De-escalation of axillary treatment in breast cancer: current evidence and insights_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

PENG Yuan ,  WANG Shu

Department of Breast, Peking University People’s Hospital, Beijing 100044, P. R. China;

Corresponding author：

WANG Shu, Email: shuwang@pkuph.edu.cn

Keywords：

breast cancer; axillary lymph node; de-escalation therapy

DOI：

10.7507/1007-9424.202509071

Video：

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The treatment of breast cancer has fully entered the era of precision therapy. Sentinel lymph node biopsy (SLNB) first replaced axillary lymph node dissection (ALND) in breast cancer patients with negative clinical lymph nodes. Subsequent clinical studies have confirmed the feasibility of using SLNB alone in selected patients with limited lymph node metastasis, which has changed clinical practice. For even lower-risk patients, there is growing evidence supporting the complete omission of axillary surgery. Furthermore, with the emerging evidence from studies on axillary preservation after neoadjuvant therapy in patients from cN⁺ to cN0 status, it has become possible for these patients to avoid ALND. Even for those with persistent node-positive disease after neoadjuvant therapy, the possibility of avoiding ALND is under clinical investigation. However, it is important to acknowledge the remaining uncertainties in clinical practice. These include the challenges to the conventional concept of radical resection, the balance between axillary surgery and radiotherapy, the implications of de-escalated axillary staging on systemic therapy decisions. Careful evaluation and a balanced integration of surgery, radiotherapy, and systemic therapy are crucial to achieving truly precise de-escalation in axillary management.

1.	Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol, 2010, 11(10): 927-933.
2.	Ashikaga T, Krag DN, Land SR, et al. Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection. J Surg Oncol, 2010, 102(2): 111-118.
3.	Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA, 2011, 305(6): 569-575.
4.	Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: THE ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA, 2017, 318(10): 918-926.
5.	Giuliano AE, Ballman K, McCall L, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 randomized trial. Ann Surg, 2016, 264(3): 413-420.
6.	Lucci A, McCall LM, Beitsch PD, et al. Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group Trial Z0011. J Clin Oncol, 2007, 25(24): 3657-3663.
7.	Galimberti V, Cole BF, Zurrida S, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol, 2013, 14(4): 297-305.
8.	Galimberti V, Cole BF, Viale G, et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol, 2018, 19(10): 1385-1393.
9.	de Boniface J, Filtenborg Tvedskov T, Rydén L, et al. Omitting axillary dissection in breast cancer with sentinel-node metastases. N Engl J Med, 2024, 390(13): 1163-1175.
10.	Donker M, van Tienhoven G, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol, 2014, 15(12): 1303-1310.
11.	Sávolt Á, Péley G, Polgár C, et al. Eight-year follow up result of the OTOASOR trial: the optimal treatment of the axilla-surgery or radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: a randomized, single centre, phase Ⅲ, non-inferiority trial. Eur J Surg Oncol, 2017, 43(4): 672-679.
12.	Gentilini OD, Botteri E, Sangalli C, et al. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: the SOUND randomized clinical trial. JAMA Oncol, 2023, 9(11): 1557-1564.
13.	Reimer T, Stachs A, Veselinovic K, et al. Axillary surgery in breast cancer—primary results of the INSEMA Trial. N Engl J Med, 2025, 392(11): 1051-1064.
14.	Kuehn T, Bauerfeind I, Fehm T, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol, 2013, 14(7): 609-618.
15.	Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA, 2013, 310(14): 1455-1461.
16.	Boughey JC, Ballman KV, Hunt KK, et al. Axillary ultrasound after neoadjuvant chemotherapy and its impact on sentinel lymph node surgery: results from the American College of Surgeons Oncology Group Z1071 trial (Alliance). J Clin Oncol, 2015, 33(30): 3386-3393.
17.	Boileau JF, Poirier B, Basik M, et al. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol, 2015, 33(3): 258-264.
18.	Kuemmel S, Heil J, Rueland A, et al. A prospective, multicenter registry study to evaluate the clinical feasibility of targeted axillary dissection (TAD) in node-positive breast cancer patients. Ann Surg, 2022, 276(5): e553-e562. doi: 10.1097/SLA.0000000000004572.
19.	Caudle AS, Yang WT, Krishnamurthy S, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol, 2016, 34(10): 1072-1078.
20.	Montagna G, Mrdutt MM, Sun SX, et al. Omission of axillary dissection following nodal downstaging with neoadjuvant chemotherapy. JAMA Oncol, 2024, 10(6): 793-798.
21.	Cabioglu N, Koçer HB, Karanlik H, et al. De-escalation of nodal surgery in clinically node-positive breast cancer. JAMA Surg, 2025, 160(3): 257-266.
22.	Mamounas E, Bandos H, White J, et al. Loco-regional irradiation in patients with biopsy-proven axillary node involvement at presentation who become pathologically node-negative after neoadjuvant chemotherapy: primary outcomes of NRG oncology/NSABP B-51/RTOG 1304 [abstract] // 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 GS02-07. doi: 10.1158/1538-7445.SABCS23-GS02-07.
23.	Henke G, Knauer M, Ribi K, et al. Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (TAXIS): study protocol for a multicenter, randomized phase-Ⅲ trial. Trials, 2018, 19(1): 667. doi: 10.1186/s13063-018-3021-9.
24.	Weber WP, Matrai Z, Hayoz S, et al. Tailored axillary surgery in patients with clinically node-positive breast cancer: pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101). Breast, 2021, 60: 98-110.
25.	Jagsi R, Chadha M, Moni J, et al. Radiation field design in the ACOSOG Z0011 (Alliance) Trial. J Clin Oncol, 2014, 32(32): 3600-3606.
26.	Appelgren M, Sackey H, Wengström Y, et al. Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial. Breast, 2022 Jun: 63: 16-23.63-16.
27.	Goyal A, Mann GB, Fallowfield L, et al. POSNOC-POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: a randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes. BMJ Open, 2021, 11(12): e054365.
28.	Rastogi P, O’Shaughnessy J, Martin M, et al. Adjuvant abemaciclib plus endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, high-risk early breast cancer: results from a preplanned monarche overall survival interim analysis, including 5-year efficacy outcomes. J Clin Oncol, 2024, 42(9): 987-993.
29.	Hortobagyi GN, Lacko A, Sohn J, et al. A phase Ⅲ trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial. Ann Oncol, 2025, 36(2): 149-157.

1. Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol, 2010, 11(10): 927-933.
2. Ashikaga T, Krag DN, Land SR, et al. Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection. J Surg Oncol, 2010, 102(2): 111-118.
3. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA, 2011, 305(6): 569-575.
4. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: THE ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA, 2017, 318(10): 918-926.
5. Giuliano AE, Ballman K, McCall L, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 randomized trial. Ann Surg, 2016, 264(3): 413-420.
6. Lucci A, McCall LM, Beitsch PD, et al. Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group Trial Z0011. J Clin Oncol, 2007, 25(24): 3657-3663.
7. Galimberti V, Cole BF, Zurrida S, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol, 2013, 14(4): 297-305.
8. Galimberti V, Cole BF, Viale G, et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol, 2018, 19(10): 1385-1393.
9. de Boniface J, Filtenborg Tvedskov T, Rydén L, et al. Omitting axillary dissection in breast cancer with sentinel-node metastases. N Engl J Med, 2024, 390(13): 1163-1175.
10. Donker M, van Tienhoven G, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol, 2014, 15(12): 1303-1310.
11. Sávolt Á, Péley G, Polgár C, et al. Eight-year follow up result of the OTOASOR trial: the optimal treatment of the axilla-surgery or radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: a randomized, single centre, phase Ⅲ, non-inferiority trial. Eur J Surg Oncol, 2017, 43(4): 672-679.
12. Gentilini OD, Botteri E, Sangalli C, et al. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: the SOUND randomized clinical trial. JAMA Oncol, 2023, 9(11): 1557-1564.
13. Reimer T, Stachs A, Veselinovic K, et al. Axillary surgery in breast cancer—primary results of the INSEMA Trial. N Engl J Med, 2025, 392(11): 1051-1064.
14. Kuehn T, Bauerfeind I, Fehm T, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol, 2013, 14(7): 609-618.
15. Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA, 2013, 310(14): 1455-1461.
16. Boughey JC, Ballman KV, Hunt KK, et al. Axillary ultrasound after neoadjuvant chemotherapy and its impact on sentinel lymph node surgery: results from the American College of Surgeons Oncology Group Z1071 trial (Alliance). J Clin Oncol, 2015, 33(30): 3386-3393.
17. Boileau JF, Poirier B, Basik M, et al. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol, 2015, 33(3): 258-264.
18. Kuemmel S, Heil J, Rueland A, et al. A prospective, multicenter registry study to evaluate the clinical feasibility of targeted axillary dissection (TAD) in node-positive breast cancer patients. Ann Surg, 2022, 276(5): e553-e562. doi: 10.1097/SLA.0000000000004572.
19. Caudle AS, Yang WT, Krishnamurthy S, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol, 2016, 34(10): 1072-1078.
20. Montagna G, Mrdutt MM, Sun SX, et al. Omission of axillary dissection following nodal downstaging with neoadjuvant chemotherapy. JAMA Oncol, 2024, 10(6): 793-798.
21. Cabioglu N, Koçer HB, Karanlik H, et al. De-escalation of nodal surgery in clinically node-positive breast cancer. JAMA Surg, 2025, 160(3): 257-266.
22. Mamounas E, Bandos H, White J, et al. Loco-regional irradiation in patients with biopsy-proven axillary node involvement at presentation who become pathologically node-negative after neoadjuvant chemotherapy: primary outcomes of NRG oncology/NSABP B-51/RTOG 1304 [abstract] // 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 GS02-07. doi: 10.1158/1538-7445.SABCS23-GS02-07.
23. Henke G, Knauer M, Ribi K, et al. Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (TAXIS): study protocol for a multicenter, randomized phase-Ⅲ trial. Trials, 2018, 19(1): 667. doi: 10.1186/s13063-018-3021-9.
24. Weber WP, Matrai Z, Hayoz S, et al. Tailored axillary surgery in patients with clinically node-positive breast cancer: pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101). Breast, 2021, 60: 98-110.
25. Jagsi R, Chadha M, Moni J, et al. Radiation field design in the ACOSOG Z0011 (Alliance) Trial. J Clin Oncol, 2014, 32(32): 3600-3606.
26. Appelgren M, Sackey H, Wengström Y, et al. Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial. Breast, 2022 Jun: 63: 16-23.63-16.
27. Goyal A, Mann GB, Fallowfield L, et al. POSNOC-POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: a randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes. BMJ Open, 2021, 11(12): e054365.
28. Rastogi P, O’Shaughnessy J, Martin M, et al. Adjuvant abemaciclib plus endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, high-risk early breast cancer: results from a preplanned monarche overall survival interim analysis, including 5-year efficacy outcomes. J Clin Oncol, 2024, 42(9): 987-993.
29. Hortobagyi GN, Lacko A, Sohn J, et al. A phase Ⅲ trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial. Ann Oncol, 2025, 36(2): 149-157.

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