Upfront Axillary Surgical Management: Remaining Questions
Main Article Content
Abstract
Early breast cancer is treated with curative intent by a network of incredibly interconnected disciplines. There are certain points in each discipline’s decision-making that can affect one of the others, and one such point is axillary surgery. Because removing all the lymph nodes from the cancer-containing historically provided the most accurate lymph node information to other disciplines, standard-of-care axillary surgery had been removal of all axillary lymph nodes with an axillary lymph node dissection (ALND). The benefit of an accurate ALND was soon outweighed, though, by its plethora of associated morbidities. This sparked numerous landmark clinical trials that ultimately demonstrated the safety of ALND omission. Following these trials there has been a trend toward de-escalating axillary surgery whenever possible. This review will explore the remaining questions in upfront axillary surgical management, specifically focusing on hormone receptor-positive (HR+) breast cancer patients, and the accompanying challenges for systemic therapy administration decisions.
Keywords:
Axillary Surgery, Breast Cancer, Hormone Receptor-Positive (HR ) Breast Cancer, Axillary Lymph Node Dissection (ALND), Axillary Surgery De-escalation, Systemic Therapy Decisions, Early Breast Cancer Management
Article Details
How to Cite
MARIN, Chelsea; HUSTON, Alissa; WEISS, Anna.
Upfront Axillary Surgical Management: Remaining Questions.
Medical Research Archives, [S.l.], v. 12, n. 11, nov. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6045>. Date accessed: 12 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i11.6045.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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14. 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. Nov 1 2023;9(11):1557-1564. doi:10.1001/jamaoncol.2023.3759
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16. 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. Oct 9 2013;310(14):1455-61. doi:10.1001/jama.2013.278932
17. Mamounas EP, Brown A, Anderson S, et al. Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. Apr 20 2005;23(12):2694-702. doi:10.1200/JCO.2005.05.188
18. 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. Jun 2013;14(7):609-18. doi:10.1016/S1470-2045(13)70166-9
19. 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. Jan 20 2015;33(3):258-64. doi:10.1200/JCO.2014.55.7827
20. Classe JM, Loaec C, Gimbergues P, et al. Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study. Breast Cancer Res Treat. Jan 2019;173(2):343-352. doi:10.1007/s10549-018-5004-7
21. Kalinsky K, Barlow WE, Gralow JR, et al. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med. Dec 16 2021;385(25):2336-2347. doi:10.1056/NEJMoa 2108873
22. Cardoso F, van't Veer LJ, Bogaerts J, et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med. Aug 25 2016;375(8):717-29. doi:10.1056/NEJMoa1602253
23. Mamtani A, Barrio AV, King TA, et al. How Often Does Neoadjuvant Chemotherapy Avoid Axillary Dissection in Patients With Histologically Confirmed Nodal Metastases? Results of a Prospective Study. Ann Surg Oncol. Oct 2016;2 3(11):3467-3474. doi:10.1245/s10434-016-5246-8
24. Laws A, Hughes ME, Hu J, et al. Impact of Residual Nodal Disease Burden on Technical Outcomes of Sentinel Lymph Node Biopsy for Node-Positive (cN1) Breast Cancer Patients Treated with Neoadjuvant Chemotherapy. Ann Surg Oncol. Nov 2019;26(12):3846-3855. doi:10. 1245/s10434-019-07515-4
25. Weiss A, Wong S, Golshan M, et al. Patterns of Axillary Management in Stages 2 and 3 Hormone Receptor-Positive Breast Cancer by Initial Treatment Approach. Ann Surg Oncol. Dec 2019;2 6(13):4326-4336. doi:10.1245/s10434-019-07785-y
26. Fisher B, Montague E, Redmond C, et al. Comparison of radical mastectomy with alternative treatments for primary breast cancer. A first report of results from a prospective randomized clinical trial. Cancer. Jun 1977;39(6 Suppl):2827-39. doi:10.1002/1097-0142(197706)39:6<2827::aid-cncr2820390671>3.0.co;2-i
27. Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. Aug 22 2002;347 (8):567-75. doi:10.1056/NEJM oa020128
28. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. Jul 12 2018;379(2):111-121. doi:10.1056/NEJMoa 1804710
29. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. Dec 30 2004 ;351(27):2817-26. doi:10.1056/NEJMoa041588
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32. Giuliano AE, Edge SB, Hortobagyi GN. Eighth Edition of the AJCC Cancer Staging Manual: Breast Cancer. Ann Surg Oncol. Jul 2018;25(7):1783-1785. doi:10.1245/s10434-018-6486-6
33. Marin C, Zijing C, Li Y, et al. Biology is Queen: 21 gene recurrence score has stronger prognostic ability than lymph node burden. 2024:
34. Kantor O, Weiss A, Burstein HJ, Mittendorf EA, King TA. Sentinel Lymph Node Biopsy Alone is Adequate for Chemotherapy Decisions in Postmenopausal Early-Stage Hormone-Receptor-Positive, HER2-Negative Breast Cancer with One to Three Positive Sentinel Lymph Nodes. Ann Surg Oncol. Nov 2022;29(12):7674-7682. doi:10.1245/s 10434-022-12032-y
35. Farley C, Bassett R, Meric-Bernstam F, et al. To Dissect or Not to Dissect: Can We Predict the Presence of Four or More Axillary Lymph Node Metastases in Postmenopausal Women with Clinically Node-Negative Breast Cancer? Ann Surg Oncol. Dec 2023;30(13):8327-8334. doi:10.1245/s 10434-023-14245-1
36. Rocco N, Ghilli M, Curcio A, et al. Is routine axillary lymph node dissection needed to tailor systemic treatments for breast cancer patients in the era of molecular oncology? A position paper of the Italian National Association of Breast Surgeons (ANISC). Eur J Surg Oncol. Feb 2024;50(2):107954. doi:10.1016/j.ejso.2024.107954
37. Weber WP, Matrai Z, Hayoz S, et al. Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer. JAMA Surg. Oct 1 2023;158(10): 1013-1021. doi:10.1001/jamasurg.2023.2840
38. de Boniface J, Appelgren M, Szulkin R, et al. Completion axillary lymph node dissection for the identification of pN2-3 status as an indication for adjuvant CDK4/6 inhibitor treatment: a post-hoc analysis of the randomised, phase 3 SENOMAC trial. Lancet Oncol. Sep 2024;25(9):1222-1230. doi:10.1016/S1470-2045(24)00350-4
39. FDA approves ribociclib with an aromatase inhibitor and ribociclib and letrozole co-pack for early high-risk breast cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ribociclib-aromatase-inhibitor-and-ribociclib-and-letrozole-co-pack-early-high-risk-0
40. Fasching PA, Stroyakovskiy D, Yardley D, et al. LBA13 - Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (Pts) with HR+/HER2− early breast cancer (EBC): 4-year outcomes from the NATALEE trial. 2024:
41. Pilewskie M, Sevilimedu V, Eroglu I, et al. How Often Do Sentinel Lymph Node Biopsy Results Affect Adjuvant Therapy Decisions Among Postmenopausal Women with Early-Stage HR(+)/HER2(-) Breast Cancer in the Post-RxPONDER Era? Ann Surg Oncol. Oct 2022;29(10) :6267-6273. doi:10.1245/s10434-022-12193-w
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2. Dees EC, Shulman LN, Souba WW, Smith BL. Does information from axillary dissection change treatment in clinically node-negative patients with breast cancer? An algorithm for assessment of impact of axillary dissection. Ann Surg. Sep 1997;226(3):279-86; discussion 286-7. doi:10.1097 /00000658-199709000-00007
3. Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. Oct 2 1997;337(14):956-62. doi:10.1056/ NEJM199710023371402
4. Peintinger F, Reitsamer R, Stranzl H, Ralph G. Comparison of quality of life and arm complaints after axillary lymph node dissection vs sentinel lymph node biopsy in breast cancer patients. Br J Cancer. Aug 18 2003;89(4):648-52. doi:10.1038 /sj.bjc.6601150
5. 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. Oct 2010;11(10):927-33. doi:10.1016/S1470-2045(10)70207-2
6. Veronesi U, Viale G, Paganelli G, et al. Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg. Apr 2010;251(4):595-600. doi:10.1097/SLA.0b013 e3181c0e92a
7. Krag DN, Anderson SJ, Julian TB, et al. Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol. Oct 2007;8(10):881-8. doi:10.1016/S1470-2045(07)70278-4
8. 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. Apr 2013;14(4):297-305. doi:10.1016/S147 0-2045(13)70035-4
9. Sola M, Alberro JA, Fraile M, et al. Complete axillary lymph node dissection versus clinical follow-up in breast cancer patients with sentinel node micrometastasis: final results from the multicenter clinical trial AATRM 048/13/2000. Ann Surg Oncol. Jan 2013;20(1):120-7. doi:10.1245/s1 0434-012-2569-y
10. 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. Feb 9 2011;305(6):569-75. doi:10.1001/jama.2011.90
11. 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. Nov 2014;15(12):1303-10. doi:10.1016/S14 70-2045(14)70460-7
12. Savolt A, Peley G, Polgar 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. Apr 2017;43(4):672-679. doi:10.1016/j.ejso.2016.12.011
13. de Boniface J, Filtenborg Tvedskov T, Ryden L, et al. Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases. N Engl J Med. Apr 4 2024;390(13):1163-1175. doi:10.1056/ NEJMoa2313487
14. 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. Nov 1 2023;9(11):1557-1564. doi:10.1001/jamaoncol.2023.3759
15. Martelli G, Boracchi P, De Palo M, et al. A randomized trial comparing axillary dissection to no axillary dissection in older patients with T1N0 breast cancer: results after 5 years of follow-up. Ann Surg. Jul 2005;242(1):1-6; discussion 7-9. doi:10.1097/01.sla.0000167759.15670.14
16. 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. Oct 9 2013;310(14):1455-61. doi:10.1001/jama.2013.278932
17. Mamounas EP, Brown A, Anderson S, et al. Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. Apr 20 2005;23(12):2694-702. doi:10.1200/JCO.2005.05.188
18. 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. Jun 2013;14(7):609-18. doi:10.1016/S1470-2045(13)70166-9
19. 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. Jan 20 2015;33(3):258-64. doi:10.1200/JCO.2014.55.7827
20. Classe JM, Loaec C, Gimbergues P, et al. Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study. Breast Cancer Res Treat. Jan 2019;173(2):343-352. doi:10.1007/s10549-018-5004-7
21. Kalinsky K, Barlow WE, Gralow JR, et al. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med. Dec 16 2021;385(25):2336-2347. doi:10.1056/NEJMoa 2108873
22. Cardoso F, van't Veer LJ, Bogaerts J, et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med. Aug 25 2016;375(8):717-29. doi:10.1056/NEJMoa1602253
23. Mamtani A, Barrio AV, King TA, et al. How Often Does Neoadjuvant Chemotherapy Avoid Axillary Dissection in Patients With Histologically Confirmed Nodal Metastases? Results of a Prospective Study. Ann Surg Oncol. Oct 2016;2 3(11):3467-3474. doi:10.1245/s10434-016-5246-8
24. Laws A, Hughes ME, Hu J, et al. Impact of Residual Nodal Disease Burden on Technical Outcomes of Sentinel Lymph Node Biopsy for Node-Positive (cN1) Breast Cancer Patients Treated with Neoadjuvant Chemotherapy. Ann Surg Oncol. Nov 2019;26(12):3846-3855. doi:10. 1245/s10434-019-07515-4
25. Weiss A, Wong S, Golshan M, et al. Patterns of Axillary Management in Stages 2 and 3 Hormone Receptor-Positive Breast Cancer by Initial Treatment Approach. Ann Surg Oncol. Dec 2019;2 6(13):4326-4336. doi:10.1245/s10434-019-07785-y
26. Fisher B, Montague E, Redmond C, et al. Comparison of radical mastectomy with alternative treatments for primary breast cancer. A first report of results from a prospective randomized clinical trial. Cancer. Jun 1977;39(6 Suppl):2827-39. doi:10.1002/1097-0142(197706)39:6<2827::aid-cncr2820390671>3.0.co;2-i
27. Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. Aug 22 2002;347 (8):567-75. doi:10.1056/NEJM oa020128
28. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. Jul 12 2018;379(2):111-121. doi:10.1056/NEJMoa 1804710
29. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. Dec 30 2004 ;351(27):2817-26. doi:10.1056/NEJMoa041588
30. Sparano JA, Gray RJ, Makower DF, et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. Nov 19 2015 ;373(21):2005-14. doi:10.1056/NEJMoa1510764
31. Johnston SRD, Toi M, O'Shaughnessy J, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. Jan 2023;24(1):77-90. doi:10.1016/S1470-2045(22)00694-5
32. Giuliano AE, Edge SB, Hortobagyi GN. Eighth Edition of the AJCC Cancer Staging Manual: Breast Cancer. Ann Surg Oncol. Jul 2018;25(7):1783-1785. doi:10.1245/s10434-018-6486-6
33. Marin C, Zijing C, Li Y, et al. Biology is Queen: 21 gene recurrence score has stronger prognostic ability than lymph node burden. 2024:
34. Kantor O, Weiss A, Burstein HJ, Mittendorf EA, King TA. Sentinel Lymph Node Biopsy Alone is Adequate for Chemotherapy Decisions in Postmenopausal Early-Stage Hormone-Receptor-Positive, HER2-Negative Breast Cancer with One to Three Positive Sentinel Lymph Nodes. Ann Surg Oncol. Nov 2022;29(12):7674-7682. doi:10.1245/s 10434-022-12032-y
35. Farley C, Bassett R, Meric-Bernstam F, et al. To Dissect or Not to Dissect: Can We Predict the Presence of Four or More Axillary Lymph Node Metastases in Postmenopausal Women with Clinically Node-Negative Breast Cancer? Ann Surg Oncol. Dec 2023;30(13):8327-8334. doi:10.1245/s 10434-023-14245-1
36. Rocco N, Ghilli M, Curcio A, et al. Is routine axillary lymph node dissection needed to tailor systemic treatments for breast cancer patients in the era of molecular oncology? A position paper of the Italian National Association of Breast Surgeons (ANISC). Eur J Surg Oncol. Feb 2024;50(2):107954. doi:10.1016/j.ejso.2024.107954
37. Weber WP, Matrai Z, Hayoz S, et al. Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer. JAMA Surg. Oct 1 2023;158(10): 1013-1021. doi:10.1001/jamasurg.2023.2840
38. de Boniface J, Appelgren M, Szulkin R, et al. Completion axillary lymph node dissection for the identification of pN2-3 status as an indication for adjuvant CDK4/6 inhibitor treatment: a post-hoc analysis of the randomised, phase 3 SENOMAC trial. Lancet Oncol. Sep 2024;25(9):1222-1230. doi:10.1016/S1470-2045(24)00350-4
39. FDA approves ribociclib with an aromatase inhibitor and ribociclib and letrozole co-pack for early high-risk breast cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ribociclib-aromatase-inhibitor-and-ribociclib-and-letrozole-co-pack-early-high-risk-0
40. Fasching PA, Stroyakovskiy D, Yardley D, et al. LBA13 - Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (Pts) with HR+/HER2− early breast cancer (EBC): 4-year outcomes from the NATALEE trial. 2024:
41. Pilewskie M, Sevilimedu V, Eroglu I, et al. How Often Do Sentinel Lymph Node Biopsy Results Affect Adjuvant Therapy Decisions Among Postmenopausal Women with Early-Stage HR(+)/HER2(-) Breast Cancer in the Post-RxPONDER Era? Ann Surg Oncol. Oct 2022;29(10) :6267-6273. doi:10.1245/s10434-022-12193-w
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