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The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02–6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (≤40: HR: 1.79; 95%-CI: 1.28–2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35–1.84) and node positivity (HR: 2.00; 95%-CI: 1.74–2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55–0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy.

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References

  1. Fisher B, Anderson S, Fisher ER et al (1991) Significance of ipsilateral breast tumour recurrence after lumpectomy. Lancet 338:327–331. doi:10.1016/0140-6736(91)90475-5

    Article  PubMed  CAS  Google Scholar 

  2. Van Dongen JA, Voogd AC, Fentiman IS et al (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 92:1143–1150. doi:10.1093/jnci/92.14.1143

    Article  PubMed  Google Scholar 

  3. Fisher B, Anderson S, Bryant J et al (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 347:1233–1241. doi:10.1056/NEJMoa022152

    Article  PubMed  Google Scholar 

  4. Veronesi U, Cascinelli N, Mariani L et al (2002) Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227–1232. doi:10.1056/NEJMoa020989

    Article  PubMed  Google Scholar 

  5. Arriagada R, Le MG, Guinebretiere JM, Dunant A, Rochard F, Tursz T (2003) Late local recurrences in a randomised trial comparing conservative treatment with total mastectomy in early breast cancer patients. Ann Oncol 14:1617–1622. doi:10.1093/annonc/mdg452

    Article  PubMed  CAS  Google Scholar 

  6. Early Breast Cancer Trialists’ Collaborative Group (1995) Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials. Early Breast Cancer Trialists’ Collaborative Group. N Engl J Med 333:1444–1455. doi:10.1056/NEJM199511303332202

    Article  Google Scholar 

  7. Voogd AC, Nielsen M, Peterse JL et al (2001) Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials. J Clin Oncol 19:1688–1697

    PubMed  CAS  Google Scholar 

  8. Kroman N, Holtveg H, Wohlfahrt J et al (2004) Effect of breast-conserving therapy versus radical mastectomy on prognosis for young women with breast carcinoma. Cancer 100:688–693. doi:10.1002/cncr.20022

    Article  PubMed  Google Scholar 

  9. Lu WL, Jansen L, Post WJ, Bonnema J, Van de Velde JC, De Bock GH (2008) Impact on survival of early detection of isolated breast recurrences after the primary treatment for breast cancer: a meta-analysis. Breast Cancer Res Treat [Epub ahead of print]

  10. Clarke M, Collins R, Darby S et al (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366:2087–2106

    PubMed  CAS  Google Scholar 

  11. Van Dongen J, Bartelink H, Fentiman IS et al (1992) Randomized clinical trial to assess the value of breast-conserving therapy in stage I and II breast cancer, EORTC 10801 trial. J Natl Cancer Inst Monogr 11:15–18

    PubMed  Google Scholar 

  12. Van Dongen JA, Bartelink H, Fentiman IS et al (1992) Factors influencing local relapse and survival and results of salvage treatment after breast-conserving therapy in operable breast cancer: EORTC trial 10801, breast conservation compared with mastectomy in TNM stage I and II breast cancer. Eur J Cancer 28A:801–805. doi:10.1016/0959-8049(92)90118-L

    Article  PubMed  Google Scholar 

  13. Clahsen PC, Van de Velde C, Julien JP et al (1996) Improved local control and disease-free survival after perioperative chemotherapy for early-stage breast cancer. A European Organization for Research and Treatment of Cancer, Breast Cancer Cooperative Group Study. J Clin Oncol 14:745–753

    PubMed  CAS  Google Scholar 

  14. Elkhuizen PH, Van Slooten HJ, Clahsen PC et al (2000) High local recurrence risk after breast-conserving therapy in node-negative premenopausal breast cancer patients is greatly reduced by one course of perioperative chemotherapy: a European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group Study. J Clin Oncol 18:1075–1083

    PubMed  CAS  Google Scholar 

  15. Van der Hage J, Van deVelde C, Julien JP et al (2001) Improved survival after one course of perioperative chemotherapy in early breast cancer patients. Long-term results from the European Organization for Research and Treatment of Cancer (EORTC) trial 10854. Eur J Cancer 37:2184–2193. doi:10.1016/S0959-8049(01)00294-5

    Article  PubMed  Google Scholar 

  16. Van der Hage J, Van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 19:4224–4237

    PubMed  Google Scholar 

  17. Broet P, De la Rochefordiere A, Scholl SM et al (1999) Analyzing prognostic factors in breast cancer using a multistate model. Breast Cancer Res Treat 54:83–89. doi:10.1023/A:1006197524405

    Article  PubMed  CAS  Google Scholar 

  18. Putter H, Fiocco M, Geskus RB (2007) Tutorial in biostatistics: competing risks and multi-state models. Stat Med 26:2389–2430. doi:10.1002/sim.2712

    Article  PubMed  CAS  Google Scholar 

  19. Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW (2007) An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat 107:309–330. doi:10.1007/s10549-007-9556-1

    Article  PubMed  CAS  Google Scholar 

  20. Arriagada R, Rutqvist LE, Johansson H, Kramar A, Rotstein S (2008) Predicting distant dissemination in patients with early breast cancer. Acta Oncol 47:1113–1121. doi:10.1080/02841860701829661

    Article  PubMed  Google Scholar 

  21. Coulombe G, Tyldesley S, Speers C et al (2007) Is mastectomy superior to breast-conserving treatment for young women? Int J Radiat Oncol Biol Phys 67:1282–1290. doi:10.1016/j.ijrobp.2006.11.032

    PubMed  Google Scholar 

  22. Bollet MA, Sigal-Zafrani B, Mazeau V et al (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 82:272–280. doi:10.1016/j.radonc.2007.01.001

    Article  PubMed  Google Scholar 

  23. Van Nes JG, Van de Velde CJ (2006) The preferred treatment for young women with breast cancer—mastectomy versus breast conservation. Breast 15(Suppl 2):S3–S10. doi:10.1016/S0960-9776(07)70009-7

    PubMed  Google Scholar 

  24. Kemperman H, Borger J, Hart A, Peterse H, Bartelink H, Van Dongen J (1995) Prognostic factors for survival after breast conserving therapy for stage I and II breast cancer. The role of local recurrence. Eur J Cancer 31A:690–698. doi:10.1016/0959-8049(94)00526-B

    Article  PubMed  CAS  Google Scholar 

  25. Touboul E, Buffat L, Belkacemi Y et al (1999) Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys 43:25–38. doi:10.1016/S0360-3016(98)00365-4

    PubMed  CAS  Google Scholar 

  26. Cowen D, Jacquemier J, Houvenaeghel G, Viens P, Puig B, Bardou VJ, Resbeut M, Maraninchi D (1998) Local and distant recurrence after conservative management of “very low-risk” breast cancer are dependent events: a 10-year follow-up. Int J Radiat Oncol Biol Phys 41:801–807. doi:10.1016/S0360-3016(98)00144-8

    PubMed  CAS  Google Scholar 

  27. Engel J, Eckel R, Aydemir U, Aydemir S, Kerr J, Schlesinger-Raab A, Dirschedl P, Hölzel D (2003) Determinants and prognoses of locoregional and distant progression in breast cancer. Int J Radiat Oncol Biol Phys 55:1186–1195. doi:10.1016/S0360-3016(02)04476-0

    PubMed  Google Scholar 

  28. Elkhuizen PH, Hermans J, Leer JW, Van de Vijver MJ (2001) Late local recurrences with high mitotic count and early local recurrences following breast-conserving therapy are associated with increased risk on distant metastasis. Int J Radiat Oncol Biol Phys 50:387–396. doi:10.1016/S0360-3016(01)01469-9

    Article  PubMed  CAS  Google Scholar 

  29. Fourquet A, Campana F, Zafrani B et al (1989) Prognostic factors of breast recurrence in the conservative management of early breast cancer: a 25-year follow-up. Int J Radiat Oncol Biol Phys 17:719–725

    PubMed  CAS  Google Scholar 

  30. Van der Sangen M, Van de Poll-Franse L, Roumen RM et al (2006) The prognosis of patients with local recurrence more than 5 years after breast conservation therapy for invasive breast carcinoma. Eur J Surg Oncol 32:34–38. doi:10.1016/j.ejso.2005.10.005

    Article  PubMed  Google Scholar 

  31. Punglia RS, Morrow M, Winer EP, Harris JR (2007) Local therapy and survival in breast cancer. N Engl J Med 356:2399–2405. doi:10.1056/NEJMra065241

    Article  PubMed  CAS  Google Scholar 

  32. Halsted WS (1907) The results of radical operations for the cure of carcinoma of the breast. Ann Surg 46:1–19

    Article  PubMed  CAS  Google Scholar 

  33. Fisher B (1980) Laboratory and clinical research in breast cancer—a personal adventure: the David A. Karnofsky Memorial Lecture. Cancer Res 40:3863–3874

    PubMed  CAS  Google Scholar 

  34. Ragaz J, Jackson SM, Le N et al (1997) Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 337:956–962. doi:10.1056/NEJM199710023371402

    Article  PubMed  CAS  Google Scholar 

  35. Nielsen HM, Overgaard M, Grau C, Jensen AR, Overgaard J (2006) Loco-regional recurrence after mastectomy in high-risk breast cancer—risk and prognosis. An analysis of patients from the DBCG 82 b&c randomization trials. Radiother Oncol 79:147–155. doi:10.1016/j.radonc.2006.04.006

    Article  PubMed  Google Scholar 

  36. Bartelink H, Horiot JC, Poortmans PM et al (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 25:3259–3265. doi:10.1200/JCO.2007.11.4991

    Article  PubMed  Google Scholar 

  37. Livi L, Stefanacci M, Scoccianti S et al (2007) Adjuvant hypofractionated radiation therapy for breast cancer after conserving surgery. Clin Oncol (R Coll Radiol) 19:120–124. doi:10.1016/j.clon.2006.11.006

    CAS  Google Scholar 

  38. Van der Leest M, Evers L, Van der Sangen MJ et al (2007) The safety of breast-conserving therapy in patients with breast cancer aged ≤40 years. Cancer 109:1957–1964. doi:10.1002/cncr.22639

    Article  PubMed  Google Scholar 

  39. Vrieling C, Collette L, Fourquet A et al (2003) Can patient-, treatment- and pathology-related characteristics explain the high local recurrence rate following breast-conserving therapy in young patients? Eur J Cancer 39:932–944. doi:10.1016/S0959-8049(03)00123-0

    Article  PubMed  CAS  Google Scholar 

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Correspondence to G. H. de Bock or C. J. van de Velde.

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de Bock, G.H., Putter, H., Bonnema, J. et al. The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model. Breast Cancer Res Treat 117, 401–408 (2009). https://doi.org/10.1007/s10549-008-0300-2

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  • DOI: https://doi.org/10.1007/s10549-008-0300-2

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