Axillary Recurrence Research Articles

Abstract PS01-03: What to expect from the No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS] trial (KBCSG-21): Clinicopathologic characteristics and axillary lymph node status of enrolled patients

Abstract Purpose: The primary role of sentinel lymph node biopsy (SLNB) for early breast cancer (BC) is axillary staging. In terms of clearance of axillary disease or prevention of recurrence, its role may be limited considering the low axillary recurrence rate of less than 2% even though false-negative rates are 5-10% and the 25% additional axillary lymph node (ALN) detection in the ALND arms of the ACOSOG Z0011 and AMAROS trials. The NAUTILUS trial (NCT04303715) randomized cT1-2/N0 BC patients planned for breast-conserving surgery to evaluate the non-inferiority of omitting SLNB regarding 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients. We aimed to investigate the clinicopathologic characteristics and ALN status of the subjects enrolled in the NAUTILUS trial. Methods: NAUTILUS trial randomized 1,734 subjects into SLNB or no-SLNB arms from September 2020 to October 2022. Axillary ultrasonography was mandatory to determine clinical N0, defined as no suspicious ALN or no tumor on ultrasound-guided biopsy of suspicious ALN. Clinicopathologic variables and the ALN status of the SLNB arm were analyzed. Results: Among 1,734 enrolled subjects, 828 (50.3%) and 818 (49.7%) subjects in the SLNB and no-SLNB arms, respectively, were included for analysis. Clinical and pathologic T stage, hormonal receptor/HER2 status, histologic grade, age, menopausal status, and Ki-67 were evenly distributed between the two groups (p = 0.554, 0.350, 0.056, 0.369, 0.623, 0.725 and 0.214, respectively). Median age was 55.3 (range, 48.0-62.0) years, and 661 (40.2%) were premenopausal. Overall, 30 (1.8%), 1,382 (84.0%), and 229 (13.9%) subjects were pTmic, pT1, and pT2, respectively, and median tumor size was 1.3 cm (range, 0.1-5.0). In the SLNB group, 94 (11.4%) had ALN metastasis, of which 9 (1.1%), 78 (9.4%), and 5 (0.6%) were pN1mic, pN1, and pN2-3, respectively (Table 1). According to pathologic tumor size, 5.8% (16/279), 11.4% (48/421), and 23.8% (30/126) were ALN positive for ≤ 1.0 cm, >1.0cm & ≤ 2.0 cm, and > 2.0 & ≤ 5.0 cm, respectively. The clinical and pathologic tumor size distribution among subjects with ALN metastasis were 23 (24.5%), 43 (45.7%), 9 (9.6%) and 16 (17.0%), 48 (51.1%), 30 (31.9%), respectively, for ≤ 1.0 cm, >1.0cm & ≤ 2.0 cm, and > 2.0 & ≤ 5.0 cm (Table 2). Among them, 12 (12.8%) received subsequent ALND. There was no difference in ALN metastasis rate according to molecular subtype, histologic grade, age, menopausal status, and Ki-67 (p= 0.812, 0.204, 0.671, and 0.101, respectively). Conclusions: The NAUTILUS trial completed enrollment of 1,734 subjects, among which 1,646 are available to analyze basic clinicopathologic characteristics. The trial included 229 (13.9%) pT2 and 661 (40.2%) premenopausal subjects and is expected to show the impact of SLNB omission in these subgroups. Data lock is expected in October 2027. Patients characteristics SLNB, sentinel lymph node biopsy; LVI, lymphovascular invasion; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; HER2, anti-human epidermal growth factor-2; BCS, breast conserving surgery; TM, total mastectomy; ALND, axillary lymph node dissection Basic characteristics for sentinel lymph node biopsy group a revealed no lymph node metastasis by fine needle aspiration or gun biopsy ALN, axillary lymph node; LN, lymph node Citation Format: Jai Min Ryu, Han-Byoel Lee, Sei Hyun Ahn, Il-Yong Chung, Seeyoun Lee, Seho Park, Woosung Lim, Joon Jeong, Jeong Eon Lee, Eunhye Kang, Ji Hyun Chang, Jung Min Chang, Woo Kyung Moon, Wonshik Han, Eun-Kyu Kim. What to expect from the No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS] trial (KBCSG-21): Clinicopathologic characteristics and axillary lymph node status of enrolled patients [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 PS01-03.

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.

Abstract GS02-08: Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer

Abstract Background: Multiple studies have shown a low risk of ipsilateral breast events (IBE) or other recurrences for selected patients age 65-70 or older with Stage I breast cancers treated with breast conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy (RT). We designed a prospective single-arm trial, IDEA (Individualized Decisions for Endocrine therapy Alone), to see if younger postmenopausal patients could also be successfully treated without RT, adding a genomic assay to classic selection factors. Methods: Postmenopausal patients aged 50-69 with pT1N0 unifocal invasive breast cancer with margins 2 mm or wider after BCS whose tumors were ER+, PR+, and Her2- with Oncotype DX 21-gene recurrence score (RS) 18 or lower were eligible to avoid RT if they consented to take at least 5 years of ET and surveillance on study. The primary endpoint was the rate of breast cancer recurrence at 5 years of follow-up after BCS. A valid 5–year assessment was defined as a clinical assessment within 4 months prior to the 5-year anniversary or later. Follow-up time was calculated from the date of BCS until first recurrence [ipsilateral breast events (IBE) or regional or distant failures] or to last clinical follow-up. The time-to-event endpoint was calculated using the product-limit method of Kaplan and Meier measured from the date of BCS. Results: 200 eligible patients were enrolled from 13 US institutions between June 2015 and October 2018. Median age was 63 years (IQR 58-66); mean RS was 11.2 (SD 4.8). Tumors were grade 1 in 85 patients, grade 2 in 109, and grade 3 in 6. Mean tumor size was 10 mm (SD 4.6). Lymphovascular invasion was present in 16 tumors and an extensive intraductal component in 11. Median follow-up time was 5.21 years (IQR 5.01-5.97); 8 of 14 patients with less than 56 months of follow-up were lost to follow-up. Overall and breast cancer-specific survival rates at 5 years were both 100%; 2 deaths occurred later than 5 years. The 5-year freedom from recurrence was 99% (95% CI, 96%-100%). One of the two events occurring by 5 years was an isolated axillary recurrence at 21 months treated with axillary dissection and breast and regional nodal irradiation. The other was an IBE at 49 months, treated with repeat BCS. Both these patients had been compliant with ET. Six additional patients recurred later than 5 years after BCS (5 IBEs, 1 IBE plus regional recurrence). Crude rates of IBE for the entire follow-up period for patients aged 50-59 and 60-69 were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall relapse were 5.0% (3/60) and 3.6% (5/140). Conclusions: This multicenter trial of ET without RT following BCS achieved a very low risk of relapse for postmenopausal patients with Stage I cancers using a genomic assay in combination with classic clinical and biologic features for treatment selection, including for patients younger than age 60. IDEA demonstrates a 5-year probability of recurrence consistent with or lower than the 4% risk estimated a priori, and the patients accrued were younger when compared to prior prospective trials (e.g., PRIME II, minimum age 65; CALGB 9343, minimum age 70; LUMINA, median age 67). The results of ongoing NRG BR007 trial, which randomly allocates women meeting these eligibility criteria to receive RT or not, and similar randomized and single-arm studies will help determine whether the option of avoiding initial RT can be offered to a broader group of women than current guidelines recommend. Long-term follow-up beyond the 5-year required period of ET will be important to determine if the risk of recurrence increases, particularly after discontinuation of ET. Citation Format: Reshma Jagsi, Kent Griffith, Eleanor Harris, Jean Wright, Abram Recht, Alphonse Taghian, Lucille Lee, Meena Moran, William Small, Candice Johnstone, Asal Rahimi, Gary Freedman, Mahvish Muzaffar, Bruce Haffty, Kathleen Horst, Simon Powell, Jody Sharp, Michael Sabel, Anne Schott, Mahmoud El-Tamer. Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I 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 GS02-08.

Abstract PO4-19-10: Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy In HER-2 Positive/Triple Negative Breast Cancer Patients With Excellent Radiologic Response to the Breast and Axilla

Abstract Background Neoadjuvant chemotherapy (NACT) for breast cancer (BC) is downstaging inoperable tumors into operable tumors and de-escalating breast/axillary surgery. According to advanced NACT, dual human epidermal growth factor-2 (HER2) blockage in HER2-positive BC, carboplatin, and immunotherapy in triple-negative breast cancer (TNBC) revealed pathologic complete response (ypCR) rates of up to 68% and 80%, the indications for NACT have expanded to early BC and the expected ypCR rate has increased. Therefore, it may be reasonable to consider omitting surgery in cases with excellent responses to NACT. Although sentinel lymph node biopsy (SLNB) is minimally invasive, some patients still experience complications such as lymphedema, pain, sensory loss, and axillary web syndrome. Several recent retrospective studies and pilot prospective studies have reported axillary pathologic complete response (ApCR) is highly correlated with breast pathologic complete response (BpCR). In cN0 with HER2+ BC and TNBC, the ApCR rate in BpCR after NACT was reported up to 100%, and in cN1 with HER2+ BC and TNBC, the ApCR rate in BpCR after NACT was reported about 85%. There are many studies predicting BpCR using radiologic imaging such as breast mammography (MMG), ultrasonography (USG), and magnetic resonance imaging (MRI). However, the combination of tri-modality (MMG, USG, MRI) could not confirm BpCR. The current study is screened in cT1-3N0-1M0, HER2+ or TNBC, and planned breast-conserving surgery (BCS) patients after NACT with excellent response at the combination of tri-modality imaging (breast MMG, breast USG, breast MRI) and with expected BpCR at physical examination. Methods Trial design The ASLAN trial is a prospective, multicenter, single-arm, clinical study. The five tertiary care hospitals in South Korea are participating which are members of the Korean Breast Cancer Study Group (KBCSG). Eligibility Inclusion criteria: women aged 20-69; cT1-3N0-1M0; HER2+ or TNBC (defined by ER-negative (< 10% positive cells in IHC) and PR-negative (< 10% positive cells in IHC)); expected complete remission at physical examination and radiological expected Tumor size ≤ 2cm or non-mass enhancement ≤ 4cm at breast MRI after standard NACT; planned breast-conserving surgery (BCS) with whole-breast irradiation; ECOG performance status 0-1. Exclusion criteria: SLNB before NACT; previous axillary surgery; bilateral BC; pregnancy. Intervention In eligible patients, BCS was performed. After BCS, patients who showed BpCR are enrolled with the omission of SLNB. Patients with no BpCR proceed with routine axillary surgery. Sample size calculation The assumption for an acceptable 5-year RFS ≥84% is based on previous study findings. The calculated total case number for per-protocol analysis is N=178. By Jun 2023, 153 patients had been enrolled and the target accrual of 178 patients is expected to be complete by Dec 2023. Study outcomes Primary endpoint: 5-year recurrence-free survival. Secondary endpoint: local recurrence-free survival, breast cancer-specific survival, overall survival, ipsilateral axillary recurrence interval, distant metastasis-free survival, contralateral breast-free survival, re-operation rate according to breast biopsy after NACT, adverse event, and quality of life. Accrual Plans The first patient was enrolled on Sep 2021. Among 223 patients who were screened, 153 patients have been enrolled in Jun 2023. We plan to complete the target accrual by Dec 2023. Conclusion The primary aim of the ASLAN trial is to demonstrate the oncologic safety of omitting axillary surgery for the excellent response after NACT in HER2+ or TNBC, early breast cancer patients undergoing BCS and adjuvant RT ASLAN trial, altogether with the EUBREAST-01 and ASCIS trials, will answer the very important question that may alter the axillary surgery in highly selected patients after NACT Citation Format: Jai Min Ryu, Wonshik Han, Han-Byoel Lee, Sung Gwe Ahn, Hee Jeong Kim, Hyung Seok Park, Ji Soo Choi, Hyunjun Lee, Hae Young Kim, Jeong Eon Lee. Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy In HER-2 Positive/Triple Negative Breast Cancer Patients With Excellent Radiologic Response to the Breast and Axilla [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 PO4-19-10.

Abstract PO4-23-01: Imaging tailored axillary approach combined with radiotherapy eliminates axillary lymph node dissection in low-volume axillary disease after neoadjuvant chemotherapy

Abstract ABSTRACT Background Individualized treatment strategies are highlighted for breast cancer patients in the last decades. Therefore aggressive surgical approaches have begun to evolve towards minimally invasive tailored interventions. SLNB is widely used in patients who received neoadjuvant treatment (NAC) and axillary lymph node dissection (ALND) is recommended for patients with axillary residual disease after NAC. In our study, we investigated regional recurrence rates in patients with limited axillary residual disease after NAC who underwent imaging-guided (MR+USG) axillary surgery plus radiotherapy (RT) instead of ALND. Materials and Methods 139 patients whose clinical stages were T1-3 and N1 at the time of diagnosis, who had a clinically good or complete axillary response after neoadjuvant therapy, and who had axillary residue (≤3 pathological lymph nodes) with favorable response to NAC (>50% fibrotic changes) in the final pathological examination were included in the study. The tumor stage and the number of pathological lymph nodes were assessed by USG, MMG, MR, and PET-CT examination (The minimum number of lymph nodes to be removed was determined according to imaging findings). All patients underwent imaging-guided SLNB (blue dye) and imaging-guided palpable lymph node excision. The patients were re-evaluated with their final pathology results in the multidisciplinary councils for suitable further treatments, ALND or RT. Peripheral lymphatic radiotherapy was applied to patients whose radiology and pathology results were compatible and no further surgery was done. The patients whose radiologically detected number of positive nodes was inconsistent with the number of metastases in pathology examination and who were presumed to have the gross residual disease underwent ALND. These patients were excluded from the study. Results The median age was 47 years. The median number of lymph nodes excised was 4. The total number of excised lymph nodes was between 1-3 in 64 (46%) patients and between 4-6 in 62 (45%) patients. 13 (9%) patients had ≥7 lymph nodes. 1 metastatic lymph node was found in all patients with 1 positive lymph node according to imaging findings. Of 41 patients with 2 radiologically positive lymph nodes, 1 metastatic lymph node was found in 17 (41%) patients, 2 metastatic lymph nodes in 22 (53%), and 3 metastatic lymph nodes in 2 (5%) patients respectively. Radiology reported 3 positive lymph nodes in 22 patients, of which 1 metastatic lymph node was found in 8 (36%), 2 metastatic lymph nodes in 10 (45%), and 3 metastatic lymph nodes in 4 (18%). The median follow-up period was 44 months. One patient had breast recurrence at the 31st month and one patient had lymphatic recurrence in the supraclavicular area at the 39th month. Systemic recurrence was noted in 6 (4.3%) patients. No axillary recurrence occurred during the follow-up period. Conclusions Patients with pathological-suspicious ≤ 3 lymph nodes shown by imaging (USG, MR, and PET-CT) who responded to NAC but still have residual disease in the axilla can be safely treated with SLNB(blue dye)+imaging-guided axillary approach and adjuvant RT. This approach eliminates the need for ALND in patients with low-volume residual axillary disease. Table. Patient characteristics Citation Format: Mahmut Muslumanoglu, Baran Mollavelioglu, Selman Emiroglu, Hasan Karanlik, Mustafa Tukenmez, Kamuran Ibis, Aysel Bayram, Ravza Yılmaz, Neslihan Cabıoğlu, Abdullah Igci. Imaging tailored axillary approach combined with radiotherapy eliminates axillary lymph node dissection in low-volume axillary disease after 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 PO4-23-01.

A case of sentinel node-negative breast cancer with axillary lymph node recurrence 10 years after surgery

A case of sentinel node-negative breast cancer with axillary lymph node recurrence 10 years after surgery

Implementation of the Targeted Axillary Dissection Procedure in Clinically Node-Positive Breast Cancer: A Retrospective Analysis.

The targeted axillary dissection (TAD) procedure is used in clinically positive lymph node (cN+) breast cancer to assess whether pathological complete response (pCR) is achieved after neoadjuvant systemic therapy (NST) to decide on de-escalation of axillary lymph node dissection (ALND). In this study, we review the implementation of the TAD procedure in a large regional breast cancer center. All TAD procedures between 2016 and 2022 were reviewed. The TAD procedure consists of marking pre-NST the largest suspected metastatic lymph node(s) using a radioactive I-125 seed. During surgery, the marked node was excised together with a sentinel node procedure. Axillary therapy (ALND, axillary radiotherapy, or nothing) recommendations were based on the amount of suspected positive axillary lymph nodes (ALNs < 4 or ≥ 4) pre-NST and if pCR was achieved after NST. A total of 312 TAD procedures were successfully performed in 309 patients. In 134 (43%) cases, pCR of the TAD lymph nodes were achieved. Per treatment protocol, 43 cases (14%) did not receive any axillary treatment, 218 cases (70%) received adjuvant axillary radiotherapy, and 51 cases (16%) underwent an ALND. During a median follow-up of 2.8 years, 46 patients (14%) developed recurrence, of which 11 patients (3.5%) had axillary recurrence. Introduction of the TAD procedure has resulted in a reduction of 84% of previously indicated ALNDs. Moreover, 18% of cases did not receive adjuvant axillary radiotherapy. These data show that implementation of de-escalation axillary treatment with the TAD procedure appeared to be successful.

Comparison of Clinical Breast Exam to Breast MRI Surveillance in Patients Following Nipple-Sparing Mastectomy

BackgroundNipple sparing mastectomy (NSM) is increasingly being performed for patients with breast cancer. However, optimal postoperative surveillance has not been defined. MethodsA prospectively maintained database identified patients with in-situ and invasive cancer who underwent NSM between 2007-2021. Clinical data on postoperative breast surveillance and interventions were collected. Patients who had MRI surveillance versus clinical breast exam (CBE) alone were compared with respect to tumor characteristics, recurrence, and survival. ResultsA total of 483 NSMs were performed on 399 patients. 255 (63.9%) patients had invasive ductal carcinoma, 31 (7.8%) invasive lobular carcinoma, 92 (23.1%) DCIS, 6 (1.5%) mixed ductal and lobular carcinoma, 9 (2.3%) others, and 6 (1.5%) unknown. Postoperatively, 265 (66.4%) patients were followed with CBE alone and 134 (33.6%) had surveillance MRIs. At a median follow-up of 33 months, 20 patients (5.0%) developed in-breast recurrence, 6 patients had (1.5%) an axillary recurrence, and 28 with (7.0%) distant recurrence. 14 (53.8%) LRR were detected in the CBE group and 12 (46.2%) were detected in the MRI group (P = .16). Overall survival (OS) was 99%, with no difference in OS between patients who had CBE alone versus MRI (P = .46). MRI was associated with higher biopsy rates compared to CBE alone (15.8% vs. 7.8%, P = .01). ConclusionsCompared to CBE alone, the use of screening MRI following NSM results in higher rate of biopsy and no difference in overall survival.

Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study

Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P=0.09) and overall survival (OS) (log-rank P=0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n=17) than in the IDC group (n=10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population. Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment. Umberto VeronesiFoundation.

The use of blue dye alone for sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with initially node-positive breast cancer

IntroductionFalse-negative sentinel lymph node biopsy (SLNB) rates following neoadjuvant chemotherapy (NACT) in initially node-positive (cN1/2) breast cancer patients are high, but decrease when lymph nodes are clipped, ≥3 sentinel lymph nodes (SLN) are removed or dual-tracer localization (radioisotope and blue dye) is used. Radiotracer, however, is often unavailable and outcomes with blue dye alone are unknown. Materials and methodsInitially cT1-4, cN1/2 patients treated with NACT in 2013–2023 who underwent SLNB using blue dye alone were evaluated regarding SLN identification, axillary recurrence, disease-free and overall survival rates. ResultsOf 119 patients included, 19 remained cN1/2 after NACT. SLNB was performed using blue dye alone in 100 ycN0 cases (84%), with an identification rate of 96%. The SLN was negative in 70/119 cases (i.e. 59% avoided axillary dissection). The number of SLN detected was ≥3 in 55/70 cases (78%) (median 3.1; 1–6). Median age was 49 years (25–84). Most were T2 (n = 40, 57.1%), N1 (n = 64, 91.4%). Predominant subtypes were ERBB2 (52.9%) and triple-negative (20%). No axillary recurrence occurred over a median 36-month period. Five-year disease-free and overall survival were, respectively, 85.9% (95%CI: 74–99.8) and 96.3% (95%CI: 89.4–100). The ERBB2 subtype (1.99, 95%CI: 1.02–3.85, p = 0.04) and N1 lymph node status (2.58, 95%CI: 1.54–9.10, p = 0.03) were associated with a greater likelihood of undergoing SLNB alone without axillary dissection. ConclusionsSLNB with blue dye alone following NACT in initially cN1/2 patients avoided axillary dissection in almost 60% of cases, with no recurrences during the period evaluated. Longer follow-up studies are necessary.

Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Human Epidermal Growth Factor 2-Positive/Triple-Negative Breast Cancer Patients With Excellent Response.

The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT. ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1-3N0-1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life. Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients. ClinicalTrials.gov Identifier: NCT04993625. Registered on August 6, 2021. Clinical Research Information Service Identifier: KCT0006371. Registered on July 22, 2021.

Quality assurance of radiation therapy after breast-conserving surgery among patients in the BOOG 2013-08 trial

Background and purposeIn the BOOG 2013-08 trial (NCT02271828), cT1-2N0 breast cancer patients were randomized between breast conserving surgery with or without sentinel lymph node biopsy (SLNB) followed by whole breast radiotherapy (WBRT). While awaiting primary endpoint results (axillary recurrence rate), this study aims to perform a quality assurance analysis on protocol adherence and (incidental) axillary radiation therapy (RT) dose. Materials and methodsPatients were enrolled between 2015 and 2022. Data on prescribed RT and (in 25% of included patients) planning target volumes (PTV) parameters were recorded for axillary levels I-IV and compared between treatment arms. Multivariable linear regression analysis was performed to determine prognostic variables for incidental axillary RT dose. Results1,439/1,461 included patients (98.5%) were treated according to protocol and 87 patients (5.9%) received regional RT (SLNB 10.9%, no-SLNB 1.5 %). In 326 patients included in the subgroup analysis, the mean incidental PTV dose at axilla level I was 59.5% of the prescribed breast RT dose. In 5 patients (1.5%) the mean PTV dose at level I was ≥95% of the prescribed breast dose. No statistically or clinically significant differences regarding incidental axillary RT dose were found between treatment arms. Tumour bed boost (yes/no) was associated with a higher incidental mean dose in level I (R2 = 0.035, F(6, 263) = 1.532, p 0.168). ConclusionThe results indicate that RT-protocol adherence was high, and that incidental axillary RT dose was low in the BOOG 2013-08 trial. Potential differences between treatmentarms regarding the primary endpoint can thus not be attributed to different axillary radiation doses.

Immunocytochemical markers, molecular testing and digital cytopathology for aspiration cytology of metastatic breast carcinoma.

Fine-needle aspiration cytology (FNAC) is a versatile diagnostic procedure uniquely suited for tissue biopsy of breast carcinomas and axillary metastases and/or recurrences. With the expanding treatment options and accompanying theragnostic tests, it is crucial to recognize the developments on ancillary testing and digital cytopathology techniques related to aspiration cytology of metastatic breast carcinoma. In this review, we aim to summarize and update the evidence of immunocytochemistry, for the detection of carcinoma cells (epithelial markers), confirmation of breast primary (breast-specific markers), assessment of surrogate immunostains (hormone receptors, ki-67 proliferative index and HER2) and theragnostic biomarkers, with discussion on potential diagnostic pitfalls, followed by the application of molecular tests, and digital cytopathologic techniques for assessing metastatic breast carcinoma in cytology.

Conservative Axillary Surgery May Prevent Arm Lymphedema without Increasing Axillary Recurrence in the Surgical Management of Breast Cancer.

Axillary lymph node dissection (ALND) has been associated with postoperative morbidities, including arm lymphedema, shoulder dysfunction, and paresthesia. Sentinel lymph node (SLN) biopsy emerged as a method to assess axillary nodal status and possibly obviate the need for ALND in patients with clinically node-negative (cN0) breast cancer. The majority of breast cancer patients are eligible for SLN biopsy only, so ALND can be avoided. However, there are subsets of patients in whom ALND cannot be eliminated. ALND is still needed in patients with three or more positive SLNs or those with gross extranodal or matted nodal disease. Moreover, ALND has conventionally been performed to establish local control in clinically node-positive (cN+) patients with a heavy axillary tumor burden. The sole method to avoid ALND is through neoadjuvant chemotherapy (NAC). Recently, various forms of conservative axillary surgery have been developed in order to minimize arm lymphedema without increasing axillary recurrence. In the era of effective multimodality therapy, conventional ALND may not be necessary in either cN0 or cN+ patients. Further studies with a longer follow-up period are needed to determine the safety of conservative axillary surgery.

This house believes that: MARI/TAD is better than sentinel node biopsy after PST for cN+ patients.

The increasing use and effectiveness of primary systemic treatment (PST) enables tailored locoregional treatment. About one third of clinically node positive (cN+) breast cancer patients achieve pathologic complete response (pCR) of the axilla, with higher rates observed in Human Epidermal growth factor Receptor (HER)2-positive or triple negative (TN) breast cancer subtypes. Tailoring axillary treatment for patients with axillary pCR is necessary, as they are unlikely to benefit from axillary lymph node dissection (ALND), but may suffer complications and long-term morbidity such as lymphedema and impaired shoulder motion. By combining pre-PST and post-PST axillary staging techniques, ALND can be omitted in most cN+patients with pCR. Different post-PST staging techniques (MARI/TAD/SN) show low or ultra-low false negative rates for detection of residual disease. More importantly, trials using the MARI (Marking Axillary lymph nodes with Radioactive Iodine seeds) procedure or sentinel lymph node biopsy (SLNB) as axillary staging technique post-PST have already shown the safety of tailoring axillary treatment in patients with an excellent response. Tailored axillary treatment using the MARI procedure in stage I-III breast cancer resulted in 80% reduction of ALND and excellent five-year axillary recurrence free interval (aRFI) of 97%. Similar oncologic outcomes were seen for post-SLNB in stage I-II patients. The MARI technique requires only one invasive procedure pre-NST and a median of one node is removed post-PST, whereas for the SLNB and TAD techniques two to four nodes are removed. A disadvantage of the MARI technique is its use of radioactive iodine, which is subject to extensive regulations.

Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since surgery for examination of axillary nodes is not performed with curative intent. To determine whether the omission of axillary surgery is noninferior to SLNB in patients with small BC and a negative result on preoperative axillary lymph node ultrasonography. The SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound) trial was a prospective noninferiority phase 3 randomized clinical trial conducted in Italy, Switzerland, Spain, and Chile. A total of 1463 women of any age with BC up to 2 cm and a negative preoperative axillary ultrasonography result were enrolled and randomized between February 6, 2012, and June 30, 2017. Of those, 1405 were included in the intention-to-treat analysis. Data were analyzed from October 10, 2022, to January 13, 2023. Eligible patients were randomized on a 1:1 ratio to receive SLNB (SLNB group) or no axillary surgery (no axillary surgery group). The primary end point of the study was distant disease-free survival (DDFS) at 5 years, analyzed as intention to treat. Secondary end points were the cumulative incidence of distant recurrences, the cumulative incidence of axillary recurrences, DFS, overall survival (OS), and the adjuvant treatment recommendations. Among 1405 women (median [IQR] age, 60 [52-68] years) included in the intention-to-treat analysis, 708 were randomized to the SLNB group, and 697 were randomized to the no axillary surgery group. Overall, the median (IQR) tumor size was 1.1 (0.8-1.5) cm, and 1234 patients (87.8%) had estrogen receptor-positive ERBB2 (formerly HER2 or HER2/neu), nonoverexpressing BC. In the SLNB group, 97 patients (13.7%) had positive axillary nodes. The median (IQR) follow-up for disease assessment was 5.7 (5.0-6.8) years in the SLNB group and 5.7 (5.0-6.6) years in the no axillary surgery group. Five-year distant DDFS was 97.7% in the SLNB group and 98.0% in the no axillary surgery group (log-rank P = .67; hazard ratio, 0.84; 90% CI, 0.45-1.54; noninferiority P = .02). A total of 12 (1.7%) locoregional relapses, 13 (1.8%) distant metastases, and 21 (3.0%) deaths were observed in the SLNB group, and 11 (1.6%) locoregional relapses, 14 (2.0%) distant metastases, and 18 (2.6%) deaths were observed in the no axillary surgery group. In this randomized clinical trial, omission of axillary surgery was noninferior to SLNB in patients with small BC and a negative result on ultrasonography of the axillary lymph nodes. These results suggest that patients with these features can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan. ClinicalTrials.gov Identifier: NCT02167490.

Strict versus Liberal Use of Sentinel Node Biopsy in Breast Cancer Surgery: Any Clinical Outcome Differences? A 20-Year Clinical Experience

Introduction: As applied to early breast cancer (BC) patients, sentinel node biopsy (SNB) has undergone major changes over the years, especially concerning the widening of indication criteria or skipping systematic axillary lymph node dissection (ALND) after a positive SN. We aimed to ascertain whether a strict versus a more liberal use of SNB resulted in different clinical outcomes in our clinical experience. Methods: We studied consecutive BC patients undergoing SNB between January 1, 2000, and March 31, 2020. There were 1,587 patients and 1,634 SNB procedures. Cases were divided into two study groups: the “strict” SNB group (unifocal tumors up to 35 mm in which ALND was always performed for a positive SN, amounting to 1,183 SNBs), and the “liberal” SNB group (extended tumor size up to selected T3 cases, as well as multifocal or bilateral disease, and patients with previous contralateral BC, not always followed by ALND after a positive SN, amounting to 451 SNBs). Patients were closely followed up to the end of the study. Results: Clinico-pathological variables were strikingly different between study groups, with the liberal group showing a higher risk profile. Cox regression analysis for disease recurrence did not show significant differences in axillary, lymph node, or locoregional recurrence rates or distant relapse. There were no differences in survival between groups. Conclusion: It seems reasonable to adopt the liberal SNB approach, as the goal of surgical management in early BC patients must be attaining optimal locoregional disease control, no matter the differences in distant metastatic spread rates across different BC risk profiles.

Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial).

Breast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects. This multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival. This study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity. The Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results. ClinicalTrials.gov, identifier number NCT04889924.

Impact of axillary surgery on outcome of clinically node positive breast cancer treated with neoadjuvant chemotherapy.

Axillary Lymph Node Dissection (ALND) is recommended for breast cancer patients who present with clinically node positive disease (cN1) especially if they have residual nodal disease (ypN+) following neoadjuvant therapy (NAT). It is unknown whether axillary dissection improves outcome for these patients. A prospectively maintained database was used to identify all patients who were diagnosed with cTis-T4N1M0 breast cancer treated with NAT. In our study, of 292 cN1 breast cancer patients who received NAT, we compared ALND with targeted axillary surgery (TAS) in ypN+ patients. ALND was performed in 75% of the ypN+ subgroup, while 25% underwent TAS. Axillary recurrence occurred in four ALND patients, but no recurrence was observed in the TAS group (p = 0.21). Five-year axillary recurrence-free survival was 100% for TAS and 90% for ALND (p = 0.21). Overall survival at five years was 97% for TAS and 85% for ALND (p = 0.39). Disease-free survival rates at five years were 51% for TAS and 61% for ALND (p = 0.9). Clinicopathological variables were similar between the groups, although some differences were noted. ALND patients had smaller clinical tumor size, larger pathological tumor size, more lymph nodes retrieved, larger tumor deposits, higher rates of extranodal extension, and greater prevalence of macrometastatic nodal disease. Tumor subtype and size of lymph node tumor deposit independently predicted survival. Axillary recurrence is infrequent in cN1 patients treated with NAT. Our study found that ALND did not reduce the occurrence of axillary recurrence or enhance overall survival. It is currently uncertain which patients benefit from axillary dissection.

Efficacy and safety comparison between axillary lymph node dissection with no axillary surgery in patients with sentinel node-positive breast cancer: a systematic review and meta-analysis

BackgroundThis systematic review and meta-analysis aimed to study the evidence on the efficacy and safety of omitting axillary lymph node dissection (ALND) for patients with clinically node-negative but sentinel lymph node (SLN)-positive breast cancer using all the available evidence.MethodsThe Embase, Medline, and Cochrane Library databases were searched through February 25, 2023. Original trials that compared only the sentinel lymph node biopsy (SLNB) with ALND as the control group for patients with clinically node-negative but SLN-positive breast cancer were included. The primary outcomes were axillary recurrence rate, total recurrence rate, disease-free survival (DFS), and overall survival (OS). Meta-analyses were performed to compare the odds ratio (OR) in rates and the hazard ratios (HR) in time-to-event outcomes between both interventions. Based on different study designs, tools in the revised Cochrane risk of bias tool were used for randomized trials and the risk of bias in nonrandomized studies of interventions to assess the risk of bias for each included article. Funnel plots and Egger's test were used for the publication’s bias assessment.ResultsIn total, 30 reports from 26 studies were included in the systematic review (9 reports of RCTs, 21 reports of retrospective cohort studies). According to our analysis, omitting ALND in patients with clinically node-negative but SLN-positive breast cancer had a similar axillary recurrence rate (OR = 0.95, 95% confidence interval (CI): 0.76–1.20), DFS (HR = 1.02, 95% CI: 0.89–1.16), and OS (HR = 0.97, 95% CI: 0.92–1.03), but caused a significantly lower incidence of adverse events and benefited in locoregional recurrence rate (OR = 0.76, 95% CI: 0.59–0.97) compared with ALND.ConclusionFor patients with clinically node-negative but SLN-positive breast cancer (no matter the number of the positive SLN), this review showed that SLNB alone had a similar axillary recurrence rate, DFS, and OS, but caused a significantly lower incidence of adverse events and showed a benefit for the locoregional recurrence compared with ALND. An OS benefit was found in the Macro subset that used SLNB alone versus complete ALND. Therefore, omitting ALND is feasible in this setting.Trial registrationCRD 42023397963