial risk for LRR. Adjuvant RT, including comprehensive nodal irradiation, should be strongly considered in these women.

[Strategies in case of metastatic sentinel lymph node in breast cancer]. / Stratégies en cas de positivité du ganglion sentinelle dans les cancers du sein.

Management strategy of micro or macro metastatic sentinel lymph node(s) (SLNs) in breast cancer has dramatically changed over the past ten years and the publication of five randomized trials results: ACOSOG Z0011, IBCSG 23-01, and AATRM comparing axillary lymph node dissection (ALND) versus SLNs biopsy alone; and AMAROS and OTOASOR comparing ALND versus axillary radiotherapy. Despite methodological limitations of several of these trials, notably ACOSOG Z0011, the international recommendations (ASCO, NCCN) and the expert consensus of St Gallen do not recommend the performance of a complementary ALND in case of macro or micro metastatic SLN, if all ACOSOG Z0011 inclusion criteria are met. Moreover, in the context of a mastectomy, with one or two positive SLN and a wall irradiation indication, an axillary radiotherapy can be proposed as an alternative to ALND. Additionally, ALND is also indicated in extracapsular involvement or when three or more SLNs are metastatic. This change in strategy led to a significant decrease on the number of ALNDs performed and resulted on the abandon of SLNs extemporaneous examination. In France, there are no national recommendations on axillary management in the context of SLN involvement. Moreover, a multitude of different local guidelines, led to very heterogeneous practices in our country. The next evolution on axillary management strategy will be the implementation of a SLNs procedure after neoadjuvant chemotherapy (NAC) for patients with lymph node involvement proven before NAC and for whom NAC has allowed axillary downstaging.

Axillary Surgery Following Neoadjuvant Chemotherapy - Multidisciplinary Guidance From the Association of Breast Surgery, Faculty of Clinical Oncology of the Royal College of Radiologists, UK Breast Cancer Group, National Coordinating Committee for Breast Pathology and British Society of Breast Radiology.

AIMS: These multidisciplinary guidelines aim to provide clinically helpful, evidence-based recommendations on the surgical management of the axilla in patients who have received neo-adjuvant chemotherapy for early breast cancer. MATERIALS & METHODS: Following a review of published evidence, a writing group representing all disciplines quorate within a breast cancer multidisciplinary meeting prepared the guidelines. KEY RECOMMENDATIONS: In patients presenting with clinically node negative axillae, sentinel node biopsy (SNB) may be performed prior to or on completion of neo-adjuvant chemotherapy (NACT). In patients presenting with clinically node positive axillae, SNB may be safely considered following completion of NACT. Four nodes should be removed with dual mapping. If evidence of complete pathological response of previous metastases is seen, axillary radiotherapy may be offered. If residual cancer (isolated tumour cells, micro- or macrometastes) is seen within the SNB, offer axillary node dissection.

Impact of modern-day axillary treatment on patient reported arm morbidity and physical functioning in breast cancer patients.

PURPOSE: To reduce arm morbidity, routine axillary lymph node dissection (ALND) is often omitted or replaced by axillary radiotherapy (AxRT) in patients with limited nodal involvement. We evaluated patient-reported arm morbidity and physical functioning in breast cancer patients undergoing modern-day axillary treatment. METHODS: All patients within the UMBRELLA cohort undergoing local radiotherapy with sentinel lymph node biopsy (SLNB), ALND and/or AxRT were selected. Patient-reported arm morbidity and physical functioning were assessed with EORTC QLQ C30/BR23 questionnaires up to eighteen months after initiation of radiotherapy. Patient-reported outcomes were compared between patients with SLNB only, ALND only, AxRT (level I-II), AxRT (level I-IV) or AxRT plus ALND by means of mixed model analysis. RESULTS: In total, 949 patients were identified; 641 (68%) SLNB only, 57 (6%) ALND only, 94 (10%) AxRT level I-II, 72 (8%) AxRT level I-IV and 85 (9%) ALND + AxRT. SLNB only resulted in the least arm morbidity scores. ALND + AxRT resulted in most arm morbidity, with clinically relevant differences at 18 months. AxRT (level I-II or level I-IV) resulted in significantly less arm symptoms in the first 3 months compared to ALND. Arm symptom scores between those receiving AxRT on levels I-II and I-IV were similar. CONCLUSION: Of all axillary management strategies, ALND plus AxRT is associated with worst patient-reported outcomes. AxRT resulted in less arm morbidity compared to ALND. Selective radiotherapy treatment of the axilla, i.e. radiotherapy of levels I-II only instead of levels I-IV, did not lead to clinically relevant reduced arm morbidity.

Can Complete Axillary Node Dissection Be Safely Omitted in Patients with Early Breast Cancer When the Sentinel Node Biopsy Is Positive for Malignancy? An Update for Clinical Practice.

The sentinel lymph node biopsy (SLNB) has become the new standard-of-care for patients with clinically node-negative invasive breast cancer. The focused examination of fewer lymph nodes in addition to improvements in histopathological and molecular analysis have increased the rate at which micrometastases and isolated tumor cells are identified. We reviewed the literature and summarized the evidence regarding the need for complete axillary lymph node dissection (ALND) following the finding of a positive sentinel node biopsy through the identification of the most important outcomes and evaluation of quality of evidence. The article focuses on the safe omission of complete ALND when the axillary lymph nodes contain macrometastases and provides an overview of the topic primarily based on level 1 evidence derived from randomized clinical trials with a critical appraisal of the ACOSOG Z0011 trial.

The State of Surgical Axillary Management and Adjuvant Radiotherapy for Early-stage Invasive Breast Cancer in the Modern Era.

BACKGROUND: For clinical T1-2N0 breast cancer, sentinel lymph node biopsy (SLNB) has been shown in American College of Surgeons Oncology Group (ACOSOG) Z0011 to be sufficient for women with 1 to 2 positive sentinel lymph nodes with no added benefit for completion axillary lymph node dissection (ALND). Z0011 specified whole breast radiotherapy (RT) using standard tangential fields; however, later analysis showed variation in field design. We assessed nationwide practice patterns and examined factors associated with patients undergoing completion ALND and subsequent radiation field design. PATIENTS AND METHODS: Women with clinical T1-2N0 breast cancer who underwent breast-conserving surgery, axillary staging, and whole breast RT in 2012 to 2013 were identified in the National Cancer Database. Multivariable logistic regression modeling was used to examine axillary management and RT, adjusting for demographic and clinicopathologic factors. RESULTS: Among 83,555 patients meeting criteria, 9.3% underwent upfront ALND, 75.8% underwent SLNB only, and 14.9% underwent SLNB with completion ALND. From 2012 to 2013, upfront SLNB increased from 90.1% to 91.4% (odds ratio, 1.14; P < .001). Among 9474 patients that underwent SLNB with 1 to 2 positive sentinel nodes, 31.2% received completion ALND. Among patients with 1 to 2 positive sentinel nodes, SLNB increased from 65.8% to 72.1% from 2012 to 2013 (P < .001). For patients with 1 to 2 positive lymph nodes that underwent SLNB only, 63.4% underwent breast RT, whereas 36.6% received breast and nodal RT. CONCLUSIONS: Nationwide practice patterns of axillary management vary. Despite an increasing rate of SLNB, many patients still receive upfront and completion ALND. Furthermore, there is significant variation in RT field design, and modern treatment guidelines are warranted for this patient population.

Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (TAXIS): study protocol for a multicenter, randomized phase-III trial.

BACKGROUND: Complete lymph node removal through conventional axillary dissection (ALND) has been standard treatment for breast cancer patients for almost a century. In the 1990s, however, and in parallel with the advent of the sentinel lymph node (SLN) procedure, ALND came under increasing scrutiny due to its association with significant patient morbidity. Several studies have since provided evidence to suggest omission of ALND, often in favor of axillary radiation, in selected clinically node-negative, SLN-positive patients, thus supporting the current trend in clinical practice. Clinically node-positive patients, by contrast, continue to undergo ALND in many cases, if only for the lack of studies re-assessing the indication for ALND in these patients. Hence, there is a need for a clinical trial to evaluate the optimal treatment for clinically node-positive breast cancer patients in terms of surgery and radiotherapy. The TAXIS trial is designed to fill this gap by examining in particular the value of tailored axillary surgery (TAS), a new technique for selectively removing positive lymph nodes. METHODS: In this international, multicenter, phase-III, non-inferiority, randomized controlled trial (RCT), including 34 study sites from four different countries, we plan to randomize 1500 patients to either receive TAS followed by ALND and regional nodal irradiation excluding the dissected axilla, or receive TAS followed by regional nodal irradiation including the full axilla. All patients undergo adjuvant whole-breast irradiation after breast-conserving surgery and chest-wall irradiation after mastectomy. The main objective of the trial is to test the hypothesis that treatment with TAS and axillary radiotherapy is non-inferior to ALND in terms of disease-free survival of clinically node-positive breast cancer patients in the era of effective systemic therapy and extended regional nodal irradiation. The trial was activated on 31 July 2018 and the first patient was randomized on 7 August 2018. DISCUSSION: Designed to test the hypothesis that TAS is non-inferior to ALND in terms of curing patients and preventing recurrences, yet is significantly superior in reducing patient morbidity, this trial may establish a new worldwide treatment standard in breast cancer surgery. If found to be non-inferior to standard treatment, TAS may significantly contribute to reduce morbidity in breast cancer patients by avoiding surgical overtreatment. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03513614. Registered on 1 May 2018. www.kofam.ch , ID: NCT03513614 . Registered on 17 June 2018. EudraCT No.: 2018-000372-14.

Quantifying radiation dose delivered to individual shoulder muscles during breast radiotherapy.

BACKGROUND AND PURPOSE: Radiotherapy is an effective treatment for managing breast cancer, but patients may experience shoulder morbidity after completing radiotherapy. There is a knowledge gap regarding how the inclusion of the regional lymphatics in radiation treatment regimens influence the radiation dose delivered to the underlying shoulder musculature. MATERIAL AND METHODS: Five standardized radiation treatment regimens were developed from the computed tomography (CT) scans of 11 patients: tangent fields only (T), high tangent fields (HT), T+supraclavicular fossa and axillary apex with an anterior oblique beam (SCV), T+SCV+axillary nodes with an anterior oblique beam (SCV+AX), and T+SCV+AX with the nodal regions treated with a directly opposed beam configuration (DO). The muscle volumes for nine shoulder muscles anatomically located with the treatment regimens were segmented from the same CT scans. The effect of the nine muscles and five treatment regimens on the percentage of each muscle receiving at least 48Gy (V48Gy) was analyzed with two-way and one-way repeated measures ANOVAs. RESULTS: A statistically significant interaction existed between the nine shoulder muscles and five treatment regimens (p<0.001) on the V48Gy dose. Subsequent one-way analyses found statistically significant main effects of treatment plan on the V48Gy dose for each muscle (p<0.001). The pectoralis major and minor had the greatest V48 doses across the five treatments regimens. The HT, SCV+AX and DO treatment regimens produced statistically significant increases in the V48 dose of the latissimus dorsi and teres major. The infraspinatus, subscapularis, supraspinatus, teres minor, and trapezius only observed statistically significant V48 doses when treated with a DO plan. CONCLUSIONS: These findings highlight the muscles (pectoralis major, pectoralis minor, latissimus dorsi, and teres major) that may exhibit future morbidity after radiation, and indicate that nodal RT delivered with a DO beam arrangement delivers the highest muscle dose.

Can axillary radiotherapy replace axillary dissection for patients with positive sentinel nodes? A systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of axillary radiotherapy (ART) with that of completion axillary lymph node dissection (cALND) in clinically node-negative breast cancer patients with a positive sentinel lymph node. METHODS: A literature search was performed in PubMed, EMBASE and Cochrane Library by using the search terms "breast cancer", "sentinel lymph node biopsy", "axillary radiotherapy" or "regional node irradiation" for articles published between 2004 and 2016. Only randomized controlled trials that included patients with positive sentinel nodes were included in the meta-analysis. RESULTS: Two randomized controlled trials and three retrospective studies were identified. The reported overall survival rate (hazard ratio [HR] = 1.09, 95% confidence interval [CI]: 0.75-1.43, P = 0.365), disease-free survival rate (HR = 1.01, 95% CI: 0.58-1.45, P = 0.144), and axillary recurrence rate (1.2% and 0.4%, and 1.3% and 0.8%, respectively) were similar in both groups. The absence of knowledge on the extent of nodal involvement in the ART group appeared to have no major impact on the administration of adjuvant systemic therapy. CONCLUSIONS: ART is not inferior to cALND in the patients with clinically node-negative breast cancer who had a positive sentinel lymph node. Information obtained by using cALND after SLNB may have no major impact on the administration of adjuvant systemic therapy.

[Prophylactic axillary radiotherapy for breast cancer]. / Radiothérapie axillaire prophylactique des cancers du sein.

Adjuvant radiotherapy, after breast conserving surgery or mastectomy for breast cancer, improves overall survival while decreasing the risk of recurrence. However, prophylactic postoperative radiotherapy of locoregional lymph nodes for breast cancer, particularly of the axillary region, is still controversial since the benefits and the risks due to axillary irradiation have not been well defined. To begin with, when performing conformal radiotherapy, volume definition is crucial for the analysis of the risk-benefit balance of any radiation treatment. Definition and contouring of the axillary lymph node region is discussed in this work, as per the recommendations of the European Society for Radiotherapy and Oncology (ESTRO). Axillary recurrences are rare, and the recent trend leads toward less aggressive surgery with regard to the axilla. In this literature review we present the data that lead us to avoid adjuvant axillary radiotherapy in pN0, pN0i+ and pN1mi patients even without axillary clearance and to perform it in some other situations. Finally, we propose an update about the potential toxicity of adjuvant axillary irradiation, which is essential for therapeutic decision-making based on current evidence, and to guide us in the evolution of our techniques and indications of axillary radiotherapy.

Towards optimal management of the axilla in the context of a positive sentinel node biopsy in early breast cancer.

The sentinel lymph node biopsy (SLNB) was initially pioneered for staging melanoma in 1994 and it has been subsequently validated by several trials, and has become the new standard of care for patients with clinically node negative invasive breast cancer. The focussed examination of fewer lymph nodes in addition to improvements in histopathological and molecular analysis has increased the rate at which micrometastases and isolated tumour cells are identified. In this article we review the literature regarding the optimal management of the axilla when the SLNB is positive for metastatic disease based on level 1 evidence derived from randomised clinical trials.

High Ki67 predicts unfavourable outcomes in early breast cancer patients with a clinically clear axilla who do not receive axillary dissection or axillary radiotherapy.

AIM: Axillary dissection is increasingly forgone in early breast cancer patients with a clinically negative axilla. The GRISO 053 randomised trial recruited 435 patients of age over 45 years, tumour ≤1.4 cm and clinically negative axilla, to assess the importance of axillary radiotherapy versus no axillary radiotherapy in patients not given axillary dissection. In the present study on a subgroup GRISO cases our aim was to assess the prognostic importance of tumour biological factors after more than 10 years of follow-up. METHODS: We retrospectively assessed biological factors in a subgroup of 285 GRISO cases (145 given axillary radiotherapy; 140 not given axillary radiotherapy) with complete biologic, therapeutic and follow-up information, using multivariable Cox proportional hazards regression modelling. RESULTS: Only 10-year cumulative incidence of distant metastasis was lower in the axillary radiotherapy (1%) than no axillary radiotherapy arm (7%) (p=0.037). Irrespective of study arm, hormone receptor positivity had significantly favourable effects on 10-year disease-free survival (DFS) and overall survival. human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes were associated with lower 10-year DFS (60% and 76%, respectively) than luminal A (96%) and B (91%) (p=0.001). Ten-year DFS for high (≥14%) Ki67 cancers was lower than for low Ki67 cancers (p=0.027); however, this effect was mainly confined to the no axillary radiotherapy arm. CONCLUDING STATEMENT: For patients with clinically node-negative small breast cancer not given axillary dissection, 10-year DFS is worsened by HER2 positivity, triple-negative phenotype and high Ki67. Axillary radiotherapy counteracts the negative prognostic effect of high Ki67 in patients not receiving axillary dissection.