De-escalation of axillary surgery in breast cancer : patient experiences, arm morbidity, and health-related quality of life

<p dir="ltr">In breast cancer surgery for node-positive disease, axillary staging surgery is typically performed alongside the tumour removal. Arm morbidity is a known consequence of axillary lymph node dissection (ALND). Although current studies are investigating the de-escalation of axillary surgery in sentinel node-positive breast cancer, its consequences on arm morbidity remains insufficiently understood. This thesis aims to increase the knowledge on how different axillary staging surgical methods affect patient-reported arm morbidity, health-related quality of life (HRQoL), and everyday life.</p><p dir="ltr">Study I evaluated the impact of omitting of ALND on arm morbidity and HRQoL in patients with 1-2 sentinel lymph node macrometastases undergoing primary surgery. One-year patient-reported outcome measures (PROMs) from 976 participants in the randomised SENOMAC trial (Sweden and Denmark) were analysed (sentinel lymph node biopsy [SLNB] only: n=501, SLNB+ALND: n=475). PROMs were reported using EORTC QLQ-C30, EORTC QLQ-BR23, and Lymph- ICF-UL questionnaires between March 2015 and June 2019. One year after surgery, the SLNB only group reported significantly lower arm morbidity than the SLNB+ALND group, although no significant differences in overall HRQoL were seen.</p><p dir="ltr">Study II was a descriptive qualitative study exploring women's experiences of arm impairment following axillary staging surgery. Six focus group discussions were held with 28 relapse-free, Swedish-speaking women between September and December 2022. The qualitative content analysis resulted in one overall theme, "Balancing challenges and personal resources", and three categories: "Sense-making", "Daily life", and "Driving force". Participants described varying degrees of arm-related challenges. While most were satisfied with their everyday life in relation to arm symptoms, those with more pronounced arm impairment experienced a negative impact on everyday life. Key coping strategies included understanding symptoms, adapting routines, and the use of empowering resources.</p><p dir="ltr">Study III, a cross-sectional cohort study, evaluated the reliability and validity of the Swedish version of the Lymph-ICF-UL questionnaire. Between October 2024 and March 2025, 27 Swedish-speaking women without diagnosed lymphoedema, who had one year earlier undergone surgery for node-positive breast cancer, participated. The study included back-translation into English, test-retest analysis, assessment of internal consistency and construct validity, as well as evaluation of face and content validity. The instrument demonstrated good stability and internal consistency, with moderate to good construct validity. Face and content validity supported its use in assessing arm dysfunction after axillary staging surgery.</p><p dir="ltr">Study IV was an international, prospective cohort study examining the association between patient-reported arm morbidity and ALND, targeted axillary dissection (TAD), or SLNB following neoadjuvant chemotherapy (NACT) for breast cancer. PROMs from 1,293 women across 15 countries who had converted to clinical node negativity through NACT were assessed using the Lymph-ICF-UL questionnaire. Data were collected between June 2020 and January 2025, with surgery performed no later than 30 June 2023. Findings indicate that ALND is associated with a worse progression of arm morbidity from preoperative status to one-year post-surgery compared to TAD or SLNB. Adjusted odds indicated a higher likelihood of severe arm-related physical dysfunction following ALND than after TAD or SLNB.</p><p dir="ltr">In summary, SLNB and TAD seems to be associated with better preservation of arm function compared to ALND. Although significant differences in arm morbidity were observed, HRQoL did not differ between groups. However, women in the interview study who experienced more severe arm impairment also described a negative impact on their everyday lives. These findings support the ongoing de-escalation of axillary staging in breast cancer care. However, the long-term consequences of arm morbidity and HRQoL remain to be fully understood.</p><h3>List of scientific papers</h3><p dir="ltr">I. <b>Appelgren M,</b> Sackey H, Wengström Y, Johansson K, Ahlgren J, Andersson Y, Bergkvist L, Frisell J, Lundstedt D, Rydén L, Sund M, Alkner S, Vrou Offersen B, Filtenborg Tvedskov T, Christiansen P, de Boniface J, on behalf of the SENOMAC Trialists' Group. Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial. The Breast. 2022;63(3):16-23. <a href="https://doi.org/10.1016/j.breast.2022.02.013" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.breast.2022.02.013</a></p><p dir="ltr">II. <b>Appelgren M,</b> Wengström Y, de Boniface J, Sackey H. 'Balancing Challenges and Personal Resources': A Qualitative Study of Women's Experiences of Arm Impairment After Axillary Surgery for Breast Cancer. JAN. 2025; 81(6):3156-3165. <a href="https://doi.org/10.1111/jan.16517" rel="noreferrer" target="_blank">https://doi.org/10.1111/jan.16517</a></p><p dir="ltr">III. <b>Appelgren M,</b> Sackey H, Lindgren A, Johansson K, de Boniface J, Wengström Y. Validation of the Swedish Lymphoedema Functioning, Disability and Health (Lymph-ICF-UL) Questionnaire: A Cross-Cultural Psychometric study. [Submitted]</p><p dir="ltr">IV. <b>Appelgren M,</b> Sackey H, Banys-Paluchowski M, Hartmann S, Lundholm C, Wihlfahrt K, Berger T, Aktas Sezen B, Jursik K, Wagner J, Wengström Y, Hauptmann M, Schroth J, Thill M, Ditsch N, Stickeler E, Peintinger F, Vanhoeij M, Dostalek L, Kontos M, Zippel D, Gentilini OD, Di Micco R, Schlichting E, Rebaza LP, Murawa D, Pinto D, Bonci E-A, Rubio I, Gasparri ML, Hein A, Thiemann E, Holmstrand Zetterlund L, Karadeniz Cakmak G, Kühn T, de Boniface J, on behalf of the AXSANA Study Group. Patient-reported arm morbidity following axillary staging surgery after neoadjuvant chemotherapy for breast cancer: one-year results from the EUBREAST-3 AXSANA cohort study. [Manuscript]</p>