Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial

Jana de Boniface, Jan Frisell, Yvette Andersson, Leif Bergkvist, Johan Ahlgren, Lisa Rydén, Roger Olofsson Bagge, Malin Sund, Hemming Johansson, Dan Lundstedt, SENOMAC Trialists’ Group, Peer Christiansen, Tove Filtenborg Tvedskov, Birgitte Offersen, Toralf Reimer, Thorsten Kühn, Michalis Kontos, Oreste Gentilini, Jana de Boniface, Jan Frisell, Yvette Andersson, Leif Bergkvist, Johan Ahlgren, Lisa Rydén, Roger Olofsson Bagge, Malin Sund, Hemming Johansson, Dan Lundstedt, SENOMAC Trialists’ Group, Peer Christiansen, Tove Filtenborg Tvedskov, Birgitte Offersen, Toralf Reimer, Thorsten Kühn, Michalis Kontos, Oreste Gentilini

Abstract

Background: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference.

Methods: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1:1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years.

Discussion: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.

Trial registration: NCT 02240472 , retrospective registration date September 14, 2015 after trial initiation on January 31, 2015.

Trial registration: ClinicalTrials.gov NCT02240472 NCT02240472.

Keywords: Axillary lymph node dissection; Breast cancer; Macrometastasis; Sentinel lymph node biopsy; Survival.

Figures

Fig. 1
Fig. 1
Flow chart of inclusion pathways in the SENOMAC Trial depending on the use of frozen section at sentinel node biopsy

References

    1. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989;63(1):181–187. doi: 10.1002/1097-0142(19890101)63:1<181::AID-CNCR2820630129>;2-H.
    1. Fisher B, Bauer M, Wickerham DL, Redmond CK, Fisher ER, Cruz AB, et al. Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer. 1983;52(9):1551–1557. doi: 10.1002/1097-0142(19831101)52:9<1551::AID-CNCR2820520902>;2-3.
    1. Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW. An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat. 2008;107(3):309–330. doi: 10.1007/s10549-007-9556-1.
    1. Sobin LH, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. 7th Edition. ISBN: 978-1-4443-3241-4 ed. Oxford: Wiley-Blackwell; 2009.
    1. Nieweg OE, Jansen L, Valdés Olmos RA, Rutgers E, Peterse JL, Hoefnagel KA, et al. Lymphatic mapping and sentinel lymph node biopsy in breast cancer. Eur J Nucl Med. 1999;26(Suppl 4):S11–S16. doi: 10.1007/s002590050572.
    1. Andersson Y, de Boniface J, Jönsson PE, Ingvar C, Liljegren G, Bergkvist L, et al. Axillary recurrence rate 5 years after negative sentinel node biopsy for breast cancer. Br J Surg. 2012;99(2):226–231. doi: 10.1002/bjs.7820.
    1. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino 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(10):927–933. doi: 10.1016/S1470-2045(10)70207-2.
    1. Pepels MJ, Vesthens JH, de Boer M, Smidt M, van Diest PJ, Borm GF, et al. Safety of avoiding routine use of axillary dissection in early stage breast cancer: a systematic review. Breast Cancer Res Treat. 2011;125(2):301–313. doi: 10.1007/s10549-010-1210-7.
    1. van der Ploeg IM, Nieweg OE, van Rijk MC, Valdés Olmos RA, Kroon BB. Axillary recurrence after a tumour-negative sentinel node biopsy in breast cancer patients: a systematic review and meta-analysis of the literature. Eur J Surg Oncol. 2008;34(12):1277–1284. doi: 10.1016/j.ejso.2008.01.034.
    1. Veronesi U, Galimberti V, Mariani L, Gatti G, Paganelli G, Viale G, et al. Sentinel node biopsy in breast cancer: early results in 953 patients with negative sentinel node biopsy and no axillary dissection. Eur J Cancer. 2005;41(2):231–237. doi: 10.1016/j.ejca.2004.05.009.
    1. Celebioglu F, Perbeck L, Frisell J, Gröndal E, Svensson L, Danielsson R. Lymph drainage studied by lymphoscintigraphy in the arms after sentinel node biopsy compared with axillary lymph node dissection following conservative breast cancer surgery. Acta Radiol. 2007;48(5):488–495. doi: 10.1080/02841850701305440.
    1. Land SR, Kopec JA, Julian TB, Brown AM, Anderson SJ, Krag DN, et al. Patient-reported outcomes in sentinel node-negative adjuvant breast cancer patients receiving sentinel-node biopsy or axillary dissection: National Surgical Adjuvant Breast and Bowel Project phase III protocol B-32. J Clin Oncol. 2010;28(25):3929–3936. doi: 10.1200/JCO.2010.28.2491.
    1. Lucci A, McCall LM, Beitsch PD, Whitworth PW, Reintgen DS, Blumencrantz PW, et al. 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. doi: 10.1200/JCO.2006.07.4062.
    1. Sackey H, Magnuson A, Sandelin K, Liljegren G, Bergkvist L, Fülep Z, et al. Arm lymphoedema after axillary surgery in women with invasive breast cancer. Br J Surg. 2014;101(4):390–397. doi: 10.1002/bjs.9401.
    1. Degnim AC, Griffith KA, Sabel MS, Hayes DF, Cimmino VM, Diehl KM, et al. Clinicopathologic eatures of metastasis in nonsentinel lymph nodes of breast carcinoma patients. Cancer. 2003;98(11):2307–2315. doi: 10.1002/cncr.11803.
    1. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencrantz PW, 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(6):569–575. doi: 10.1001/jama.2011.90.
    1. Caudle AS, Hunt KK, Tucker SL, Hoffman K, Gainer SM, Lucci A, et al. American College of Surgeons Oncology Group (ACOSOG) Z0011: impact on surgeon practice patterns. Ann Surg Oncol. 2012;19(10):3144–3151. doi: 10.1245/s10434-012-2531-z.
    1. Gainer SM, Hunt KK, Beitsch P, Caudle AS, Mittendorf EA, Lucci A. Changing behavior in clinical practice in response to the ACOSOG Z0011 trial: a survey of the American Society of Breast Surgeons. Ann Surg Oncol. 2012;19(10):3152–3158. doi: 10.1245/s10434-012-2523-z.
    1. Giuliano AE, Morrow M, Duggal S, Julian TB. Should ACOSOG Z0011 change practice with respect to axillary lymph node dissection for a positive sentinel lymph node biopsy in breast cancer? Clin Exp Metastasis. 2012;29(7):687–692. doi: 10.1007/s10585-012-9515-z.
    1. Latosinsky S, Berrang TS, Cutter CS, George R, Olivotto I, Julian TB, et al. CAGS and ACS evidence based reviews in surgery. 40. Axillary dissection versus no axillary dissection in women with invasive breast cancer and sentinel node metastasis. Can J Surg. 2012;55(1):66–69. doi: 10.1503/cjs.036011.
    1. Galimberti V, Cole BF, Zurrida S, Viale G, Luini A, Veronesi P, Baratella P, 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. doi: 10.1016/S1470-2045(13)70035-4.
    1. Park J, Fey JV, Naik AM, Borgen PI, Van Zee KJ, Cody HS., 3rd 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. doi: 10.1097/01.sla.0000250439.86020.85.
    1. Pepels MJ, de Boer M, Bult P, van Dijck JA, van Deurzen CH, Menke-Pluymers MB, et al. Regional recurrence in breast cancer patients with sentinel node micrometastases and isolated tumor cells. Ann Surg. 2012;255(1):116–121. doi: 10.1097/SLA.0b013e31823dc616.
    1. Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, et al. Radiotherapy or surgery of the axilla after a positive senintel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15:1303–1310. doi: 10.1016/S1470-2045(14)70460-7.
    1. Devoogdt N, De Groef A, Hendrickx A, Damstra R, Christiaansen A, Geraerts I, et al. Lymphoedema functioning, disability and health questionnaire (Lymph-ICF): reliability and validity. Phys Ther. 2011;91(6):944–957. doi: 10.2522/ptj.20100087.
    1. Herdman M, Gudex C, Lloyd A, Janssen MF, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) Qual Life Res. 2011;20(10):1727–1736. doi: 10.1007/s11136-011-9903-x.
    1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365–376. doi: 10.1093/jnci/85.5.365.
    1. Bjordal K, de Graeff A, Fayers PM, Hammerlid E, van Pottelsberghe C, Curran D, et al. A 12 country field study of the EORTC QLQ-C30 (version 3.0) and the head and neck cancer specific module (EORTC QLQ-H&N35) in head and neck patients. EORTC Quality of Life Group. Eur J Cancer. 2000;36(14):1796–1807. doi: 10.1016/S0959-8049(00)00186-6.
    1. Sprangers MA, Groenvold M, Arraras JI, Franklin J, te Velde A, Muller M, et al. The European Organisation for Research and Treatment of Cancer Breast Cancer Specific Quality of Life Questionnaire Module: first results from a three-country field study. J Clin Oncol. 1996;14:2756–2768. doi: 10.1200/JCO.1996.14.10.2756.
    1. Offersen BV, Boersma LJ, Kirkove C, Hol S, Aznar MC, Biete Sola A, et al. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer. Radiother Oncol. 2015;114:3–10. doi: 10.1016/j.radonc.2014.11.030.
    1. Gondos A, Jansen L, Heil J, Schneeweiss A, Voogd AC, Frisell J, et al. Time trends in axilla management among early breast cancer patients: persisting major variation in clinical practice across European centers. Acta Oncol. 2016;55(6):712–719. doi: 10.3109/0284186X.2015.1136751.
    1. Giuliano AE, Ballman K, McCall L, Beitsch P, Whitworth PW, Blumencrantz P, 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 Z001 randomized trial. Ann Surg. 2016;264(3):413–420. doi: 10.1097/SLA.0000000000001863.
    1. Schmidt-Hansen M, Bromham N, Haster E, Reed MW. Axillary surgery in women with sentinel node-positive operable breast cancer: a systematic review with meta-analyses. Spring. 2016;5:85. doi: 10.1186/s40064-016-1712-9.
    1. Kenny TC, Dove J, Shabahang M, Woll N, Hunsinger M, Morgan A, et al. Widespread implications of ACOSOG Z0011: effect on total mastectomy patients. Am Surg. 2016;82(1):53–58.
    1. Ataseven B, von Minckwitz G. The impact of neoadjuvant treatment on surgical options and outcomes. Ann Surg Oncol. 2016; [Epub ahead of print]
    1. Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, 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(7):609–618. doi: 10.1016/S1470-2045(13)70166-9.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren