Abstract GS4-03: Patient-reported outcomes (PROs) for the intergroup sentinel mamma study (INSEMA, GBG75, ABCSG43): Persistent impact of axillary surgery on arm and breast symptoms in early breast cancer
Authors: Gerber Bernd , Stachs Angrit , Veselinovic Kristina , Polata Silke , Müller Thomas , Kühn Thorsten , Heil Jörg , Ataseven Beyhan , Reitsamer Roland , Hildebrandt Guido , Knauer Michael , Golatta Michael , Stefek Andrea , Zahm Dirk-Michael , Thill Marc , Nekljudova Valentina , Krug David , Seither Fenja , Loibl Sibylle , Reimer Toralf 
Published: March 2022

Abstract
Background: Despite increasing evidence disfavoring axillary lymph node dissection (ALND) for locoregional control, it remains part of guidelines for breast cancer (BC) treatment. In an attempt to re-evaluate standard local therapy, the INSEMA trial was designed to assess non-inferiority of avoiding sentinel lymph node biopsy (SLNB) or completion ALND (cALND) in early-stage clinically node-negative BC patients. Here we present PROs from the INSEMA trial. Methods: INSEMA (NCT02466737) investigates non-inferiority of invasive disease-free survival (iDFS) after no axillary surgical staging versus SLNB (first randomization 1:4) in patients with clinically node-negative BC (tumor size ≤5 cm) and primary breast-conserving surgery (BCS). In case of pN1a(sn) in the SLNB arm, patients underwent a second randomization to either SLNB alone or cALND (1:1). PROs were assessed at baseline (pre-surgery) and at 1, 3, 6, 12, and 18 months after final axillary surgery using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) and its breast cancer (BR23) module. Higher scores of C30 and BR23 (range 0-100) indicate better functioning and global health status (GHS)/quality of life (QoL) or worse symptom severity, respectively. The QoL scores were compared using the Mann-Whitney U test based on the safety set. Results: Between September 2015 and April 2019, 5,502 patients were recruited for the 1st randomization and 5,173 of them were included in the intent-to-treat set (4,138 SLNB vs 1,035 no SLNB). Patient and tumor characteristics were well-balanced between treatment arms. Median age at diagnosis was 62.0 years (range 24.0 - 89.0). Overall, recruited patients presented with low-risk BC marked by 85.6% clinically stage T1, 98.5% hormone-receptor positivity, 2.4% HER2-positivity, and 3.7% G3 tumors. The majority (73.5%) had an invasive carcinoma of no special type (72.8% in SLNB vs 76.0% in no SLNB arm) and 87.0% had Ki-67 ≤ 20%. Questionnaire completion response remained high throughout the trial: n=3,915 (75.7%) returned questionnaires at 1 month after final axillary surgery, n=3,938 (76.1%) at 3 months, n=4,024 (77.8%) at 6 months, n=3,907 (75.5%) at 12 months, and n=3,637 (70.3%) at 18 months. All QoL baseline parameters regarding GHS, functional scales, and symptom scales/items were well-balanced between arms (total 4,117 SLNB vs 1,056 no SLNB as treated; 270 of 4,117 received cALND). There were significant differences for the BRBS (breast symptoms) and BRAS (arm symptoms) scores favoring the no SLNB group in all post-baseline assessments Patients in the SLNB group showed persistent higher scores for BRAS (differences in mean values ≥5.0 points at all times of assessment) including pain, arm swelling, and impaired mobility in all postoperative visits with the highest difference at 1 month after final surgery (mean scores, 23.6 vs. 12.8, p&lt;0.001). Differences between treatment arms regarding BRBS including pain, breast swelling, hypersensitivity, and other skin problems showed a smaller range, but still a continuous trend for improved QoL in the no SLNB arm. Scoring of the QLQ-C30 questionnaire revealed no relevant differences between the treatment groups postoperatively. Conclusions: This is one of the first randomized trials investigating the omission of SLNB in clinically node-negative patients and the first to report QoL data. Patients with no SLNB benefitted regarding arm symptoms/functioning while no relevant differences in other QoL scales were seen. Data for the primary outcome of the study (iDFS) are expected for the end of 2024.
Citation Format: Bernd Gerber, Angrit Stachs, Kristina Veselinovic, Silke Polata, Thomas Müller, Thorsten Kühn, Jörg Heil, Beyhan Ataseven, Roland Reitsamer, Guido Hildebrandt, Michael Knauer, Michael Golatta, Andrea Stefek, Dirk-Michael Zahm, Marc Thill, Valentina Nekljudova, David Krug, Fenja Seither, Sibylle Loibl, Toralf Reimer. Patient-reported outcomes (PROs) for the intergroup sentinel mamma study (INSEMA, GBG75, ABCSG43): Persistent impact of axillary surgery on arm and breast symptoms in early breast cancer [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 GS4-03.