Management of the axilla in breast cancer patients has evolved from routine axillary lymph node dissection (ALND) for all patients to a highly selective approach based on the assessment of the sentinel lymph nodes (SLNs) as well as tumor and patient characteristics. Although ALND continues to have an important role in staging and regional control for many breast cancer patients, recent trial results question the need for routine ALND in patients who have positive SLNs.
Methods
Not all axillary disease becomes clinically detectable or relevant with respect to recurrence and survival. Therefore, recent trends indicate that many surgeons have omitted ALND in subgroups of patients, particularly those with clinically node-negative, SLN-positive, early-stage breast cancer undergoing breast-conserving therapy with postoperative irradiation. This review explores trends in axillary management, focusing primarily on the clinical implications of the results from the American College of Surgeons Oncology Group (ACOSOG) Z0011 randomized controlled trial.
Results
According to the results of the ACOSOG Z0011 trial, the use of SLN dissection alone did not result in inferior survival compared with ALND in patients with limited SLN disease treated with breast-conserving therapy. This subgroup of women was spared the morbidity associated with ALND. However, several points of debate, including the smaller than anticipated sample size, the older study population, and the length of follow-up, suggest caution when applying these findings to all women with breast cancer.
Conclusions
Although the findings of ACOSOG Z0011 are impressive, in clinical practice they are applicable to a limited number of women with breast cancer: those with T1-2 primary tumors with clinically negative axilla and 1 to 2 positive SLNs undergoing breast-conserving surgery and adjuvant whole-breast irradiation. The next generation of clinical trials may answer some of the remaining questions regarding how best to manage the axilla in additional subsets of patients undergoing treatment of breast cancer.
References
1.
HalstedW.S.. I. The results of radical operations for the cure of carcinoma of the breast.Ann Surg.1907; 46(1): 1–19.
2.
FisherB., MontagueE., RedmondC.. Comparison of radical mastectomy with alternative treatments for primary breast cancer: a first report of results from a prospective randomized clinical trial.Cancer.1977; 39(6 suppl): 2827–2839.
3.
FisherB., JeongJ.H., AndersonS.. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation.N Engl J Med.2002; 347(8): 567–575.
4.
FisherB., RedmondC., PoissonR.. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer.N Engl J Med.1989; 320(13): 822–828.
5.
VeronesiU., SaccozziR., Del VecchioM.. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast.N Engl J Med.1981; 305(1): 6–11.
6.
Early stage breast cancer: consensus statement. NIH consensus development conference, June 18-21, 1990.Cancer Treat Res.1992; 60: 383–393.
7.
GiulianoA.E., KirganD.M., GuentherJ.M.. Lymphatic mapping and sentinel lymphadenectomy for breast cancer.Ann Surg.1994; 220(3): 391–401.
8.
MorrowM., RademakerA.W., BethkeK.P.. Learning sentinel node biopsy: results of a prospective randomized trial of two techniques.Surgery.1999; 126(4): 714–722.
9.
VeronesiU., PaganelliG., GalimbertiV.. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes.Lancet.1997; 349(9069): 1864–1867.
10.
McLaughlinS.A., WrightM.J., MorrisK.T.. Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements.J Clin Oncol.2008; 26(32): 5213–5219.
11.
LangerI., GullerU., BerclazG.. Morbidity of sentinel lymph node biopsy (SLN) alone versus SLN and completion axillary lymph node dissection after breast cancer surgery: a prospective Swiss multicenter study on 659 patients.Ann Surg.2007; 245(3): 452–461.
12.
LucciA., McCallL.M., BeitschP.D.. 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.
13.
KragD.N., AndersonS.J., JulianT.B.. 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.
14.
SmidtM.L., JanssenC.M., KusterD.M.. Axillary recurrence after a negative sentinel node biopsy for breast cancer: incidence and clinical significance.Ann Surg Oncol.2005; 12(1): 29–33.
15.
TakeiH., SuemasuK., KurosumiM.. Recurrence after sentinel lymph node biopsy with or without axillary lymph node dissection in patients with breast cancer.Breast Cancer.2007; 14(1): 16–24.
16.
ChungM.A., SteinhoffM.M., CadyB.. Clinical axillary recurrence in breast cancer patients after a negative sentinel node biopsy.Am J Surg.2002; 184(4): 310–314.
17.
LangerI., MartiW.R., GullerU.. Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analysis of 150 patients after SLN biopsy.Ann Surg.2005; 241(1): 152–158.
18.
LymanG.H., GiulianoA.E., SomerfieldM.R.. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in earlystage breast cancer.J Clin Oncol.2005; 23(30): 7703–7720.
19.
BeversT.B., AndersonB.O., BonaccioE.. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis.J Natl Compr Canc Netw.2009; 7(10): 1060–1096.
20.
KimT., GiulianoA.E., LymanG.H.. Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis.Cancer.2006; 106(1): 4–16.
21.
KamathV.J., GiulianoR., DauwayE.L.. Characteristics of the sentinel lymph node in breast cancer predict further involvement of higher-echelon nodes in the axilla: a study to evaluate the need for complete axillary lymph node dissection.Arch Surg.2001; 136(6): 688–692.
22.
CserniG.. Sentinel lymph-node biopsy-based prediction of further breast cancer metastases in the axilla.Eur J Surg Oncol.2001; 27(6): 532–538.
23.
van DeurzenC.H., de BoerM., MonninkhofE.M.. Nonsentinel lymph node metastases associated with isolated breast cancer cells in the sentinel node.J Natl Cancer Inst.2008; 100(22): 1574–1580.
24.
HwangR.F., Gonzalez-AnguloA.M., YiM.. Low locoregional failure rates in selected breast cancer patients with tumor-positive sentinel lymph nodes who do not undergo completion axillary dissection.Cancer.2007; 110(4): 723–730.
25.
TanE.Y., HoB., ChenJ.J.. Predictors of nonsentinel nodal involvement to aid intraoperative decision making in breast cancer patients with positive sentinel lymph nodes.ISRN Oncol.2011; 2011: 539503.
26.
ParkJ., FeyJ.V., NaikA.M.. A declining rate of completion axillary dissection in sentinel lymph node-positive breast cancer patients is associated with the use of a multivariate nomogram.Ann Surg.2007; 245(3): 462–468.
27.
The American Society of Breast Surgeons. Consensus Statement on Guidelines for Performing Sentinel Lymph Node Dissection in Breast Cancer. Fourth Revision. Approved December 5, 2008, Board of Directors, The American Society of Breast Surgeons. https://www.breastsurgeons.org/statements/slnd.php. Accessed April 22, 2012.
28.
GiulianoA.E., HuntK.K., BallmanK.V.. 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.
29.
GiulianoA.E., McCallL., BeitschP.. 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(3): 426–433.
30.
GrubeB.J., GiulianoA.E.. Observation of the breast cancer patient with a tumor-positive sentinel node: implications of the ACOSOG Z0011 trial.Semin Surg Oncol.2001; 20(3): 230–237.
31.
VeronesiU., PaganelliG., VialeG.. Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series.J Natl Cancer Inst.1999; 91(4): 368–373.
32.
KragD., WeaverD., AshikagaT.. The sentinel node in breast cancer: a multicenter validation study.N Engl J Med.1998; 339(14): 941–946.
33.
GiulianoA.E., JonesR.C., BrennanM.. Sentinel lymphadenectomy in breast cancer.J Clin Oncol.1997; 15(6): 2345–2350.
34.
CadyB., StoneM.D., SchulerJ.G.. The new era in breast cancer: invasion, size, and nodal involvement dramatically decreasing as a result of mammographic screening.Arch Surg.1996; 131(3): 301–308.
35.
GiulianoA.E., HawesD., BallmanK.V.. Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer.JAMA.2011; 306(4): 385–393.
36.
LatosinskyS., DabbsK., MoffatF.. Canadian Association of General Surgeons and American College of Surgeons Evidence-Based Reviews in Surgery. 27. Quality-of-life outcomes with sentinel node biopsy versus standard axillary treatment in patients with operable breast cancer: randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer. The ALMANAC Trial.Can J Surg.2008; 51(6): 483–485.
37.
BilimoriaK.Y., BentremD.J., HansenN.M.. Comparison of sentinel lymph node biopsy alone and completion axillary lymph node dissection for node-positive breast cancer.J Clin Oncol.2009; 27(18): 2946–2953.
38.
YiM., GiordanoS.H., Meric-BernstamF.. Trends in and outcomes from sentinel lymph node biopsy (SLNB) alone vs. SLNB with axillary lymph node dissection for node-positive breast cancer patients: experience from the SEER database.Ann Surg Oncol.2010; 17(suppl 3): 343–351.
39.
Van ZeeK.J., ManassehD.M., BevilacquaJ.L.. A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy.Ann Surg Oncol.2003; 10(10): 1140–1151.
40.
DegnimA.C., ReynoldsC., PantvaidyaG.. Nonsentinel node metastasis in breast cancer patients: assessment of an existing and a new predictive nomogram.Am J Surg.2005; 190(4): 543–550.
41.
LambertL.A., AyersG.D., HwangR.F.. Validation of a breast cancer nomogram for predicting nonsentinel lymph node metastases after a positive sentinel node biopsy.Ann Surg Oncol.2006; 13(3): 310–320.
42.
van la ParraR.F., ErnstM.F., BevilacquaJ.L.. Validation of a nomogram to predict the risk of nonsentinel lymph node metastases in breast cancer patients with a positive sentinel node biopsy: validation of the MSKCC breast nomogram.Ann Surg Oncol.2009; 16(5): 1128–1135.
43.
MittendorfE.A., HuntK.K., BougheyJ.C.. Incorporation of sentinel lymph node metastasis size into a nomogram predicting nonsentinel lymph node involvement in breast cancer patients with a positive sentinel lymph node.Ann Surg.2012; 255(1): 109–115.
44.
KohrtH.E., OlshenR.A., BermasH.R.. New models and online calculator for predicting nonsentinel lymph node status in sentinel lymph node positive breast cancer patients.BMC Cancer.2008; 8: 66.
45.
GalimbertiV., CoelB.F., ZurridaS.. Update of International Breast Cancer Study Group trial 23-01 to compare axillary dissection versus no axillary dissection in patients with clinically node negative breast cancer and micrometastases in the sentinel node. 34th Annual San Antonio Breast Cancer Symposium; December 6-10, 2011. San Antonio, Texas.
46.
MorrowM., GiulianoA.E.. To cut is to cure: can we really apply Z11 in practice?Ann Surg Oncol.2011; 18(9): 2413–2415.
47.
BeadleB.M., WoodwardW.A., BuchholzT.A.. The impact of age on outcome in early-stage breast cancer.Semin Radiat Oncol.2011; 21(1): 26–34.
48.
MilesR.C., GullerudR.E., LohseC.M.. Local recurrence after breast-conserving surgery: multivariable analysis of risk factors and the impact of young age.Ann Surg Oncol.2012; 19(4): 1153–1159.
49.
FisherB., RedmondC., BrownA.. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial.J Clin Oncol.1986; 4(4): 459–471.
50.
Adjuvant tamoxifen in the management of operable breast cancer: the Scottish Trial.Report from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh.Lancet.1987; 2(8552): 171–175.
51.
FisherB., CostantinoJ., RedmondC.. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors.N Engl J Med.1989; 320(8): 479–484.
52.
SlamonD.J., Leyland-JonesB., ShakS.. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.N Engl J Med.2001; 344(11): 783–792.
53.
RomondE.H., PerezE.A., BryantJ.. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.N Engl J Med.2005; 353(16): 1673–1684.
54.
Piccart-GebhartM.J., ProcterM., Leyland-JonesB.. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.N Engl J Med.2005; 353(16): 1659–1672.
55.
CaudleA.S., HuntK.K., KuererH.M.. Multidisciplinary considerations in the implementation of the findings from the American College of Surgeons Oncology Group (ACOSOG) Z0011 study: a practice-changing trial.Ann Surg Oncol.2011; 18(9): 2407–2412.
56.
CrabbS.J., CheangM.C., LeungS.. Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metastases in primary breast cancer.Clin Breast Cancer.2008; 8(3): 249–256.
57.
MittendorfE.A., SahinA.A., TuckerS.L.. Lymphovascular invasion and lobular histology are associated with increased incidence of isolated tumor cells in sentinel lymph nodes from early-stage breast cancer patients.Ann Surg Oncol.2008; 15(12): 3369–3377.
58.
FisherB., RedmondC., FisherE.R.. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation.N Engl J Med.1985; 312(11): 674–681.
59.
GrecoM., AgrestiR., CascinelliN.. Breast cancer patients treated without axillary surgery: clinical implications and biologic analysis.Ann Surg.2000; 232(1): 1–7.
60.
MartelliG., MiceliR., DaidoneM.G.. 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(1): 125–133.
61.
GrillsI.S., KestinL.L., GoldsteinN.. 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(3): 658–670.
62.
ReznikJ., CicchettiM.G., DegaspeB.. Analysis of axillary coverage during tangential radiation therapy to the breast.Int J Radiat Oncol Biol Phys.2005; 61(1): 163–168.
63.
SchlembachP.J., BuchholzT.A., RossM.I.. Relationship of sentinel and axillary level I-II lymph nodes to tangential fields used in breast irradiation.Int J Radiat Oncol Biol Phys.2001; 51(3): 671–678.
64.
GaddM., HarrisJ., TaghianA.. Prospective study of axillary radiation without axillary dissection for breast cancer patients with a positive sentinel node. 28th Annual San Antonio Breast Cancer Symposium; December 8-11, 2005; San Antonio, Texas.
65.
StraverM.E., MeijnenP., van TienhovenG.. Role of axillary clearance after a tumor-positive sentinel node in the administration of adjuvant therapy in early breast cancer.J Clin Oncol.2010; 28(5): 731–737.
66.
OlivottoI.A., ChuaB., ElliottE.A.. A clinical trial of breast radiation therapy versus breast plus regional radiation therapy in early-stage breast cancer: the MA20 trial.Clin Breast Cancer.2003; 4(5): 361–363.
67.
WhelanT.J., OlivottoI., AckermanI.. NCIC-CTG MA.20: an intergroup trial of regional nodal irradiation in early breast cancer.J Clin Oncol.2011; 29(suppl): LBA1003. Abstract.
68.
HafftyB.G., HuntK.K., HarrisJ.R.. Positive sentinel nodes without axillary dissection: implications for the radiation oncologist.J Clin Oncol.2011; 29(34): 4479–4481.
