Breast Cancer Research and Treatment

, Volume 167, Issue 3, pp 751–759 | Cite as

Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery

  • Rinaa S. Punglia
  • Wei Jiang
  • Stuart R. Lipsitz
  • Melissa E. Hughes
  • Stuart J. Schnitt
  • Michael J. Hassett
  • Larissa Nekhlyudov
  • Ninah Achacoso
  • Stephen Edge
  • Sara H. Javid
  • Joyce C. Niland
  • Richard L. Theriault
  • Yu-Ning Wong
  • Laurel A. Habel



A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions.


Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC).


Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5–12%), 23% (95% CI 13–32%), and 51% (95% CI 26–75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well.


This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.


Ductal carcinoma in situ Recurrence risk Risk score 



We would like to thank Luana Acton for her help with the Kaiser patient database, Jane C. Weeks for her guidance with the NCCN dataset, and Deborah Schrag for her time and suggestions.


This work was supported by Contract No. HHSA29020050016I from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, as part of the Developing Evidence to Inform Decisions About Effectiveness program. The views expressed in this article are those of the authors, and no official endorsement by AHRQ or the US Department of Health and Human Services is intended or should be inferred. This work was also supported by Grant No. CA89393 from the National Cancer Institute to the Dana-Farber Cancer Institute, Grant No. R01 CA 81302 to Kaiser Permanente Northern California, and Grant no. 2U19CA079689 to Group Health Cooperative (Habel, Project Leader).

Compliance with ethical standards

Conflict of interest

None of the authors have any conflict of interest related to the subject matter presented. Author Wong is currently employed by Janssen Scientific Affairs.

Ethical approval

This article is a retrospective review of patient data, and has received IRB approval for data collection from each of the institutions providing patient data and from DFCI/HCC IRB for the analysis. This article does not contain any studies with animals or human participants performed by any of the authors.


  1. 1.
    Sumner WE 3rd, Koniaris LG, Snell SE, Spector S, Powell J, Avisar E, Moffat F, Livingstone AS, Franceschi D (2007) Results of 23,810 cases of ductal carcinoma-in-situ. Ann Surg Oncol 14(5):1638–1643CrossRefPubMedGoogle Scholar
  2. 2.
    Bijker N, Meijnen P, Peterse JL, Bogaerts J, Van Hoorebeeck I, Julien JP, Gennaro M, Rouanet P, Avril A, Fentiman IS et al (2006) Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853–a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol 24(21):3381–3387CrossRefPubMedGoogle Scholar
  3. 3.
    Fisher B, Land S, Mamounas E, Dignam J, Fisher ER, Wolmark N (2001) Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience. Semin Oncol 28(4):400–418CrossRefPubMedGoogle Scholar
  4. 4.
    Emdin SO, Granstrand B, Ringberg A, Sandelin K, Arnesson LG, Nordgren H, Anderson H, Garmo H, Holmberg L, Wallgren A (2006) SweDCIS: radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening. Acta Oncol 45(5):536–543CrossRefPubMedGoogle Scholar
  5. 5.
    Houghton J, George WD, Cuzick J, Duggan C, Fentiman IS, Spittle M (2003) Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet 362(9378):95–102CrossRefPubMedGoogle Scholar
  6. 6.
    Fisher B, Dignam J, Wolmark N, Wickerham DL, Fisher ER, Mamounas E, Smith R, Begovic M, Dimitrov NV, Margolese RG et al (1999) Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet 353(9169):1993–2000CrossRefPubMedGoogle Scholar
  7. 7.
    Fisher ER, Dignam J, Tan-Chiu E, Costantino J, Fisher B, Paik S, Wolmark N (1999) Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma. Cancer 86(3):429–438CrossRefPubMedGoogle Scholar
  8. 8.
    Solin LJ, Fourquet A, Vicini FA, Haffty B, Taylor M, McCormick B, McNeese M, Pierce LJ, Landmann C, Olivotto IA et al (2001) Mammographically detected ductal carcinoma in situ of the breast treated with breast-conserving surgery and definitive breast irradiation: long-term outcome and prognostic significance of patient age and margin status. Int J Radiat Oncol Biol Phys 50(4):991–1002CrossRefPubMedGoogle Scholar
  9. 9.
    Cutuli B, Cohen-Solal-le Nir C, de Lafontan B, Mignotte H, Fichet V, Fay R, Servent V, Giard S, Charra-Brunaud C, Lemanski C et al (2002) Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centers’ experience. Int J Radiat Oncol Biol Phys 53(4):868–879CrossRefPubMedGoogle Scholar
  10. 10.
    Bijker N, Peterse JL, Duchateau L, Julien JP, Fentiman IS, Duval C, Di Palma S, Simony-Lafontaine J, de Mascarel I, van de Vijver MJ (2001) Risk factors for recurrence and metastasis after breast-conserving therapy for ductal carcinoma-in-situ: analysis of European Organization for Research and Treatment of Cancer Trial 10853. J Clin Oncol 19(8):2263–2271CrossRefPubMedGoogle Scholar
  11. 11.
    Vicini FA, Kestin LL, Goldstein NS, Chen PY, Pettinga J, Frazier RC, Martinez AA (2000) Impact of young age on outcome in patients with ductal carcinoma-in-situ treated with breast-conserving therapy. J Clin Oncol 18(2):296–306CrossRefPubMedGoogle Scholar
  12. 12.
    Vicini FA, Recht A (2002) Age at diagnosis and outcome for women with ductal carcinoma-in-situ of the breast: a critical review of the literature. J Clin Oncol 20(11):2736–2744CrossRefPubMedGoogle Scholar
  13. 13.
    Jhingran A, Kim JS, Buchholz TA, Katz A, Strom EA, Hunt KK, Sneige N, McNeese MD (2002) Age as a predictor of outcome for women with DCIS treated with breast-conserving surgery and radiation: The University of Texas M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 54(3):804–809CrossRefPubMedGoogle Scholar
  14. 14.
    Gilleard O, Goodman A, Cooper M, Davies M, Dunn J (2008) The significance of the Van Nuys prognostic index in the management of ductal carcinoma in situ. World J Surg Oncol 6:61CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    MacAusland SG, Hepel JT, Chong FK, Galper SL, Gass JS, Ruthazer R, Wazer DE (2007) An attempt to independently verify the utility of the Van Nuys Prognostic Index for ductal carcinoma in situ. Cancer 110(12):2648–2653CrossRefPubMedGoogle Scholar
  16. 16.
    Silverstein MJ (2003) The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am J Surg 186(4):337–343CrossRefPubMedGoogle Scholar
  17. 17.
    McCormick B, Winter K, Hudis C, Kuerer HM, Rakovitch E, Smith BL, Sneige N, Moughan J, Shah A, Germain I et al (2015) RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation. J Clin Oncol 33(7):709–715CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Wong JS, Kaelin CM, Troyan SL, Gadd MA, Gelman R, Lester SC, Schnitt SJ, Sgroi DC, Silver BJ, Harris JR et al (2006) Prospective study of wide excision alone for ductal carcinoma in situ of the breast. J Clin Oncol 24(7):1031–1036CrossRefPubMedGoogle Scholar
  19. 19.
    Hughes L, Wang M, Page D, Gray R, Solin LJ, Davidson NE, Lowen M, Ingle JN, Wood W (2006) Five year results of intergroup study E5194: local excision alone (without radiation treatment) for selected patients with ductal carcinoma in situ (DCIS). Breast Cancer Res Treat 100(Suppl 1):S15Google Scholar
  20. 20.
    Baxter NN, Virnig BA, Durham SB, Tuttle TM (2004) Trends in the treatment of ductal carcinoma in situ of the breast. J Natl Cancer Inst 96(6):443–448CrossRefPubMedGoogle Scholar
  21. 21.
    Smith BD, Haffty BG, Buchholz TA, Smith GL, Galusha DH, Bekelman JE, Gross CP (2006) Effectiveness of radiation therapy in older women with ductal carcinoma in situ. J Natl Cancer Inst 98(18):1302–1310CrossRefPubMedGoogle Scholar
  22. 22.
    Rakovitch E, Pignol JP, Chartier C, Hanna W, Kahn H, Wong J, Mai V, Paszat L (2007) The management of ductal carcinoma in situ of the breast: a screened population-based analysis. Breast Cancer Res Treat 101(3):335–347CrossRefPubMedGoogle Scholar
  23. 23.
    Yen TW, Kuerer HM, Ottesen RA, Rouse L, Niland JC, Edge SB, Theriault RL, Weeks JC (2007) Impact of randomized clinical trial results in the national comprehensive cancer network on the use of tamoxifen after breast surgery for ductal carcinoma in situ. J Clin Oncol 25(22):3251–3258CrossRefPubMedGoogle Scholar
  24. 24.
    Allred DC, Anderson SJ, Paik S, Wickerham DL, Nagtegaal ID, Swain SM, Mamounas EP, Julian TB, Geyer CE Jr, Costantino JP et al (2012) Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: a study based on NSABP Protocol B-24. J Clin Oncol. PubMedPubMedCentralGoogle Scholar
  25. 25.
    Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J, Sanchez H, Jimenez C, Stewart K, Chew K et al (2010) Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J Natl Cancer Inst 102(9):627–637CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Rudloff U, Jacks LM, Goldberg JI, Wynveen CA, Brogi E, Patil S, Van Zee KJ (2010) Nomogram for predicting the risk of local recurrence after breast-conserving surgery for ductal carcinoma in situ. J Clin Oncol 28(23):3762–3769CrossRefPubMedGoogle Scholar
  27. 27.
    Solin LJ, Gray R, Baehner FL, Butler SM, Hughes LL, Yoshizawa C, Cherbavaz DB, Shak S, Page DL, Sledge GW Jr et al (2013) A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst 105(10):701–710CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Fleming ID, Henson CJ et al (eds) (1997) American Joint Committee on Cancer. AJCC cancer staging handbook, 5th edn. Lipincott, Williams, and Wilkins, PhiladelphiaGoogle Scholar
  29. 29.
    Weeks JC (1997) Outcomes assessment in the NCCN. Oncology (Huntingt) 11(11A):137–140Google Scholar
  30. 30.
    Weeks J (1999) Outcomes assessment in the NCCN: 1998 update. National Comprehensive Cancer Network. Oncology (Huntingt) 13(5A):69–71Google Scholar
  31. 31.
    Niland JC (1998) NCCN Internet-based data system for the conduct of outcomes research. Oncology (Huntingt) 12(11A):142–146Google Scholar
  32. 32.
    Niland JC (2000) NCCN outcomes research database: data collection via the Internet. Oncology (Huntingt) 14(11A):100–103Google Scholar
  33. 33.
    Greene FL, Page DL, Fleming ID et al (eds) (2002) American Joint Commission on Cancer. AJCC cancer staging handbook, 6th edn. Springer, ChicagoGoogle Scholar
  34. 34.
  35. 35.
    Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA (1982) Evaluating the yield of medical tests. J Am Med Assoc 247(18):2543–2546CrossRefGoogle Scholar
  36. 36.
    Habel LA, Capra AM, Achacoso NS, Janga A, Acton L, Puligandla B, Quesenberry CP Jr (2010) Mammographic density and risk of second breast cancer after ductal carcinoma in situ. Cancer Epidemiol Biomark Prev 19(10):2488–2495CrossRefGoogle Scholar
  37. 37.
    Collins LC, Achacoso N, Haque R, Nekhlyudov L, Fletcher SW, Quesenberry CP Jr, Schnitt SJ, Habel LA (2013) Risk factors for non-invasive and invasive local recurrence in patients with ductal carcinoma in situ. Breast Cancer Res Treat 139(2):453–460CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Bollen KA, Jackman RW (1990) Regression diagnostics: an expository treatment of outliers and influential cases. In: Fox J, Long JS (eds) Modern methods of data analysis. Sage, Newbury Park, pp 257–291Google Scholar
  39. 39.
    Punglia RS, Schnitt SJ, Weeks JC (2013) Treatment of ductal carcinoma in situ after excision: would a prophylactic paradigm be more appropriate? J Natl Cancer Inst 105(20):1527–1533CrossRefPubMedGoogle Scholar
  40. 40.
    Io Medicine (2009) Initial national priorities for comparative effectiveness research. National Academies Press, Washington, DCGoogle Scholar
  41. 41.
    Partridge A, Adloff K, Blood E, Dees EC, Kaelin C, Golshan M, Ligibel J, de Moor JS, Weeks J, Emmons K et al (2008) Risk perceptions and psychosocial outcomes of women with ductal carcinoma in situ: longitudinal results from a cohort study. J Natl Cancer Inst 100(4):243–251CrossRefPubMedGoogle Scholar
  42. 42.
    Welch HG, Passow HJ (2014) Quantifying the benefits and harms of screening mammography. JAMA Intern Med 174(3):448–454CrossRefPubMedGoogle Scholar
  43. 43.
    Yi M, Meric-Bernstam F, Kuerer HM, Mittendorf EA, Bedrosian I, Lucci A, Hwang RF, Crow JR, Luo S, Hunt KK (2012) Evaluation of a breast cancer nomogram for predicting risk of ipsilateral breast tumor recurrences in patients with ductal carcinoma in situ after local excision. J Clin Oncol 30(6):600–607CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Collins LC, Achacoso N, Haque R, Nekhlyudov L, Quesenberry CP Jr, Schnitt SJ, Habel LA, Fletcher SW (2015) Risk prediction for local breast cancer recurrence among women with DCIS treated in a community practice: a nested, case-control study. Ann Surg Oncol 22(Suppl 3):S502–508CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Rinaa S. Punglia
    • 1
  • Wei Jiang
    • 2
  • Stuart R. Lipsitz
    • 2
  • Melissa E. Hughes
    • 3
  • Stuart J. Schnitt
    • 4
  • Michael J. Hassett
    • 3
  • Larissa Nekhlyudov
    • 5
  • Ninah Achacoso
    • 6
  • Stephen Edge
    • 7
  • Sara H. Javid
    • 8
  • Joyce C. Niland
    • 9
  • Richard L. Theriault
    • 10
  • Yu-Ning Wong
    • 11
  • Laurel A. Habel
    • 6
    • 12
  1. 1.Department of Radiation OncologyDana-Farber Cancer InstituteBostonUSA
  2. 2.Department of Surgery, Center for Surgery and Public HealthBrigham and Women’s HospitalBostonUSA
  3. 3.Division of Population Sciences, Department of Medical Oncology, Center for Outcomes and Policy ResearchDana-Farber Cancer InstituteBostonUSA
  4. 4.Department of PathologyBeth Israel Deaconess Medical CenterBostonUSA
  5. 5.Department of MedicineBrigham & Women’s Hospital, Harvard Medical SchoolBostonUSA
  6. 6.Division of ResearchKaiser Permanente Northern CaliforniaOaklandUSA
  7. 7.Department of Surgery, Roswell Park Cancer InstituteUniversity at BuffaloBuffaloUSA
  8. 8.Department of SurgeryUniversity of Washington Medical Center, University of Washington School of MedicineSeattleUSA
  9. 9.Department of Diabetes and Cancer Discovery ScienceCity of Hope, Comprehensive Cancer CenterDuarteUSA
  10. 10.Department of Breast Medical OncologyThe University of Texas, M. D. Anderson Cancer CenterHoustonUSA
  11. 11.Department of Medical OncologyFox Chase Cancer CenterPhiladelphiaUSA
  12. 12.Department of Health Research and PolicyStanford University School of MedicineStanfordUSA

Personalised recommendations