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

Guido Henke, Michael Knauer, Karin Ribi, Stefanie Hayoz, Marie-Aline Gérard, Thomas Ruhstaller, Daniel R Zwahlen, Simone Muenst, Markus Ackerknecht, Hanne Hawle, Florian Fitzal, Michael Gnant, Zoltan Mátrai, Bettina Ballardini, Andreas Gyr, Christian Kurzeder, Walter P Weber, Guido Henke, Michael Knauer, Karin Ribi, Stefanie Hayoz, Marie-Aline Gérard, Thomas Ruhstaller, Daniel R Zwahlen, Simone Muenst, Markus Ackerknecht, Hanne Hawle, Florian Fitzal, Michael Gnant, Zoltan Mátrai, Bettina Ballardini, Andreas Gyr, Christian Kurzeder, Walter P Weber

Abstract

Background: Complete lymph node removal through conventional axillary dissection (ALND) has been standard treatment for breast cancer patients for almost a century. In the 1990s, however, and in parallel with the advent of the sentinel lymph node (SLN) procedure, ALND came under increasing scrutiny due to its association with significant patient morbidity. Several studies have since provided evidence to suggest omission of ALND, often in favor of axillary radiation, in selected clinically node-negative, SLN-positive patients, thus supporting the current trend in clinical practice. Clinically node-positive patients, by contrast, continue to undergo ALND in many cases, if only for the lack of studies re-assessing the indication for ALND in these patients. Hence, there is a need for a clinical trial to evaluate the optimal treatment for clinically node-positive breast cancer patients in terms of surgery and radiotherapy. The TAXIS trial is designed to fill this gap by examining in particular the value of tailored axillary surgery (TAS), a new technique for selectively removing positive lymph nodes.

Methods: In this international, multicenter, phase-III, non-inferiority, randomized controlled trial (RCT), including 34 study sites from four different countries, we plan to randomize 1500 patients to either receive TAS followed by ALND and regional nodal irradiation excluding the dissected axilla, or receive TAS followed by regional nodal irradiation including the full axilla. All patients undergo adjuvant whole-breast irradiation after breast-conserving surgery and chest-wall irradiation after mastectomy. The main objective of the trial is to test the hypothesis that treatment with TAS and axillary radiotherapy is non-inferior to ALND in terms of disease-free survival of clinically node-positive breast cancer patients in the era of effective systemic therapy and extended regional nodal irradiation. The trial was activated on 31 July 2018 and the first patient was randomized on 7 August 2018.

Discussion: Designed to test the hypothesis that TAS is non-inferior to ALND in terms of curing patients and preventing recurrences, yet is significantly superior in reducing patient morbidity, this trial may establish a new worldwide treatment standard in breast cancer surgery. If found to be non-inferior to standard treatment, TAS may significantly contribute to reduce morbidity in breast cancer patients by avoiding surgical overtreatment.

Trial registration: ClinicalTrials.gov, ID: NCT03513614. Registered on 1 May 2018. www.kofam.ch , ID: NCT03513614 . Registered on 17 June 2018. EudraCT No.: 2018-000372-14.

Keywords: Axillary lymph node dissection; Axillary radiotherapy; Breast cancer surgery; Clinically node-positive; Disease-free survival; Overall survival; Quality of life; Tailored axillary surgery.

Conflict of interest statement

Ethics approval and consent to participate

The TAXIS study protocol SAKK 23/16 – IBCSG 57–18 – ABCSG-53, the patient information and consent form, as well as all other trial-related documents have been approved by the Lead EC for Northwest/Central Switzerland (EKNZ) in agreement with local legal requirements for formal authorization. The Lead EC authorization number is: 2018–00838. Any amendment to the protocol or patient information and consent form will be submitted for authorization to these institutions. Any substantial amendment to the protocol (except for safety reasons) can only be implemented at a site after obtaining written authorization by the corresponding regulatory bodies.

Patient recruitment only took place after the site had officially been opened for accrual by the SAKK CC. Sites in Switzerland have to adhere to the Swiss Human Research Act and all applicable local regulatory guidelines. Sites in foreign countries have to adhere to national law and locally applicable regulatory guidelines. Central ethical approval has been confirmed from the Lead EC for Northwest/Central Switzerland (authorization number: 2018–00838) and we will not begin recruiting at other centers in the trial until local ethical approval has been obtained.

TAXIS is carried out in accordance with the principles enunciated in the current version of the Declaration of Helsinki, the guidelines of Good Clinical Practice (GCP) issued by the ICH, the applicable Swiss Human Research Act and its associated ordinances and the requirements from the Swiss and European regulatory bodies [–53].

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
TAXIS trial flow chart
Fig. 2
Fig. 2
TAXIS trial timeline

References

    1. EUCAN. . Accessed 06 Apr 2018.
    1. Tsai RJ, Dennis LK, Lynch CF, Snetselaar LG, Zamba GKD, Scott-Conner C. The risk of developing arm lymphedema among breast cancer survivors: a meta-analysis of treatment factors. Ann Surg Oncol. 2009;16(7):1959–1972. doi: 10.1245/s10434-009-0452-2.
    1. Agresti R, Martelli G, Sandri M, et al. Axillary lymph node dissection versus no dissection in patients with T1N0 breast cancer: a randomized clinical trial (INT09/98) Cancer. 2014;120(6):885–893. doi: 10.1002/cncr.28499.
    1. Martelli G, Boracchi P, Ardoino I, et al. Axillary dissection versus no axillary dissection in older patients with T1N0 breast cancer: 15-year results of a randomized controlled trial. Ann Surg. 2012;256(6):920–924. doi: 10.1097/SLA.0b013e31827660a8.
    1. Martelli G, Boracchi P, De PM, et al. A randomized trial comparing axillary dissection to no axillary dissection in older patients with T1N0 breast cancer: results after 5 years of follow-up. Ann Surg. 2005;242(1):1–6. doi: 10.1097/01.sla.0000167759.15670.14.
    1. Rudenstam CM, Zahrieh D, Forbes JF, 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(3):337–344. doi: 10.1200/JCO.2005.01.5784.
    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(10):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(9):599–609. doi: 10.1093/jnci/djj158.
    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(6):546–553. doi: 10.1056/NEJMoa012782.
    1. Galimberti V, Cole BF, 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(4):297–305. doi: 10.1016/S1470-2045(13)70035-4.
    1. Giuliano AE, Hunt KK, Ballman KV, 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. Giuliano AE, 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(3):426–432.
    1. Donker M, van Tienhoven G, Straver ME, 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(12):1303–1310. doi: 10.1016/S1470-2045(14)70460-7.
    1. Louis-Sylvestre C, Clough K, Asselain B, et al. Axillary treatment in conservative management of operable breast cancer: dissection or radiotherapy? Results of a randomized study with 15 years of follow-up. J Clin Oncol. 2004;22(1):97–101. doi: 10.1200/JCO.2004.12.108.
    1. Savolt A, Peley G, Polgar C, et al. Eight-year follow up result of the OTOASOR trial: The Optimal Treatment Of the Axilla — Surgery Or Radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: a randomized, single centre, phase III, non-inferiority trial. Eur J Surg Oncol. 2017;43(4):672–679. doi: 10.1016/j.ejso.2016.12.011.
    1. Veronesi U, Orecchia R, Zurrida S, et al. Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy. Ann Oncol. 2005;16(3):383–388. doi: 10.1093/annonc/mdi089.
    1. Bilimoria KY, Bentrem DJ, Hansen NM, et al. 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. doi: 10.1200/JCO.2008.19.5750.
    1. Weber WP, Barry M, Stempel MM, et al. A 10-year trend analysis of sentinel lymph node frozen section and completion axillary dissection for breast cancer: are these procedures becoming obsolete? Ann Surg Oncol. 2012;19(1):225–232. doi: 10.1245/s10434-011-1823-z.
    1. Giuliano AE. Reply to letter: Are the standard tangential breast irradiation fields used in the ACOSOG Z0011 Trial really covering the entire axilla? Ann Surg. 2013;257:1. doi: 10.1097/SLA.0b013e31827ba041.
    1. Jagsi R, Chadha M, Moni J, et al. Radiation field design in the ACOSOG Z0011 (Alliance) Trial. J Clin Oncol. 2014;32(32):3600–3606. doi: 10.1200/JCO.2014.56.5838.
    1. Budach W, Kammers K, Boelke E, Matuschek C. Adjuvant radiotherapy of regional lymph nodes in breast cancer — a meta-analysis of randomized trials. Radiat Oncol. 2013;8:267. doi: 10.1186/1748-717X-8-267.
    1. Poortmans PM, Collette S, Kirkove C, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 2015;373(4):317–327. doi: 10.1056/NEJMoa1415369.
    1. Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373(4):307–316. doi: 10.1056/NEJMoa1415340.
    1. Thorsen LB, Offersen BV, Dano H, et al. DBCG-IMN: a population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. J Clin Oncol. 2016;34(4):314–320. doi: 10.1200/JCO.2015.63.6456.
    1. McGale P, Taylor C, Correa C, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383(9935):2127–2135. doi: 10.1016/S0140-6736(14)60488-8.
    1. Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 2015;26(8):1533–1546. doi: 10.1093/annonc/mdv221.
    1. van Roozendaal LM, de Wilt JH, van Dalen T, et al. The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial (BOOG 2013-07) BMC Cancer. 2015;15:610. doi: 10.1186/s12885-015-1613-2.
    1. Cools-Lartigue J, Sinclair A, Trabulsi N, et al. Preoperative axillary ultrasound and fine-needle aspiration biopsy in the diagnosis of axillary metastases in patients with breast cancer: predictors of accuracy and future implications. Ann Surg Oncol. 2013;20(3):819–827. doi: 10.1245/s10434-012-2609-7.
    1. Gooch Jessica, King Tari A., Eaton Anne, Dengel Lynn, Stempel Michelle, Corben Adriana D., Morrow Monica. The Extent of Extracapsular Extension May Influence the Need for Axillary Lymph Node Dissection in Patients with T1–T2 Breast Cancer. Annals of Surgical Oncology. 2014;21(9):2897–2903. doi: 10.1245/s10434-014-3752-0.
    1. Moorman A. M., Bourez R. L. J. H., Heijmans H. J., Kouwenhoven E. A. Axillary Ultrasonography in Breast Cancer Patients Helps in Identifying Patients Preoperatively with Limited Disease of the Axilla. Annals of Surgical Oncology. 2014;21(9):2904–2910. doi: 10.1245/s10434-014-3674-x.
    1. Pilewskie Melissa, Mautner Starr Koslow, Stempel Michelle, Eaton Anne, Morrow Monica. Does a Positive Axillary Lymph Node Needle Biopsy Result Predict the Need for an Axillary Lymph Node Dissection in Clinically Node-Negative Breast Cancer Patients in the ACOSOG Z0011 Era? Annals of Surgical Oncology. 2015;23(4):1123–1128. doi: 10.1245/s10434-015-4944-y.
    1. van Wely BJ, de Wilt JH, Schout PJ, et al. Ultrasound-guided fine-needle aspiration of suspicious nodes in breast cancer patients; selecting patients with extensive nodal involvement. Breast Cancer Res Treat. 2013;140(1):113–118. doi: 10.1007/s10549-013-2624-9.
    1. Union for International Cancer Control (UICC). TNM Classification of Malignant Tumours. Ed. by Brierley JD, Gospodarowicz MK, Wittekind C. 8th Edition. Oxford, UK ; Hoboken, NJ: John Wiley & Sons, Inc., 2017.
    1. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31(1):103–115. doi: 10.2307/2529712.
    1. Boughey JC, Ballman KV, Le-Petross HT, et al. Identification and resection of clipped node decreases the false-negative rate of sentinel lymph node surgery in patients presenting with node-positive breast cancer (T0-T4, N1-N2) who receive neoadjuvant chemotherapy: results fom ACOSOG Z1071 (Alliance). Ann Surg. 2016;263(4):802-7.
    1. Caudle Abigail S., Yang Wei T., Krishnamurthy Savitri, Mittendorf Elizabeth A., Black Dalliah M., Gilcrease Michael Z., Bedrosian Isabelle, Hobbs Brian P., DeSnyder Sarah M., Hwang Rosa F., Adrada Beatriz E., Shaitelman Simona F., Chavez-MacGregor Mariana, Smith Benjamin D., Candelaria Rosalind P., Babiera Gildy V., Dogan Basak E., Santiago Lumarie, Hunt Kelly K., Kuerer Henry M. Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection. Journal of Clinical Oncology. 2016;34(10):1072–1078. doi: 10.1200/JCO.2015.64.0094.
    1. Donker M, Straver ME, Wesseling J, et al. Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg. 2015;261(2):378–382. doi: 10.1097/SLA.0000000000000558.
    1. Siso Christian, de Torres Juan, Esgueva-Colmenarejo Antonio, Espinosa-Bravo Martin, Rus Neus, Cordoba Octavi, Rodriguez Roberto, Peg Vicente, Rubio Isabel T. Intraoperative Ultrasound-Guided Excision of Axillary Clip in Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Therapy (ILINA Trial) Annals of Surgical Oncology. 2017;25(3):784–791. doi: 10.1245/s10434-017-6270-z.
    1. NCCN Guidelines. . Accessed 06 Apr 2018.
    1. Donker M, Drukker CA, Valdes Olmos RA, et al. Guiding breast-conserving surgery in patients after neoadjuvant systemic therapy for breast cancer: a comparison of radioactive seed localization with the ROLL technique. Ann Surg Oncol. 2013;20(8):2569–2575. doi: 10.1245/s10434-013-2921-x.
    1. Hargreaves AC, Mohamed M, Audisio RA. Intra-operative guidance: methods for achieving negative margins in breast conserving surgery. J Surg Oncol. 2014;110(1):21–25. doi: 10.1002/jso.23645.
    1. S3 Guideline. . Accessed 06 Apr 2018.
    1. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28(8):1700–12.
    1. Senkus E, Kyriakides S, Ohno S, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v8–30. doi: 10.1093/annonc/mdv298.
    1. Brady MJ, Cella DF, Mo F, et al. Reliability and validity of the Functional Assessment of Cancer Therapy-Breast quality-of-life instrument. J Clin Oncol. 1997;15(3):974–986. doi: 10.1200/JCO.1997.15.3.974.
    1. Coster S, Poole K, Fallowfield LJ. The validation of a quality of life scale to assess the impact of arm morbidity in breast cancer patients post-operatively. Breast Cancer Res Treat. 2001;68(3):273–282. doi: 10.1023/A:1012278023233.
    1. Verordnung über klinische Versuche mit Heilmitteln (VKlin) vom 17. Oktober 2001 (Stand am 1. Januar 2008)/Ordonnance sur les essais cliniques de produits thérapeutiques (OClin) du 1 juillet 2004 (Etat le 1er janvier 2008). (). Accessed 06 Apr 2018.
    1. Declaration of Helsinki (as amended in Tokyo, Venice, Hong Kong, Somerset West, Edinburgh and Seoul, and clarified in Washington and Tokyo). 2008, October. ().
    1. HRA. Bundesgesetz über die Forschung am Menschen (Humanforschungsgesetz, HFG) vom 30. September 2011 (Stand am 1. Januar 2014) / Loi fédérale relative à la recherche sur l'être humain (Loi relative à la recherche sur l'être humain, LRH) du 30 septembre 2011 (Etat le 1er janvier 2014), 810.30. In: Goverment, editor.: . Accessed 06 Apr 2018.
    1. Del Bianco P, Zavagno G, Burelli P, et al. Morbidity comparison of sentinel lymph node biopsy versus conventional axillary lymph node dissection for breast cancer patients: results of the sentinella-GIVOM Italian randomised clinical trial. Eur J Surg Oncol. 2008;34(5):508–513. doi: 10.1016/j.ejso.2007.05.017.
    1. Fleissig A, Fallowfield LJ, Langridge CI, et al. Post-operative arm morbidity and quality of life. Results of the ALMANAC randomised trial comparing sentinel node biopsy with standard axillary treatment in the management of patients with early breast cancer. Breast Cancer Res Treat. 2006;95(3):279–293. doi: 10.1007/s10549-005-9025-7.
    1. Dabakuyo TS, Fraisse J, Causeret S, et al. A multicenter cohort study to compare quality of life in breast cancer patients according to sentinel lymph node biopsy or axillary lymph node dissection. Ann Oncol. 2009;20(8):1352–1361. doi: 10.1093/annonc/mdp016.
    1. Directive 2001/20/EC of the European Parliament and of the Council. 2001. . Accessed 06 Apr 2018.
    1. DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013;14(6):500–515. doi: 10.1016/S1470-2045(13)70076-7.
    1. Purushotham AD, Upponi S, Klevesath MB, et al. Morbidity after sentinel lymph node biopsy in primary breast cancer: results from a randomized controlled trial. J Clin Oncol. 2005;23(19):4312–4321. doi: 10.1200/JCO.2005.03.228.
    1. Belmonte R, Garin O, Segura M, Pont A, Escalada F, Ferrer M. Quality-of-life impact of sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer patients. Value Health. 2012;15(6):907–915. doi: 10.1016/j.jval.2012.06.003.
    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 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. Wang Z, Wu LC, Chen JQ. Sentinel lymph node biopsy compared with axillary lymph node dissection in early breast cancer: a meta-analysis. Breast Cancer Res Treat. 2011;129(3):675–689. doi: 10.1007/s10549-011-1665-1.
    1. Kootstra J, Hoekstra-Weebers JE, Rietman H, et al. Quality of life after sentinel lymph node biopsy or axillary lymph node dissection in stage I/II breast cancer patients: a prospective longitudinal study. Ann Surg Oncol. 2008;15(9):2533–2541. doi: 10.1245/s10434-008-9996-9.
    1. De Gournay E, Guyomard A, Coutant C, et al. Impact of sentinel node biopsy on long-term quality of life in breast cancer patients. Br J Cancer. 2013;109(11):2783–2791. doi: 10.1038/bjc.2013.658.
    1. Nesvold IL, Reinertsen KV, Fossa SD, Dahl AA. The relation between arm/shoulder problems and quality of life in breast cancer survivors: a cross-sectional and longitudinal study. J Cancer Surviv. 2011;5(1):62–72. doi: 10.1007/s11764-010-0156-4.
    1. Smith MJ, Gill PG, Wetzig N, et al. Comparing patients’ and clinicians’ assessment of outcomes in a randomised trial of sentinel node biopsy for breast cancer (the RACS SNAC trial) Breast Cancer Res Treat. 2009;117(1):99–109. doi: 10.1007/s10549-008-0202-3.
    1. Aerts PD, De Vries J, Van der Steeg AF, Roukema JA. The relationship between morbidity after axillary surgery and long-term quality of life in breast cancer patients: the role of anxiety. Eur J Surg Oncol. 2011;37(4):344–349. doi: 10.1016/j.ejso.2011.01.016.
    1. Sackey H, Johansson H, Sandelin K, et al. Self-perceived, but not objective lymphoedema is associated with decreased long-term health-related quality of life after breast cancer surgery. Eur J Surg Oncol. 2015;41(4):577–584. doi: 10.1016/j.ejso.2014.12.006.
    1. Eton DT, Cella D, Yost KJ, et al. A combination of distribution- and anchor-based approaches determined minimally important differences (MIDs) for four endpoints in a breast cancer scale. J Clin Epidemiol. 2004;57(9):898–910. doi: 10.1016/j.jclinepi.2004.01.012.
    1. Devoogdt N, Van Kampen M, Geraerts I, Coremans T, Christiaens MR. Lymphoedema Functioning, Disability and Health questionnaire (Lymph-ICF): reliability and validity. Phys Ther. 2011;91(6):944–957. doi: 10.2522/ptj.20100087.
    1. Kohrt HE, Nouri N, Nowels K, Johnson D, Holmes S, Lee PP. Profile of immune cells in axillary lymph nodes predicts disease-free survival in breast cancer. PLoS Med. 2005;2(9):e284. doi: 10.1371/journal.pmed.0020284.
    1. Gupta R, Babb JS, Singh B, et al. The numbers of FoxP3+ lymphocytes in sentinel lymph nodes of breast cancer patients correlate with primary tumor size but not nodal status. Cancer Investig. 2011;29(6):419–425. doi: 10.3109/07357907.2011.585193.
    1. Mansfield AS, Heikkila P, von Smitten K, Vakkila J, Leidenius M. Metastasis to sentinel lymph nodes in breast cancer is associated with maturation arrest of dendritic cells and poor co-localization of dendritic cells and CD8+ T cells. Virchows Arch. 2011;459(4):391–398. doi: 10.1007/s00428-011-1145-3.
    1. Mansfield AS, Heikkila PS, Vaara AT, von Smitten KA, Vakkila JM, Leidenius MH. Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancer. BMC Cancer. 2009;9:231. doi: 10.1186/1471-2407-9-231.
    1. Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol. 2010;28(10):1677–1683. doi: 10.1200/JCO.2009.23.7610.
    1. Solin LJ, Gray R, Goldstein LJ, et al. Prognostic value of biologic subtype and the 21-gene recurrence score relative to local recurrence after breast conservation treatment with radiation for early stage breast carcinoma: results from the Eastern Cooperative Oncology Group E2197 study. Breast Cancer Res Treat. 2012;134(2):683–692. doi: 10.1007/s10549-012-2072-y.
    1. Drukker CA, Elias SG, Nijenhuis MV, et al. Gene expression profiling to predict the risk of locoregional recurrence in breast cancer: a pooled analysis. Breast Cancer Res Treat. 2014;148(3):599–613. doi: 10.1007/s10549-014-3188-z.
    1. Boileau JF, 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(3):258–264. doi: 10.1200/JCO.2014.55.7827.
    1. 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(7):609–618. doi: 10.1016/S1470-2045(13)70166-9.
    1. RISAS Procedure in Node Positive Breast Cancer Following NAC. .
    1. SenTa: Registry Trial to Evaluate the Clinical Utilization of Targeted Axillary Dissection (TAD). . Accessed 06 Apr 2018.
    1. Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005;97(3):188–194. doi: 10.1093/jnci/dji021.
    1. Holmes D, Colfry A, Czerniecki B, et al. Performance and practice guideline for the use of neoadjuvant systemic therapy in the management of breast cancer. Ann Surg Oncol. 2015;22(10):3184–3190. doi: 10.1245/s10434-015-4753-3.
    1. Andic F, Ors Y, Davutoglu R, Baz Cifci S, Ispir EB, Erturk ME. Evaluation of skin dose associated with different frequencies of bolus applications in post-mastectomy three-dimensional conformal radiotherapy. J Exp Clin Cancer Res. 2009;28:41. doi: 10.1186/1756-9966-28-41.
    1. Vu TT, Pignol JP, Rakovitch E, Spayne J, Paszat L. Variability in radiation oncologists’ opinion on the indication of a bolus in post-mastectomy radiotherapy: an international survey. Clin Oncol (R Coll Radiol) 2007;19(2):115–119. doi: 10.1016/j.clon.2006.10.004.
    1. Tieu MT, Graham P, Browne L, Chin YS. The effect of adjuvant postmastectomy radiotherapy bolus technique on local recurrence. Int J Radiat Oncol Biol Phys. 2011;81(3):e165–e171. doi: 10.1016/j.ijrobp.2011.01.002.
    1. Abel S, Renz P, Trombetta M, et al. Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: is bolus ever necessary? Pract Radiat Oncol. 2017;7(3):167–172. doi: 10.1016/j.prro.2016.10.018.
    1. Pignol JP, Vu TT, Mitera G, Bosnic S, Verkooijen HM, Truong P. Prospective evaluation of severe skin toxicity and pain during postmastectomy radiation therapy. Int J Radiat Oncol Biol Phys. 2015;91(1):157–164. doi: 10.1016/j.ijrobp.2014.09.022.
    1. Brosteanu O, Houben P, Ihrig K, et al. Risk analysis and risk adapted on-site monitoring in noncommercial clinical trials. Clin Trials. 2009;6(6):585–596. doi: 10.1177/1740774509347398.
    1. . 2013.
    1. Bartelink H, Maingon P, Poortmans P, et al. Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lancet Oncol. 2015;16(1):47–56. doi: 10.1016/S1470-2045(14)71156-8.
    1. Jones HA, Antonini N, Hart AA, et al. Impact of pathological characteristics on local relapse after breast-conserving therapy: a subgroup analysis of the EORTC boost versus no boost trial. J Clin Oncol. 2009;27(30):4939–4947. doi: 10.1200/JCO.2008.21.5764.
    1. Vrieling C, van Werkhoven E, Maingon P, et al. Prognostic factors for local control in breast cancer after long-term follow-up in the EORTC Boost vs No Boost Trial: a randomized clinical trial. JAMA Oncol. 2017;3(1):42–48. doi: 10.1001/jamaoncol.2016.3031.
    1. Offersen BV, Boersma LJ, Kirkove C, et al. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer. Radiother Oncol. 2015;114(1):3–10. doi: 10.1016/j.radonc.2014.11.030.
    1. Offersen BV, Boersma LJ, Kirkove C, et al. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer, version 1.1. Radiother Oncol. 2016;118(1):205–208. doi: 10.1016/j.radonc.2015.12.027.
    1. Feng M, Moran JM, Koelling T, et al. Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer. Int J Radiat Oncol Biol Phys. 2011;79(1):10–18. doi: 10.1016/j.ijrobp.2009.10.058.
    1. Prescribing, Recording, and Reporting Intensity-Modulated Photon-Beam Therapy (IMRT) (ICRU Report 83). .
    1. The SKAGEN Trial 1: moderately hypofractionated loco-regional adjuvant radiation therapy of early breast cancer combined with a simultaneous integrated boost in patients with an indication for boost: DBCG HYPO II, a randomised clinically controlled trial. . Accessed 06 Apr 2018.
    1. Landin J, Weber WP. Lymph node surgery—Stepwise retirement for the breast surgeon? Breast Care (Basel) 2016;11(4):282–286. doi: 10.1159/000448697.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다