Post-mastectomy pain syndrome (PMPS) is a frequent and burdensome complication of breast cancer surgery, manifesting as persistent pain following mastectomy, typically with neuropathic characteristics. This review synthesizes current knowledge on the epidemiology, prevention, and treatment of PMPS, and highlight knowledge gaps to inform future research. PMPS occurs in 28-52% of patients. It is associated with impairment in quality of life, and reductions in physical and psychosocial functioning. Consistently identified risk factors include younger age, extensive axillary surgery, total mastectomy, and preexisting chronic pain. Perioperative preventive strategies, such as topical EMLA cream, pregabalin, PECS II block, i.v. dexmedetomidine and flurbiprofen axetil, show potentially promising effects in reducing the incidence or severity of PMPS. Treatment options for established PMPS with potentially promising effects include topical capsaicin, amitriptyline, venlafaxine, multimodal pharmacological therapy, thermal radiofrequency of the stellate ganglion, and mindfulness-based cognitive therapy. For both preventive and therapeutic strategies, heterogeneity in study design, dosing regimens, and outcome frameworks, as well as the small sample size of most studies, limit the strength of evidence. Large knowledge gaps exist in the understanding of the molecular mechanisms associated with PMPS. Future research focusing on the molecular mechanisms promoting PMPS can facilitate the development of novel effective preventive and therapeutic strategies. Large-scale well-powered clinical trials on interventions aiming to prevent and treat PMPS are highly needed to inform evidence-based clinical practice. Future clinical studies should also aim to identify biomarkers that predict the efficacy of interventions in individual patients, thereby supporting personalized medicine.

Background. Axillary lymph node biopsy (ALND) has traditionally been considered the gold standard for axillary staging and treatment in clinically node-positive breast cancer patients. However, in patients with nodal disease, the therapeutic benefit of ALND is uncertain. This study, based on a large cohort, aims to evaluate breast cancer-specific survival depending on the extent of axillary surgery in non-metastatic breast cancer using real-world data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods. This retrospective cohort study comprised 825,240 patients diagnosed with breast cancer between 2000 and 2020. Results. ALND was associated with a worse survival outcome in pN0 and pN1 populations (respectively, hazard ratio [HR] 1.16; 95% confidence interval [CI] 1.12-1.2; p < 0.001 and HR 1.38; 95%CI 1.3-1.46; p < 0.001). In pN2 and pN3 populations, there was ~4.3% relative reduction in the hazard of breast cancer-related death for each additional node removed; and higher positive-to-removed lymph node ratio was associated with worse prognosis (HR 3.450; 95%CI 2.99-3.98; p < 0.001). Conclusions. SLNB is associated with significantly better specific survival compared to ALND in negative/low axillary involvement, in higher axillary involvement categories extensive axillary surgery was associated with better prognosis.

Abstract Early breast cancer (EBC) treatment is multimodal; as more effective systemic therapies become available, decision-making and personalised treatment selection become more complex, although factors such as tumour size, grade and nodal status remain important. Advances in treatment are driving an evolution in care. This study sought to understand the UK breast cancer management landscape and challenges facing healthcare professionals (HCPs) in relation to decision-making around axillary surgery in patients with ER+ HER2- disease. HCPs involved in EBC patient management (n=70; 29 medical oncologists, 13 clinical oncologists, 10 surgeons, 13 pharmacist prescribers and 5 nurses) were surveyed August to December 2023. NICE guidance states that patients with radiologically detected node-positive (N+) disease should be offered axillary node clearance (ANC). However, only 21% of HCPs stated their multidisciplinary teams would perform ANC with 1 involved node identified pre-operatively and 30% where 2 nodes were seen. Approximately 40% stated the decision to carry out ANC would depend on other factors such as tumour size, comorbidities and age. However, of those citing other factors, 56% said this decision would be to inform further treatment. Similarly, following a positive sentinel lymph node biopsy (SLNB), only 11% would perform ANC for a single positive node, and 30% for 2 involved nodes. Again, almost 40% said the ANC decision would depend on other factors, but here 81% of those said that the decision for ANC would be to inform further treatment. For greater burdens of nodal disease, ANC was much more likely in both radiologically detected and SLNB detected nodal disease. These findings show that for patients with a low burden of radiologically detected axillary nodal disease, only a small proportion routinely undergoes ANC, in contrast to NICE recommendations. However, this proportion is higher in those with a positive SLNB. It appears that some patients may undergo ANC to inform further treatment decisions. Given that more extensive axillary surgery does not improve outcomes, but is associated with significant morbidity, it is clear that improved methods to inform decisions about further adjuvant treatment are required. Citation Format: Stuart A McIntosh, Helen Flint, Julie Douglas, Philipp A. Dietrich, Victoria Bush, Richard Simcock. Factors influencing axillary node clearance in early breast cancer care in the UK in 2023 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-09-12.

Abstract Purpose/Objective(s): Many women with axillary node-positive breast cancer benefit from regional nodal irradiation (RNI) in terms of improved cancer control outcomes. RNI unintentionally exposes the shoulder structures to radiation, which can lead to morbidity. We previously demonstrated that intensity modulated radiation therapy (IMRT) results in less radiation dose to the shoulder compared to 3D conformal radiation therapy (3DCRT). We set to determine if the dosimetric advantage of IMRT translates into a clinically meaningful reduction in shoulder morbidity. Materials/Methods: This study is registered on clinicaltrials.gov (NCT03786354). We enrolled patients that were to receive RNI after mastectomy (Mx) or lumpectomy (Lump) with axillary staging (axillary lymph node dissection [ALND] or sentinel node biopsy [SNB]). All patients received 50 Gy in 25 fractions to the breast or chestwall and RNI. Patients were non-randomly assigned to either Arm IMRT or Arm B 3DCRT on the basis of a treatment planning algorithm that defaults to 3DCRT but transitions to IMRT based on dosimetric criteria. The primary endpoint was shoulder/arm morbidity at 1 year post-RNI in IMRT patients using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Based on limited existing data at the time, we estimated that the 1-year DASH score would be 20 in patients that had undergone RNI with 3DCRT and that IMRT would reduce the 1-year DASH to ≤10. A sample size of 27 patients would have 80% power to detect this 10-point difference in DASH score. We enrolled 27 patients on Arm 3DCRT to establish the average DASH score in this cohort. Results: Patients were enrolled from 1/2019-3/2022. After loss to follow-up, there were 29 patients evaluable for the primary endpoint in Arm IMRT and 27 patients in Arm 3DCRT with similar ages (median age=50 years vs. 51 years, p=0.83) but trend towards higher rates of Mx (72% vs. 51%, p=0.11) and ALND (90% vs.78%, p=0.23) in Arm IMRT vs. Arm 3DCRT. In arm IMRT, the mean baseline (post-surgery/pre-RNI) DASH was 12.8(SD 11.0) and increased to a mean of 15.4(SD 15.1) at 1-year. In arm 3DCRT, the mean baseline DASH was 14.0(SD 12.9) and increased to a mean of 14.8(SD 13.2) at 1-year. Decrease in DASH scores was more frequent in Arm IMRT vs. 3DCRT (51.7% vs. 37.0%, p=0.27). In the entire cohort, patients treated with Mx and patients treated with ALND tended to have worse 1-year DASH scores: 17.6 (SD 15.9) Mx vs. 11.0(SD 9.4) Lump, p=0.06; 16.4(SD 14.7) ALND vs. 8.4(SD 8.0) SNB, p=0.03. Conclusion: This study did not meet its primary endpoint but the similar 1-year DASH scores in Arm IMRT and Arm 3DCRT may reflect IMRT compensating for the more extensive axillary and breast surgery in that arm. More than 50% of patients in Arm IMRT experienced a decrease in DASH score. These findings suggest that prospective investigation of IMRT for RNI in the setting of SNB remains worthy of study. Analysis of secondary endpoints including objective range of motion assessments and shoulder muscle dosimetry are forthcoming. Citation Format: Jose Bazan, Julie Stephens, Sachin R. Jhawar, Sasha Beyer, Karen Hock, Julia R. White. Prospective Evaluation of Shoulder Morbidity in Patients with Lymph Node-Positive Breast Cancer Receiving Regional Nodal Irradiation [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-09-09.

Abstract This study evaluated whether lymphedema, patient-reported arm and shoulder morbidity and quality of life one year after axillary surgery are affected by stage or axillary surgery type between early stage patients and patients with locally advanced breast cancer who underwent surgery following neoadjuvant therapy. By determining the risk factors associated with severe lymphedema and deterioration of patient-reported outcomes, lymphedema could be prevented by early intervention to improve the prognosis of lymphedema and quality of life. Material and Methods: Between January 2021 and May 2022, a total of 253 breast cancer patients, 128 early stage and 125 locally advanced stage who underwent surgery including sentinel lymph node biopsy (SLNB) with/without axillary lymph node dissection (ALND) following neoadjuvant therapy were included in this study. The patients who underwent upfront surgery were defined as early-stage, and those who underwent surgery following neoadjuvant chemotherapy were considered as having locally advanced breast cancer (LABC) who have also participated in the prospective MF18-03 registry trial. Patients were prospectively evaluated by the SF-12 quality of life and QUICK-DASH hand, arm, and shoulder range of motion questionnaires and circumferential tape measurements of the arm width to evaluate the lymphedema before surgery, and 6 month- and 12-month assessments. The volume difference of 10% or more in the operated arm compared to the healthy arm was considered as lymphedema. Results: In the assessment of SF-12 quality of life questionnaire, there was a decrease in physical function scores at the 6th month despite recovery at the 12th month in both groups compared to the initial preoperative scores (p&amp;lt; 0,001). Moreover, patients with locally advanced breast cancer were found to have decreased SF-12 general health (p=0.024), vitality (p=0.034), and mental health scores in one year after surgery (p=0.004). Patients with mastectomy and locally advanced breast cancer were more likely to have a diminished arm and shoulder function as assessed with the QUICK-DASH questionnaire at the 6th and 12th months compared to those with breast conservation (6. month, p=0,009, 12. month, p=0.004), and early breast cancer, respectively (6. month, p=0.014, 12. month, p&amp;lt; 0.001) In the present cohort, lymphedema was detected in 19 (7.5%) patients including 16 cases with mild (11-20%), 2 cases with moderate (21-40%), and one case with severe (41-80%) lymphedema one year after surgery. Axillary dissection was found to be associated with an increased risk of lymphedema (SLNB, 5.0% vs ALND, 17.6%; p=0.005). Similarly, removal of &amp;gt;6 lymph nodes was also associated with an increased risk of lymphedema that was not statistically significant (&amp;lt;6 LNs, 6.4% vs &amp;gt;6LNs, 10.8%; p=0.277). Among those with LABC, however, patients with removal &amp;gt;6 LNs were more likely to have lymphedema (&amp;gt;6 LNs, 15.4% vs &amp;lt;6 LNs, 5.8%; p=0.096). Conclusion: These findings suggest that only an extensive axillary surgery was associated with an increased risk of breast cancer-related lymphedema. Patients with a mastectomy were more likely to have diminished arm and shoulder function compared to those with breast conservation. Furthermore, patients with locally advanced breast cancer were more likely to have a dispaired quality of life score and a limited arm and shoulder function regardless of the presence of lymphedema. Early prompt diagnosis and therapy of lymphedema can therefore potentially improve quality of life. Citation Format: Halime Gul Kilic, Selman Emiroglu, Ekin Ozgorgu, Mustafa Tukenmez, Atilla Bozdogan, Mahmut Muslumanoglu, Vahit Ozmen, Dilsad Sindel, Abdullah Igci, Aydan Oral, Neslihan Cabıoğlu. PATIENT REPORTED OUTCOMES IN TERMS OF ARM AND SHOULDER FUNCTIONS AND QUALITY OF LIFE AND LYMPHEDEMA ARE AFFECTED BY THE STAGE, AND EXTENT OF AXILLARY SURGERY IN THE EARLY POSTOPERATIVE PERIOD OF PATIENTS WITH BREAST CANCER [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-03.

Abstract Management of the axilla has evolved significantly over time, with a trend toward less extensive axillary surgery. While historically, all patients underwent axillary lymph node dissection (ALND) due to the Halstedian belief that ALND was essential for the cure of breast cancer, advances in systemic therapy, radiotherapy, and understanding of tumor biology have resulted in the abandonment of ALND for a large proportion of patients having upfront surgery with limited nodal disease, and in those with no residual nodal disease after neoadjuvant systemic therapy. Over time, axillary management has become increasingly complicated, with significant variability in real-world management for different clinical scenarios. In this talk, we will address challenging scenarios in axillary management, both in the upfront surgery setting and after neoadjuvant chemotherapy (NAC). In the upfront surgery setting, we will address management of a positive sentinel node in patients treated with mastectomy, management of ≥ 3 positive sentinel nodes after lumpectomy or mastectomy, and the use of sentinel lymph node biopsy for patients with clinically node-positive hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer. In the setting of patients receiving NAC, we will discuss the optimal approach to the axilla in patients with residual disease after NAC, and in those with locally advanced breast cancer. As we move away from ALND in low-risk scenarios where data from randomized and prospective trials have demonstrated oncologic safety, we await results from ongoing clinical trials to provide us with high-level evidence regarding the safety of omission of ALND in high-risk patients with more extensive nodal disease. Citation Format: A. Barrio. Demystifying the Axilla: Challenging scenarios in the upfront surgery setting and after NAC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED05-01.

Abstract Objectives The role of axillary surgery in the management of breast cancer (BC) has evolved considerably over the past decades, with only a few routine indications for axillary lymph node dissection (ALND) remaining in clinical practice. However, de-escalation of axillary surgery, especially in BC patients with 1-3 positive sentinel lymph nodes (SLNs) challenges the recently established criteria for adjuvant treatment (i.e., combination therapy with abemaciclib, endocrine therapy, and chemotherapy in patients with ≥ 4 positive nodes). The question remains as to whether these patients should undergo further ALND to determine whether ≥ 4 nodes are positive. To further investigate the latest controversies in axillary management of BC patients and predict the presence of ≥ 4 axillary lymph node metastasis, we evaluated and compared patients ≥ 4 positive nodes in the per-protocol population of the SINODAR-ONE clinical trial. Patients in the standard arm (ALND) of the per-protocol population were evaluated, and a comparison of characteristics between patients with ≥ 4 metastatic lymph nodes versus patients with 1-3 metastatic lymph nodes was performed. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Multivariable analysis was performed using a logistic regression model to identify independent predictors of ≥4 axillary lymph node metastasis. Results: Overall, 403 cN0 T1-2 BC patients in the per-protocol population were randomized to receive ALND. Of these, 65 and 338 patients presented with ≥ 4 or 1-3 axillary lymph node metastasis, respectively. Invasive lobular BC (26.2% versus 14.5% if other histology, odds ratio (OR)=4.185, 95% confidence interval (95%CI)= 1.284-1.443, p= 0.041), G3 (38.5% versus 21.3% if G1-2, OR=5.930, 95%CI= 2.134-2.289, p= 0.015), pT2 (46.2% versus 30.5% if pT1, OR=5.260, 95%CI= 15.330-16.346, p= 0.022), and 2 positive SLNs (32.3% versus 13.6% if 1 positive SLN, OR=13.188, 95%CI= 1.179-1.280, p&amp;lt; 0.0001) were found to significantly increase the probability to present ≥4 axillary lymph node metastasis at definitive histopathological evaluation. Conclusions: The introduction of abemaciclib and other combination therapies has the potential to impact the surgical management of the axilla. Our results suggest that a minority of cN0 T1-2 BC patients may be understaged if ALND is not performed. However, the improvements and increasing effectiveness of combination therapies may sufficiently control and treat the axillary tumor-burden left behind, potentially reducing the need for extensive axillary surgery, as demonstrated by the promising 3-year oncological outcomes of the SINODAR-ONE trial. Although ALND may still be considered, after multidisciplinary team discussion, in individual patients presenting with specific risk factors for additional axillary disease (lobular, G3, pT2 BC with 2 positive SLNs), our suggestion is that routine ALND is not indicated for systemic therapy decision-making in the upfront surgical setting. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Andrea Sagona, Erika Barbieri, Alberto Bottini, Alberto Testori, Valentina Errico, Simone Di Maria Grimaldi, Giulia Caraceni, Shadya Darwish, Giuseppe Canavese, Corrado Tinterri. To dissect or not to dissect? The surgeon’s perspective on the prediction of ≥ 4 axillary lymph node metastasis in cN0 T1-2 breast cancer: A comparative analysis of the per-protocol population of the SINODAR-ONE clinical trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-04.

Abstract Introduction: Accurate assessment of axillary lymph nodes is crucial in the management of early breast cancer (EBC), especially in clinically node negative (cN0) axilla to avoid extensive axillary surgery. Clinical examination alone underestimates nodal disease in nearly 30% women with cN0 axilla. The current study compares, in cN0 axilla, the benefit of axillary ultrasonography (USG) and clinical axillary examination under anesthesia (EUA) to predict involvement of axillary lymph nodes. The gold standard in these patients however remains pathological evaluation after sentinel node biopsy/low axillary sampling (SNB/LAS) and a complete axillary lymph node dissection (ALND) if node positive. Methodology: Prospectively, 500 women with cN0 EBC were enrolled from Aug 2015 to April 2023 in a study approved by Institutional Ethics Committee. After informed consenting, a preoperative axillary USG was carried out in addition to standard breast imaging to determine number of axillary node(s) and its architecture. The USG assessment was labeled as suspicious or not and the result was blinded to the surgeons. A USG-guided FNAC was not performed as it would then be difficult to blind the surgeon and pathologist preoperatively. During surgery, an initial axillary EUA was performed before starting and any suspicious node was documented. This was followed by axillary staging by standard dual tracer SNB/LAS. A complete axillary dissection was done (level 1-3) if any node was positive on frozen section evaluation or final histopathology. Axillary node histopathology was the gold standard for comparison of effectiveness of clinical exam, USG, EUA, and SNB/LAS for prediction of axilla. Standard diagnostic tests such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were used. Results: Thirty-six patients were excluded in the final analysis (disease progression, chemotherapy first, or had a surgery elsewhere). Of the eligible 464 cN0 patients, 129 were detected to have axillary metastases (27.8%) in final histopathology. The 2 interventions namely USG axilla, EUA were compared to final axillary nodal histopathology. Axillary USG reported suspicious/indeterminate node(s) in 129 (27.8%) patients. USG had a low sensitivity of 46.5% and a low PPV of 46.5% to identify a positive node. However, the specificity and NPV both were 79.4%. Axillary USG was 70.2% accurate in predicting axillary nodal involvement. EUA also had sensitivity of 60% and low PPV of 14.8%. However, the specificity of EUA was 73.4%, NPV of 95.9%; higher than that of USG. EUA was 72.4% accurate. SNB/LAS had the sensitivity of 93.3%, specificity 79.2%, NPV 82.9%, PPV 91.6% and accuracy rate 89.2% in predicting a positive axilla. Conclusions: While the fallacy of clinical exam remains at 27.8%, both USG alone (without FNAC) and EUA failed in predicting a positive axillary node. EUA fared better at predicting a negative axilla. USG guided FNAC would perhaps improve the sensitivity of USG, however additional investigations are difficult in resource constraint and high-volume center, especially, when surgical interventions like SNB or LAS remain standard of care. Table 1 Citation Format: Vani Parmar, Zeal Sanghvi, Shalaka Joshi, Nita Nair, Palak Popat, Seema Kembhavi, Souwmyashree KN, Soujanya Mynalli, Purvi Thakkar, Garvit Chitkara, Sangeeta Desai, Tanuja Shet, Rajendra Badwe. Prospective non-randomized study to compare accuracy of clinical examination under anesthesia, axillary ultrasound and histo-pathological evaluation for axillary nodal staging in women with clinically N0 early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-03.

Objective: Lymphedema is a progressive, debilitating condition affecting up to 250 million people worldwide. Caused by the accumulation of proteinaceous interstitial fluid secondary to lymphatic destruction, extravasation of protein-rich fluid occurs when fluid formation exceeds lymphatic transport capacity, furthermore, leading to increased intralymphatic pressure, valvular incompetence, and dermal backflow, preceding eventual irreversible extremity enlargement, progressive fibrosis with lymphatic obstruction, and luminal obliteration. In western countries, damage or removal of regional lymph nodes by surgery, radiation, tumor invasion, or as a result of infection or inflammation are the most common causes of secondary lymphedema, with the greatest prevalence among those who undergo extensive axillary surgery followed by axillary radiation, noting incidences of 24-49% after mastectomy. The variability of lymphedema and increased healthcare cost in association, reins focus and elucidates the vital importance of discovering techniques to abate disease potentiation while implementing healthful strategies. Surgical techniques aim to diminish the size of the affected extremity, with resultant improvement in appearance, function, and prevention of infection; notably, growing bodies of evidence support the effectiveness of modern surgical techniques in ameliorating the long-term disability and functional impairment. Such technique of autologous vascularized lymph node transfer will be examined here. Consequently, irrespective of surgical approach, vascularized lymph node transfer affords inherent risks of postoperative chyle leaks. While previous trials have demonstrated Adherus Dural Sealant as being 99.1% effective in preventing cerebrospinal fluid (CSF) leaks through 14 days of postoperative follow-up, we will reveal Adherus Dural Sealant results within and throughout our institution, in preventing postoperative chyle leaks after vascularized lymph node transfer. Methods: In this study, we evaluate ten patients who underwent vascularized lymph node transfer between 2018 and 2021, at our single institution. Results: Within our patient population, there were a total of 13 vascularized lymph node transfers performed, with zero postoperative chyle leaks or donor site complications. Conclusion: The core plastic surgery concept of replacing “like” with “like” is no more evident than in the restoration of healthy lymph nodes to a limb in which lymphatic flow has been disrupted. In parallel to the aforementioned concept, via utilization of Adherus Dural Sealant within the supraclavicular lymph node basin and no evidence of chyle leaks in the postoperative period, we pose a novel sealant technique in lymph node harvest that has demonstrated success in minimizing complications following vascularized lymph node transfer throughout our patient series. Further research, characterization, and long-term supraclavicular lymph node basin follow-up are vital, to clarify and potentially expand upon its indications for use. Corresponding Author: Kaitlyn Stevens, DO, 6100 E. Colony Rd., Elsie, MI 48831

Axillary-Lateral Thoracic Vessel Juncture Radiotherapy Dose Constraints for Predicting Long-Term Lymphedema Risk in Patients with Breast Cancer

Based on the ACOSOG Z0011 trial, women who undergo breast conservation therapy (BCT) and have limited disease in the axilla on sentinel lymph node (SLN) biopsy do not require axillary lymph node dissection (ALND). In this study we investigate the incidence of ALND in patients undergoing elective mastectomy with limited disease in the axilla to identify how many women may have been spared additional axillary surgery if they chose BCT. All women with invasive breast cancer treated at a single tertiary care breast center from 2010-2018 who were candidates for BCT but elected mastectomy and underwent SLN biopsy were identified through retrospective review of a prospectively maintained database. The primary outcome of interest was the incidence of ALND in women found to have a limited burden of disease in the axilla (1-2 positive SLNs). The study population comprised 151 patients with invasive breast cancer eligible for BCT who chose mastectomy. On final pathology, 34 patients had 1-2 positive SLNs, and 16 of these patients underwent completion ALND. These 16 patients out of 151 overall lumpectomy candidates electing mastectomy (10.6%) could have been spared ALND if they did not elect mastectomy. BCT candidates electing mastectomy have a 10.6% chance of undergoing more extensive axillary surgery than would have been recommended with BCT alone. The increased risk of undergoing additional axillary surgery should be incorporated into the preoperative discussion for patients choosing between BCT and mastectomy.

Quantifying Risk of Ipsilateral Arm Lymphedema Causing Functional Impairment in Breast Cancer Patients: Results From a Prospective, Multi-Centre International Study of Treatment Toxicity

Utilization of sentinel lymph node biopsy (SLNB) in breast cancer patients with positive nodes after neoadjuvant chemotherapy (NAC) has increased. We examine axillary response rates after NAC in patients with clinical N2-3 disease to determine whether SLNB should be considered. Breast cancer patients with clinical N2-3 (AJCC 7th Edition) disease who received NAC followed by surgery were selected from our institutional tumor registry (2009-2018). Axillary response rates were assessed. Ninety-nine patients with 100 breast cancers were identified: 59 N2 (59.0%) and 41 (41.0%) N3 disease; 82 (82.0%) treated with axillary lymph node dissection (ALND) and 18 (18.0%) SLNB. The majority (99.0%) received multiagent NAC. In patients undergoing ALND, cCR was observed in 20/82 patients (24.4%), pathologic complete response (pCR) in 15 patients (18.3%), and axillary pCR in 17 patients (20.7%). In patients with a cCR, pCR was identified in 60.0% and was most common in HER2+ patients (34.6%). In this analysis of patients with clinical N2-3 disease receiving NAC, 79.3% of patients had residual nodal disease at surgery. However, 60.0% of patients with a cCR also had a pCR. This provides the foundation to consider evaluating SLNB and less extensive axillary surgery in this select group.

BackgroundGiven reports of low response rates to neoadjuvant chemotherapy (NAC) in invasive lobular carcinoma (ILC), we evaluated whether use of alternative strategies such as neoadjuvant endocrine therapy (NET) is increasing. Additionally, we investigated whether NET is associated with more breast conservation surgery (BCS) and less extensive axillary surgery in those with ILC.Patients and MethodsWe queried the NCDB from 2010 to 2016 and identified all women with stage I–III hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2−) ILC who underwent surgery. We used Cochrane–Armitage tests to evaluate trends in utilization of the following treatment strategies: NAC, short-course NET, long-course NET, and primary surgery. We compared rates of BCS and extent of axillary surgery stratified by clinical stage and tumor receptor subtype for each treatment strategy.ResultsAmong 69,312 cases of HR+/HER2− ILC, NAC use decreased slightly (from 4.7 to 4.2%, p = 0.007), while there was a small but significant increase in long-course NET (from 1.6 to 2.7%, p < 0.001). Long-course NET was significantly associated with increased BCS in patients with cT2–cT4 disease and less extensive axillary surgery in clinically node positive patients with HR+/HER2− tumors.ConclusionsPrimary surgery remains the most common treatment strategy in patients with ILC. However, NAC use decreased slightly over the study period, while the use of long-course NET had a small increase and was associated with more BCS and less extensive axillary surgery.

Disparities in the Use of Sentinel Lymph Node Dissection for Early Stage Breast Cancer

Abstract Background: Selective removal of initially suspicious axillary lymph nodes in breast cancer patients downstaged by primary systemic therapy (PST) improves the accuracy of surgical staging and provides the opportunity for less extensive axillary surgery. Different techniques for this targeted lymph node biopsy (TLNB) have been evaluated. These are either prohibited for radiation safety reasons (radioactive seeds) in some countries, or revealed low identification rates for the target lymph node (TLN) in prospective feasibility trials (wire localization of clip-marked TLN). Therefore, an alternative TLN marking procedure avoiding radiation exposure, specialized intraoperative equipment, high costs and preoperative localization procedures is urgently needed. Tattooing TLNs with highly purified carbon suspension prior to PST and identifying the TLN intraoperatively by visual examination, is a method combining low costs with high patient comfort. Because of the data scarcity on the feasibility of TLNB by carbon tattooing, the TATTOO trial was initiated. Trial design: The Tattoo trial is a single-arm, multicentric, prospective feasibility trial. Before initiation of PST, ultrasound-guided fine needle aspiration or core needle biopsy of the most suspicious ipsilateral axillary lymph node (TLN) is performed and a highly purified carbon suspension then injected into the cortex of the sampled lymph node and the adjacent soft tissue. After completion of PST, TLNB and axillary lymph node dissection Level I/II is performed in all patients. In those with clinical and sonographical axillary down-staging, sentinel lymph node (SLN) biopsy is additionally performed. Eligibility criteria: Prior to tattooing, written informed consent is obtained. Female patients aged at least 18 years, with histologically confirmed invasive uni- or bilateral breast cancer with clinically or sonographically suspicious axillary lymph nodes and planned PST without signs of distant metastases are eligible. Specific aims: The primary outcome of the trial is the intraoperative identification rate (IR) of the carbon-labeled TLN after PST. Secondary outcomes are the concordance rate (CR) of sentinel lymph nodes (SLN) and TLN, the false negative rate (FNR) of targeted axillary dissection (TAD, i.e. SLNB biopsy + TLNB) and complications associated with the procedure. Statistical methods: IR is defined as the proportion of patients with intraoperatively visually detectable TLNs of all patients. CR is expressed as the proportion of patients in whom TLNB and SLN biopsy reveal the same lymph nodes. The proportion of patients with negative TLN and/or SLN but with metastatic axillary lymph nodes on ALND out of all patients with positive lymph nodes will be reported as FNR. Complications associated with tattooing (i.e. bleeding, pain, adverse tattoo effects) are reported. Statistical analyses will be carried out using IBM SPSS statistics version 25. Present and target accrual: Patient accrual was initiated in November 2017. Until now, 84 patients have been included by three sites in Germany and Sweden. The target enrollment of 100 patients is estimated to be reached by August 2019 and the final trial report is planned for 2020. Contact information Steffi Hartmann, MD (steffi.hartmann@kliniksued-rostock.de) Citation Format: Steffi Hartmann, Angrit Stachs, Thorsten Kühn, Antje Winckelmann, Jana de Boniface, Bernd Gerber, Toralf Reimer. Feasibility of carbon tattooing for targeted lymph node biopsy in breast cancer patients treated by primary systemic therapy (TATTOO trial) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-01-01.

Inflammatory breast cancer (IBC) is an aggressive variant for which axillary lymph node (LN) dissection following neoadjuvant chemotherapy (NACT) remains standard of care. But with increasingly effective systemic therapy, it is unclear whether more limited axillary surgery may be appropriate in some IBC patients. We sought to examine whether extent of axillary LN surgery was associated with overall survival (OS) for IBC. Female breast cancer patients with non-metastatic IBC (cT4d) diagnosed 2010-2014 were identified in the National Cancer Data Base. Cox proportional hazards modeling was used to estimate the association between extent of axillary surgery (≤ 9 vs ≥ 10 LNs removed) and OS after adjusting for covariates, including post-NACT nodal status (ypN0 vs ypN1-3) and radiotherapy receipt (yes/no). 3471 patients were included: 597 (17.2%) had cN0 disease, 1833 (52.8%) had cN1 disease, and 1041 (30%) had cN2-3 disease. 49.9% of cN0 patients were confirmed to be ypN0 on post-NACT surgical pathology. Being ypN0 (vs ypN1-3) was associated with improved adjusted OS for all patients. Radiotherapy was associated with improved adjusted OS for cN1 and cN2-3 patients but not for cN0 patients. Regardless of ypN status, there was a trend towards improved adjusted OS with having ≥ 10 (vs ≤ 9) LNs removed for cN2-3 patients (HR 0.78, 95% CI 0.60-1.01, p = 0.06) but not for cN0 patients (p = 0.83). A majority of IBC patients in our study presented with node-positive disease, and for those presenting with cN2-3 disease, more extensive axillary surgery is potentially associated with improved survival. For cN0 patients, however, more extensive axillary surgery was not associated with a survival benefit, suggesting an opportunity for more personalized care.

Breast-conserving surgery (BCS) and radiotherapy reduce breast cancer recurrence but can cause functional deficits in breast cancer survivors. A cross-sectional study quantified the long-term pathophysiological impact of these treatments on biomechanical measures of shoulder stiffness and ultrasound shear wave elastography measures of the shear elastic modulus of the pectoralis major (PM). Nine node-positive patients treated with radiotherapy to the breast and regional nodes after BCS and axillary lymph node dissection (Group 1) were compared to nine node-negative patients treated with radiotherapy to the breast alone after BCS and sentinel node biopsy (Group 2) and nine healthy age-matched controls. The mean follow-up for Group 1 and Group 2 patients was 988 days and 754 days, respectively. Shoulder stiffness did not differ between the treatment groups and healthy controls (p = 0.23). The PM shear elastic modulus differed between groups (p = 0.002), with Group 1 patients exhibiting a stiffer PM than Group 2 patients (p < 0.001) and healthy controls (p = 0.027). The mean prescribed radiotherapy dose to the PM was significantly correlated with passive shear elastic modulus (p = 0.018). Breast cancer patients undergoing more extensive axillary surgery and nodal radiotherapy did not experience long-term functional deficits to shoulder integrity but did experience long-term mechanical changes of the PM.

We sought to evaluate the impact of chemotherapy sequence on survival by comparing node-positive invasive lobular carcinoma (ILC) patients who received neoadjuvant (NACT) and adjuvant (ACT) chemotherapy. cT1-4c, cN1-3 ILC patients in the National Cancer Data Base (2004-2013) who underwent surgery and chemotherapy were divided into NACT and ACT cohorts. Kaplan-Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. Five thousand five hundred fifty-one (35.6%) of 15 573 ILC patients treated with chemotherapy received NACT. NACT patients had similar rates of pT3/4 disease (26.6% vs 26.2%), nodal involvement (median 3 vs 4), and number of lymph nodes examined (median 13 vs 14) but higher rates of mastectomy (81.8% vs 74.5%, P < 0.001) vs ACT patients. 3.4% of NACT patients experienced pathologic complete response (pCR). Unadjusted 10-year OS was worse for NACT vs ACT patients (65.1% vs 54.4%, log-rank P < 0.001). After adjustment for known covariates, NACT continued to be associated with worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.25-1.52). In node-positive ILC, NACT yielded low rates of pCR, was not associated with lower rates of mastectomy or less extensive axillary surgery, and was associated with worse survival vs ACT, suggesting limited benefit for these patients.

Abstract The study objective was to evaluate preoperative Wirefree Localization (WFL) placement success rate and device stability 31-365 days prior to successful surgery in patients with node-positive breast cancer prior to neoadjuvant treatment (NAT). Background: Wirefree nonradioactive Localization (WFL) has become a standard of care in over 40,000 breast cancer patients in 300 US sites. The radiologist/surgeon performs preoperative WFL of the positive breast or axillary lymph node (LN) using Mammography (MG), Ultrasound (US) or CT guidance. In August 2018, the FDA expanded clearance of long-term breast WFL to soft tissue and LN. Results of this study further support the ACOSOG-Z1071 subset findings that selected patients with node-positive disease and NAT may be eligible for sentinel lymph node (SLN) surgery and may potentially require less extensive axillary surgery. Long-term (31-365 day) preoperative localization of the biopsy proven positive LN may represent a more practical approach to supplement SLN in NAT patients. Methods: This prospective pilot study enrolled 33 breast cancer patients aged 28-74 (10 Caucasian, 12 African American, 11 Hispanic), with clinical T1-4, N0-2, M0 disease who planned NAT. WFL was performed prior to NAT response and 31 - 365 days preoperatively in the breast and/or positive axillary LN (19 LN only, 4 both breast and LN, 10 breast only). Descriptive statistics were used. Results: This subset analysis showed 23/33 patients were node-positive (10-51 mm size). WFL placements were successful (0-10 mm from center) in all 23/23 patients via US guidance (22 patients, LN 8-35 mm deep to skin) and CT guidance (1 patient, LN 90 mm deep to skin). WFL stability (0 mm migration) throughout NAT was documented on all standard of care (SOC) preoperative surveillance imaging MG, US, MRI, CT and specimen X-rays (0-222 days). Both the target LN and WFL were well visualized on 9/9 MRI and 8/8 PET/CT SOC imaging. WFL successfully supplemented SLN final surgery in 11/23 subjects to date. Conclusions: WFL of positive LN may be successfully performed prior to NAT response, when the lesion is clearly visualized on imaging. Since successful NAT can result in a complete or partial imaging response, a simpler pre-NAT image-guided WFL may replace the more difficult and less reliable localization post-NAT response. The latter can contribute to incomplete removal of the targeted LN, and unintended larger, more disfiguring cancer surgery. This subset analysis provides preliminary information to suggest that up front WFL of positive LN may be performed long-term prior to NAT response with no significant adverse events or device migration. Long-term (31-365 day) preoperative WFL of the biopsy proven positive LN may represent a more practical approach to supplement SLN in NAT patients. If larger scale studies confirm these findings, this may prove a clinically relevant paradigm shift for future LN positive patients to ensure that the targeted LN is successfully removed, potentially requiring fewer and/or less extensive radiology and surgical procedures. ClinicalTrials.gov NCT03015649 accrual: 33/33 Citation Format: Hayes MK, Wright HR, Bloomquist EV. Preoperative wirefree localization of positive axillary lymph nodes 31-365 days prior to surgery: A proposed practical approach to supplement SLN in neoadjuvant therapy patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-41.