Diagnosing and Managing the Malignant Axilla in Breast Cancer
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Purpose of Review
The management of the malignant axilla remains a controversial topic. Although many issues have been resolved with the results of randomised controlled trials, there are still areas where evidence is lacking. This review will focus on the current diagnostic methods used to detect lymph node (LN) metastases as well as the impact of volume of LN disease on the choice of axillary management. The roles of surgical excision, radiotherapy and systemic therapy as treatment modalities for LN metastases will also be explored with particular emphasis on the use of neo-adjuvant chemotherapy (NACT). Lastly, new innovations in contrast-enhanced ultrasound (CEUS) will be discussed as a potential test for precise and personalised axillary staging.
The results of the ACOSOG Z011 trial are widely accepted and axillary conservation is now part of mainstream practice in many parts of the World for patients with sentinel lymph node (SLN) metastases and clinical T1/ T2 N0 M0 tumours who had breast-conserving surgery alongside adjuvant whole breast radiotherapy and systemic therapy. Determining the volume of metastatic disease in the axilla is important for treatment decisions and de-escalation of axillary surgery after NACT in patients with biopsy proven pretreatment LN metastases may become part of routine practice for selected patients once long-term outcomes are known. Novel methods to identify LN metastases have been developed over the last 10 years including the use of injected microbubbles and CEUS to locate and biopsy sentinel lymph nodes (SLN). Technological advances including ultrafast and super-resolution ultrasound have the potential to increase the diagnostic accuracy of axillary CEUS.
The main drawback to current axillary management is the lack of a reliable objective test to quantify LN metastases. The de-escalation of axillary surgery is timely but without an objective non-invasive imaging test to replace the axillary lymph node dissection (ALND), clinicians are reliant on predictive medicine rather than precision diagnostics to plan individual treatment. New innovations in CEUS have the potential to provide a reproducible non-invasive test, which can be used in the future to investigate LN metastases in patients with breast cancer.
KeywordsBreast cancer Axillary staging Lymph node metastases Sentinel lymph node Contrast-enhanced ultrasound (CEUS) Microbubbles Neo-adjuvant chemotherapy Ultrafast ultrasound Super-resolution ultrasound
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.History of Breast Cancer. Medical therapy of breast cancer 2003. Editors Z Rayter and J Mansi. Cambridge University Press.Google Scholar
- 3.• Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Keleman PR, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017;318:918–26 (Of importance: The long-term results of the ACOSOG Z0011 trial have changed practice across the World and now mean that many patients with SLN metastases can opt for axillary conservation). PubMedPubMedCentralCrossRefGoogle Scholar
- 4.de Boniface J, Frisell J, Bergkvist L, Andersson Y, on behalf of the Swedish Breast Cancer Group and the Swedish Society of Breast Surgery. Ten-year report on axillary recurrence after negative sentinel node biopsy for breast cancer from the Swedish Multicentre Cohort Study. BJS. 2017;104:238–47.CrossRefGoogle Scholar
- 5.Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Constantino JP, 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;11:927–33.PubMedPubMedCentralCrossRefGoogle Scholar
- 14.Diepstraten SCE, Sever AR, Buckens CFM, Veldhuis WB, van Dalen T, van den Bosch MAAJ, et al. Value of preoperative ultrasound-guided axillary lymph node biopsy for preventing completion axillary lymph node dissection in breast cancer: a systematic review and meta-analysis. Ann Surg Oncol. 2014;21(1):51–9.PubMedCrossRefGoogle Scholar
- 15.https://associationofbreastsurgery.org.uk/media/64840/nhs-bsp-abs-audit-2016-2017.pdf. Accessed November 2018.
- 20.• Cox K, Taylor-Phillips S, Sharma N, Weeks J, Mills P, Sever A, et al. Enhanced pre-operative axillary staging using intradermal microbubbles and contrast-enhanced ultrasound to detect and biopsy sentinel lymph nodes in breast cancer: a potential replacement for axillary surgery. Br J Radiol. 2017;90:20170626 (Of importance: This study firstly confirmed the limitations of the microbubble/CEUS SLN biopsy as a test to identify all LN metastases but importantly also showed that patients with a normal grey-scale axillary ultrasound and benign biopsy of SLN with CEUS were unlikely to have high-volume ultrasound occult LN metastases). CrossRefGoogle Scholar
- 24.Esfehani MH, Yazdankhah-Kenari A, Omranipour R, Mahmoudzadeh HA, Shahriaran S, Zafarghandi MR, et al. Validation of contrast enhanced ultrasound technique to wire localization of sentinel lymph node in patients with early breast cancer. Indian J Surg Oncol. 2015;6:370–3.PubMedPubMedCentralCrossRefGoogle Scholar
- 25.Oral presentation SSJ02-06, RSNA 2016, Chicago, USA.Google Scholar
- 26.Nielsen Moody A, Bull J, Culpan AM, Munyombwe T, Sharma N, Whitaker M, et al. Preoperative sentinel lymph node identification, biopsy and localization using contrast enhanced ultrasound (CEUS) in patients with breast cancer: a systemic review and meta-analysis. Clin Radiol. 2017;72:959–71.PubMedCrossRefGoogle Scholar
- 27.Sever A, Broillet A, Schneider M, Cox K, Jones S, Weeks J, et al. Dynamic visualization of lymphatic channels and sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasound in a swine model and patients with breast cancer. J Ultrasound Med. 2010;29:1699–704.PubMedCrossRefGoogle Scholar
- 28.Cox K, Sever A, Jones S, Weeks J, Mills P, Devalia H, et al. Validation of a technique using microbubbles and contrast enhanced ultrasound (CEUS) to biopsy sentinel lymph nodes (SLN) in pre-operative breast cancer patients with a normal grey-scale axillary ultrasound. Eur J Surg Oncol. 2013;39:760–5.PubMedCrossRefGoogle Scholar
- 30.Cooper KL, Meng Y, Harnan S, Ward SE, Fitzgerald P, Papaioannou D, et al. Positron emission tomography (PET) and magnetic resonance imaging (MRI) for the assessment of axillary lymph node metastases in early breast cancer: systematic review and economic evaluation. Health Technol Assess. 2011;15(4):iii–v.PubMedPubMedCentralCrossRefGoogle Scholar
- 31.• Bromham N, Schmidt-Hansen M, Astin M, Hasler E, Reed MW. Axillary treatment for operable primary breast cancer (Review). Cochrane Database Syst Rev. 2017;1:CD004561 (Of importance: This systematic review succinctly evaluates all of the available evidence relating to axillary treatment in patients with breast cancer. Moderate quality evidence indicates that patients treated with lesser axillary surgery such as sampling or SLNB do not have a reduced chance of survival when compared with those who had ALND; patients who do not have any axillary LN removed are at increased risk of locoregional recurrence). PubMedGoogle Scholar
- 42.• Galimberti V, Cole BF, Viale G, Veronesi P, Vicini E, Intra M, 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;19:1385–93 (Of importance: This trial reported that in patients with SLN micrometastases, ALND did not improve disease-free survival, local recurrence, or regional recurrence). PubMedCrossRefGoogle Scholar
- 43.de Boniface FJ, Andersson Y, Bergkvist L, Ahlgren J, Ryden L, et al. Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomised controlled SENOMAC trial. BMC Cancer. 2017;17(1):379.PubMedPubMedCentralCrossRefGoogle Scholar
- 50.Grills IS, Kestin LL, Goldstein N, Mitchell C, Martinez A, Ingold J, et al. Risk factors for regional nodal failure after breast-conserving therapy: regional nodal irradiation reduces rate of axillary failure in patients with four or more positive lymph nodes. Int J Radiat Oncol Biol Phys. 2003;56:658–70.PubMedCrossRefGoogle Scholar
- 52.Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde C, Mansel RE, 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;15:1303–10.PubMedPubMedCentralCrossRefGoogle Scholar
- 58.Fisher B, Brown A, Mamounas E, Wieland S, Robidoux A, Margolese RG, 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;15:2483–93.PubMedCrossRefGoogle Scholar
- 59.Mamtani A, Barrio AV, King TA, Van Zee KJ, Plitas G, Pilewskie M, 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. 2016;23:3467–74.PubMedPubMedCentralCrossRefGoogle Scholar
- 64.Caudle AS, Yang WT, Krishnamurthy S, Mittendorf EA, Black DM, Gilcrease MZ, 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;34:1072–8.PubMedPubMedCentralCrossRefGoogle Scholar
- 66.Mamounas EP WJ, Bandos H, Julian TB, Kahn AJ, Shaitelman SF et al. NSABP B-51/RTOG 1304: randomized phase III clinical trial evaluating the role of postmastectomy chest wall and regional nodal XRT (CWRNRT) and post-lumpectomy RNRT in patients (pts) with documented positive axillary (Ax) nodes before neoadjuvant chemotherapy (NC) who convert to pathologically negative axillary nodes after NC. J Clin Oncol 2014: 32. https://doi.org/10.1200/jco.2014.32.15_suppl.tps1141.
- 67.Tanter, M. and M. Fink, Ultrafast imaging in Biomedical Ultrasound. IEEE T. UFFC. 2014;61(1):102–119.Google Scholar
- 68.Tortoli, P., Bassi L., Boni E., Dallai A., Guidi F., Ricci S. ULA-OP: an advanced open platform for ultrasound research. IEEE T. UFFC, 2009;56(10):2207–2216.Google Scholar