Breast Cancer Research and Treatment

, Volume 156, Issue 2, pp 391–400 | Cite as

Very low local recurrence rates after breast-conserving therapy: analysis of 8485 patients treated over a 28-year period

  • S. C. J. Bosma
  • F. van der Leij
  • E. van Werkhoven
  • H. Bartelink
  • J. Wesseling
  • S. Linn
  • E. J. Rutgers
  • M. J. van de Vijver
  • P. H. M. ElkhuizenEmail author


The purpose of this study was to study the impact of changes in clinical practice on outcome in patients treated with breast-conserving therapy (BCT) over a period of 28 years. Patients with early invasive breast cancer, who were treated with BCT at the Netherlands Cancer Institute between 1980 and 2008, were studied. Clinical characteristics, treatment and outcome were compared between groups (1980–1987; 1988–1998; 1999–2008). The main endpoint analyzed was ipsilateral breast tumor recurrence (IBTR). 8485 patients with a median follow-up of 9 years (IQR 6–14 years) were analyzed. The cumulative 5- and 10-year IBTR incidences were, respectively, 2 and 5 % for the whole cohort and 4 and 9 % in patients ≤40 years. Young age was a significant risk factor for IBTR in multivariable analysis. IBTR-free interval was better for patients who received a RT boost (HR 0.65) or systemic therapy (HR 0.52). In later years, patients less often received a boost and more often underwent adjuvant systemic treatment. 761 patients (9.0 %) underwent a re-excision; the tumor resection margins were tumor free for 85 %. In later years (1999–2008), 89 % of patients had a tumor-free margin. The margin status of invasive carcinoma did not influence IBTR, DM rate, or OS. Between 1980 and 2008, locoregional control after BCT remained stable with low IBTR rates, even in young patients. These good results were achieved under the policy of accepting close or focally positive margins, indicating this is a safe approach. The results of this study may help in lowering the re-excision rates, which are high in many centers.


Breast cancer Breast-conserving therapy Tumor-free margins Local control 



We thank the Medical Registry staff and Stella Mook for providing baseline data.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

Supplementary material

10549_2016_3732_MOESM1_ESM.docx (24 kb)
Supplementary material 1 (DOCX 23 kb)


  1. 1.
    Litiere S, Werutsky G, Fentiman IS, Rutgers E, Christiaens MR, Van Limbergen E, Baaijens MH, Bogaerts J, Bartelink H (2012) Breast conserving therapy versus mastectomy for stage I-II breast cancer: 20 year follow-up of the EORTC 10801 phase 3 randomised trial. Lancet Oncol 13(4):412–419. doi: 10.1016/S1470-2045(12)70042-6 CrossRefPubMedGoogle Scholar
  2. 2.
    Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N (2002) Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347(16):1233–1241. doi: 10.1056/NEJMoa022152 CrossRefPubMedGoogle Scholar
  3. 3.
    Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E (2002) Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347(16):1227–1232. doi: 10.1056/NEJMoa020989 CrossRefPubMedGoogle Scholar
  4. 4.
    van Dongen JA, Voogd AC, Fentiman IS, Legrand C, Sylvester RJ, Tong D, van der Schueren E, Helle PA, van Zijl K, Bartelink H (2000) Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 92(14):1143–1150CrossRefPubMedGoogle Scholar
  5. 5.
    Poortmans P, Aznar M, Bartelink H (2012) Quality indicators for breast cancer: revisiting historical evidence in the context of technology changes. Semin Rad Oncol 22(1):29–39. doi: 10.1016/j.semradonc.2011.09.007 CrossRefGoogle Scholar
  6. 6.
    Harlan LC, Clegg LX, Abrams J, Stevens JL, Ballard-Barbash R (2006) Community-based use of chemotherapy and hormonal therapy for early-stage breast cancer: 1987-2000. J Clin Oncol 24(6):872–877. doi: 10.1200/JCO.2005.03.5840 CrossRefPubMedGoogle Scholar
  7. 7.
    Sukel MP, van de Poll-Franse LV, Nieuwenhuijzen GA, Vreugdenhil G, Herings RM, Coebergh JW, Voogd AC (2008) Substantial increase in the use of adjuvant systemic treatment for early stage breast cancer reflects changes in guidelines in the period 1990-2006 in the southeastern Netherlands. Eur J Cancer 44(13):1846–1854. doi: 10.1016/j.ejca.2008.06.001 CrossRefPubMedGoogle Scholar
  8. 8.
    Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N (2014) Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 32(33):3744–3752. doi: 10.1200/JCO.2014.55.5730 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Early Breast Cancer Trialists’ Collaborative G, Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444. doi: 10.1016/S0140-6736(11)61625-5 CrossRefGoogle Scholar
  10. 10.
    Cabioglu N, Hunt KK, Buchholz TA, Mirza N, Singletary SE, Kuerer HM, Babiera GV, Ames FC, Sahin AA, Meric-Bernstam F (2005) Improving local control with breast-conserving therapy: a 27-year single-institution experience. Cancer 104(1):20–29. doi: 10.1002/cncr.21121 CrossRefPubMedGoogle Scholar
  11. 11.
    van der Leest M, Evers L, van der Sangen MJ, Poortmans PM, van de Poll-Franse LV, Vulto AJ, Nieuwenhuijzen GA, Brenninkmeijer SJ, Creemers GJ, Voogd AC (2007) The safety of breast-conserving therapy in patients with breast cancer aged < or = 40 years. Cancer 109(10):1957–1964. doi: 10.1002/cncr.22639 CrossRefPubMedGoogle Scholar
  12. 12.
    Louwman WJ, Voogd AC, van Dijck JA, Nieuwenhuijzen GA, Ribot J, Pruijt JF, Coebergh JW (2008) On the rising trends of incidence and prognosis for breast cancer patients diagnosed 1975-2004: a long-term population-based study in southeastern Netherlands. Cancer Causes Control 19(1):97–106. doi: 10.1007/s10552-007-9075-8 CrossRefPubMedGoogle Scholar
  13. 13.
    Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R (2011) 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 378(9804):1707–1716. doi: 10.1016/S0140-6736(11)61629-2 CrossRefPubMedGoogle Scholar
  14. 14.
    Richtlijn ‘Behandeling van het Mammacarcinoom’ – Utrecht – Kwaliteitsinstituut voor de Gezondheidszorg CBO/Vereniging van de Integrale Kankercentra en Nationaal Borstkanker Overleg Nederland (NABON).
  15. 15.
    Borger J, Kemperman H, Hart A, Peterse H, van Dongen J, Bartelink H (1994) Risk factors in breast-conservation therapy. J Clin Oncol 12(4):653–660PubMedGoogle Scholar
  16. 16.
    Poortmans PM, Collette L, Bartelink H, Struikmans H, Van den Bogaert WF, Fourquet A, Jager JJ, Hoogenraad W, Muller RP, Dubois JB, Bolla M, Van Der Hulst M, Warlam-Rodenhuis CC, Pierart M, Horiot JC, Oncology ER, Breast Cancer G (2008) The addition of a boost dose on the primary tumour bed after lumpectomy in breast conserving treatment for breast cancer. A summary of the results of EORTC 22881-10882 “boost versus no boost” trial. Cancer Radiother 12(6–7):565–570. doi: 10.1016/j.canrad.2008.07.014 CrossRefPubMedGoogle Scholar
  17. 17.
    Bontenbal M, Nortier JW, Beex LV, Bakker P, Hupperets PS, Nooij MA, van Veelen H, Vreugdenhil G, Richel DJ, Blijham GH (2000) Adjuvant systemic therapy for patients with resectable breast cancer: guideline from the Dutch National Breast Cancer Platform and the Dutch Society for Medical Oncology. Ned Tijdschr Geneeskd 144(21):984–989PubMedGoogle Scholar
  18. 18.
    Bartelink H, Maingon P, Poortmans P, Weltens C, Fourquet A, Jager J, Schinagl D, Oei B, Rodenhuis C, Horiot JC, Struikmans H, Van Limbergen E, Kirova Y, Elkhuizen P, Bongartz R, Miralbell R, Morgan D, Dubois JB, Remouchamps V, Mirimanoff RO, Collette S, Collette L, European Organisation for R, Treatment of Cancer Radiation O, Breast Cancer G (2015) 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 16(1):47–56. doi: 10.1016/S1470-2045(14)71156-8 CrossRefPubMedGoogle Scholar
  19. 19.
    Elkhuizen PH, van de Vijver MJ, Hermans J, Zonderland HM, van de Velde CJ, Leer JW (1998) Local recurrence after breast-conserving therapy for invasive breast cancer: high incidence in young patients and association with poor survival. Int J Radiat Oncol Biol Phys 40(4):859–867CrossRefPubMedGoogle Scholar
  20. 20.
    Bollet MA, Sigal-Zafrani B, Mazeau V, Savignoni A, de la Rochefordiere A, Vincent-Salomon A, Salmon R, Campana F, Kirova YM, Dendale R, Fourquet A (2007) Age remains the first prognostic factor for loco-regional breast cancer recurrence in young (<40 years) women treated with breast conserving surgery first. Radiother Oncol 82(3):272–280. doi: 10.1016/j.radonc.2007.01.001 CrossRefPubMedGoogle Scholar
  21. 21.
    Vrieling C, Collette L, Fourquet A, Hoogenraad WJ, Horiot JC, Jager JJ, Bing Oei S, Peterse HL, Pierart M, Poortmans PM, Struikmans H, Van den Bogaert W, Bartelink H, Eortc Radiotherapy BCG (2003) Can patient-, treatment- and pathology-related characteristics explain the high local recurrence rate following breast-conserving therapy in young patients? Eur J Cancer 39(7):932–944CrossRefPubMedGoogle Scholar
  22. 22.
    Bartelink H, Bourgier C, Elkhuizen P (2012) Has partial breast irradiation by IORT or brachytherapy been prematurely introduced into the clinic? Radiother Oncol 104(2):139–142. doi: 10.1016/j.radonc.2012.07.010 CrossRefPubMedGoogle Scholar
  23. 23.
    van Laar C, van der Sangen MJ, Poortmans PM, Nieuwenhuijzen GA, Roukema JA, Roumen RM, Tjan-Heijnen VC, Voogd AC (2013) Local recurrence following breast-conserving treatment in women aged 40 years or younger: trends in risk and the impact on prognosis in a population-based cohort of 1143 patients. Eur J Cancer. doi: 10.1016/j.ejca.2013.05.030 PubMedGoogle Scholar
  24. 24.
    Bouganim N, Tsvetkova E, Clemons M, Amir E (2013) Evolution of sites of recurrence after early breast cancer over the last 20 years: implications for patient care and future research. Breast Cancer Res Treat 139(2):603–606. doi: 10.1007/s10549-013-2561-7 CrossRefPubMedGoogle Scholar
  25. 25.
    Ernst MF, Voogd AC, Coebergh JW, Poortmans PM, Roukema JA (2004) Using loco-regional recurrence as an indicator of the quality of breast cancer treatment. Eur J Cancer 40(4):487–493. doi: 10.1016/j.ejca.2003.10.014 CrossRefPubMedGoogle Scholar
  26. 26.
    Mook S, Van’t Veer LJ, Rutgers EJ, Ravdin PM, van de Velde AO, van Leeuwen FE, Visser O, Schmidt MK (2011) Independent prognostic value of screen detection in invasive breast cancer. J Natl Cancer Inst 103(7):585–597. doi: 10.1093/jnci/djr043 CrossRefPubMedGoogle Scholar
  27. 27.
    van der Heiden-Loo M, de Munck L, Visser O, Westenend PJ, van Dalen T, Menke MB, Rutgers EJ, Peeters PH (2012) Variation between hospitals in surgical margins after first breast-conserving surgery in the Netherlands. Breast Cancer Res Treat 131(2):691–698. doi: 10.1007/s10549-011-1809-3 CrossRefGoogle Scholar
  28. 28.
    Jones HA, Antonini N, Hart AA, Peterse JL, Horiot JC, Collin F, Poortmans PM, Oei SB, Collette L, Struikmans H, Van den Bogaert WF, Fourquet A, Jager JJ, Schinagl DA, Warlam-Rodenhuis CC, Bartelink H (2009) 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 27(30):4939–4947. doi: 10.1200/JCO.2008.21.5764 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Houssami N, Morrow M (2014) Margins in breast conservation: a clinician’s perspective and what the literature tells us. J Surg Oncol 110(1):2–7. doi: 10.1002/jso.23594 CrossRefPubMedGoogle Scholar
  30. 30.
    Morrow M, Jagsi R, Alderman AK, Griggs JJ, Hawley ST, Hamilton AS, Graff JJ, Katz SJ (2009) Surgeon recommendations and receipt of mastectomy for treatment of breast cancer. J Am Med Assoc 302(14):1551–1556. doi: 10.1001/jama.2009.1450 CrossRefGoogle Scholar
  31. 31.
    McCahill LE, Single RM, Aiello Bowles EJ, Feigelson HS, James TA, Barney T, Engel JM, Onitilo AA (2012) Variability in reexcision following breast conservation surgery. J Am Med Assoc 307(5):467–475. doi: 10.1001/jama.2012.43 CrossRefGoogle Scholar
  32. 32.
    Chagpar AB, Killelea BK, Tsangaris TN, Butler M, Stavris K, Li F, Yao X, Bossuyt V, Harigopal M, Lannin, Pusztai L, Horowitz NR (2015) A randomized, controlled trial of cavity shave margins in breast cancer. N Engl J Med. doi: 10.1056/NEJMoa1504473 Google Scholar
  33. 33.
    van der Heiden-Loo M, Siesling S, Wouters MW, van Dalen T, Rutgers EJ, Peeters PH (2015) The value of ipsilateral breast tumor recurrence as a quality indicator: hospital variation in the Netherlands. Ann Surg Oncol. doi: 10.1245/s10434-015-4626-9 Google Scholar
  34. 34.
    Moran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, Klimberg S, Chavez-MacGregor M, Freedman G, Houssami N, Johnson PL, Morrow M (2014) Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Int J Radiat Oncol Biol Phys 88(3):553–564. doi: 10.1016/j.ijrobp.2013.11.012 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Wapnir IL, Anderson SJ, Mamounas EP, Geyer CE Jr, Jeong JH, Tan-Chiu E, Fisher B, Wolmark N (2006) Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol 24(13):2028–2037. doi: 10.1200/JCO.2005.04.3273 CrossRefPubMedGoogle Scholar
  36. 36.
    Anderson SJ, Wapnir I, Dignam JJ, Fisher B, Mamounas EP, Jeong JH, Geyer CE Jr, Wickerham DL, Costantino JP, Wolmark N (2009) Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol 27(15):2466–2473. doi: 10.1200/JCO.2008.19.8424 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Gaffney DK, Tsodikov A, Wiggins CL (2003) Diminished survival in patients with inner versus outer quadrant breast cancers. J Clin Oncol 21(3):467–472CrossRefPubMedGoogle Scholar
  38. 38.
    Bentzon N, During M, Rasmussen BB, Mouridsen H, Kroman N (2008) Prognostic effect of estrogen receptor status across age in primary breast cancer. Int J Cancer 122(5):1089–1094. doi: 10.1002/ijc.22892 CrossRefPubMedGoogle Scholar
  39. 39.
    Bartelink H, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, Jager JJ, Hoogenraad WJ, Oei SB, Warlam-Rodenhuis CC, Pierart M, Collette L (2007) Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol 25(22):3259–3265. doi: 10.1200/JCO.2007.11.4991 CrossRefPubMedGoogle Scholar
  40. 40.
    Blamey RW, Bates T, Chetty U, Duffy SW, Ellis IO, George D, Mallon E, Mitchell MJ, Monypenny I, Morgan DA, Macmillan RD, Patnick J, Pinder SE (2013) Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: british Association of Surgical Oncology (BASO) II trial. Eur J Cancer 49(10):2294–2302. doi: 10.1016/j.ejca.2013.02.031 CrossRefPubMedGoogle Scholar
  41. 41.
    Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP, Wood WC (2013) Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol 31(19):2382–2387. doi: 10.1200/JCO.2012.45.2615 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Sanders ME, Scroggins T, Ampil FL, Li BD (2007) Accelerated partial breast irradiation in early-stage breast cancer. J Clin Oncol 25(8):996–1002. doi: 10.1200/JCO.2006.09.7436 CrossRefPubMedGoogle Scholar
  43. 43.
    Drukker CA, Elias SG, Nijenhuis MV, Wesseling J, Bartelink H, Elkhuizen P, Fowble B, Whitworth PW, Patel RR, de Snoo FA, van’t Veer LJ, Beitsch PD, Rutgers EJ (2014) Gene expression profiling to predict the risk of locoregional recurrence in breast cancer: a pooled analysis. Breast Cancer Res Treat 148(3):599–613. doi: 10.1007/s10549-014-3188-z CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Radiation OncologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Statistics DepartmentThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  3. 3.Department of PathologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  4. 4.Department of Medical OncologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  5. 5.Department of PathologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  6. 6.Department of SurgeryThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  7. 7.Department of PathologyAcademical Medical CenterAmsterdamThe Netherlands

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