Full Axillary Lymph Node Dissection Research Articles

Abstract PO4-19-04: AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 4336 patients from 284 study sites and 26 countries were enrolled in the study between June 2020 and June 2023. Among 3722 patients with a defined surgical concept 1631 women were scheduled for TAD, 1483 for ALND, 469 for SLNB, 25 for TLNB and 109 for other procedures. A target lymph node was marked in 2309 patients, most frequently using clips/coils (1850, 80.1%), followed by magnetic seeds (219, 9.5%), carbon ink (171, 7.4%), radar marker (80, 3.5%), radioactive seeds (4, 0.2%) and other techniques (24, 1.0%). Funding: AGO-B, GBG, Claudia-von Schilling Foundation, Ehmann Foundation, Eugen und Irmgard Hahn Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Contact information: Prof. Dr. Thorsten Kühn Department of Gynecology and Obstetrics University of Ulm, Germany Baumreute 37 D-73730 Esslingen Germany E-Mail: kuehn.thorsten@t-online.de Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Davide Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michalis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Bilge Aktas Sezen, Rosa Di Micco, Dawid Murawa, Geeta Kadayaprath, David Pinto, Florentia Peintinger, Matilda Appelgren, Janine M. Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Elisabeth Thiemann, Markus Hahn, Michael Schrauder, Semra Gunay, Gunay Gurleyik, Nina Helidon, Hagigat Valiyeva, Ashutosh Kothari, Marian Vanhoeij, Andraz Perhavec, Tsvetomir Ivanov, Dov Zippel, Lia Rebaza, Sarun Thongvitokomarn, Sibylle Loibl, Maggie Banys-Paluchowski. AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [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 PO4-19-04.

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

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

Abstract OT1-08-01: AXSANA – EUBREAST3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with clinically axillary lymph node involvement metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR23, Lymph-ICF and SOC 13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 2347 patients from 247 study sites and 23 countries were enrolled in the study between June 2020 and June 2022. Among 1804 patients with a defined surgical concept 758 women were scheduled for ALND, 722 for TAD, 232 for SLNB, 16 for TLNB and 19 for other procedures. A target lymph node was marked in 1215 patients, most frequently using clips/coils (982, 82.0%), followed by magnetic seeds (100, 8.4%), carbon ink (99, 8.3%), radar marker (21, 1.8%), radioactive seeds (5, 0.4%), and other techniques (8, 0.7%). Citation Format: Thorsten Kühn. AXSANA – EUBREAST3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-08-01.

Axillary staging in node-positive breast cancer converting to node negativity through neoadjuvant chemotherapy: Current evidence and perspectives.

Over the recent years, axillary staging of initially node-positive breast cancer patients converting to clinical node negativity after neoadjuvant chemotherapy has seen rapid changes. This narrative review aims to give a contemporary overview over published evidence and clinical practice, and thus provide some guidance to the surgical community in the process of re-evaluating and re-shaping surgical practice. The search strategy aimed at finding relevant studies. Only articles in English were considered. The introduction of modern techniques offer more precise staging surgery and thus hopefully reduced arm morbidity. Clinical practice has however diverged both within countries and internationally. While some countries have adapted de-escalated axillary staging techniques such as targeted axillary dissection, targeted lymph node biopsy or sentinel lymph node biopsy, others continue to recommend a full axillary lymph node dissection. With the implementation of new techniques, many questions arise, regarding aspects of oncological safety, technical performance, budget and practicality, patient selection and indications for different levels of axillary staging procedures. There is a growing body of evidence on de-escalation of axillary surgery in the setting of cN+ → ycN0 breast cancer treated with neoadjuvant chemotherapy. However, standards differ between countries and future studies are necessary to fully assess the optimal strategy for these patients.

Conservative axillary surgery is emerging in the surgical management of breast cancer.

Axillary lymph node dissection (ALND) has been the standard axillary treatment for breast cancer for a long time. However, ALND is associated with postoperative morbidities, including local sensory dysfunction, reduced shoulder mobility and most notably arm lymphedema. Recently, ALND can be avoided not only in clinically node-negative (cN0) patients with negative sentinel lymph nodes (SLNs), but also in patients with less than 3 positive SLNs receiving breast radiation, axillary radiation, or a combination of the two. Moreover, SLN biopsy has been adopted for use in clinically node-positive (cN +) patients presenting as cN0 after neoadjuvant chemotherapy (NAC); ALND may be avoided in cN + patients who convert to SLN-negative following NAC. Patients who undergo SLN biopsy alone have less postsurgical morbidities than those who undergo ALND. Nevertheless, ALND is still required in a select group of patients. A variety of conservative approaches to ALND have been developed to spare arm lymphatics to minimize arm lymphedema. These conservative procedures seem to decrease the incidence of lymphedema without increasing axillary recurrence. In the era of effective multimodality therapy, full conventional ALND removing all microscopic axillary disease may now be unnecessary in both cN0 patients and cN + patients. Regardless, emerging procedures for ALND should still be considered as investigational approaches, as further studies with longer follow-up are necessary to determine the safety of conservative ALND to spare arm lymphatics.

Abstract OT1-04-04: AXSANA - EUBREAST 3 (axillary surgery after neoadjuvant treatment): An international prospective multicenter cohort study of the EUBREAST study group to evaluate different surgical methods of axillary staging (sentinel lymph node biopsy, targeted axillary dissection, axillary dissection) in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy (NCT04373655)

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy alone (SLNB) are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study is initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis and are scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: On June 30th 157 study sites from 15 countries are open for recruitment (Austria 2, Czech Republic 1, Finland 1, Germany 112, Greece 3, Italy 1, Norway 1, Poland 3, Portugal 5, Romania 2, Russia 1, Sweden 4, Switzerland 4, Spain 6, Turkey 11). 620 patients have been included in the study. Among patients who converted to ycN0 status, 144 have been scheduled for ALND, 157 for TAD and 49 for SLNB. The study is still open for further international study sites. Funding: AGO-B, Claudia-von Schilling Foundation, Ehmann Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Target accrual: 3000 patients worldwide Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michaelis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Rosa Di Micco, Dawid Murawa, David Pinto, Florentia Peintinger, Christine Solbach, Matilda Appelgren, Jens-Uwe Blohmer, Michael Weigel, Gabriele Kaltenecker, Michael Schrauder, Janine Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Alexander Sergeevich Emelyanov, Elisabeth Thiemann, Semra Gunay, Sybille Loibl, Maggie Banys-Paluchowski. AXSANA - EUBREAST 3 (axillary surgery after neoadjuvant treatment): An international prospective multicenter cohort study of the EUBREAST study group to evaluate different surgical methods of axillary staging (sentinel lymph node biopsy, targeted axillary dissection, axillary dissection) in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy (NCT04373655) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-04-04.

Is ultrasound-guided fine needle aspiration biopsy of axillary lymph nodes a viable alternative to sentinel lymph node biopsy?

Axillary lymph node (ALN) ultrasound-guided fine needle aspiration biopsy (US-FNAB), a minimally invasive procedure, may be used for the preoperative evaluation of ALN status of breast cancer patients. Despite the relative ease of use and low cost, paucity of comparative studies and variation in the reported sensitivity of FNAB preclude its clinical utility in evaluation of ALNs. This study aims to determine the accuracy of US-FNAB in detecting metastasis in ALN pre-operatively and to assess US-FNAB as a viable alternative to sentinel lymph node (SLN) excision. The 228 consecutive ALN US-FNABs with subsequent histologic follow up performed from 2005 to 2020 in patients with breast carcinoma were retrospectively evaluated. FNAB results were correlated with histologic diagnosis. Sensitivity, specificity, accuracy, and risk of malignancy of FNAB were calculated. 157/228 (69%) FNABs were concordant with histology, 37/228 (16%) discordant. Positive FNAB findings correlated with primary tumor size, grade, number of metastatic lymph nodes and size of metastases. FNAB with negative diagnosis carried a 22% risk of malignancy, atypical 43%, suspicious 80%, and positive a 100% risk of malignancy (100% positive predictive value [PPV]). The sensitivity and specificity were 78% and 95% respectively; accuracy was 77%. SLN biopsy was avoided in all 82 (36%) cases with positive FNAB results. Negative FNAB result does not exclude metastatic carcinoma. With 100% PPV, full ALN dissection and/or neoadjuvant chemotherapy can be safely planned after a positive FNAB result, avoiding SLN biopsy, reducing management costs and shortening time interval to definitive therapy.

Comparison of survival outcomes for axillary surgery extent based on intraoperative sentinel lymph node biopsy result after neoadjuvant chemotherapy for breast cancer.

To investigate the survival difference between limited axillary surgery and full axillary lymph node dissection (ALND) in patients with 1-3 positive sentinel lymph node biopsies (SLNBs) after neoadjuvant chemotherapy (NAC). We retrospectively analyzed data from 676 patients who underwent surgery between 2007 and 2017 with cT1-4, cN0-3, cM0 breast cancer at the time of diagnosis and 1-3 positive SLNBs after NAC. The patients received either SLNB only or completed level I or II ALND based on SLNB results. After propensity score matching, 483 patients who had undergone SLNB only (n = 188) and ALND (n = 295) were included. We examined overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival and compared them between the subgroups. At a median follow-up of 59.4months, no significant statistical difference was observed in overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival between SLNB only and ALND. No significant differences were observed in the 5-year axillary recurrence-free survival (93.1% vs. 94.0%, hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.43-2.05, p = 0.876) and 5-year overall survival (97.7% vs. 97.3%, HR = 1.65, 95% CI = 0.58-4.65, p = 0.347) between the two groups. Our analysis suggests that SLNB alone may be a possible option for patients with 1-3 sentinel node-positive breast cancer following NAC without significant compromise of recurrence or overall survival.

Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study.

Simple SummaryCurrently, it is unclear which kind of axillary staging surgery breast cancer patients with lymph node metastasis should receive after neoadjuvant chemotherapy. For decades, these patients have been treated with a full axillary lymph node dissection, even if they converted to clinical node negativity. However, the removal of a large number of lymph nodes during the procedure can increase arm morbidity and impact quality of life. Therefore, several studies investigated less radical surgical strategies in this setting, such as sentinel lymph node biopsy or targeted axillary dissection, i.e., removal of a previously marked node combined with sentinel node removal. In this review, we summarize current evidence on the different surgical techniques and compare national and international recommendations. We show that many questions regarding oncological safety of different surgery types and the optimal marking technique remain unanswered and present the multinational prospective cohort study AXSANA that will address these open issues.In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).

Abstract OT-04-02: The AXSANA trial (AXillary Surgery After NeoAdjuvant treatment): An international prospective multicenter cohort study of the EUBREAST study group to evaluate different surgical methods of axillary staging (sentinel lymph node biopsy, targeted axillary dissection, axillary dissection) in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy (NCT04373655)

Abstract Background The optimal surgical staging of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still unclear. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy alone (SLNB) are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the radicality of axillary surgery in this patient group. Trial design The EUBREAST study group initiated an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. Participants are patients with cT1-3 tumors with axillary lymph node metastasis confirmed by core biopsy or fine needle aspiration and scheduled for neoadjuvant systemic therapy. The trial is funded by the AGO-B Study Group, the Claudia von Schilling Foundation for Breast Cancer Research and the AWOgyn (Working Group for Reconstructive Surgery in Oncology-Gynecology) and supported by the NOGGO (North-Eastern German Society of Gynaecologic Oncology) and the German Breast Group. Primary endpoints: 5-year invasive disease-free survival, 3-year axillary recurrence rate and health-related quality of life (HRQoL). HRQoL will be evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ BR 23, Lymph ICF and SOC-13) at baseline and 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. Present accrual (July 7th 2020): 5. The first study participant has been recruited in June 2020. Target accrual: 3000 patients from EUBREAST member states (20) Citation Format: Maggie Banys-Paluchowski, Elmar Stickeler, Jana de Boniface, Oreste Gentilini, Marc Thill, Steffi Hartmann, Marina Mangold, Christine Solbach, Jens-Uwe Blohmer, Michael Untch, Matilda Appelgren, Hans-Christian Kolberg, Thorsten Kühn, EUBREAST. The AXSANA trial (AXillary Surgery After NeoAdjuvant treatment): An international prospective multicenter cohort study of the EUBREAST study group to evaluate different surgical methods of axillary staging (sentinel lymph node biopsy, targeted axillary dissection, axillary dissection) in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy (NCT04373655) [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-04-02.

Periclavicular Lymph Node Activation Maintains the Lymphatic Circulation of Upper Extremity Following Breast Cancer Surgery with Axillary Lymph Node Dissection

Backgrounds: Axillary lymph node dissection (ALND) can cause breast cancer-related lymphedema (BCRL). However, ALND does not always produce lymphedema to the breast cancer survivors. Therefore, we aimed to investigate the correlation between the finding of lymphoscintigraphy and lymphedema in patients undergoing breast cancer surgery with ALND. Methods and Results: Patients with BCRL (n = 73, mean age: 53.92 ± 11.13 years) after full ALND (levels I, II, and III) were retrospectively included in this study. All patients underwent lymphoscintigraphy and according to the findings of the imaging, patients were divided into three groups: negative group, periclavicular lymph nodes (P-LN) activation, and axillary lymph nodes (A-LN) activation. According to the extent of radiation therapy, groups were classified as the following: no radiation group (None), breast radiation group (BI), and breast irradiation in addition to P-LN (BI+PC). The percentage difference in the upper extremities was used as the marker of severity of lymphedema. The subjects in the negative group, P-LN, and A-LN were 34 (46.6%), 33 (45.2%), and 6 (8.2%) patients, respectively. The findings of lymphangiography showed statistically significant relationship with the severity of lymphedema. The extent of radiation therapy did not have statistically significant relationship. Despite ALND, 53.4% patients had active L/N capable of removing the upper limb lymphatic fluids and 45.2% patients showed activation of collateral formation of lymphatic circulation after ALND. Conclusion: The collateral lymphatic formation was provoked after breast cancer operation with ALND, which decreased the severity of lymphedema in breast cancer survivors.

Axillary reverse mapping in patients undergoing axillary dissection -a short review of the literature

Axillary lymph node dissection (ALND) can be avoided not only in patients with negative sentinel lymph nodes (SLNs) but also in those with one or two positive SLNs receiving breast or axillary radiation. However, ALND has remained the standard treatment for patients with clinically positive nodes (cN+). Although axillary reverse mapping (ARM) was developed to map and preserve arm lymphatic drainage during ALND, it could not be indicated for cN + patients because metastatic rate of ARM nodes is high. However, a new type of conservative ALND with ARM attempts to preserve ARM lymphatics and nodes except SLNs and other suspicious palpable nodes, including suspicious ARM nodes. This procedure allowed reduction of the rate of arm lymphedema without increasing axillary recurrence, although patients received postoperative chemotherapy and high-risk patients underwent axillary radiation. Thus, a traditional full ALND may not be necessary for cN + patients in the era of effective multimodality therapy.

Number of sentinel lymph nodes (SLN) removed in breast cancer (BC) patients undergoing sentinel lymph node biopsy (SLNB) in the province of Saskatchewan, Canada: Real-world experience.

e19240 Background: SLNB is considered standard of care for BC patient's undergoing surgery. This standard of care is based on several randomized, prospective clinical trials showing non inferiority of this procedure compared to full axillary lymph node dissection (FALND). Retrieval of less than 3 lymph nodes at the time of SLN biopsy has been shown to be associated with decrease in disease specific survival. In the NSABP B-32 study, removal of two SLN rather than one almost halved the false negative rate. SK has an area of 651,900 square kilometer, with a small population of 1,098,352. This population is widely distributed throughout the province with variable access to health care. This study provides us with a unique opportunity to see if data obtained in clinical trials can be replicated in community settings. Methods: After approval from SK Cancer Agency and research ethics board of University of SK. Female Patient’s with BC who underwent SLNB from Jan 2010 to Dec 2014, were identified using cancer registry. 529 charts were reviewed retrospectively. Exclusion criteria’s were Male BC, pathology other than invasive ductal or lobular, locally advanced or metastatic disease, T4 tumors, patients who received neo adjuvant therapy, patients who had declined or were unable to receive post-operative recommended adjuvant systemic or radiation therapy, patients with full axillary lymph node dissection. Data was analyzed using SAS 9.4 software. Results: Rate of 1, 2 and 3 or more SLN was 21, 35 and 44% respectively. The median number of lymph nodes retrieved were 2. 14% of patients had positive lymph nodes. 259/529 (48.9 %) of patients used both vital blue dye and radiotracer method for detection of SLN. In 510/529 (96.4%) radiotracer method was used to detect lymph nodes. Blue dye was used in 264/529 (49.9%). Median number of SLN retrieved using both methods were 2. No change in median number of SNL retrieved in different quadrants and central part of the breast were noted, the number remained 2. Conclusions: Our review showed that rate of single lymph node retrieval was lower than what is reported in US SEER data base study of 37%, however the number of median lymph node retrieval was 2 which is considered less than optimal with reported higher rate of false negative rate. We did not attempt to look at disease-specific survival as our sample size is small. Continued data evaluation of established practice is required to improve quality of care and replication of advances established in clinical trials.

Full axillary lymph node dissection and increased breast epidermal thickness 1 year after radiation therapy for breast cancer.

We previously reported a prospective study showing axillary lymph node dissection (ALND) is associated with increased breast skin thickening during and 6 weeks post-radiation therapy (RT), and now report ALND's long-term impact at 1 year. Among 66 women who received whole breast RT after lumpectomy, objective ultrasound measurements of epidermal thickness over four quadrants of the treated breast were measured at five time points: before RT, week 6 of RT, and 6 weeks, 6 months, and 1 year post-RT. Skin thickness ratio (STRA) was generated by normalizing for corresponding measurements of the contralateral breast. A total of 2,436 ultrasound images were obtained. Among 63 women with evaluable data at 1 year, mean STRA significantly increased at 6 months (absolute mean increase of 65%, SD 0.054), and remained elevated at 1 year post-RT (absolute mean increase of 44%, SD 0.048). In multivariable analysis, ALND compared to sentinel lymph node biopsy, longer interval between surgery and RT, increased baseline STRA, and Caucasian race predicted for more severe changes in STRA at 1 year compared to baseline (all P < .05). In the setting of whole breast RT, our findings suggest that ALND has long-term repercussions on breast skin thickening.

Stepwise En Bloc Resection of Breast Implant-Associated Anaplastic Large Cell Lymphoma with Oncologic Considerations.

Guidelines published by the National Comprehensive Cancer Network state that standard of care treatment for the majority of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is surgical resection. This cancer is generally indolent, and if confined to the capsule, curative treatment is usually surgery alone. An en bloc resection involves a total capsulectomy, explantation, complete excision of associated masses, and excision of any involved lymph node(s). Patients with surgical control of disease have favorable long-term overall and event-free survival. Oncologic principles should be applied when resecting BIA-ALCL, and a complete oncologic resection is essential to cure patients of the disease. Incomplete resections, partial capsulectomies, and positive margins are all associated with high rates of disease recurrence and have potential for progression of the disease. Routine sentinel lymph node biopsy is unnecessary and full axillary lymph node dissection is rarely indicated except in cases of proven involvement of multiple nodes. Lymphoma oncology consultation and disease staging by imaging is performed prior to surgery. Importantly, en bloc resection is indicated only for an established diagnosis of BIA-ALCL, and is not recommended for merely suspicious or prophylactic surgeries. The purpose of this article was to demonstrate a stepwise approach to surgical ablation of BIA-ALCL with an emphasis on oncologic considerations critical to disease prognosis.

Full Axillary Lymph Node Dissection and Increased Breast Epidermal Thickness One Year After Radiation for Breast Cancer

Full Axillary Lymph Node Dissection and Increased Breast Epidermal Thickness One Year After Radiation for Breast Cancer

The Sentinel Node with Isolated Breast Tumor Cells or Micrometastases. Benefits and Risks of Axillary Dissection.

Sentinel lymph node (SLN) biopsy has become the standard procedure to identify metastases in axillary nodes in breast cancer. Even after careful SLN examination additional micrometastases and isolated tumor cells (ITCs) are sometimes found, resulting in a need for delayed axillary lymph node dissection (ALND). This study was undertaken to assess prognostic factors identifying additional axillary lymph node (ALN) metastases at delayed ALND. To define the impact of late ALND regarding their outcome, 162 breast cancer patients with 169 operated breasts treated between 2010 and 2012 were evaluated, with follow-up through 2016. Data were collected on the patients, histology and biologic profile of the cancer, lymph node involvement, recurrence of breast cancer and adverse effects of ALND. With thorough examination and immunohistochemical stainings twenty-nine of 168 SLN biopsies (28 patients, 17% of the patients) showed micrometastases or ITC, and a full ALND was performed at a later time. During these ALNDs 13 to 31 lymph nodes were removed. Additional ALN metastases were found in three (10%) patients. Two (7%) of the 28 patients with triple-negative cancer deceased of metastatic breast cancer. Three patients (11%) reported adverse effects of ALND requiring physiotherapy due to pain, stiffness, swelling or arm oedema. Tumor factors such as molecular subtype (p=0.002), tumor size (p=0.004), and proliferation index (Ki-67) (p=0.003) correlated with higher numbers of ALN metastases. Since most patients with micrometastases found in the primary operation showed no additional positive lymph nodes, completion ALND may not be required in patients with micrometastases or ITCs in the SLN. In our study, the predictive factors for additional ALN metastases were tumur size, molecular subtype and proliferation index. It is conceivable that the features of the primary tumor, rather than the amount of cancer cells in the SLN, might serve to identify patients in whom ALDN can be avoided.

What Is a False Negative Sentinel Node Biopsy: Definition, Reasons and Ways to Minimize It?

Sentinel node biopsy helps in assessing the involvement of axillary lymph node without the morbidity of full axillary lymph node dissection, namely arm and shoulder pain, paraesthesia and lymphoedema. The various methods described in the literature identify the sentinel lymph nodes in approximately 96% of cases and associated with a false negativity rate of 5 to 10%. A false negative sentinel node is defined as the proportion of cases in whom sentinel node biopsy is reported as negative, but the rest of axillary lymph node(s) harbours cancer cells. The possible causes of a false negative sentinel lymph node may be because of blocked lymphatics either by cancer cells or following fibrosis of previous surgery/radiotherapy, and an alternative pathway opens draining the blue dye or isotope to another uninvolved node. The other reasons may be two lymphatic pathways for a tumour area, the one opening to a superficial node and the other in deep nodes. Sometimes, lymphatics do not relay into a node but traverse it going to a higher node. In some patients, the microscopic focus of metastasis inside a lymph node is so small-micrometastasis (i.e. between 0.2 and 2mm) or isolated tumour cells (i.e. less than 0.2mm) that is missed by the pathologist. The purpose of this review is to clear some fears lurking in the mind of most surgeons about the false negative sentinel lymph node (FNSLN).

Diagnostic Performance of Indocyanine Green-Guided Sentinel Lymph Node Biopsy in Breast Cancer: A Meta-Analysis.

BackgroundThe diagnostic performance of indocyanine green (ICG) fluorescence-guided sentinel lymph node biopsy (SLNB) for the presence of metastases in breast cancer remains unclear.ObjectiveWe performed a meta-analysis to investigate the diagnostic performance of ICG-guided SLNB.MethodsEligible studies were identified from searches of the databases PubMed and EMBASE up to September 2015. Studies that reported the detection rate of ICG fluorescence-guided SLNB with full axillary lymph node dissection and histological or immunohistochemical examinations were included. A meta-analysis was performed to generate pooled detection rate, sensitivity, specificity, false negative rate, diagnostic odds ratio (DOR) and a summary receiver operator characteristic curve (SROC).ResultsNineteen published studies were included to generate a pooled detection rate, comprising 2594 patients. The pooled detection rate was 0.98 (95% confidence interval [CI], 0.96–0.99). Six studies finally met the criteria for meta-analysis, which yielded a pooled sensitivity of 0.92 (95% CI, 0.85–0.96), specificity 1 (95% CI, 0.97–1), and DOR 311.47 (95% CI, 84.11–1153.39). The area under the SROC was 0.9758. No publication bias was found.ConclusionICG fluorescence-guided SLNB is viable for detection of lymph node metastases in breast cancer. Large-scale randomized multi-center trials are necessary to confirm our results.

Abstract P3-01-10: Sentinel lymph node biopsy after neoadjuvant chemotherapy for patients with clinically node-positive breast cancer: A single institution retrospective evaluation

Abstract Background: In patients with clinically node-negative breast cancer sentinel lymph node biopsy (SLNB) offers accurate staging information with considerably less morbidity than a full axillary lymph node dissection (ALND). However, for clinically node-positive (cN1) patients who undergo neoadjuvant chemotherapy SLNB is thought to have a high false-negative rate and not suitable for this population. We sought to evaluate the false-negative rate (FNR) of SLNB following chemotherapy in patients initially presenting with cN1 breast cancer at a single institution. Methods: Patients undergoing neoadjuvant chemotherapy diagnosed with cN1 breast cancer between October 2004 and February 2014 were identified from the University of California, San Francisco cancer registry. All patients underwent single agent mapping with Tc99 and SLNB followed by completion axillary lymph node dissection (ALND). Pathologic complete response, number of sentinel nodes removed and FNR were calculated. Results: Of the 80 patients who underwent SLNB and ALND, 43 had residual metastatic disease in the nodes producing a nodal pCR of 46.25% (95%CI. 35.0%-57.8%). In 14 patients, cancer was not identified in the SLNs but was discovered in the lymph nodes retrieved by ALND, resulting in an overall FNR of 32.6% (95% CI, 19.1%-48.5%). 49 patients had only 1 SLN removed. Of the patients with only 1 SLN removed, a false-negative SLN was identified in 9 of the 21 patients with a positive node for a FNR of 42.9% (95% CI, 21.8%-66.0%). Of the patient with more than 1 SLN removed, 5 of 18 patients with a positive node had a false-negative SLN yielding a FNR of 27.8% (95% CI, 9.7%-53.5%). Only 14 patients had more than two SLNs excised. Conclusion: Recent studies including the French GANEA 2 and ACOSOG Z1071 trials demonstrated a significant decrease in FNR when more than 1 SLN was excised. In this retrospective study however a single SLN was sampled from most patients. The FNR from this study was more than three times the generally accepted threshold of 10%. This substantial FNR further supports the need to remove more than 1 SLN during surgery in order to accurately assess nodal disease. Furthermore the implementation of a dual mapping technique would likely facilitate this process. Citation Format: Gallant E, Ewing C, Wong J, Esserman L, Alvarado M. Sentinel lymph node biopsy after neoadjuvant chemotherapy for patients with clinically node-positive breast cancer: A single institution retrospective evaluation. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-10.