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The goal of regional treatments in breast cancer should be to eradicate any disease within lymph nodes, avoid regional recurrences, minimize the risk of distant metastases, and improve survival. In addition, regional treatments should focus on reducing potential morbidities and optimizing the long-term quality of life of breast cancer survivors. While data from recent surgical and radiation trials have helped clarify many issues regarding regional treatment, there still remains controversy as to the optimal approach for patients with “intermediate risk” disease. Two large radiation oncology studies (MA.20 and EORTC2292-10925) evaluated whether more extensive lymphatic treatment benefited patients with higher-risk lymph node-negative, or lower risk lymph node-positive disease. A meta-analysis of these two studies suggested that the addition of regional nodal irradiation (RNI) to the level III axillary, supraclavicular and upper internal mammary lymph nodes conferred an improvement in disease free survival and distant metastasis free survival as well as a 1–2% overall survival advantage. However, other studies have suggested that many patients with positive sentinel lymph nodes who are treated with breast conservation including breast irradiation may safely avoid the morbidity and costs of further axillary treatment (whether surgical or radiotherapy-based). In general, patients with 1–3 positive lymph nodes or high-risk, node negative stage II breast cancer represent a diverse population who require individualized, rather than group-based, risk assessment when considering RNI. This article will propose a strategic methodology to assess the modern day breast cancer patient's need for RNI in the setting of changing surgical, radiation, and systemic therapies. [ABSTRACT FROM AUTHOR]

Optimal regional management in breast cancer patients has yet to be established. In patients who are clinically node-negative, but sentinel lymph node biopsy (SLNB)-positive, the treatment paradigm has shifted toward the de-escalation of further axillary management. In patients with 2 or fewer positive sentinel nodes, the standard of practice has shifted away from complete axillary lymph node dissection (ALND) as a result of the ACOSOG Z0011 trial. The role of regional nodal irradiation (RNI) to the axilla, supraclavicular and internal mammary regions has also been investigated in the setting of positive SLNB in trials such as the MA20 and EORTC 22922. Having shown evidence of benefit in locoregional control, efforts are now focused on comparing ALND with RNI in patients with limited nodal disease. Results of early trials such as AMAROS suggest noninferiority of radiotherapy. In patients with node-positive or locally advanced disease, neoadjuvant chemotherapy (NAC) is often used to downsize or downstage the disease. The utility of SLNB after NAC has been investigated, with discordant results reported from a number of trials. Current trials in progress seek to validate the noninferiority of RNI compared with ALND in patients with limited nodal disease, or in some trials, the complete omission of further axillary management. There is a global paradigm shift toward de-escalation of axillary management on the basis of recent evidence suggesting lack of benefit from overaggressive treatment. In this review we aim to summarize the seminal trials addressing regional management in breast cancer to illustrate this fact., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Standard of care in breast cancer management is well-defined. However, some gray zones still exist, in particular adjuvant radiotherapy indications in case of pN1mi breast cancer. Here we propose to define their prognosis, to underpin the benefit of adjuvant treatments in such patients' management and to define lymphedema risk, which is the most common late side effect of locoregional treatments., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: We analyzed the toxicity and cosmetic outcomes for patients who had undergone 3-dimensional conformal radiotherapy with a hypofractionated schedule and identified the risk factors associated with such a schedule., Materials and Methods: A total of 143 patients were treated for breast cancer (stage 0-III) with a hypofractionated radiation schedule after breast-conserving surgery from 2006 to 2011. Most patients received 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction to the whole breast plus an additional simultaneous integrated or sequential boost to the tumor bed., Results: The median follow-up period was 36 months. Mild acute skin toxicity was observed in 62%; 7% of the patients developed moderate skin toxicity, but no grade 4 toxicity was observed. The prevalence of fibrosis within the boost area was 5%, but no grade ≥ 2 was observed. The prevalence of fibrosis of any grade was greater in the nonboost (23%) than in the boost area. Of all the patients, 91% had good or excellent cosmetic outcomes. From the multivariate analysis, the incidence of epithelitis correlated with the patient's treated volume (P = .044). The incidence of acute toxicity correlated with the boost type to the tumor bed and the total treatment dose (P = .012 and P = .002, respectively). Also, a poor to fair cosmetic outcome was significantly associated statistically with the surgery type (P = .05), boost type (P = .004), and total dose (P = .001)., Conclusion: Delivering whole-breast irradiation with a hypofractionated schedule of 42.4 Gy plus a simultaneous integrated boost to the tumor bed appears to be a safe and effective technique, with good cosmetic results and lower toxicity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Summary: The role of immune surveillance in controlling the spread of breast cancer to the regional nodes is poorly understood. In theory regional nodal irradiation (RNI) might compromise this host function. However the clinical evidence suggests that the risk of regional recurrence is lower in patients with early breast cancer whose axilla has been irradiated compared to no axillary treatment. The role of RNI after breast conserving surgery has not been well studied. A policy of level III clearance and only irradiating the axilla for residual disease and a selective policy of axillary irradiation in node positive patients after sentinel node biopsy or lower axillary node sample is recommended. Irradiation of the medial supraclavicular fossa after axillary dissection is suggested where there are four or more nodes involved on axillary dissection. There is little data to inform selection of patients for RNI after neoadjuvant systemic therapy. The role of postmastectomy radiotherapy (PMRT) was largely established on the basis of comprehensive RNI. It is unclear whether irradiating less than the chest wall and peripheral lymphatics confers the same level of benefit. The role of PMRT in women with 1–3 involved nodes remains controversial and investigational. Biological factors such as oestrogen and progesterone receptor status and HER-2 protein expression may play a role in determining benefits from PMRT. The role of internal mammary nodal irradiation is unclear. The individualisation of RNI based on molecular and genetic factors should be a priority for research. The benefits of RNI need to be carefully balanced against the risks of cardiotoxicity, pneumonitis, lymphoedema, brachial plexopathy and secondary malignancy. [Copyright &y& Elsevier]

Introduction: Sentinel lymph node biopsy alone has become an acceptable alternative to elective axillary lymph node dissection in patients with clinically node-negative early-stage breast cancer. Approximately 70 percent of the patients undergoing breast surgery develop side effects caused by the axillary lymph node dissection (axillary pain, shoulder stiffness, lymphedema and paresthesias)., Aim: The current standard treatment is to perform completion axillary lymph node dissection in patients with positive sentinel lymph node biopsy. However, randomized clinical trials of axillary dissection versus axillary irradiation failed to show survival differences between the two types of axillary treatment. The National Institute of Oncology, Budapest conducted a single centre randomized clinical study. The OTOASOR (Optimal Treatment of the Axilla - Surgery or Radiotherapy) trial compares completion axillary lymph node dissection to axillary nodal irradiation in patients with sentinel lymph node-positive primary invasive breast cancer., Method: Patients with primary invasive breast cancer (clinically lymph node negative and less than or equal to 3 cm in size) were randomized before surgery for completion axillary lymph node dissection (arm A-standard treatment) or axillary nodal irradiation (arm B-investigational treatment). Sentinel lymph node biopsy was performed by the radio-guided method. The use of blue-dye was optional. Sentinel lymph nodes were investigated with serial sectioning at 0.5 mm levels by haematoxylin and eosin staining. In the investigational treatment arm patients received 50Gy axillary nodal irradiation instead of completion axillary lymph node dissection. Adjuvant treatment was recommended and patients were followed up according to the actual institutional guidelines., Results: Between August 2002 and June 2009, 2106 patients were randomized for completion axillary lymph node dissection (1054 patients) or axillary nodal irradiation (1052 patients). The two arms were well balanced according to the majority of main prognostic factors. Sentinel lymph node was identified in 2073 patients (98.4%) and was positive in 526 patients (25.4%). Fifty-two sentinel lymph node-positive patients were excluded from the study (protocol violation, patient's preference). Out of the remaining 474 patients, 244 underwent completion axillary lymph node dissection and 230 received axillary nodal irradiation according to randomization. The mean length of follow-up to the first event and the mean total length of follow-up were 41.9 and 43.3 months, respectively, and there were no significant differences between the two arms. There was no significant difference in axillary recurrence between the two arms (0.82% in arm A and 1.3% in arm B). There was also no significant difference in terms of overall survival between the arms at the early stage follow-up., Conclusions: The authors conclude that after a mean follow-up of more than 40 months axillary nodal irradiation may control the disease in the axilla as effectively as completion axillary lymph node dissection and there was also no difference in terms of overall survival.

Objective: The Hungarian National Institute of Oncology has just closed a single-center randomized clinical study. The Optimal Treatment of the Axilla-Surgery or Radiotherapy (OTOASOR) trial compares completion axillary lymph node dissection (cALND) with regional nodal irradiation (RNI) in patients with sentinel lymph node-positive (SLN+) primary invasive breast cancer. In the investigational treatment arm, patients received 50 Gy RNI instead of cALND. In these patients we had information only about the sentinel lymph node (SLN) status, but the further axillary nodal involvement remained unknown. The aim of this study was to investigate whether the result of cALND influenced the recommendation for adjuvant treatment in patients with SLN+ breast cancer., Patients and Methods: Patients with SLN+ primary breast cancer were randomized for cALND (arm A, standard treatment) or RNI (arm B, investigational treatment). Adjuvant systemic treatments were given according to the standard institutional protocol, and patients were followed according to the actual institutional guidelines., Results: Between August 2002 and June 2009, 474 SLN+ patients were randomized to cALND (arm A, standard treatment = 244 patients) or RNI (arm B, investigational treatment = 230 patients). The 2 arms were well balanced according to the majority of main prognostic factors. However, more patients were premenopausal (34% vs. 27%; P = .095) and had pT2-3 tumors (57% vs. 40%; P = .003) in the completion axillary lymph node dissection (ALND) arm. On the other hand, there were more patients with known human epidermal growth factor receptor type 2 positive tumor (12% vs. 17%, P = .066) in the RNI arm. In the ALND and RNI arms, 78% (190/244) and 69% (159/230), respectively, received chemotherapy (P = .020). Endocrine therapy was administered in 87% (213/244) of the patients in the ALND arm and 89% (204/230) of the patients in the RNI arm (P = .372). Six patients (2.5%) on arm A and 13 patients (5.7%) on arm B received adjuvant trastuzumab treatment (P = not significant). Subgroup analyses explored that more frequent administration of adjuvant chemotherapy in arm A was associated with the higher percentage of premenopausal patients and patients with larger (pT2-3) tumors., Conclusions: The result of cALND after positive SLN biopsy seems to have no major impact on the administration of adjuvant systemic therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)