Breast Cancer Research and Treatment

, Volume 161, Issue 1, pp 173–179 | Cite as

Breast-cancer subtype, age, and lymph node status as predictors of local recurrence following breast-conserving therapy

  • Lior Z. Braunstein
  • Alphonse G. Taghian
  • Andrzej Niemierko
  • Laura Salama
  • Alexander Capuco
  • Jennifer R. Bellon
  • Julia S. Wong
  • Rinaa S. Punglia
  • Shannon M. MacDonald
  • Jay R. HarrisEmail author
Brief Report



Advances in breast-conserving therapy (BCT) have yielded local control rates comparable or superior to those of mastectomy. In this study, we sought to identify contemporary risk factors associated with local recurrence (LR) following BCT.


We analyzed a multi-institutional cohort of 2233 consecutive breast-cancer patients who underwent BCT between 1998 and 2007. Patients were stratified by age, biologic subtype (as approximated by receptor status and tumor grade), and nodal status. Patients who received HER2/neu-directed therapy were excluded due to variations in practice over the study period. The association of clinicopathologic features with LR was evaluated using Cox proportional hazards regression models.


With a median follow-up of 106 months, 69 LRs (3 %) were observed. On univariate analysis, LR was associated with non-luminal-A subtype (hazard ratio [HR] for luminal-B = 3.01, HER2 = 6.29, triple-negative [TNBC] = 4.72; p < 0.001 each), younger age (HR of oldest vs. youngest quartile = 0.43; p = 0.005), regional nodal involvement (HR for 4–9 involved nodes = 3.04; >9 nodes = 5.82; p < 0.01 for each), positive margins (HR 2.43; p = 0.005), and high grade (HR 5.37; p < 0.001). Multivariate Cox regression demonstrated that non-luminal-A subtypes (HR for luminal-B = 2.64, HER2 = 5.42, TNBC = 4.32; p < 0.001 for each), younger age (HR for age >50 = 0.56; p = 0.01), and nodal disease (HR 1.06 per involved node; p < 0.004) were associated with LR. The 8-year risk of LR was 2.8 % for node-negative patients and 5.2 % for node-positive patients.


BCT yields favorable outcomes for the large majority of patients, although increased LR was observed among those with non-luminal-A subtypes, younger age, and increasing lymph node involvement. Risk factors for LR after BCT appear to be converging with those after mastectomy in the current era.


Local recurrence Breast-conserving therapy Lumpectomy Radiotherapy Lymph node Age Subtype 


Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

The study was approved by the institutional review boards of the participating institutions and the requirement for informed consent was waived due to the retrospective nature of this analysis.


  1. 1.
    Nguyen PL, Taghian AG, Katz MS et al (2008) Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 26:2373–2378. doi: 10.1200/JCO.2007.14.4287 CrossRefPubMedGoogle Scholar
  2. 2.
    Arvold ND, Taghian AG, Niemierko A et al (2011) Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol 29:3885–3891. doi: 10.1200/JCO.2011.36.1105 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Overgaard M, Jensen MB, Overgaard J et al (1999) Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 353:1641–1648. doi: 10.1016/S0140-6736(98)09201-0 CrossRefPubMedGoogle Scholar
  4. 4.
    Overgaard M, Hansen P (1997) Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med 337(14):949–955CrossRefPubMedGoogle Scholar
  5. 5.
    Recht A, Edge SB, Solin LJ et al (2001) Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19:1539–1569PubMedGoogle Scholar
  6. 6.
    Mamounas EP, Anderson SJ, Dignam JJ et al (2012) Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol 30:3960–3966. doi: 10.1200/JCO.2011.40.8369 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Taghian A, Jeong J-H, Mamounas E et al (2004) Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project Randomized C. J Clin Oncol 22:4247–4254. doi: 10.1200/JCO.2004.01.042 CrossRefPubMedGoogle Scholar
  8. 8.
    EBCTCG (2014) 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 383:2127–2135. doi: 10.1016/S0140-6736(14)60488-8 CrossRefGoogle Scholar
  9. 9.
    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. doi: 10.1016/S0140-6736(05)67887-7 CrossRefPubMedGoogle Scholar
  10. 10.
    Metzger-Filho O, Sun Z, Viale G et al (2013) Patterns of recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from International Breast Cancer Study Group trials VIII and IX. J Clin Oncol 31:3083–3090. doi: 10.1200/JCO.2012.46.1574 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Braunstein LZ, Brock JE, Chen YH et al (2015) Invasive lobular carcinoma of the breast: local recurrence after breast-conserving therapy by subtype approximation and surgical margin. Breast Cancer Res Treat 149:555–564. doi: 10.1007/s10549-015-3273-y CrossRefPubMedGoogle Scholar
  12. 12.
    Truong PT, Sadek BT, Lesperance MF et al (2014) Is biological subtype prognostic of locoregional recurrence risk in women with pT1-2N0 breast cancer treated with mastectomy? Int J Radiat Oncol Biol Phys 88:57–64. doi: 10.1016/j.ijrobp.2013.09.024 CrossRefPubMedGoogle Scholar
  13. 13.
    Wallgren a (2003) Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group trials I through VII. J Clin Oncol 21:1205–1213. doi: 10.1200/JCO.2003.03.130 CrossRefPubMedGoogle Scholar
  14. 14.
    Jagsi R, Raad RA, Goldberg S et al (2005) Locoregional recurrence rates and prognostic factors for failure in node-negative patients treated with mastectomy: implications for postmastectomy radiation. Int J Radiat Oncol Biol Phys 62:1035–1039. doi: 10.1016/j.ijrobp.2004.12.014 CrossRefPubMedGoogle Scholar
  15. 15.
    Darby S, McGale P, Correa C et al (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 378:1707–1716. doi: 10.1016/S0140-6736(11)61629-2 CrossRefPubMedGoogle Scholar
  16. 16.
    Truong PT, Lesperance M, Culhaci A et al (2005) Patient subsets with T1–T2, node-negative breast cancer at high locoregional recurrence risk after mastectomy. Int J Radiat Oncol Biol Phys 62:175–182. doi: 10.1016/j.ijrobp.2004.09.013 CrossRefPubMedGoogle Scholar
  17. 17.
    NCCN (2015) NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Breast Cancer Version 32015:1–187Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Lior Z. Braunstein
    • 1
    • 4
  • Alphonse G. Taghian
    • 2
  • Andrzej Niemierko
    • 2
  • Laura Salama
    • 2
  • Alexander Capuco
    • 3
  • Jennifer R. Bellon
    • 3
  • Julia S. Wong
    • 3
  • Rinaa S. Punglia
    • 3
  • Shannon M. MacDonald
    • 2
  • Jay R. Harris
    • 3
    Email author
  1. 1.Harvard Radiation Oncology ProgramBostonUSA
  2. 2.Department of Radiation OncologyMassachusetts General HospitalBostonUSA
  3. 3.Departments of Radiation OncologyDana Farber Cancer Institute/Brigham and Women’s HospitalBostonUSA
  4. 4.Department of Radiation OncologyMemorial Sloan Kettering Cancer CenterNew YorkUSA

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