Axillary Radiotherapy Research Articles

The effect of omitting axillary dissection and the impact of radiotherapy on patients with breast cancer sentinel node macrometastases: a cohort study following the ACOSOG Z0011 and AMAROS trials.

To report the outcomes of implementing the ACOSOG Z0011 and AMAROS trials relevant to clinical practice, and to define target groups in whom to avoid or recommend axillary radiotherapy (ART). We also aimed to analyse the reduction in morbidity when axillary lymph node dissection (ALND) was omitted. A retrospective cohort study of T1-T2 patients with macrometastases at sentinel lymph node (SLN) who were treated between 2011 and 2020. Breast surgery included either lumpectomy or mastectomy. Patients with ≤ 2 positive SLN were divided into two cohorts by whether they received ART or not. Survival outcomes and morbidity were analysed by Kaplan-Meyer curves and Cox-regression, respectively. 260 pN1a patients were included and ALND was avoided in 167 (64.2%). According the Z0011 results, 72 (43.1%) received no further ART; and based on AMAROS criteria 95 (56.9%) received ART. Median follow-up was 54months. The 5-year overall survival was 96.8% in the non-RT cohort and 93.4% in the RT cohort (p = 0.19), while the respective 5-year disease-free survivals were 100% and 92.3% (p = 1.06). Lymphedema developed in 3.6% of patients after SLNB versus 43% after ALND (OR 20.25; 95%CI 8.13-50.43). Decreased upper-extremity range of motion appeared in 8.4% of patients after SLNB versus 31.2% after ALND (OR 4.95; 95%CI 2.45-9.98%). Our study confirms that omitting ALND is safe and has high survival rates in patients with T1-T2 tumours and ≤ 2 positive SLNs. Adding ART could be a treatment option for patients who present other risk factors. Avoiding ALND with or without ART was associated with significantly less arm morbidity.

Axillary Lymph Node Dissection versus Axillary Radiation in Patients with Positive Sentinel Lymph Node Biopsy in Early Breast Cancer

Abstract Background: Patients with cancer detected in a sentinel lymph node biopsy have under gone axillary lymph node dissection (ALND), which is an effective but invasive surgical procedure associated with adverse side effects, such as lymph-edema and difficulty moving the arm. Axillary radiation delivers outcomes that are similar to axillary lymph node dissection and with fewer side effects. Aim of Study: To define which patient may benefit from axillary dissection and who may benefit from axillary radiation without the hazards of axillary dissection in Patients with positive sentinel lymph node biopsy in early breast cancer patients. Patients and Methods: The 150 female patients with suc-cessful lymphatic mapping for early breast cancer T1 and T2, who were clinically node-negative,were randomly assigned prior to SLNB to receive either ALND(n=75) or axillary radiotherapy (n=75). The first 75 patients who were positive for SLNB were eligible for ALND (standard level I and II clearance) and the second consecutive positive 75 patients of the study were eligible for axillary radiotherapy. Results: Lymphedema rates were (2.6%) in the axillary dissection group and no arm edema in the axillary radiotherapy group. Long thoracic nerve injury rates were (2%) in the axillary dissection group and no nerve injury in the axillary radiation group, although no other nerve or vascular injuries were reported within two groups. Five year axillary recurrence rates (0.7% ALND vs 0.2% axillary radiotherapy). Most patients received adjuvant chemotherapy (68.6%) and/or endocrine therapy (31.4%) 47. Conclusion: Axillary radiation in patients with sentinel lymph node biopsy positive in early breast cancer may be considered as a standard therapy instead of axillary lymph node dissection.

Axillary management in T1-3N1M0 breast cancer patients with needle biopsy proven nodal metastases at presentation after neoadjuvant chemotherapy (ATNEC).

TPS600 Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillary nodes in 40% to 70% of patients. This raises questions about the benefit of further axillary treatment in those patients with no evidence of residual nodal disease (ypN0) after NACT. Methods: Design: ATNEC is a phase 3, randomised (1:1), multi-centre trial, with embedded economic evaluation, comparing standard axillary treatment (axillary lymph node dissection [ALND] or axillary radiotherapy [ART]) with no further axillary treatment in T1-3N1M0 breast cancer patients with needle biopsy proven axillary nodal metastases, who after NACT have no residual nodal disease (ypN0) on dual tracer sentinel node biopsy (SNB) and removal of at least 3 nodes (sentinel nodes and marked involved node). Stratification: Institution, type of surgery (breast conserving surgery vs mastectomy), receptor status (triple negative vs HER2 positive vs ER positive and/or PR positive and HER2 negative). Inclusion criteria are: Age ≥ 18, Male or female, T1-3N1M0 breast cancer at diagnosis (pre-NACT), FNA or core biopsy confirmed axillary nodal metastases at presentation, ER and HER2 status evaluated on primary tumour, received standard NACT as per local guidelines, ultrasound of the axilla at completion of NACT, dual tracer SNB after NACT and at least 3 nodes removed (sentinel nodes and marked node), no evidence of nodal metastases post NACT (ypN0). Exclusion criteria are: bilateral invasive breast cancer, SNB prior to NACT, marked node not removed except where at least one node removed shows evidence of down-staging with complete pathological response e.g. fibrosis/scarring and at least 3 nodes removed, previous ipsilateral axillary surgery, previous cancer within last 5 years or concomitant malignancy except basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, in situ or stage 1 melanoma, contra- or ipsilateral in situ breast cancer. Aims: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy - who after NACT have no residual nodal disease on SNB (ypN0) - is non-inferior to axillary treatment in terms of disease free survival, and reduces the risk of lymphoedema at 5 years. Statistical methods: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Radiotherapy quality assurance: Study has in-built radiotherapy QA programme that will be co-ordinated by National Radiotherapy Trials QA (RTTQA) group. Target accrual: 1900. Trial status: Recruiting. Number of sites: 100. Clinical trial information: NCT04109079.

Quality of Life for Women with Breast Cancer-Related Lymphedema: The Importance of Collaboration between Physical Medicine and Rehabilitation and General Surgery Clinics

Background: The aim of this study was to examine the clinical characteristics and quality of life (QOL) of patients with BCRL (breast cancer-related lymphedema).Methods: In this cross-sectional descriptive study, patients' characteristics such as age, body mass index (BMI: kg/m²), history of chemotherapy (CT), radiotherapy (RT), hormone replacement therapy (HRT), neoadjuvant therapy (NT), cancer stages, and types of surgery were recorded. Patients were evaluated using the ‘Disabilities of the Arm, Shoulder and Hand questionnaire’ (DASH), the ‘Lymphedema Quality of Life Questionnaire’ (LYMQOL-ARM), and a visual analogue scale (VAS). Results: A total of 68 women with the mean age of 52.50±9.33 and BMI 29.240 ± 5.05 kg/m² were recruited after breast cancer surgery in this study: thirty-three patients (48.5%) in Stage 0; 24 (35.3%) in Stage 1; 10 (14.7%) in Stage 2; and 1 (1.5%) in Stage 3. No statistically significant difference was found in the QOL according to treatments received after the diagnosis of breast cancer surgery, RT (except the appearance domain of QOL), CT, HRT, or NT. In patients who had received axillary dissection in combination with RT, a statistically significant association was observed between QOL related to body image and symptoms (p=0.009 and p=0.017, respectively). A statistically significant difference was found only in body image and clinical symptom domains according to the lymphedema stage (p=0.027 and p=0.002, respectively). It was observed that as shoulder pain (VAS) and disability (DASH) scores increased, scores of all domains of QOL increased except the overall domain in QOL (p<0.05). Conclusion: It was observed that clinical symptoms and body image parameters in QOL were associated with the lymphedema stage and the number of lymph nodes dissected. It was concluded that axillary dissection with axillary RT and RT alone after breast cancer surgery is associated with body image. Our study revealed that body image perception is related to the quality of life in patients with BCRL. Optimal management of the negative effects of self-reported lymphedema evaluated in the latency phase on quality of life requires coordination between Physical Medicine and Rehabilitation and General Surgery Clinics.

Extrapolation of ACOSOG Z0011 trial results-A survey of breast cancer providers.

We surveyed breast providers from a national oncology cooperative group to evaluate axillary management recommendations for patients with 1-2 positive sentinel lymph nodes (+SLNs) with scenarios not explicitly included in the Z0011 trial. These scenarios included patients underrepresented (premenopausal, HER2+/triple-negative tumors, and invasive lobular carcinoma) or excluded (treated with mastectomy or neo-adjuvant chemotherapy [NAC]) from the ACOSOG Z0011 trial. Survey response rate was 94/149 (64%). For patients in underrepresented groups, 45-63% of providers recommended no further axillary treatment. For mastectomy patients, 45-55% recommended multi-disciplinary discussion. 83% felt more data are needed to change practice, but 41% believed there would be significant accrual challenges to a clinical trial. For patients treated with NAC, recommendations varied widely. 85% felt more data are needed to change practice, but 26% felt there would be significant accrual challenges. For all scenarios, 86-100% of radiation oncologists recommended axillary radiation, while surgeons more often recommended no further axillary treatment. Traditional randomized trials are likely not feasible to provide answers to these critical management questions, so more pragmatic or big data studies may be needed.

P075 - Evaluation of the effect of axillary radiotherapy dose and the development of lymphodema in breast cancer patients

P075 - Evaluation of the effect of axillary radiotherapy dose and the development of lymphodema in breast cancer patients

Evaluating the Impact of Immediate Lymphatic Reconstruction for the Surgical Prevention of Lymphedema.

Breast cancer-related lymphedema affects one in five patients. Its risk is increased by axillary lymph node dissection and regional lymph node radiotherapy. The purpose of this study was to evaluate the impact of immediate lymphatic reconstruction or the lymphatic microsurgical preventative healing approach on postoperative lymphedema incidence. The authors performed a retrospective review of all patients referred for immediate lymphatic reconstruction at the authors' institution from September of 2016 through February of 2019. Patients with preoperative measurements and a minimum of 6 months' follow-up data were identified. Medical records were reviewed for demographics, cancer treatment data, intraoperative management, and lymphedema incidence. A total of 97 women with unilateral node-positive breast cancer underwent axillary nodal surgery and attempt at immediate lymphatic reconstruction over the study period. Thirty-two patients underwent successful immediate lymphatic reconstruction with a mean patient age of 54 years and body mass index of 28 ± 6 kg/m2. The median number of lymph nodes removed was 14 and the median follow-up time was 11.4 months (range, 6.2 to 26.9 months). Eighty-eight percent of patients underwent adjuvant radiotherapy of which 93 percent received regional lymph node radiotherapy. Mean L-Dex change was 2.9 units and mean change in volumetry by circumferential measurements and perometry was -1.7 percent and 1.3 percent, respectively. At the end of the study period, we found an overall 3.1 percent rate of lymphedema. Using multiple measurement modalities and strict follow-up guidelines, the authors' findings support that immediate lymphatic reconstruction at the time of axillary surgery is a promising, safe approach for lymphedema prevention in a high-risk patient population. Therapeutic, IV.

Abstract OT-04-03: Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101 - TAXIS): A multicenter randomized phase III trial

Abstract Background Main weaknesses of neoadjuvant chemotherapy (NACT) to avoid axillary dissection (ALND) in patients with clinically node-positive breast cancer are frequent failure of achieving nodal pathologic complete response (pCR) and administration of chemotherapy even though not indicated otherwise in many cases. Tailored axillary surgery (TAS) was designed to selectively remove positive nodes and omit ALND in patients with clinically node-positive breast cancer either in the upfront surgery setting or in case of residual nodal disease after neoadjuvant therapy, which distinguishes this trial from all others ongoing and published. Trial design In this international, multi-center, phase-III, non-inferiority randomized controlled trial, including 61 study sites from six 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 only followed by regional nodal irradiation including the full axilla. TAS consists of selective removal of the sentinel lymph nodes (SLNs) and all palpably suspicious findings, thereby tailoring the extent of axillary surgery to the extent of axillary disease, followed by specimen radiography to document removal of the clip placed in the sampled node. Imaging-guided localization is encouraged to increase the chances of clip removal. All patients undergo adjuvant whole-breast irradiation after breast conserving surgery and chest wall irradiation after mastectomy. Inclusion of internal mammary nodes is recommended irrespective of treatment arm. ClinicalTrials.gov Identifier: NCT03513614. Inclusion criteria - Clinically node-positive breast cancer (all molecular subtypes allowed) - Node-positivity palpable or detectable only by imaging at time of initial diagnosis - Newly diagnosed or isolated in-breast recurrence or second ipsilateral breast cancer after previous breast conserving surgery and sentinel procedure and at least 3 years disease free and no prior axillary dissection or axillary RT. - In case of prior neoadjuvant treatment: residual disease (including residual ITCs) confirmed by pathology at the time of surgery - Clipping of sampled axillary lymph node Exclusion criteria - Absence of clip in the specimen radiography - Palpable disease left behind in the axilla after TAS - No SLN identified in the axilla Specific aims To test the hypothesis that treatment with TAS and axillary radiotherapy is non-inferior to ALND in terms of disease-free survival (DFS) of clinically node-positive breast cancer patients. Secondary objective is to test if quality of life is significantly better with TAS and axillary radiotherapy compared to ALND. Statistical methods With type I error 5% and power 80%, 385 events will be needed to show non-inferiority of TAS and axillary RT in comparison to ALND with a non-inferiority hazard ratio (HR) of 1.289 (corresponding to a DFS at 5 years of 80% in the ALND arm and 75% in the TAS and axillary RT arm), including one interim analysis for efficacy/futility after 20% of the required events have occurred. The sample size needed is 1500 patients (750 per arm). The HR and one-sided 95% confidence interval will be calculated using a Cox regression model based on the per-protocol set. Present accrual and target accrual The trial was activated on 31 July 2018 and the first patient was randomized on 07 August 2018. As of 03 July 2020, 291 patients have been randomized. Accrual is currently running according to protocol and is planned until end of 2023 with the primary endpoint analysis expected in 2029. Contact information Prof. Dr. Walter Paul Weber, University Hospital Basel; Tel: +41 61 328 61 49; Walter.Weber@usb.ch Citation Format: Walter Paul Weber, Guido Henke, Stefanie Hayoz, Karin Ribi, Stefanie Seiler, Charlotte Maddox, Thomas Ruhstaller, Daniel Rudolf Zwahlen, Simone Muenst, Markus Ackerknecht, Florian Fitzal, Mihály Újhelyi, Christian Kurzeder, Loïc Lelièvre, Christoph Tausch, Daniel Egle, Jörg Heil, Zoltan Matrai, Michael Knauer. Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101 - TAXIS): A multicenter randomized phase III trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-04-03.

Abstract OT-04-01: Axillary management in T1-3N1M0 breast cancer patients with needle biopsy proven nodal metastases at presentation after neoadjuvant chemotherapy - ATNEC (ClinicalTrials.gov NCT04109079)

Abstract Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillary lymph nodes in 40% to 70% of patients. This has raised questions about the benefit of further axillary treatment in these patients with no evidence of residual disease in the lymph nodes. Trial design: A multi-centre phase III randomised controlled trial with embedded economic evaluation in which participants will be randomised in a 1:1 ratio. Study participants: T1-3N1M0 breast cancer patients aged 18 years or older, with needle biopsy proven nodal metastases, who after NACT have no residual cancer in the lymph nodes on dual tracer sentinel node biopsy and removal of at least 3 lymph nodes (sentinel nodes and marked involved node). Intervention: Participants in the experimental group will not receive further axillary treatment (axillary lymph node dissection [ALND] or axillary radiotherapy [ART]), after NACT and surgery. Participants in the control group will receive further axillary treatment (ALND or ART) after NACT and surgery, as per local guidelines. Stratification: Institution, type of breast surgery (breast conserving surgery (BCS) vs mastectomy), receptor status (triple negative vs HER2 positive vs ER status positive and/or PR status positive and HER2 negative) Eligible participants will be/should have:•Age ≥ 18•Male or female •T1-3N1M0 breast cancer at diagnosis (prior to NACT) •FNA or core biopsy confirmed axillary nodal metastases at presentation •Oestrogen receptor and HER2 status evaluated on primary tumour •Received standard NACT as per local guidelines (Patients undergoing neoadjuvant endocrine therapy as part of another clinical trial are eligible) •Ultrasound of the axilla at completion of NACT •Undergo dual tracer sentinel node biopsy after NACT and at least 3 nodes removed (sentinel nodes and marked node). If axillary node sampling is performed following failed localisation of sentinel nodes, patient will be eligible if at least 3 nodes removed (including the marked node) •No evidence of nodal metastases post NACT (isolated tumour cells, micro or macro metastasis) Participants will be excluded if they have any one of the following:•Bilateral invasive breast cancer•Sentinel node biopsy prior to NACT•Marked node not removed except where at least one node removed showsoevidence of down-staging with complete pathological response e.g. fibrosis or scarring and at least 3 nodes removed•Previous axillary surgery on the same body side as the scheduled targeted sampling•Any previous cancer within last 5 years or concomitant malignancy except basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix oin situ or stage 1 melanoma, contra- or ipsilateral in situ breast cancer Specific aims: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS), and reduces the risk of lymphoedema at 5 years.Statistical methods: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Target accrual: 1900, Number of sites: ~100 ClinicalTrials.gov: NCT04109079 Contact information: atnec@warwick.ac.uk Disclaimer: This study is funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (Reference - HTA NIHR128311). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Citation Format: Amit Goyal, Sophie Cramp, Duncan Wheatley, Andrea Marshall, Shama Puri, Tara Homer, Luke Vale, Romaana Mir, Zohal Nabi, Janice Rose, Helen Teresa Edwards, Samreen Ahmed, Abeer Shaaban, Beatrix Elsberger, Julie Bruce, Sophie Gasson, Valerie Speirs, Jacqui Shaw, Helen Higgins, Janet Dunn. Axillary management in T1-3N1M0 breast cancer patients with needle biopsy proven nodal metastases at presentation after neoadjuvant chemotherapy - ATNEC (ClinicalTrials.gov NCT04109079) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-04-01.

Abstract PS1-26: Sentinel lymph node biopsy alone in locally advanced breast cancer after neoadjuvant chemotherapy: Turkish multicentric neosenti-turk MF-18-02-study

Abstract BACKGROUND: Omitting axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB) in patients with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NAC) is still controversial. In this study, we evaluated factors affecting local recurrence and outcome in patients with LABC, who underwent SLNB alone after NAC. METHODS: Between 2004 to 2018, 320 patients with clinically node-positive LABC who received NAC and underwent SLNB alone after negative axillary staging were analyzed. All patients had breast and/or regional nodal irradiation. RESULTS: Median age was 46 (23-70). Of those, 228 patients had ypN0 disease (71.25%), whereas 92 patients had ypN(+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastasis (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 37 months (24-172), one patient (0.3%) with macrometastatic SLN having extracapsular extension was found to have locoregional recurrence at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were found as 87% and 95%, respectively. Patients with cT3&4 (HR=2.22, 95% CI; 1.07-4.62), non-luminal molecular pathology (HR=2.71, 95% CI, 1.23-5.97), and non-pCR in the breast (HR=2.21, 95% CI, 0.94-5.17) were found to have an increased HR compared to others in 5-year DFS. However, no significant differences could be found between patients ypN0, ypN-ITC&micrometastasis and ypN-macrometastasis regarding 5-year DFS and DSS rates. CONCLUSIONS: ALND could be safely avoided in selected patients with LABC who underwent SLNB after NAC having cT1-2, luminal pathology, breast and/or nodal pCR or low volume nodal disease, as long as axillary radiotherapy is provided. Citation Format: Neslihan Cabioglu, Hasan Karanlık, Mahmut Muslumanoglu, Guldeniz Karadeniz Çakmak, Didem Can Trablus, Mustafa Tukenmez, Yeliz E. Ersoy, Cihan Uras, Baha Zengel, Selman Emiroğlu, Ayfer Kamalı Polat, Levent Yeniay, Enver Ozkurt, Halil Kara, Kamuran Ibis, Adnan Aydiner, Vahit Ozmen, Abdullah Igci. Sentinel lymph node biopsy alone in locally advanced breast cancer after neoadjuvant chemotherapy: Turkish multicentric neosenti-turk MF-18-02-study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-26.

Abstract SP023: State of the art treatment for neoadjuvant/adjuvant triple negative breast cancer

Abstract Systemic therapy for triple negative breast cancer (TNBC) is currently limited to chemotherapy, with the major questions being the nature and timing of the chemotherapy and optimizing locoregional management of the primary tumor. While TNBC carries the worst prognosis of the clinical subtypes, this prognosis has improved with modern treatment approaches (Cossetti RJ, JCO 2015), and there are subsets within TNBC that have excellent outcomes. Giving the chemotherapy neoadjuvantly has real clinical value. Cytoreduction can facilitate breast conserving surgery (BCS); 42-53% of patients considered ineligible convert to BCS-eligible after chemotherapy (Golshan M et al, Ann Surg 2015 and JAMA Surg 2020). A negative sentinel lymphadenectomy post-chemotherapy is reliable if dual tracer is used and at least three sentinel nodes are retrieved (Boughey J, JAMA 2013), and a high proportion of node-positive breast cancer can be converted to node-negative, allowing omission of axillary dissection and minimizing risk of lymphedema (Pilewskie M, Morrow M, JAMA Oncol 2017). Two ongoing trials in patients with up-front node-positive disease are examining omitting radiation in those converting to node-negative (NSABP B-51, NCT01872975), and axillary radiation instead of dissection in those that remain pathologically node-positive (A011202, NCT01901094). Pathologic complete response (pCR) to chemotherapy across all subtypes of breast cancer carries a markedly better prognosis compared with residual disease. In CALGB 40603, at over 5 years’ followup, 86% of pCR versus 57% of residual disease patients were event-free (Sikov W, SABCS 2019). CREATE-X enrolled approximately 900 patients with HER2-negative tumors and residual disease after chemotherapy, one-third TNBC, who were randomized to the addition of capecitabine versus standard adjuvant treatment. At 3.5 years’ followup, there was a benefit to adding capecitabine, driven by the TNBC subset in whom there was an absolute 14% difference in disease-free and 8.5% difference in overall survival (Masuda, NEJM 2017). For these two reasons (surgical optimization and risk stratification with treatment decisions driven by residual disease status), in TNBC patients appropriate for chemotherapy neoadjuvant timing is preferred. The nature of the regimens has evolved also during the modern era. The key improvements in chemotherapy includes the addition of taxanes to anthracyclines (Hayes DF, NEJM 2007), the use of dose dense schedules made possible through the development of growth factors (Citron M, JCO 2003), and efforts to minimize anthracycline use. The ABC Trials were a joint analysis of several trials examining anthracycline/taxane-based regimens (TAC or dose-dense AC-T) versus a similar duration (six cycles) of docetaxel plus cyclophosphamide (TC). While underpowered for subset analyses, in the 1300 TNBC patient cohort, anthracycline/taxane regimens outperformed TC, although the absolute benefits were modest in node-negative (2.5%) compared with node-positive (>10%) (Blum J, JCO 2017). For this reason, the preferred regimen in TNBC remains anthracycline/taxane-based. A separate consideration is the incorporation of platinums. Several trials have demonstrated that adding carboplatin significantly increases the pCR rate. However the impact on relapse has been mixed (in underpowered trials); it is reasonable to add in high clinical risk where surgical optimization is desired but is not considered a standard addition to reduce risk of recurrence. Future advances include further surgical and radiation optimization, the potential for using clinical and biomarker analyses to identify low risk TNBC that need no chemotherapy at all, and the incorporation of immune checkpoint inhibitors, which in two neoadjuvant trials have demonstrated significantly increased pCR. Citation Format: LA Carey. State of the art treatment for neoadjuvant/adjuvant triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP023.

Abstract PD4-04: Tailored axillary surgery to omit axillary lymph node dissection independently from the use of neoadjuvant chemotherapy in patients with clinically node-positive breast cancer: Pre-specified subproject within TAXIS (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101)

Abstract Introduction: We developed tailored axillary surgery (TAS) to selectively remove positive nodes and omit axillary lymph node dissection (ALND) in patients with clinically node-positive breast cancer irrespective of the use of neoadjuvant chemotherapy. In this study, we evaluate the performance of this novel surgical concept that tailors the extent of axillary surgery to the extent of axillary disease. Methods: A prospective study was pre-specified to assess the performance of TAS in the international multicenter phase-III TAXIS trial randomizing patients with clinically node-positive breast cancer to undergo ALND or axillary radiation after TAS. TAS consists of selective removal of all palpably suspicious findings and the SLNs followed by specimen radiography to document removal of the clip placed in the sampled node. Imaging-guided localization is encouraged to increase the chances of clip removal. Only patients with confirmed nodal disease at the time of surgery can be randomized in TAXIS; the first 200 randomized patients were analyzed together with the ones achieving nodal pCR in this study. ClinicalTrials.gov Identifier: NCT03513614. Results: A total of 296 patients with a median age of 56.5 years (range: 25-88 years) were included at 28 breast centers from four European countries, 125 (42.3%) of whom underwent NACT and 75 (25.3%) of whom had nodal pCR. Subtype was hormone receptor (HR) positive (+) and human epidermal growth factor receptor 2 (HER2) negative (-) in 194 (65.5%), HR+/HER2+ in 40 (13.5%), HR-/HER2+ in 17 (5.7%) and HR-/HER2- in 39 (13.2%) patients. Breast-conserving surgery was performed in 178 patients (60%) and mastectomy in 117 (40%). Imaging-guided localization was attempted in 258 patients (87.2%) and was successful in 243 (82.1%). TAS removed a median of two (interquartile range [IQR] 0-3) palpably suspicious lesions and two (IQR 1-3) SLNs, thereby successfully removing the clip in 279 (94.3%) patients. There were no significant differences by use of imaging-guided localization (94.6% with vs 92.1% without, p=0.47) or type of clip (p=0.19), but a trend toward lower rate of clip removal after NACT (91.2% with vs 96.5% without NACT, p=0.075). Palpable disease was left behind after TAS in two (2.1%) patients and no SLN was detected in three (3.1%). In the 200 randomized patients with confirmed nodal disease at the time of surgery, lymph node metastases were palpable at the time of initial diagnosis in 102 (51%) patients and detectable only by imaging in 98 (49%). The median number of lymph nodes removed by TAS was four (IQR 2-8), two (IQR 1-4) of which were positive. Completion ALND following TAS removed additional positive nodes in 71 of 100 (71%) patients in the control group (20% with one additional node, 9% with 2, 8% with 3, 6% with 4, and 28% with >4). The median number of additional lymph nodes removed by ALND was 14 (IQR 10-18), two (IQR 0-6) of which were positive. Of the 200 randomized patients, one in the TAS group received a radiotherapy boost and one in the ALND group returned to the operating room for residual suspicious findings on imaging. Discussion: The present results suggest that TAS has the potential to become the new axillary surgery standard in patients with clinically node-positive breast cancer. TAS was successfully performed in the vast majority of patients, with no further improvement by imaging-guided localization, which makes the procedure feasible at most breast centers. TAS selectively removed positive lymph nodes and was much less radical than ALND, but ALND removed additional positive nodes in more than two thirds of patients. Disease-free survival and quality of life will be assessed in the randomized trial. Citation Format: Walter Paul Weber, Guido Henke, Stefanie Hayoz, Karin Ribi, Stefanie Seiler, Charlotte Maddox, Thomas Ruhstaller, Daniel Rudolf Zwahlen, Simone Muenst, Markus Ackerknecht, Florian Fitzal, Mihály Újhelyi, Christian Kurzeder, Loïc Lelièvre, Christoph Tausch, Daniel Egle, Jörg Heil, Zoltan Matrai, Michael Knauer. Tailored axillary surgery to omit axillary lymph node dissection independently from the use of neoadjuvant chemotherapy in patients with clinically node-positive breast cancer: Pre-specified subproject within TAXIS (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-04.

Abstract PS9-35: Volumetric assessment of lymphedema with 3D sensor

Abstract Volumetric assessment of lymphedema with 3D sensor: A new practical method Secondary lymphedema of the upper extremities is an important quality-of-life issue for around 40% of patients who were treated for breast cancer and required axillary nodal dissection and radiotherapy. Volume measurement is an important aspect of diagnosis, follow up, and evaluation after conservative or surgical treatment for lymphedema. Until now, there have been complex techniques to assess volume of affected limbs: bioimpedance, liquid-displacement volumetry, CT, MRI. There is a need for a practical method of volumen assessment in lymphedema patients. The objective of the present study is to confirm whether or not 3D scanning for volumetric assessment is useful and correlates with direct perimeter measurement and indirect volume calculation. Methods: A 3D sensor (Structure Sensor, Occipital Inc) mounted on an Ipad (Apple, Inc.) was used to make a 3D model file of the affected limb, that was later analyzed by 3DsizeME software (TechMed 3D, Inc.) in a desktop computer. 3D model analysis allows to measure perimeters and volumes. Fifteen patients were measured, lymphedema and normal limbs (30 extremities) by this technique and were also measured with tape, as traditional method; results were compared to assess correlation. Results: There were not statistical difference between the two techniques (p 0.05). Table attached. Discussion: volumetric assessment by 3D sensor allows consistent and reproducible measurements. It is practical as we only need the space of an ipad, it can be performed in the clinic visit, by any doctor, nurse or physical therapist. It is not expensive, as the software charges US$10 by each analysis. It do not expose the patient to any harmful radiation, as is obtained by and infrared camera. Allows electronic records of all measurements. Average time to capture 3D model is 5 minutes. We think this new method is a valuable tool for any lymphedema clinic as volume measurement is important for disease evaluation and now, more important, with a growing field of surgical treatment for this disease. Citation Format: Alejandro Maciel-Miranda, Miriam I Otero-Hernández, Darinka Martínez-Silva, Jesus F Escrivá-Machado. Volumetric assessment of lymphedema with 3D sensor [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-35.

Abstract PS1-63: A survey of radiation oncologists on contemporary axillary management in post-mastectomy breast cancer patients

Abstract Background: Local-regional treatment (LRT) of the axilla in breast cancer has evolved over the past several decades. The AMAROS trial demonstrated that dedicated axillary radiation therapy (aRT) can provide local control and allow for less invasive axillary surgery in select patients. Since the AMAROS data was published in 2014, there are no large-scale studies specifically analyzing how this data has impacted clinical practice. Methods: An anonymous case-based survey was sent to 4,254 Radiation Oncologists (RO) who identified as practicing physicians in the US as of May 2020. Those who identified that they do not treat breast cancer patients were excluded. The survey was conducted through the Qualtrics™ platform. Descriptive analyses were performed by the survey software and analytical statistics were performed using R (v4.0.2) utilizing ANOVA, t-tests, and chi-squared analysis. Results: A total of 293 RO completed the survey. Mean years in practice was 18.4 and most were in private practice (41.4%), followed by academic practice (28.2%) and hospital-employed (25.7%). Most (65%) reported that the type of post-mastectomy breast reconstruction does not influence their axillary treatment algorithm. Cases and responses are as follows: Case 1: A 57-year-old female with a cT1N0, ER-positive, Her2-negative breast cancer undergoes mastectomy and sentinel node biopsy (SLNB). Pathology reveals a T1 tumor with 2 of 3 sentinel lymph nodes with 2mm tumor deposits. The majority (75.4%) of RO reported they would proceed with aRT, while 8.7% preferred ALND alone, 7.1% elected for both aRT and ALND, 3.3% chose no further axillary therapy, and 4.5% needed more case information to make a decision. Treatment decision was dictated by clinical trial evidence (62.2%) and national guidelines (26.4%), but 11.2% reported their decision was largely impacted by clinical experience. The ACOSOG Z11 and AMAROS trials had the largest impact on clinical decision-making. For RO who chose to treat with aRT, AMAROS and MA-20 had the highest impact in determining radiation fields, and 88.7% would give RT to both the chest wall and axilla. Choice of axillary treatment did not differ by years in practice (p=0.54), percentage of breast patients treated (p=0.22), or by clinical practice setting (p=0.44). Case 2: A 69-year-old female with a cT1N0 ER/PR-negative, Her2-positive breast cancer undergoes mastectomy and SLNB. Pathology demonstrates a T1 tumor and 4 of 4 sentinel nodes with disease but without extra-nodal extension. Treatment results were mixed: 45.5% recommended both ALND and aRT, 38.5% chose aRT alone, and 14.3% recommend ALND alone. Most (85%) cited that their decision was based upon clinical trial evidence and/or national guidelines. MA-20 and AMAROS were cited as having the highest impact on the decision to perform aRT and determining RT fields. 96.2% of those recommending RT would treat both the chest wall and axilla. On average, RO who were in practice for a shorter period of time preferred both ALND and aRT, while those in practice for more years preferred that patients undergo either ALND or aRT alone (mean 12.9 vs 20.3 years, p<0.001). Treatment decision to undergo dual or single LRT was not associated with percentage of breast patients treated (p=0.41), or by practice setting (p=0.92). Conclusion: There remains significant heterogeneity in axillary treatment patterns for N+ breast cancer patients amongst RO in the US. Those patients with significant nodal burden (≥4+ nodes) were more likely to receive additional axillary therapy, and with combination LRT when treated by RO in practice for a shorter number of years. Physician education on clinical trial inclusion criteria and development of clearer axillary treatment guidelines can aid in appropriate identification of axillary de-escalation opportunities. Citation Format: Chandler S Cortina, Carmen Bergom, Morgan Ashley Craft, British Fields, Adam Currey, Amanda L Kong. A survey of radiation oncologists on contemporary axillary management in post-mastectomy breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-63.

Abstract PS15-17: Hypofractionated versus conventional intensity modulated postmastectomy radiotherapy: Toxicity and quality of life in patients with tissue-expander breast reconstruction

Abstract Introduction: Hypofractionation (HF) in breast cancer is a radiotherapy regimen frequently used in recent years. Greater toxicity has been described in irradiated patients with heterologous breast reconstruction procedures, but it is unknown if this greater toxicity could be avoided by using hypofractionated intensity modulated radiotherapy (IMRT). The objective of this study is to describe the toxicity and complications presented in breast cancer patients that were reconstructed with a tissue expander (EXP) treated with IMRT and to determine if there are differences according to the used fractionation regimen. Method: All patients with breast cancer reconstructed with expander and treated with adjuvant IMRT to the chest wall and regional lymph nodes were included, using conventional fractionation (CF) dose of 50 Gy in 25 fractions or hypofractionated (HF) regimen dose of 45 Gy in 20 fractions. Acute and late toxicity, during treatment and at the end of follow-up, were recorded according to RTOG / EORTC and CTCAE 4.0 criteria and the BREAST Q 2.0 quality of life survey postoperative reconstruction module (QoL) was applied in the last follow-up visit. Results: 33 patients were analyzed. With a median follow-up of 17 months, 31 were treated with Tomotherapy and 2 with VMAT. CF was used in 20 and HF in 13. There was no G3 acute toxicity, and G2 was observed in only 1 patient with HF (7.6%) and in 3 with CF (15%), mainly determined by radiodermatitis. Regarding late toxicity (LT), there was only one G3 event which occurred in a patient with CF and full axillary irradiation. Grade 2 LT was not observed in patients treated with HF, whereas with CF 2 cases (10%) were reported. During the expander period, 1 patient with HF presented a complication (7,6%) and 3 with CF (15%), 2 of the latter required unscheduled surgical intervention (USI). 12 patients in the HF group underwent prosthetic replacement (92%) and 15 in the CF group (75%). After the replacement 4 patients with CF required an USI (26.6%) and none of the patients in the HF group had post replacement complications that required hospitalization. None of the previously mentioned differences were statistically significant. Regarding QoL, the patients with HF had a better late toxicity score, with an average of 96.7 vs. 82.4 points (p <0.005), and better physical well-being of the chest, with an average of 81.7 vs. 66 points, which did not reach statistical significance (p = 0.052). The rest of the scales within the module did not show any differences. Conclusions: Postmastectomy IMRT in patients with heterologous reconstruction is associated with low toxicity and complications. The use of hypofractionation presents a toxicity profile similar to that of conventional fractionation, with a tendency to less frequent complications associated with reconstruction. HF is also associated with a better QoL score in late toxicity and physical well-being of the chest. Prospective studies are required to confirm whether hypofractionation using IMRT could decrease complications and improve quality of life in patients undergoing total mastectomy and tissue-expander breast reconstruction. Citation Format: Ariel Fariña, Dagmar Alfonso, Aroldo Fernandez, Felipe Carvajal, Ana María Ciudad, Celmira Martínez, Camila Pérez, Pablo González, Hugo Marsiglia. Hypofractionated versus conventional intensity modulated postmastectomy radiotherapy: Toxicity and quality of life in patients with tissue-expander breast reconstruction [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-17.

A dosimetric study to improve the quality of nodal radiotherapy in breast cancer.

Objectives:Field-based planning for regional nodal breast radiotherapy (RT) used to be standard practice. This study evaluated a field-based posterior axillary boost (PAB) and two forward-planned intensity-modulated RT (IMRT) techniques, aiming to replace the first.Methods:Supraclavicular and axillary nodes, humeral head, brachial plexus, thyroid, and oesophagus were retrospectively delineated on 12 CT scans. Three plans, prescribed to 40.05 Gy, were produced for each patient. Breast plans consisted of field-in-field IMRT tangential fields in all three techniques. Nodal plans consisted of a field-based PAB (anterior and posterior boost beam), and 2 forward-planned techniques: simple IMRT 1 (anterior and posterior beam with limited segments), and a more advanced IMRT 2 technique (anterior and fully modulated posterior beam).Results:The nodal V90% was similar between IMRT 1: mean 99.5% (SD 1.0) and IMRT 2: 99.4% (SD 0.5). Both demonstrated significantly improved results (p = 0.0001 and 0.005, respectively) compared to the field-based PAB technique. IMRT 2 lung V12Gy and humeral head V10Gy were significantly lower (p = 0.002, 0.0001, respectively) than the field-based PAB technique. IMRT 1 exhibited significantly lower brachial plexus Dmax and humeral head V5, 10, and 15Gy doses (p = 0.007, 0.013, 0.007 and 0.007, respectively) compared to the field-based PAB technique. The oesophagus and thyroid dose difference between methods was insignificant.Conclusions:Both IMRT techniques achieved the dose coverage requirements and reduced normal tissue exposure, decreasing the risk of radiation side effects. Despite the increased cost of IMRT, compared to non-IMRT techniques 1, both IMRT techniques are suitable for supraclavicular and axillary nodal RT.Advances in knowledge:Forward-planned IMRT already resulted in significant dose reduction to organs at risk and improved planning target volume coverage.1 This new, simplified forward-planned IMRT one technique has not been published in this context and is easy to implement in routine clinical practice.

Risk Factors for Lymphedema After Breast Conservation Therapy and Oncoplastic Reduction.

Lymphedema is a known complication after the surgical management of breast cancer, yet the incidence is poorly defined after breast conserving therapy and oncoplastic reduction. The primary aim of this study was to define lymphedema incidence in this population. Furthermore, we sought to correlate demographic factors, surgical approach, and complementary treatment modalities with incidence. Data were collected retrospectively on patients who underwent breast conserving therapy at our institution from 2012 to 2015 with greater than 1 year of follow-up. Patients were excluded if they underwent breast surgery before treatment, completion mastectomy, delayed breast reconstruction, or delayed breast reduction. Five hundred and eighty-four patients met study criteria with a 11% lymphedema rate. Patients developing lymphedema had higher preoperative body mass index (P = 0.02), larger breast mass resection volume (P < 0.01), higher rate of axillary dissection (P < 0.01), increased rate of adjuvant whole-breast radiation (P = 0.03), supraclavicular radiation (P < 0.01), axillary radiation (P < 0.01), and neoadjuvant medical therapy (P < 0.01). Multivariate analysis showed breast specimen mass, axillary radiation, and neoadjuvant medical therapy, which were associated with lymphedema (P < 0.05). There was no difference in lymphedema incidence between partial mastectomy and oncoplastic reduction cohorts with independent multivariate analyses for each showing axillary radiation and neoadjuvant medical therapy were significantly associated with lymphedema (P < 0.05), although breast specimen mass was not. Elevated preoperative body mass index, radiation, axillary dissection, and neoadjuvant medical therapy are associated with an increased risk of lymphedema after breast conserving surgery. Oncoplastic reconstruction is not a risk factor for lymphedema.

Residual lymph node tumour burden following removal of a single axillary sentinel lymph with macrometastatic disease in women with screen-detected invasive breast cancer.

BackgroundWomen with screen-detected invasive breast cancer who have macrometastatic disease on axillary sentinel lymph node biopsy (SLNB) are usually offered either surgical axillary node clearance (ANC) or axillary radiotherapy. These treatments can lead to significant complications for patients. The aim of this study was to identify a group of patients who may not require completion ANC.MethodsData from the NHS Breast Screening Programme between 1 April 2012 and 31 March 2017 were interrogated to identify women with invasive breast carcinoma and a single sentinel lymph node (SLN) with macrometastatic disease who subsequently proceeded to completion ANC. Univariable and multivariable analyses were performed to identify patients with a single positive SLN who had no further lymph node metastasis on ANC.ResultsOf the 2401 women included in the cohort, the presence of non-sentinel node disease was significantly affected by: the number of nodes obtained at SLNB (odds ratio (OR) 0.49 for retrieval of more than 1 node), invasive size of tumour (OR 1.63 for size greater than 20 mm), surgical treatment (OR 1.34 for mastectomy), human epidermal growth factor receptor (HER) 2 status (OR 0.71 for HER2 positivity), and patient age (OR 1.10 for age less than 50 years; OR 1.46 for age greater than 70 years). Patients aged less than 70 years, with tumour size smaller than 2 cm, more than one node retrieved on SLNB, and who had breast-conserving surgery had a lower chance of positive non-sentinel nodes on completion ANC compared with other patients.ConclusionThis study, of a purely screen-detected breast cancer cohort, identified a subset of patients who may be spared completion ANC in the event of a single axillary SLN with macrometastasis.

Omitting radiotherapy is safe in breast cancer patients\u2009\u2265\u200970\xa0years old after breast-conserving surgery without axillary lymph node operation

To verify whether omitting radiotherapy from breast cancer treatment for patients ≥ 70 years old following breast-conserving surgery (BCS) without axillary lymph node dissection is safe. Previous studies have shown that omitting breast radiotherapy after BCS and axillary lymph node dissection is safe for elderly breast cancer patients. We aimed to evaluate the safety of BCS without axillary surgery or breast radiotherapy (BCSNR) in elderly patients with breast cancer and clinically negative axillary lymph nodes. We performed a retrospective analysis of 481 patients with breast cancer, aged ≥ 70 years, between 2010 and 2016. Of these, 302 patients underwent BCSNR and 179 underwent other, larger scope operations. Local recurrence rate, ipsilateral breast tumor recurrence (IBTR) rate, distant metastasis rate, breast-related death, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. After a median follow-up of 60 months, no significant differences in local recurrence, distant metastasis rate, breast-related death, and DFS were noted. The OS was similar (P = 0.56) between the BCSNR group (91.7%) and other operations group (93.0%). The IBTR rate was considered low in both groups, however resulted greater (P = 0.005) in the BCSNR group (5.3%) than in other operations group (1.6%). BCSNR did not affect the survival of elderly patients with breast cancer with clinically negative axillary lymph nodes. IBTR was infrequent in both groups; however, there was a significant difference between the two groups. BCSNR is a feasible treatment modality for patients with breast cancer ≥ 70 years old with clinically negative axillary lymph nodes.

Axillary surgery for breast cancer: past, present, and future.

In breast cancer surgery, there has been a major shift toward less invasive local treatment. Although axillary lymph node dissection (ALND) was an integral part of surgical treatment for breast cancer, sentinel lymph node (SLN) biopsy was developed as an accurate method for axillary staging. ALND can be avoided not only in patients with negative SLNs but also in those with one or two positive SLNs receiving breast and/or axillary radiation. On the other hand, ALND has remained the standard treatment for patients with clinically positive nodes. However, axillary reverse mapping (ARM) was developed to map and preserve arm lymphatic drainage during ALND and/or SLN biopsy. This procedure allowed reduction of the rate of arm lymphedema without increasing axillary recurrence, although patients receive postoperative chemotherapy and high-risk patients undergo axillary radiation. Standard ALND may not be necessary even for patients with clinically positive nodes who receive axillary radiation and systemic therapy. Thus, the extent of axillary surgery in breast cancer has been decreased with increased use of systemic and radiation therapy.