Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery
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.
KeywordsDuctal 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.
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.
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.
- 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
- 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
- 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
- 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.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.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
- 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
- 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
- 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
- 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.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. https://doi.org/10.1200/JCO.2010.34.0141 PubMedPubMedCentralGoogle Scholar
- 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
- 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.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.Weeks JC (1997) Outcomes assessment in the NCCN. Oncology (Huntingt) 11(11A):137–140Google Scholar
- 30.Weeks J (1999) Outcomes assessment in the NCCN: 1998 update. National Comprehensive Cancer Network. Oncology (Huntingt) 13(5A):69–71Google Scholar
- 31.Niland JC (1998) NCCN Internet-based data system for the conduct of outcomes research. Oncology (Huntingt) 12(11A):142–146Google Scholar
- 32.Niland JC (2000) NCCN outcomes research database: data collection via the Internet. Oncology (Huntingt) 14(11A):100–103Google Scholar
- 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.Firth’s modification for maximum likelihood estimation. http://support.sas.com/documentation/cdl/en/statug/63033/HTML/default/viewer.htm#statug_phreg_a0000000685.htm
- 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
- 40.Io Medicine (2009) Initial national priorities for comparative effectiveness research. National Academies Press, Washington, DCGoogle Scholar
- 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
- 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.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