{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T08:46:19Z","timestamp":1766133979663},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T00:00:00Z","timestamp":1584662400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T00:00:00Z","timestamp":1584662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Surg Oncol"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Despite the potential for residual lymph node metastases after a negative or positive sentinel lymph node biopsy (SLNB), breast cancer patients rarely experience regional recurrences (RRs). This study aimed to quantify the effects of nonsurgical treatments on RR incidence among SLNB-negative (SLNB N0) breast cancer patients.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>All primary SLNB N0-staged breast cancer patients with a diagnosis between 2005 and 2008 and 5-year follow-up data on recurrences were selected from the Netherlands Cancer Registry. The cumulative incidence function (CIF) for RR was calculated as the first event at 5\u00a0years, taking into account any other first-event (local or distant recurrence, contralateral breast cancer, or death) as competing risk. Cox regression analysis was used to model the cause-specific hazard of RR developing as the first event to quantify the effect of adjuvant systemic therapy and whole-breast radiotherapy (RT) on RR incidence at 5\u00a0years.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The study included 13,512 patients. Of these patients, 162 experienced an RR. The CIF of RR at 5\u00a0years was 1.3% (95% confidence interval [CI], 1.1\u20131.5%), whereas the CIFs for death and other events were 4.4% and 9.5%, respectively. Cox regression analysis showed hazard ratios (HRs) of 0.46 (95% CI 0.33\u20130.64), 0.31 (95% CI 0.18\u20130.55), and 0.40 (95% CI 0.24\u20130.67) respectively for patients treated by RT as a routine part of breast-conserving therapy (BCT), chemotherapy, and hormonal therapy.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>RT as routine part of BCT, chemotherapy, and hormonal therapy independently exerted a mitigating effect on the risk for the development of RR. The three methods at least halved the risk.<\/jats:p>\n<\/jats:sec>","DOI":"10.1245\/s10434-020-08356-2","type":"journal-article","created":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T16:03:50Z","timestamp":1584720230000},"page":"3402-3411","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Quantifying the Mitigating Effects of Whole-Breast Radiotherapy and Systemic Treatments on Regional Recurrence Incidence Among Breast Cancer Patients"],"prefix":"10.1245","volume":"27","author":[{"given":"Julia E. C.","family":"van Steenhoven","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Kuijer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa C.","family":"van Maaren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marleen","family":"Roos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sjoerd G.","family":"Elias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"van Diest","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Siesling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjolein L.","family":"Smidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liesbeth J.","family":"Boersma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thijs","family":"van Dalen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,20]]},"reference":[{"key":"8356_CR1","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1006\/jsre.1999.5629","volume":"84","author":"DM Miltenburg","year":"1999","unstructured":"Miltenburg DM, Miller C, Karamlou TB, Brunicardi FC. Meta-analysis of sentinel lymph node biopsy in breast cancer. J Surg Res. 1999;84:138\u201342.","journal-title":"J Surg Res."},{"key":"8356_CR2","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/cncr.21568","volume":"106","author":"T Kim","year":"2006","unstructured":"Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis. Cancer. 2006;106:4\u201316.","journal-title":"Cancer."},{"key":"8356_CR3","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s10549-010-1210-7","volume":"125","author":"MJ Pepels","year":"2011","unstructured":"Pepels MJ, Vestjens JH, de Boer M, et al. Safety of avoiding routine use of axillary dissection in early-stage breast cancer: a systematic review. Breast Cancer Res Treat. 2011;125:301\u201313.","journal-title":"Breast Cancer Res Treat."},{"key":"8356_CR4","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1016\/j.ejso.2008.01.034","volume":"34","author":"IM van der Ploeg","year":"2008","unstructured":"van der Ploeg IM, Nieweg OE, van Rijk MC, Vald\u00e9s 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;34:1277\u201384.","journal-title":"Eur J Surg Oncol."},{"key":"8356_CR5","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1002\/bjs.7360","volume":"98","author":"BJ van Wely","year":"2010","unstructured":"van Wely BJ, Teerenstra S, Schinagl DA, Aufenacker TJ, de Wilt JH, Strobbe LJ. Systematic review of the effect of external beam radiotherapy to the breast on axillary recurrence after negative sentinel lymph node biopsy. Br J Surg. 2010;98:326\u201333.","journal-title":"Br J Surg."},{"key":"8356_CR6","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1001\/jama.2011.90","volume":"305","author":"AE Giuliano","year":"2011","unstructured":"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;305:569\u201375.","journal-title":"JAMA."},{"key":"8356_CR7","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1001\/jama.2017.11470","volume":"318","author":"E Armando","year":"2017","unstructured":"Armando E, Giuliano AE, Ballman KV, et al, Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017;318:918\u201326.","journal-title":"JAMA"},{"key":"8356_CR8","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1016\/S1470-2045(14)70460-7","volume":"15","author":"M Donker","year":"2014","unstructured":"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;15:1303\u201310.","journal-title":"Lancet Oncol."},{"key":"8356_CR9","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1245\/s10434-018-6940-5","volume":"26","author":"MM Roos","year":"2019","unstructured":"Roos MM, van Steenhoven JEC, Aalders KC, et al. Regional recurrence risk following a negative sentinel node procedure does not approximate the false-negative rate of the sentinel node procedure in breast cancer patients not receiving radiotherapy or systemic treatment. Ann Surg Oncol. 2019;26:372\u20138.","journal-title":"Ann Surg Oncol."},{"key":"8356_CR10","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1056\/NEJMoa020128","volume":"347","author":"B Fisher","year":"2002","unstructured":"Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. 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;347:567\u201375.","journal-title":"N Engl J Med."},{"key":"8356_CR11","unstructured":"van der Heiden-van der Loo M. Defining the Quality of Surgical Breast Cancer Care. Utrecht University 2013, Utrecht, the Netherlands."},{"key":"8356_CR12","doi-asserted-by":"publisher","first-page":"dju288","DOI":"10.1093\/jnci\/dju288","volume":"106","author":"M Moossdorff","year":"2014","unstructured":"Moossdorff M, van Roozendaal LM, Strobbe LJ, et al. Maastricht Delphi consensus on event definitions for classification of recurrence in breast cancer research. J Natl Cancer Inst. 2014;106:dju288. https:\/\/doi.org\/10.1093\/jnci\/dju288.","journal-title":"J Natl Cancer Inst."},{"key":"8356_CR13","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1002\/bjs.6348","volume":"95","author":"BJ van Wely","year":"2008","unstructured":"van Wely BJ, Smidt ML, de Kievit IM, Wauters CA, Strobbe LJ. False-negative sentinel lymph node biopsy. Br J Surg. 2008:95:1352\u20135.","journal-title":"Br J Surg."},{"key":"8356_CR14","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.ejso.2012.04.016","volume":"38","author":"BJ van Wely","year":"2012","unstructured":"van Wely BJ, van Wildenberg FJH, Gobardhan P, et al. Axillary recurrences after sentinel lymph node biopsy: a multicentre analysis and follow-up of sentinel lymph node-negative breast cancer patients. EJSO. 2012;38:925\u201331.","journal-title":"EJSO."},{"key":"8356_CR15","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1016\/S0140-6736(11)61629-2","volume":"378","author":"Early Breast Cancer Trialists\u2019 Collaborative Group, et al.","year":"2011","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378:1707\u201316.","journal-title":"Lancet."},{"key":"8356_CR16","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1016\/j.ijrobp.2007.08.064","volume":"70","author":"R Rabinovitch","year":"2008","unstructured":"Rabinovitch R, Ballonoff A, Newman F, Finlayson C. Evaluation of breast sentinel lymph node coverage by standard radiation therapy fields. Int J Radiat Oncol Biol Phys. 2008;70:1468\u201371.","journal-title":"Int J Radiat Oncol Biol Phys."},{"key":"8356_CR17","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/S0002-9610(02)01013-9","volume":"184","author":"MA Chung","year":"2002","unstructured":"Chung MA, DiPetrillo T, Hernandez S, Masko G, Wazer D, Cady B. Treatment of the axilla by tangential breast radiotherapy in women with invasive breast cancer. Am J Surg. 2002;184:401\u20132.","journal-title":"Am J Surg."},{"key":"8356_CR18","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.ijrobp.2004.06.006","volume":"61","author":"DR Reed","year":"2005","unstructured":"Reed DR, Lindsley SK, Mann GN, et al, Axillary lymph node dose with tangential breast irradiation. Int J Radiat Oncol Biol Phys. 2005;61:358\u201364.","journal-title":"Int J Radiat Oncol Biol Phys."},{"key":"8356_CR19","doi-asserted-by":"publisher","first-page":"3824","DOI":"10.1245\/s10434-015-4413-7","volume":"22","author":"M Van Roozendaal","year":"2015","unstructured":"Van Roozendaal M, Schipper RJ, Smit L, et al. Three-dimensional breast radiotherapy and the elective radiation dose at the sentinel lymph node site in breast cancer, Ann Surg Oncol. 2015;22:3824\u201330.","journal-title":"Ann Surg Oncol."},{"key":"8356_CR20","doi-asserted-by":"publisher","first-page":"409","DOI":"10.5301\/tj.5000482","volume":"102","author":"MC De Santis","year":"2016","unstructured":"De Santis MC, Bonfantini F, Dispinzieri M, et al. Axillary coverage by whole-breast irradiation in 1 to 2 positive sentinel lymph nodes in breast cancer patients. Tumori. 2016;102:409\u201313.","journal-title":"Tumori."},{"key":"8356_CR21","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.radonc.2015.12.027","volume":"118","author":"BV Offersen","year":"2016","unstructured":"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;118:205\u20138.","journal-title":"Radiother Oncol."},{"key":"8356_CR22","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1016\/S0140-6736(05)66544-0","volume":"365","author":"Early Breast Cancer Trialists\u2019 Collaborative Group (EBCTCG)","year":"2005","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet London England. 2005;365:1687\u2013717.","journal-title":"Lancet London England."},{"key":"8356_CR23","first-page":"1","volume":"339","author":"Early Breast Cancer Trialists\u2019 Collaborative Group","year":"1992","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Lancet London, England. 1992;339:1\u201315.","journal-title":"Lancet London, England."},{"key":"8356_CR24","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.ejca.2016.05.010","volume":"63","author":"KC Aalders","year":"2016","unstructured":"Aalders KC, van Bommel ACM, van Dalen T, et al. Contemporary risk of local and regional recurrence and contralateral breast cancer in patients treated for primary breast cancer. Eur J Cancer. 2016;63:118\u201326.","journal-title":"Eur J Cancer."},{"key":"8356_CR25","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/S0140-6736(05)74803-0","volume":"365","author":"A Howell","year":"2005","unstructured":"Howell A, Cuzick M, Baum M, et al. Results of the ATAC (arimidex, tamoxifen, alone or in combination) trial after completion of 5\u00a0years\u2019 adjuvant treatment for breast cancer. Lancet. 2005;365:60\u20132.","journal-title":"Lancet."},{"key":"8356_CR26","doi-asserted-by":"publisher","first-page":"3686","DOI":"10.1200\/JCO.2005.10.517","volume":"23","author":"EP Mamounas","year":"2005","unstructured":"Mamounas EP, Bryant J, Lembersky B, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP-B28. J Clin Oncol. 2005;23:3686\u201396.","journal-title":"J Clin Oncol."},{"key":"8356_CR27","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1002\/cncr.11745","volume":"98","author":"M Baum","year":"2003","unstructured":"Baum M, Buzdar A, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (arimidex, tamoxifen alone or in combination) trial efficacy and safety update analyses. Cancer. 2003;98:1802\u201310.","journal-title":"Cancer."},{"key":"8356_CR28","doi-asserted-by":"publisher","first-page":"2303","DOI":"10.1056\/NEJMoa043681","volume":"352","author":"M Martin","year":"2005","unstructured":"Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 352:2303\u201313.","journal-title":"N Engl J Med."},{"key":"8356_CR29","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.radonc.2008.05.002","volume":"90","author":"M Mannino","year":"2009","unstructured":"Mannino M, Yarnold JR. Local relapse rates are falling after breast-conserving surgery and systemic therapy for early breast cancer: can radiotherapy ever be safely withheld? Radiother Oncol. 2009;90:14\u201322.","journal-title":"Radiother Oncol."},{"key":"8356_CR30","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1245\/s10434-014-4321-2","volume":"22","author":"RM Lanning","year":"2015","unstructured":"Lanning RM, Morrow M, Riaz N, et al. The effect of adjuvant trastuzumab on locoregional recurrence of human epidermal growth factor receptor 2-positive breast cancer treated with mastectomy. Ann Surg Oncol. 2015;22:2517\u201325.","journal-title":"Ann Surg Oncol."},{"key":"8356_CR31","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1002\/cncr.26484","volume":"118","author":"AP Kiess","year":"2012","unstructured":"Kiess AP, McArthur HL, Mahoney K, et al. Adjuvant trastuzumab reduces locoregional recurrence in woman who receive breast conservation therapy for lymph node-negative, human epidermal growth factor receptor 2-positive breast cancer. Cancer. 2012;118:1982\u20138.","journal-title":"Cancer."},{"key":"8356_CR32","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1093\/annonc\/mdx308","volume":"28","author":"G Curigliano","year":"2017","unstructured":"Curigliano G, Burstein HJ, Winter PE, 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;28:1700\u201312.","journal-title":"Ann Oncol."},{"key":"8356_CR33","doi-asserted-by":"publisher","first-page":"2294","DOI":"10.1016\/j.ejca.2013.02.031","volume":"49","author":"RW Blamey","year":"2013","unstructured":"Blamey RW, Bates T, Chetty U, et al. Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial. Eur J Cancer. 2013;49:2294\u2013302.","journal-title":"Eur J Cancer."},{"key":"8356_CR34","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1200\/JCO.2012.45.2615","volume":"31","author":"KS Hughes","year":"2013","unstructured":"Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70\u00a0years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31:2382\u20137.","journal-title":"J Clin Oncol."},{"key":"8356_CR35","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/S1470-2045(14)71221-5","volume":"16","author":"IH Kunkler","year":"2015","unstructured":"Kunkler IH, Williams LJ, Jack WJ, Cameron DA, Dixon JM. Breast-conserving surgery with or without irradiation in women aged 65\u00a0years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol. 2015;16:266\u201373.","journal-title":"Lancet Oncol."}],"container-title":["Annals of Surgical Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1245\/s10434-020-08356-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1245\/s10434-020-08356-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1245\/s10434-020-08356-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T00:28:13Z","timestamp":1616200093000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1245\/s10434-020-08356-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,20]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["8356"],"URL":"https:\/\/doi.org\/10.1245\/s10434-020-08356-2","relation":{},"ISSN":["1068-9265","1534-4681"],"issn-type":[{"value":"1068-9265","type":"print"},{"value":"1534-4681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,20]]},"assertion":[{"value":"14 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2020","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Marjolein L. Smidt discloses a financial relationship with Servier Pharma for microbiome research. The remaining authors have no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure"}}]}}