Advertisement

Contemporary approaches to the axilla in breast cancer

  • Jessica L. Thompson
    Correspondence
    Corresponding author. 145 Michigan Street NE, Suite 4400, Grand Rapids, MI, 49503, USA.
    Affiliations
    Spectrum Health Medical Group Comprehensive Breast Clinic, 145 Michigan Street NE, Suite 4400, Grand Rapids, MI, 49503, USA

    Michigan State University College of Human Medicine, Department of Surgery, 15 Michigan Street NE, Grand Rapids, MI, 49503, USA
    Search for articles by this author
  • G. Paul Wright
    Affiliations
    Spectrum Health Medical Group Comprehensive Breast Clinic, 145 Michigan Street NE, Suite 4400, Grand Rapids, MI, 49503, USA

    Michigan State University College of Human Medicine, Department of Surgery, 15 Michigan Street NE, Grand Rapids, MI, 49503, USA

    Spectrum Health Medical Group, Division of Surgical Oncology, 145 Michigan Street NE, Suite 5500, Grand Rapids, MI, 49503, USA
    Search for articles by this author
Published:December 02, 2022DOI:https://doi.org/10.1016/j.amjsurg.2022.11.036

      Highlights

      • Efforts continue to distinguish conditions where axillary interventions may be minimized to reduce therapeutic morbidity.
      • The appropriateness of regional nodal RT vs ALND for pN+ in the upfront mastectomy setting can pose a challenging dilemma.
      • Several multicenter studies are investigating the oncologic safety of less invasive axillary staging techniques after NAC.
      • Upfront surgery treatment algorithms may be a more congruent approach to management after neoadjuvant endocrine therapy.

      Abstract

      Over the past decade, axillary management in breast cancer has fundamentally shifted. The former notion that any degree of axillary nodal involvement warrants axillary lymph node dissection (ALND) has been challenged. Following publication of the ACOSOG Z0011 trial, national trends demonstrated significant reductions in ALND performance. Axillary radiotherapy in lieu of ALND is a consideration for select patients with a positive sentinel lymph node, while ongoing studies are investigating the role of adjuvant regional radiotherapy in women with positive nodes prior to neoadjuvant chemotherapy. Efforts toward de-escalation of axillary surgery continue to evolve, as do the indications for sentinel node biopsy omission in select subsets of patients. This review highlights the recent advances and neoteric approaches to local therapy of the axilla in breast cancer.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Giuliano A.E.
        • McCall L.
        • Beitsch P.
        • et al.
        Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial.
        Ann Surg. 2010; 252: 426-432
        • Giuliano A.E.
        • Hunt K.K.
        • Ballman K.V.
        • 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: 569-575
        • Black D.M.
        • Mittendorf E.A.
        Landmark trials affecting the surgical management of invasive breast cancer.
        Surg Clin. 2013; 93: 501-518
        • Giuliano A.E.
        • 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: 413-420https://doi.org/10.1097/SLA.0000000000001863
        • Donker M.
        • van Tienhoven G.
        • Straver M.E.
        • 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: 1303-1310
      1. (Version 4)NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. 2022
        • Cortina C.S.
        • Bergom C.
        • Craft M.A.
        • et al.
        A national survey of breast surgeons and radiation oncologists on contemporary axillary management in mastectomy patients.
        Ann Surg Oncol. 2021; 28: 5568-5579
        • Weiss A.
        • Lin H.
        • Babiera G.V.
        • et al.
        Evolution in practice patterns of axillary management following mastectomy in patients with 1-2 positive sentinel nodes.
        Breast Cancer Res Treat. 2019; 176: 435-444
        • The American Society of Breast Surgeons
        Consensus guideline on axillary management for patients with in-situ and invasive breast cancer: a concise overview.
        Aprrove March. 2022; 14
        • Cserni G.
        Complete sectioning of axillary sentinel nodes in patients with breast cancer. Analysis of two different step sectioning and immunohistochemistry protocols in 246 patients.
        J Clin Pathol. 2002; 55: 926-931
        • Cserni G.
        Evaluation of sentinel lymph nodes in breast cancer.
        Histopathology. 2005; 46: 69-702
        • Galimberti V.
        • Cole B.F.
        • 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: 297-305
        • Galimberti V.
        • Cole B.F.
        • 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: 1385-1393
        • Solá M.
        • Alberro J.A.
        • 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. 2013; 20: 120-127
        • Fitzsullivan E.
        • Bassett R.L.
        • Kuerer H.M.
        • et al.
        Outcomes of sentinel lymph node-positive breast cancer patients treated with mastectomy without axillary therapy.
        Ann Surg Oncol. 2017; 24: 652-659
        • Naoum G.E.
        • Roberts S.
        • Brunelle C.L.
        • et al.
        Quantifying the impact of axillary surgery and nodal irradiation on breast cancer-related lymphedema and local tumor control: long-term results from a prospective screening trial.
        J Clin Oncol. 2020; 38: 3430-3438
        • De Boniface J.
        • Frisell J.
        • Andersson Y.
        • et al.
        Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial.
        BMC Cancer. 2017; 17: 379
        • Goyal A.
        • Mann G.B.
        • Fallowfield L.
        • et al.
        Protocol: 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; 11e054365
        • Ma X.
        • Yang X.
        • Yang W.
        • Shui R.
        Prognostic value of extranodal extension in axillary lymph node-positive breast cancer.
        Sci Rep. 2021; 11: 9534
        • Gooch J.
        • King T.A.
        • Eaton A.
        • et al.
        The extent of extracapsular extension may influence the need for axillary lymph node dissection in patients with T1-T2 breast cancer.
        Ann Surg Oncol. 2014; 21: 2897-2903
        • Pierce L.J.
        • Oberman H.A.
        • Strawderman M.H.
        • Lichter A.S.
        Microscopic extracapsular extension in the axilla: is this an indication for axillary radiotherapy?.
        Int J Radiat Oncol Biol Phys. 1995; 33: 253-259
        • Bucci J.A.
        • Kennedy C.W.
        • Burn J.
        • et al.
        Implications of extranodal spread in node positive breast cancer: a review of survival and local recurrence.
        Breast. 2001; 10: 213-219
        • Abdessalam S.F.
        • Zervos E.E.
        • Prasad M.
        • et al.
        Predictors of positive axillary lymph nodes after sentinel lymph node biopsy in breast cancer.
        Am J Surg. 2001; 182: 316-320
        • Nottegar A.
        • Veronese N.
        • Senthil M.
        • et al.
        Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: a systematic review and an exploratory meta-analysis.
        Eur J Surg Oncol. 2016; 42: 919-925
        • Barrio A.V.
        • Downs-Canner S.
        • Edelweiss M.
        • et al.
        Microscopic extracapsular extension in sentinel lymph nodes does not mandate axillary dissection in z0011-eligible patients.
        Ann Surg Oncol. 2018; 27: 1617-1624
        • Kalinsky K.
        • Barlow W.E.
        • Gralow J.R.
        • et al.
        21-Gene assay to inform chemotherapy benefit in node-positive breast cancer.
        N Engl J Med. 2021; 385: 2336-2347
        • Johnston S.R.D.
        • Harbeck N.
        • Hegg R.
        • Toi M.
        • et al.
        Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2−, node-positive, high-risk, early breast cancer (monarchE).
        J Clin Oncol. 2020; 38: 3987-3998
        • Mittendorf E.A.
        • King T.A.
        • Tolaney S.M.
        Impact of RxPONDER and monarchE on the surgical management of the axilla in patients with breast cancer.
        J Clin Oncol. 2022; JCO2200173
        • 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. 2022 Oct; 29: 6267-6273
        • Mccartan D.
        • Stempel M.
        • Eaton A.
        • et al.
        Impact of body mass index on clinical axillary nodal assessment in breast cancer patients.
        Ann Surg Oncol. 2016; 23: 3324-3329
        • Fisher B.
        • Brown A.
        • Mamounas E.
        • et al.
        Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18.
        J Clin Oncol. 1997; 15: 2483-2493
        • Cortazar P.
        • Zhang L.
        • Untch M.
        • et al.
        Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.
        Lancet. 2014; 384: 164-172
        • Samiei S.
        • Simons J.M.
        • Engelen S.E.
        • et al.
        Axillary pathologic complete response after neoadjuvant systemic therapy by breast cancer subtype in patients with initially clinically node-positive disease A systematic review and meta-analysis.
        JAMA Surg. 2021; 156e210891
        • Boughey J.C.
        • Suman V.J.
        • Mittendorf E.A.
        • 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: 1455-1461
        • 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: 609-618
        • Classe J.M.
        • 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. 2019; 173: 343-352
        • Boileau J.F.
        • 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: 258-264
        • Boughey J.C.
        • Ballman K.V.
        • Le-Petross H.T.
        • et al.
        Identification and resection of the clipped node decreases the false negative rate of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who receive neoadjuvant chemotherapy: results from ACOSOG Z1071 (Alliance).
        Ann Surg. 2016; 263: 802-807
        • Caudle A.S.
        • Yang W.T.
        • 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: 1072-1078
        • Diego E.J.
        • Mcauliffe P.F.
        • Soran A.
        • et al.
        Axillary staging after neoadjuvant chemotherapy for breast cancer: a pilot study combining sentinel lymph node biopsy with radioactive seed localization of pre-treatment positive axillary lymph nodes.
        Ann Surg Oncol. 2016; 23: 1549-1553
        • Montagna G.
        • Lee M.K.
        • Sevilimedu V.
        • et al.
        Is Nodal Clipping Beneficial for Node-Positive Breast Cancer Patients Receiving Neoadjuvant Chemotherapy?.
        Ann Surg Oncol. 2022 Oct; 29: 6133-6139
        • Caudle A.S.
        • Yang W.T.
        • Mittendorf E.A.
        • et al.
        Selective surgical localization of axillary lymph nodes containing metastases in patients with breast cancer A prospective feasibility trial.
        JAMA Surg. 2015; 150: 137-143
        • Siso C.
        • de Torres J.
        • Esgueva-Colmenarejo A.
        • et al.
        Intraoperative ultrasound-guided excision of axillary clip in patients with node-positive breast cancer treated with neoadjuvant therapy (ILINA trial): a new tool to guide the excision of the clipped node after neoadjuvant treatment.
        Ann Surg Oncol. 2018; 25: 784-791
        • de Wild S.R.
        • Simons J.M.
        • Vrancken Peeters M.J.T.F.D.
        • et al.
        MINImal vs. MAXimal invasive axillary staging and treatment after neoadjuvant systemic therapy in node positive breast cancer: protocol of a Dutch multicenter registry study (MINIMAX).
        Clin Breast Cancer. 2022; 22: e59-e64
        • Banys-Paluchowski M.
        • Gasparri M.L.
        • De Boniface J.
        • et al.
        The axsana study group. Surgical management of the axilla in clinically node-positive breast cancer patients converting to clinical node negativity through neoadjuvant chemotherapy: current status, knowledge gaps, and rationale for the EUBREAST-03 AXSANA study.
        Cancers. 2021; 29 (13): 1565
        • Oncoplastic Breast Consortium (Opbc)
        Nodal recurrence following axillary downstaging with neoadjuvant chemotherapy and omission of axillary lymph node dissection (OPBC-04/EUBREAST-06).
        (2021)
      2. Comparison of axillary lymph node dissection with axillary radiation for patients with node-positive breast cancer treated with chemotherapy (ALLIANCE A011202). ClinicalTrials.gov.
        (Accessed August 19, 2022)
        • Mamounas E.P.
        • Bandos H.
        • White J.R.
        • et al.
        NRG Oncology/NSABP B-51/RTOG 1304: phase III trial to determine if chest wall and regional nodal radiotherapy (CWRNTRT) post mastectomy (Mx) or the addition of RNRT to whole breast RT post breast-conserving surgery (BCS) reduces invasive breast cancer recurrence-free interval (IBCR-FI) in patients (pts) with pathologically positive axillary (PPAx) ndoes who are ypN0 after neoadjuvant chemotherapy (NC).
        J Clin Oncol. 2019; 37TPS600
        • Klauber-Demore N.
        • Ollila D.W.
        • Moore D.T.
        • et al.
        Size of residual lymph node metastasis after neoadjuvant chemotherapy in locally advanced breast cancer patients is prognostic.
        Ann Surg Oncol. 2006; 13: 685-691
        • Maaskant-Braat A.J.
        • Van De Poll-Franse L.V.
        • Voogd A.C.
        • et al.
        Sentinel node micrometastases in breast cancer do not affect prognosis: a population-based study.
        Breast Cancer Res Treat. 2011; 127: 195-203
        • Van Nijnatten T.J.A.
        • Simons J.M.
        • Moossdorff M.
        • et al.
        Prognosis of residual axillary disease after neoadjuvant chemotherapy in clinically node-positive breast cancer patients: isolated tumor cells and micrometastases carry a better prognosis than macrometastases.
        Breast Cancer Res Treat. 2017; 163: 159-166
        • Wong S.M.
        • Almana N.
        • Choi J.
        • Hu J.
        • et al.
        Prognostic significance of residual axillary nodal micrometastases and isolated tumor cells after neoadjuvant chemotherapy for breast cancer.
        Ann Surg Oncol. 2019; 26: 3502-3509
        • Chiba A.
        • Hoskin T.L.
        • Heins C.N.
        • et al.
        Trends in neoadjuvant endocrine therapy use and impact on rates of breast conservation in hormone receptor-positive breast cancer: a national cancer data base study.
        Ann Surg Oncol. 2017; 24: 418-424
        • 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. 2019; 26: 4326-4336
        • Kantor O.
        • Wong S.
        • Weiss A.
        • et al.
        Prognostic significance of residual nodal disease after neoadjuvant endocrine therapy for hormone receptor-positive breast cancer.
        NPJ Breast Cancer. 2020; 6: 35
        • Weiss A.
        • Mittendorf E.A.
        • King T.A.
        Strategies to optimize axillary surgery in patients with breast cancer receiving neoadjuvant endocrine therapy.
        Oncology. 2020; 34: 397-404
        • Society of Surgical Oncology
        Five things physicians and patients should question.
        Choosing Wisely. 2019; (Updated June 20)
        • Van De Water W.
        • Markopoulos C.
        • Van De Velde C.J.H.
        • et al.
        Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer.
        JAMA. 2012; 307: 590-597
        • Grumpelt A.M.
        • Ignatov A.
        • Tchaikovski S.N.
        • et al.
        Tumor characteristics and therapy of elderly patients with breast cancer.
        J Cancer Res Clin Oncol. 2016; 142: 1109-1116
        • Hughes K.S.
        • Schnaper L.A.
        • Bellon J.R.
        • et al.
        Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343.
        J Clin Oncol. 2013; 31: 2382-2387
        • Martelli G.
        • Miceli R.
        • Daidone M.G.
        • et al.
        Axillary dissection versus no axillary dissection in elderly patients with breast cancer and no palpable axillary nodes: results after 15 years of follow-up.
        Ann Surg Oncol. 2011; 18: 125-133
        • Rudenstam C.M.
        • Zahrieh D.
        • Forbes J.F.
        • et al.
        Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group trial 10-93.
        J Clin Oncol. 2006; 24: 337-344
        • Hughes K.S.
        • Schnaper L.A.
        • Berry D.
        • et al.
        Lumpectomy plus tamoxifen with or without irradiation in women 70 Years of age or older with early breast cancer.
        N Engl J Med. 2004; 351: 971-977
        • Kunkler I.H.
        • Williams L.J.
        • Jack W.J.L.
        • et al.
        Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial.
        Lancet Oncol. 2015; 16: 266-273
        • Louie R.J.
        • Gaber C.E.
        • Strassle P.D.
        • et al.
        Trends in surgical axillary management in early stage breast cancer in elderly women: continued over-treatment.
        Ann Surg Oncol. 2020; 27: 3426-3433
        • Wang T.
        • Baskin A.S.
        • Dossett L.A.
        Deimplementation of the choosing wisely recommendations for low-value breast cancer surgery: a systematic review.
        JAMA Surg. 2020; 155: 759-770
        • Thompson J.
        • Le J.
        • Hop A.
        • et al.
        Impact of choosing wisely recommendations on sentinel lymph node biopsy and postoperative radiation rates in women over age 70 Years with hormone-positive breast cancer.
        Ann Surg Oncol. 2021; 28: 5716-5722
        • Karakatsanis A.
        • Daskalakis K.
        • Stålberg P.
        • et al.
        Superparamagnetic iron oxide nanoparticles as the sole method for sentinel node biopsy detection in patients with breast cancer.
        Br J Cancer. 2017; 104: 1675-1685
        • Karakatsanis A.
        • Olofsson H.
        • Stålberg P.
        • et al.
        Simplifying logistics and avoiding the unnecessary in patients with breast cancer undergoing sentinel node biopsy. A prospective feasibility trial of the preoperative injection of super paramagnetic iron oxide nanoparticles.
        Scand J Surg. 2018; 107: 130-137
      3. Delayed sentinel lymph node biopsy in ductal cancer in situ (SENTINOT_2).
        (Updated March 29, 2022. ClinicalTrials.gov)
      4. Sentinel node vs observation after axillary ultra-souND (SOUND).
        (Updated February 4, 2021. ClinicalTrials.gov)
      5. Comparison of axillary sentinel lymph node biopsy versus no axillary surgery (INSEMA).
        (Updated April 5, 2022. ClinicalTrials.gov)
      6. Omitting sentinel node procedure in breast cancer patients undergoing breast conserving therapy.
        (Updated May 4, 2018. ClinicalTrials.gov)
      7. No axillary sUrgical treatment in clinically lymph node negative patients after UltraSonography (NAUTILUS): a prospective, multicenter, phase III, clinical trial.
        (Updated April 5, 2021. ClinicalTrials.gov)
      8. Sentinel node biopsy vs observation after axillary PET (SOAPET).
        (Updated July 13, 2020. ClinicalTrials.gov)
        • Reimer T.
        • Glass A.
        • Botteri E.
        • et al.
        Avoiding axillary sentinel lymph node biopsy after neoadjuvant systemic therapy in breast cancer: rationale for the prospective, multicentric EUBREAST-01 trial.
        Cancers. 2020; 12: 3698
      9. Avoiding sentinel lymph node biopsy in breast cancer patients after neoadjuvant chemotherapy (ASICS).
        (Updated January 13, 2020. ClinicalTrials.gov)
        • Tinterri C.
        • Canavese G.
        • Bruzzi P.
        • Dozin B.
        NEONOD 2: rationale and design of a multicenter non-inferiority trial to assess the effect of axillary surgery omission on the outcome of breast cancer patients presenting only micrometastasis in the sentinel lymph node after neoadjuvant chemotherapy.
        Contemp Clin Trials Commun. 2019; 17100496
        • 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: 667