Systematic versus sentinel-lymph-node-driven axillary-lymph-node dissection in clinically node-negative patients with operable breast cancer. Results of the GF-GS01 randomized trial

P Roy, A Leizorovicz, R Villet, C Mercier, J Y Bobin, P Roy, A Leizorovicz, R Villet, C Mercier, J Y Bobin

Abstract

Purpose: Sentinel-lymph-node (SLN) resection seems to minimize systematic axillary-lymph-node dissection (sALND) side effects in operated breast cancer patients. We explored whether SLN resection achieves similar therapeutic outcomes as sALND but with fewer side effects.

Methods: A randomized, controlled, open-label trial with parallel-group design compared sALND restricted to cases with positive SLN biopsy (test arm, n = 774) versus SLN biopsy followed by sALND (control arm, n = 770).

Results: The five-year overall survivals in control and test arms were 96.42 and 95.64% (P = 0.2925). The estimated difference was nearly zero (precisely, - 0.79%, one-tailed 95% confidence interval (CI) limit - 2.44%). In a multivariate Cox model, the adjusted hazard ratio in the test arm was HR 0.81 (upper 95% CI limit 1.17). Advanced age (HR 1.05 per additional year, CI [1.03-1.08]), negative progesterone receptor (HR 2.17 [1.35-3.45]), SLN metastasis (HR 1.69 [1.03-2.79]), and only one SLN identification technique (HR 4.14 [1.21-14.18]) were associated with lower survival. Patients with ≥ 1 severe side effect at 1 month in control and test arms were 173/703 = 24.6% [21.5-28.0%] and 91/693 = 13.1% [10.7-15.9%] (P < 0.001). The estimated sensitivity of SLN biopsy (control arm) was 145/178 = 81.5% [74.8-86.7%].

Conclusions: Restricting ALND to cases with positive SLN biopsy does not affect the overall survival but reduces by 11.5% [7.5-15.6%] (P < 0.001) the risk of severe short-time side effects of sALND.

Keywords: Breast cancer; Clinical trial; Sentinel-lymph-node biopsy; Surgery; Survival.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statements

Trial GF-GS01 was carried out after approval from local institutional review boards and in accordance with assurances filed with and approved by the French Ministère de la Santé et des Affaires Sociales. Informed consent was obtained from all individual participants included in the study. The trial is registered under number (NCT00144898) in clinical.trial.gov and number RECF0322 in the database of the French Institut National du Cancer. The investigators obtained informed consent from each participant.

Figures

Fig. 1
Fig. 1
Flow chart of GF-GS01 trial
Fig. 2
Fig. 2
Overall survival curves for test and control arms

References

    1. Ivens D, Hoe AL, Podd TJ, et al. Assessment of morbidities from complete axillary dissection. Br J Cancer. 1992;66:136–138. doi: 10.1038/bjc.1992.230.
    1. Liljegren G, Holomberg L, The Uppsala Orebro Breast Study Group Arm morbidity after sector resection and axillary dissection with and without radiotherapy in breast cancer stage I. Results from a randomised trial. Eur J Cancer. 1997;33:193–199. doi: 10.1016/S0959-8049(96)00375-9.
    1. Jackson JS, Olivotto IA, Wai EMDE, et al. A decision analysis of the effect of avoiding axillary lymph node dissection in low risk women with invasive breast carcinoma. Cancer. 2000;88:1852–1862. doi: 10.1002/(SICI)1097-0142(20000415)88:8<1852::AID-CNCR14>;2-L.
    1. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391–398. doi: 10.1097/00000658-199409000-00015.
    1. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–481. doi: 10.1080/01621459.1958.10501452.
    1. Cox DR. Regression models and life-tables. J R Stat Soc Ser B Stat Methodol. 1972;34:187–220.
    1. Andersen PK, Klein JP, Zhang MJ. Testing for centre effects in multi-centre survival studies: a Monte Carlo comparison of fixed and random effects tests. Stat Med. 1999;18:1489–1500. doi: 10.1002/(SICI)1097-0258(19990630)18:12<1489::AID-SIM140>;2-#.
    1. 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. 2010;251:595–600. doi: 10.1097/SLA.0b013e3181c0e92a.
    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;11:927–933. doi: 10.1016/S1470-2045(10)70207-2.
    1. Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC trial. J Natl Cancer Inst. 2006;98:599–609. doi: 10.1093/jnci/djj158.
    1. 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. 2007;8:881–888. doi: 10.1016/S1470-2045(07)70278-4.
    1. Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med. 2003;349:546–553. doi: 10.1056/NEJMoa012782.
    1. Roy P, Estève J, Bobin JY. Methodological questions in sentinel lymph node analysis in breast cancer patients. Ann Oncol. 2000;11:1381–1385. doi: 10.1023/A:1026743914286.
    1. Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel node biopsy in early stage breast carcinoma. Cancer. 2006;106:4–16. doi: 10.1002/cncr.21568.
    1. Land SR, Kopec JA, Julian TB, et al. Patient-reported outcomes in sentinel node-negative adjuvant breast cancer patients receiving sentinel-node biopsy or axillar dissection: national surgical adjuvant breast and bowel project phase III protocol B-32. J Clin Oncol. 2010;28:3929–3936. doi: 10.1200/JCO.2010.28.2491.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe