Hand Surgery in Patients with a History of Lymphedema: A Review of Current Concepts and Opinions.

Occult breast carcinoma (OBC) refers to the clinical presentation of breast carcinoma occurring in axillary lymph node(s) without a detectable primary breast cancer. Prior studies of OBC have focused on treatment regimens. We sought to study the clinical, morphologic, and immunohistochemical features of OBCs. We retrospectively identified cases of OBC treated at our center between 1996 and 2021. All patients included in the study had biopsy-proven axillary metastatic breast carcinoma and underwent MRI after a noncontributory mammogram/ultrasound. Patients with a prior history of breast carcinoma were excluded. The study included 68 patients with a median age of 56 years (range: 31 to 84y). The morphology in 55 cases (81%) was poorly-differentiated carcinoma, no special type (ductal). The remaining tumors showed lobular, micropapillary, apocrine, clear cell, and signet ring cell morphology. Thirty-nine (57.4%) OBC were hormone receptor positive, 19 (33.3%) were HER2 positive and 13 (22.8%) tumors were triple negative. Fifty (74%) patients had a breast sampling procedure while 18 (26%) did not. Thirty-four (50%) patients underwent neoadjuvant chemotherapy. Fifty-nine (87%) patients underwent axillary lymph node dissection while 9 (13%) had sentinel lymph node biopsy only. Nineteen (56%) patients achieved a complete pathologic response in the axilla. Fourteen (21%) patients developed a recurrence: 5 in the ipsilateral breast or axilla, 1 in the contralateral axilla and mediastinum, and 8 in distant metastatic sites. The median time to recurrence was 51.9 months. The final pathologic lymph node stage was the only feature found to be significantly associated with the development of recurrence.

Systematic review and meta-analysis comparing perioperative outcomes of minimally invasive and open axillary lymph node dissection in breast cancer.

Does neoadjuvant systemic therapy in clinical T1-2 N0 human epidermal growth factor receptor 2-positive breast cancer increase the extent of axillary surgery?

Targeted axillary dissection after neoadjuvant chemotherapy in breast cancer patients with a high lymph node burden: Radiological and histological outcomes.

Desmoid tumors are benign mesenchymal neoplasms that originate from muscular fasciae and aponeuroses. Breast involvement is exceptionally rare, accounting for less than 0.2% of all breast tumors. A 41-year-old woman with a history of right-sided invasive ductal carcinoma (IDC) diagnosed in 2022 underwent breast-conserving surgery (BCS) and axillary lymph node dissection (ALND), followed by adjuvant chemotherapy, radiotherapy, and daily tamoxifen (20 mg). The tumor measured 3.5 cm at its greatest dimension, was grade 2, estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, HER2 negative, and had a Ki-67 proliferation index of 25%. Histologic examination revealed a cribriform growth pattern without associated ductal carcinoma insitu (DCIS) or lymphovascular invasion (LVI), and one of nine axillary lymph nodes was positive for metastasis. In 2023, a total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed for ovarian suppression. During routine surveillance in 2024, a new mass was detected at the 2 o'clock position in the right breast. Two core needle biopsies performed over 6 months confirmed fibromatosis. Ongoing tumor enlargement and severe pain, despite radiotherapy, led to a wide local excision. Breast fibromatosis can closely mimic carcinoma both clinically and radiologically, and histologic analysis remains essential for definitive diagnosis. Complete surgical excision with negative margins remains the treatment of choice.

Histopathological evaluation of local effects of radioactive iodine seeds in axillary lymph nodes in clinically node-positive breast cancer treated with neoadjuvant systemic therapy.

Oncological plastic surgery plays a central role in the management of cancers requiring complex reconstruction. Recent years have seen significant advances in oncology, both therapeutic and technological. The aim of this article is to provide an overview of major recent developments in oncological plastic surgery, through a selection of impactful recent studies chosen by national experts in three of the main fields of this specialty. Between October and November 2024, national experts and/or representatives of French scientific societies were invited to participate in this analysis. The covered domains included senology, soft tissue sarcoma surgery, and oncological dermatologic surgery. Each expert selected two recent articles (≤5years) deemed relevant within their field of expertise. Selected studies had to have a direct impact on clinical practice in oncological plastic surgery. Each article was validated, analyzed, and synthesized with a focus on its practical implications for reconstructive plastic surgery. Recent developments in oncological plastic surgery show profound changes in treatment strategies, largely influenced by the emergence of neoadjuvant immunotherapy and an increasingly personalized approach to reconstruction. In senology, there is a reduction in surgical indications, particularly with the decreasing use of sentinel lymph node biopsy in early breast cancer and reconsideration of axillary dissection in the presence of positive sentinel nodes (but normal axillary ultrasound). In soft tissue sarcomas, the role of the plastic surgeon is reinforced to ensure clear resection margins, and a risk-based reconstruction algorithm now guides the use of flaps in high-risk patients. In oncological dermatology, neoadjuvant immunotherapy is gaining a growing role in the treatment of advanced stages of melanoma and squamous cell carcinoma, reshaping the timing and indications for surgical intervention. Oncological plastic surgery is moving towards more targeted, less invasive approaches, integrated within multidisciplinary therapeutic strategies. In this context, understanding recent oncological advances -particularly in immunotherapy, neoadjuvant protocols, and patient selection criteria- is essential for plastic surgeons to ensure optimal and up-to-date patient care.

Surgical axillary staging in patients with node-positive breast cancer (BC) who converted to clinical node negativity through neoadjuvant chemotherapy (NACT) has changed significantly in recent years. Targeted axillary dissection (TAD) and target lymph node (TLN) biopsy (TLNB) became increasingly popular. However, data comparing marking techniques for the TLN are limited. Here, we evaluate marking techniques in the largest prospective cohort worldwide. Among patients from the ongoing prospective multicenter AXSANA (EUBREAST-03) study who received TLN marking and TAD/TLNB, we evaluated different marking methods with respect to detection and removal rates and clinical performance. Until January 6, 2025, 6,129 patients from 26 countries were enrolled. Of these patients, 2,596 had ≥1 TLN marked before NACT and completed surgery; 13.3% of the patients had ≥4 suspicious nodes at diagnosis. Pre-NACT TLN marking used a clip in 2,003 patients (77.2%), magnetic seed in 287 (11.1%), carbon ink in 192 (7.4%), radar marker in 119 (4.6%), radioactive seed in 18 (0.7%), radiofrequency identification device (RFID) in 12 (0.5%), or other methods in two (0.1%). One TLN was marked in 2,427 patients (93.5%), two TLNs in 138 (5.3%), and ≥3 in 27 patients (1%). Targeted removal of the TLN was planned in 2,100 patients (80.9%; TAD in 2,076 [80.0%] and TLNB in 24 [0.9%]). The TLN was detected and removed by TAD/TLNB in 1,915 patients (91.2%). TLN detection rate was the highest in patients whose TLNs were marked pre-NACT with markers suitable for probe-guided detection (96.6%; radioactive seed: 100%, magnetic seed: 96.9%, radar marker: 96.1%, RFID: 90%), followed by carbon ink (94.9%) and clip (89.6%; P < .001). This large prospective analysis of patients with initially clinically node-positive BC receiving NACT demonstrates that probe-guided detection markers used to mark metastatic nodes before NACT provide superior detection rates.

Cancer-related lymphedema (CRLE), a chronic complication of cancer treatment, affects 39-73% of patients post-lymph node dissection, impacting physical health, social participation, and finances. Prophylactic immediate lymphatic reconstruction (ILR) via lymphaticovenous anastomosis (LVA) has shown potential in reducing CRLE incidence by two-thirds following axillary and inguinal node dissection. However, rigorous phase III studies with long-term follow-up are still needed to confirm these promising results. This study aims to evaluate the efficacy, safety, and long-term outcomes of ILR in preventing CRLE in a prospective, controlled trial setting. A phase III randomized controlled trial will evaluate an intervention in adult patients undergoing axillary or groin node dissection for cutaneous malignancy. Block randomization will stratify participants by upper or lower extremities. Primary outcomes include lymphedema incidence and quality-of-life measures. Statistical analyses will compare lymphedema rates and quality-of-life outcomes between intervention and control groups. The primary endpoint is to assess the impact of prophylactic LVA on the presence or absence of lymphedema post axillary or groin lymphadenectomy and participant quality of life. The secondary endpoint is the incidence of complications related to nodal dissection. CRLE, a common complication of cancer surgery and radiotherapy, severely impacts patients' lives and healthcare resources. Reducing its incidence by two-thirds would significantly improve outcomes for cancer survivors and decrease treatment demands. This underscores the need for advanced research in prevention and early intervention strategies to mitigate lymphedema's burden on patients and healthcare systems. ClinicalTrials.gov ID NCT051360792021-11-02.

Background: Seroma formation remains the most frequent complication following modified radical mastectomy (MRM). The choice of dissection technique plays a role in its incidence. This study compared LigaSure with conventional electrocautery for axillary dissection in terms of seroma formation and related outcomes. Methods: A prospective randomized study was conducted on 50 female patients with unilateral FNAC/Biopsy proven breast carcinoma undergoing MRM, at Aadhar health institute, Hisar, Haryana. Patients were randomized into two groups: group A (electrocautery, n=25) and group B (LigaSure, n=25). Standardized half-pressure negative suction drains were placed in all cases. Outcomes compared in terms of operative time, daily drain output, duration of drainage, incidence of seroma formation, and number of seroma aspirations. Results: The mean operative time, was shorter in the LigaSure group, though not significant statistically. Drain output up to postoperative day 3 was significantly lower in the LigaSure group (p&lt;0.05), but from POD 4 to POD14, cumulative drain output was statistically non-significant. Seroma incidence was reduced with LigaSure (28%) compared to electrocautery (32%), though not statistically significant. The seroma aspirations were also lower in the LigaSure group in number, but non-significant. Conclusions: LigaSure reduces operative time and drainage volume, with a trend toward fewer seroma formation compared to electrocautery. Although the difference in seroma incidence did not reach statistical significance, LigaSure appears to be a safer and more efficient option for axillary dissection in MRM.

The incidence of lymphedema may be as high as 65% among breast cancer patients, varying according to the diagnostic method and locoregional treatment. Therefore, investigations of preventive methods are highly welcomed. Our goal was to conduct a systematic review of the literature about the use of axillary reverse mapping to prevent lymphedema during breast cancer treatment. We hypothesized that identification of arm-draining lymph nodes may decrease the incidence of lymphedema. On October 7, 2019, we conducted a systematic review of studies in PubMed, Cochrane Clinical Answers, and Cochrane Central Register of Controlled Trials, without time frame or language limitations, on the use of axillary reverse mapping to prevent lymphedema during breast cancer treatment. We excluded articles that investigated other uses of lymphoscintigraphy, such as lymphedema diagnosis or treatment evaluation. Of 104 potential articles found in the literature, 5 studies fulfilled the eligibility criteria. A total of 501 patients were included. Reverse mapping was done with radiography or single-photon emission computed tomography/computed tomography. Moreover, the examination was applied with different treatments, such as axillary lymph node dissection or radiotherapy, allowing preservation of noncompromised lymph nodes. Axillary reverse mapping also had prognostic value and was used with sentinel lymph node biopsy to identify patients at higher risk for lymphedema. Only one study compared the incidence of lymphedema between patients who received standard care or reverse mapping, showing significant benefits of its use. Use of axillary reverse mapping to prevent lymphedema is feasible and seems to provide valuable information for breast cancer treatment. Future studies that compare reverse mapping and standard care are still necessary.

Lymph flow measurements can assist in attaining a better understanding of the lymphatic system's function and its diseases. However, invivo assessment of lymph flow has been challenging. Transit-time ultrasound technique (TTUT) provides direct quantitative lymph flow values and has been used to successfully measure lymph flow in patients with secondary lymphedema. Currently, no measurements using TTUT in healthy subjects have been reported. The aim of this study is to measure lymph flow in healthy subjects using the TTUT. Twenty consecutive patients who had an indication for a free radial forearm flap (FRFF) reconstruction were included in the study. Patients with scars on their arms, a history of extremity lymphedema, metastatic disease, or axillary node dissection were excluded. The Transonic® Microvascular Flow Probe was used to measure lymph flow during FRFF reconstruction in accordance with the Transonic® protocol for Quantitative Patency Assessment. The subdermal superficial lymphatic collecting vessels had a mean diameter of 0.40 ± 0.10 mm (range: 0.3-0.5 mm) and a mean lymph flow velocity of 0.45 ± 0.48 mL/min (range: 0.08-1.68 mL/min). Neighboring subdermal veins measured had a mean diameter of 0.48 ± 0.11 mm (range: 0.03-0.7 mm) and a mean blood flow velocity of 0.96 ± 1.73 mL/min (range: 0.07-7.40 mL/min). The TTUT is a viable method to measure real-time lymph flow velocities in healthy subjects. Future studies with a larger sample size are required to validate the TTUT measurement accuracy and establish clinical correlations.

Lymphedema Education Advocacy Program (LEAP): Addressing Gaps in Patient Education of Breast Cancer-Related Lymphedema (BCRL).

Abstract Background: Adjuvant CDK4/6 inhibitor abemaciclib combined with endocrine therapy has demonstrated significant improvement in invasive disease-free survival among patients with high-risk, hormone receptor-positive, HER2-negative (HR+HER2-) early-stage breast cancer. Lymph node involvement is a key determinant of recurrence risk and plays a critical role in therapeutic decision-making. However, the optimal surgical management of axillary lymph nodes remains unclear when the extent of nodal involvement may influence adjuvant therapy decisions. This study aimed to investigate the proportion of real-world cases in which axillary dissection was essential for determining eligibility for adjuvant abemaciclib. Methods: We conducted a multicenter retrospective study of patients diagnosed with early-stage breast cancer between 2018 and 2025 within a national Brazilian cancer network. We evaluated the proportion of patients eligible for adjuvant abemaciclib based on phase 3 monarchE trial criteria. Indications were stratified into three sequentially applied groups (patients meeting a prior criterion were not reassigned to subsequent ones):1.Positive axillary lymph node(s) nodes and either grade 3 disease or tumor size ≥5 cm;2.Positive axillary lymph node(s) and Ki-67 ≥20%;3.Four or more positive axillary lymph nodes.Patients meeting only criterion 3 were considered reliant on axillary dissection for abemaciclib indication. Results: Among 656 patients with HR+/HER2- breast cancer, 284 (43.3%) met monarchE criteria for adjuvant abemaciclib. Median age was 49 years (range 24-83), with 52.8% being premenopausal. Ductal and lobular histologies were present in 72.2% and 16.5%, respectively. Tumor grade was 7.0% grade 1, 53.2% grade 2, and 34.5% grade 3. Clinical T stages were: 22.2% T1, 37.7% T2, 23.6% T3, and 6.7% T4. Clinical N stage was N0 in 23.2%, N1 in 49.3%, and N2-3 in 15.5%. Most patients (80.6%) had a Ki67-index ≥20%. Neoadjuvant chemotherapy was used in 46.8% of cases, and 51.1% received adjuvant chemotherapy. Axillary surgery comprised sentinel lymph node biopsy (51.4%) and axillary dissection (44.0%), with data missing in 4.6%. The distribution of criteria leading to abemaciclib indication is shown in Table 1. Discussion: This real-world study demonstrates that only a small subset of patients eligible for adjuvant abemaciclib met the criteria based solely on having four or more positive axillary lymph nodes. These findings support the notion that axillary dissection should not be pursued solely to establish eligibility for adjuvant CDK4/6 inhibitor therapy. Citation Format: L. Holland, L. Testa, C. Cavalcanti, J. F. Bessa, K. Cayres, P. H. Amor Divino, R. Naves, J. Bines, R. C. Bonadio. The impact of axillary lymph node dissection on the indication of adjuvant abemaciclib in high-risk hormone receptor-positive breast cancer: Real-world analysis from a multicenter cohort in Brazil [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-09-04.

Abstract Introduction: The radical mastectomy technique described by Halsted in 1894 was based on the concept that more extensive surgical resection increased the likelihood of patient cure. Over more than 120 years, medical knowledge about breast cancer has expanded, enabling less mutilating treatments with equal or better survival rates, especially following studies on tumor biology. Axillary surgical treatment has been a significant milestone, changing medical management and reducing the rates of axillary lymph node dissection after the publication of the American College of Surgeons Oncology Group Z0011 clinical trial, that demonstrated that patients with initial cT1-T2 tumors without palpable axillary adenopathy, undergoing breast-conserving surgery, systemic adjuvant treatment, and radiotherapy, maintained overall survival and distant recurrence-free survival rates, even with 1 or 2 metastatic axillary lymph nodes, compared to those who underwent axillary dissection. Objectives: To evaluate the applicability of the Z0011 protocol in the axillary treatment of early invasive breast cancer and its impact on reducing axillary lymph node dissection by omitting this surgical treatment. Method: This is an observational, descriptive, retrospective study based on data collected from the medical records of patients who underwent surgical treatment at a public hospital, Hospital de Base, in the Federal District, Brazil. Results: A total of 119 patients from the mastology service at Hospital de Base met the Z0011 eligibility criteria. Nine patients were excluded due to failure in patent blue migration, resulting in 110 patients included in the study. The average age of patients was 58 years (ranging from 35 to 83 years). The predominant immunohistochemical profile was luminal B (55%), followed by luminal A (30%), HER2 positive (9%), and triple-negative (6%). Among the HER2 positive patients, 80% also had positive hormone receptors (HR), while 20% were HR negative. Among the 110 patients, 27% had sentinel lymph node (SLN) metastasis. Specifically, 19% had metastasis in 1 SLN, 3% had metastasis in 2 SLNs, and 5% had metastasis in 3 or more SLNs. Consequently, 83% of patients with 1 or 2 metastatic SLNs did not undergo lymphadenectomy, representing a significant omission of axillary surgical treatment. Conclusion: The successful replication of the Z0011 protocol in our study demonstrates the significant potential for reducing axillary lymphadenectomy in patients treated at our hospital, with an observed 83% reduction in axillary dissection among patients with axillary lymph node metastasis. These findings are particularly important as they underscore the feasibility of implementing the Z0011 protocol in a public hospital setting, providing evidence that even in resource-constrained environments, it is possible to achieve substantial improvements in patient care. Keywords: Breast cancer; Sentinel lymph node; Axillary metastases; Lymphadenectomy. Citation Format: T. K. Vivan, M. Passos, V. X. Santana, F. C. Salum, C. Fuschino, A. F. Esterl, R. Pepe. Evaluation of Axillary Treatment in Patients with Early Breast Cancer According to Study Z0011 in a Public Tertiary Hospital in the Federal District, Brazil [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-05-13.

Abstract Background: Postmastectomy lymphedema remains a significant source of morbidity in breast cancer survivors. Physical therapy (PT) and occupational therapy (OT) are commonly employed for prevention and management, but optimal referral timing remains unclear. We evaluated whether early PT and OT referral after mastectomy reduces two-year lymphedema. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, which includes de-identified electronic health records from 151 healthcare organizations worldwide. We identified adult women (≥18 years) with a diagnosis of breast cancer (ICD-10: C50) who underwent mastectomy between January 1, 2000, and December 31, 2020. Patients with pre-existing lymphedema or hereditary lymphedema were excluded. Two cohorts were defined based on the timing of PT and OT initiation relative to the mastectomy date: Early cohort: PT/OT initiated within 14 days post-mastectomy (n = 5,197) and delayed cohort: PT/OT initiated more than 14 days post-mastectomy (n = 18,817). PT/OT procedures were identified using relevant CPT codes for therapy evaluations, manual lymphatic drainage, gait training, and self-care training. The primary outcome was the incidence of lymphedema occurring between 90 and 1095 days following the index event. A Cox proportional hazards model was used to assess the association between timing of PT/OT and lymphedema risk, adjusting for age, extent of breast resection, axillary dissection, and sentinel lymph node biopsy. Results: In the multivariable Cox model, early initiation of PT/OT within 14 days post-mastectomy was significantly associated with reduced lymphedema risk (HR 0.737, 95% CI 0.608-0.893, p=0.002). Sentinel lymph node biopsy was associated with a protective effect (HR 0.721, 95% CI 0.546-0.953, p=0.021). In contrast, axillary lymph node dissection was associated with more than a twofold increased risk of lymphedema (right: HR 2.217, p=0.001; left: HR 2.101, p=0.002). Bilateral mastectomy was also protective (HR 0.597, p&amp;lt;0.001), and increasing age was modestly protective (HR 0.981 per year, p&amp;lt;0.001). Unilateral breast resections were not significantly associated with lymphedema risk. Conclusion: Early initiation of PT/OT and the use of sentinel lymph node biopsy were independently associated with reduced lymphedema risk following mastectomy. In contrast, axillary lymph node dissection was strongly predictive of increased lymphedema risk. These real-world findings support current American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines advocating early rehabilitation and limited axillary surgery to minimize long-term morbidity in breast cancer survivors. Citation Format: K. Doshi, S. Afridi, N. Iyer, S. A. Haddad. Impact of early vs delayed referral to physical therapy and occupational therapy after mastectomy and the risk of postmastectomy Lymphedema: A Real-World Propensity-Matched Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-03-20.

Abstract Introduction: The safety of omitting axillary dissection (ALND) in patients with clinically node-positive breast cancer (cN+ BC) may depend on the nodal disease burden left behind in the axilla. This study aimed to evaluate nodal disease volume, quantify nodal understaging without ALND, and identify factors associated with additional nodal disease at ALND in these patients. Methods: The international phase-III TAXIS trial (NCT03513614) randomized patients with cN+ stage II-III BC to ALND or axillary radiotherapy (ART) following tailored axillary surgery (TAS). Nodal disease was detected by imaging or palpation at initial diagnosis. TAS removed sentinel, biopsied, and palpably suspicious nodes. Patients had upfront surgery or residual nodal disease after neoadjuvant chemotherapy (NACT). 1500 patients were randomized from 08/2018 to 08/2025. Results: Of 1418 patients with available data, 712 (50.2%) underwent ALND. Nodal disease was detected by imaging in 735 patients (51.8%), and by palpation in 683 (48.2%). Clinical nodal stage was cN1 in 1232 (86.9%) and cN2/3 in 186 (13.1%). Tumors were HR-positive and HER2-negative in 1140 patients (80.4%), HER2-positive in 160 (11.3%), and triple negative in 96 (6.8%). 552 patients (38.9%) underwent NACT. TAS removed a median of 5 nodes (interquartile range [IQR] 3-7), 2 (IQR 1-4) of which were positive. After TAS, ALND removed a median of 11 additional nodes (IQR 8-16), one (IQR 0-4) of which was positive. Among 712 patients undergoing ALND, additional positive nodes after TAS were removed in 430 (60.4%), AJCC pN upstaging occurred in 226 (31.7%), and 336 (47.2%) had (y)pN2/3 stage. Nodal burden by use of NACT is shown in the table. On multivariable logistic regression the number of positive nodes on TAS was associated with higher odds of having additional positive nodes on ALND in the NACT (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.21-2.03, p&amp;lt;0.001) and upfront surgery group (OR 1.39, 95%CI 1.23-1.57, p&amp;lt;0.001). Furthermore, the odds of having additional positive nodes on ALND were higher in macrometastatic vs. isolated tumor cells/micrometastatic nodal disease on TAS after NACT (OR 2.24, 95%CI 1.10-4.55, p=0.026), and in palpable vs. imaging-detected nodal disease at upfront surgery (OR 1.66, 95%CI 1.05-2.63, p=0.032). Conclusion: Nodal disease burden is high in patients included in the TAXIS trial. Among patients who underwent ALND, almost half had (y)pN2/3 disease, and 60.4% had additional positive nodes removed that were missed by TAS. Nodal disease volume on TAS was associated with higher odds of having additional positive nodes on ALND. Interim analysis raised no safety concerns in the TAXIS study, and long-term follow-up will determine if ART is oncologically non-inferior to ALND. Citation Format: W. P. Weber, C. Tausch, S. Hayoz, Z. Matrai, G. Xepapadakis, C. Simonson, V. Bjelic-Radisic, G. T. Lam, G. Montagna, M. Gnant, L. H. Rosenberger, E. de Bree, R. Satler, M. Fehr, C. Leo, L. Lelievre, S. Bucher, S. Schmid, R. Exner, K. Reisenberger, U. Beckmann, S. Muenst, G. Henke, D. R. Zwahlen, T. Ruhstaller, K. Ribi, C. Urban, A. Crown, J. E. Lee, J. Boileau, A. D. Williams, Y. Jonghan, M. L. DiNome, A. Poultsidi, E. Gonzales, S. M. Wong, A. Schulz, M. Nealeigh, S. G. Ahn, A. M. Botty van den Bruele, B. J. Chae, A. Mueller, D. Hagen, J. M. Ryu, A. Savolt, C. Kurzeder, J. Heil, D. Egle, M. Heidinger, M. Knauer. Nodal disease burden in patients with clinically node-positive breast cancer undergoing tailored axillary surgery with or without axillary dissection in the neoadjuvant and upfront surgery setting: pre-planned TAXIS study (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF2-07.

Abstract Background: TNBC exhibits a high risk of early relapse, yet predictors of time to relapse remain poorly defined. Early relapses (while on or within 12 months after ending curative therapies) are associated with chemotherapy-resistant disease and poor prognosis (median overall survival &amp;lt;12 months; Grinda et al., Eur J Cancer 2023). Identifying key factors associated with early and late relapse may help guide therapeutic interventions. This study explores associations between clinical factors and timing of relapse in patients (pts) with TNBC from the prospective CANTO cohort (NCT01993498). Methods: Early-stage TNBC pts enrolled in the CANTO cohort between 2012 and 2023 were included. Descriptive statistics were used to summarize clinical variables. Invasive disease-free survival (IDFS) was estimated with Kaplan-Meier curves from the time of study entry. The proportional hazards assumption was assessed with Schoenfeld residuals and cumulative hazard plots. A time-varying fixed-effect multivariable Cox model was built using stratification at 24 months for distinguishing early and late relapses. To identify the best-fitting multivariable model for IDFS, stepwise selection (stepAIC) was applied starting from a priori covariates, including age, grade, surgery type, and TNM stage , with additional candidates tested based on univariate results and clinical relevance. Results: Among the 999 pts included, median age was 52.9 years (IQR: 45.1-61.9). Most pts presented with stage II disease (56.3%), followed by stage I (34.4%) and stage III (9.3%). Chemotherapy was administered in 93.5% of pts: adjuvant in 51.3% and neoadjuvant in 42.2% of cases. Breast-conserving surgery was performed in 71.7% pts, mastectomy in 28.3%. Around half of the pts underwent axillary dissection (47.6%).Median follow-up was 74.3 months (IQR: 51.2-99.4). During this period, 239 iDFS events occurred, 49% within the first 24 months. The best final time-varying fixed effect multivariate model for predicting iDFS included age, BMI at diagnosis, smoking, type of surgery, grade, stage and chemotherapy exposure. TNM stage showed a strong prognostic role across the entire follow-up, with stage III disease consistently associated with higher relapse risk compared to stage I (HR: 2.44; 95% CI: 1.44-4.14; p &amp;lt; 0.001). For early relapse, underweight status (BMI &amp;lt; 18.5 Kg/m2) was the strongest predictor (HR: 3.35; 95% CI: 1.58-7.11; p = 0.002). Axillary dissection (HR: 1.60; 95% CI: 1.00-2.55; p = 0.05) and receipt of (neo)adjuvant chemotherapy (HR: 1.51; 95% CI: 0.95-2.40; p = 0.078) trended toward a signifcant increased risk of early relapse. Despite adjustment for TNM stage to account for disease severity, these treatment-related variables may act as proxies for disease burden, and some residual counfounding cannot be excluded. Late relapse was associated with older age (HR: 1.03; 95% CI: 1.01-1.04; p = 0.003), while smokers had a borderline increased risk versus non-smokers (HR: 1.61; 95% CI: 0.98-2.63; p = 0.06). Conclusions: This large cohort study shows that early and late relapses in early-stage TNBC are driven by distinct clinical factors. Our findings integrate clinicopathological variables to support the development of models reflecting individual relapse risk and timing. Early relapses, accounting for half of the events, were strongly associated with underweight status, possibly reflecting patient frailty and comorbidities, and high disease burden at diagnosis, as indicated by stage III disease and high treatment intensity, including axillary dissection and chemotherapy. Late relapses were predicted by older age and stage III disease. These data support time-aware prognostic models to guide individual-risk adapted strategies and underscore the need for biological investigations to better understand early relapse in TNBC. Citation Format: C. Benvenuti, L. Perotti, A. Martin, C. Gaudin, C. Jouannaud, M. Fournier, C. Kaderbhaï, A. Kieffer, F. Cherifi, M. Campone, F. Lerebours, P. Cottu, F. André, A. Bertaut, D. Antonio, S. Michiels, B. Pistilli, T. Grinda. Determinants of early and late relapse in patients with early triple negative breast cancer from the prospective CANTO Cohort [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-02.

Abstract Background: Lymphedema is one of the most common and disabling complications of breast cancer treatment. It develops due to impaired lymphatic drainage following surgery and/or radiotherapy, affects up to 15–30% of patients, and significantly reduces quality of life. Current strategies for lymphedema prevention include: • Sentinel lymph node biopsy: minimizes the extent of lymph node removal in the absence of metastatic involvement. • LYMPHA protocol (Lymphatic Microsurgical Preventive Healing Approach): preventive lymphovenous anastomosis (LVA) during mastectomy or axillary lymph node dissection. Both approaches aim to preserve or restore lymphatic pathways, which has been shown to reduce the risk of lymphedema. A critical step in the LYMPHA protocol is accurate visualization of lymphatic vessels, achieved through various dyes. Objective: To evaluate the effectiveness of different dyes in reverse lymphatic mapping. Materials and Methods: This study assessed the ability of different dyes to visualize lymphatic vessels originating from: • the upper limb; • the breast. Dyes used: 1. Indigo carmine (methylene blue) 2. Fluorescein (fluorescein sodium) 3. Indocyanine green Protocol: • One dye was administered for mapping lymphatic pathways from the upper limb, another from the breast. • When combined with SLNB, a radiopharmaceutical was always used alongside one of the dyes. • If axillary lymph node dissection was required, lymphatic mapping of the upper limb was performed using a different dye. Study volume: A total of 86 surgical procedures were analyzed, including: • 9 (10.08%) — indigo carmine only • 14 (15.68%) — fluorescein only • 20 (22.4%) — indocyanine only • 8 (8.96%) — indigo carmine + fluorescein • 14 (15.68%) — indigo carmine + indocyanine • 21 (23.52%) — fluorescein + indocyanine Results: Stable staining of lymphatic pathways from the breast, upper limb, and axillary lymph nodes was achieved in all cases. • At the initial stage, 4 patients receiving indigo carmine had insufficient staining; this was corrected by an additional injection of 5 ml saline. • Indocyanine green demonstrated the highest versatility, enabling transcutaneous visualization of vessels and offering advantages in complex anatomical conditions. • Fluorescein proved practical when expensive equipment was unavailable but was limited in visualization depth. • Indigo carmine was reliable, though limited in depth penetration and occasionally resulted in prolonged skin staining. No adverse events were reported. Discussion and Analysis: • The findings are consistent with international studies (Yamamoto et al., 2020; Boccardo et al., 2016), confirming the high efficacy of ICG in reverse lymphatic mapping. • Use of dye combinations enhances accuracy in identifying relevant lymphatic pathways and reduces the risk of damaging vessels draining the arm. • In resource-limited settings, methylene blue or fluorescein remain optimal choices, whereas ICG provides advantages when appropriate equipment is available. Conclusions: 1. All dyes tested were effective for reverse lymphatic mapping, providing stable staining of lymphatic pathways. 2. Each dye has unique strengths and limitations, necessitating individualized selection based on clinical context and institutional resources. 3. Availability of multiple dyes within the surgical team’s toolkit allows for flexible adaptation of strategy, improving both safety and surgical outcomes. Citation Format: T. G. Mchedlidze, V. V. Vorotnikov, I. V. Kopytych, S. A. Abdugafforov, A. V. Soinov, M. I. Mukueva, M. v. Sharavina. Comparison of dyes for reverse lymphatic mapping in breast cancer surgery [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-04-24.