Breast Cancer Research and Treatment

, Volume 174, Issue 2, pp 307–313 | Cite as

Leveraging the variable natural history of ductal carcinoma in situ (DCIS) to select optimal therapy

  • Kristin E. RojasEmail author
  • Thais A. Fortes
  • Patrick I. Borgen



Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal carcinoma. The authors sought to discuss the evidence suggesting that not all DCIS will progress to invasive disease if left untreated.


Four lines of evidence align to suggest that not all of this in-situ disease progresses to invasive cancer: its prevalence on screening mammography, studies of missed diagnoses, incidental findings in autopsy specimens, and large retrospective reviews of those treated with excision alone.


A clearer understanding of the variable history of DCIS coupled with advances in genomic profiling of the disease holds the promise of reducing widespread over-treatment of this non-invasive cancer. Additionally, identification of higher risk of recurrence subsets may select patients for whom more aggressive treatment may be appropriate.


Ductal carcinoma in situ DCIS Breast cancer Breast cancer screening Breast cancer genomic profiling Oncotype DCIS Oncotype Dx 


Compliance with ethical standards

Conflict of interest

Dr. Rojas and Dr. Fortes declare that they have no conflicts of interest. Dr. Borgen has received a speaker honorarium from Company Genomic Health, Inc.


  1. 1.
    Francis A, Thomas J, Fallowfield L, Wallis M (2015) Addressing overtreatment of screen detected DCIS: the LORIS trial. Eur J Cancer 51:2296–2303CrossRefGoogle Scholar
  2. 2.
    Ernster V, Barclay J (1997) Increases in ductal carcinoma in situ (DCIS) of the breast in relation to mammography: a dilemma. J Natl Cancer Inst Monogr 22:151–156CrossRefGoogle Scholar
  3. 3.
    Wellings S, Jensen H (1973) On the origin and progression of ductal carcinoma in the human breast. J Natl Cancer Inst 50:1111–1118CrossRefGoogle Scholar
  4. 4.
    Page D, Dupont W, Rogers L, Jensen R et al (1995) Continued local recurrence of carcinoma 15–25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy. Cancer 76:1197–1200CrossRefGoogle Scholar
  5. 5.
    Dupont W, Page D (1985) Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 312:146–151CrossRefGoogle Scholar
  6. 6.
    Tavassoli F (1998) Ductal carcinoma in situ: introduction of the concept of ductal intraepithelial neoplasia. Mod Pathol 11:140–154Google Scholar
  7. 7.
    McCaffery K, Nickel B, Moynihan R, Hersch J (2015) How different terminology for ductal carcinoma in situ impacts women’s concern and treatment preferences: a randomised comparison within a national community survey. BMJ Open 5:e008094CrossRefGoogle Scholar
  8. 8.
    Bartlett J, Nofech-Moses S, Rakovitch E (2014) Ductal carcinoma in situ of the breast: can biomarkers improve current management? Clin Chem 60:60–67CrossRefGoogle Scholar
  9. 9.
    Thompson A, Brennan K, Cox A, Gee J et al (2008) Evaluation of the current knowledge limitations in breast cancer research: a gap analysis. Breast Cancer Res 10:R26CrossRefGoogle Scholar
  10. 10.
    Leonard G, Swain S (2004) Ductal carcinoma in situ, complexities and challenges. J Natl Cancer Inst 96:906–920CrossRefGoogle Scholar
  11. 11.
    Aubele M, Mattis A, Zitzelsberger H, Walch A et al (1999) Intratumoral heterogeneity in breast carcinoma revealed by laser-microdissection and comparative genomic hybridization. Cancer Genet Cytogenet 110:94–102CrossRefGoogle Scholar
  12. 12.
    Aubele M, Cummings M, Walch A, Zitzelsberger H (2000) Heterogeneous chromosomal aberrations in intraductal breast lesions adjacent to invasive carcinoma. Anal Cell Pathol 20:17–24CrossRefGoogle Scholar
  13. 13.
    Aubele M, Mattis A, Zitzelsberger H, Walch A (2000) Extensive ductal carcinoma in situ with small foci of invasive ductal carcinoma: evidence of genetic resemblance by CGH. Int J Cancer 85:82–86CrossRefGoogle Scholar
  14. 14.
    Foschini M, Morandi L, Leonardi E, Flamminio F (2013) Genetic clonal mapping of in situ and invasive ductal carcinoma indicates the field cancerization phenomenon in the breast. Hum Pathol 44:1310–1319CrossRefGoogle Scholar
  15. 15.
    Luzzi V, Holtschlag V, Watson MA (2001) Expression profiling of ductal carcinoma in situ by laser capture microdissection and high-density oligonucleotide arrays. Am J Pathol 158:2005–2010CrossRefGoogle Scholar
  16. 16.
    Reis-Filho J, Lakhani S (2003) The diagnosis and management of pre-invasive breast disease: genetic alterations in pre-invasive lesions. Breast Cancer Res 5:313–319CrossRefGoogle Scholar
  17. 17.
    Werner M, Mattis A, Aubele M, Cummings A et al (1999) 20q13.2 amplification in intraductal hyperplasia adjacent to in situ and invasive ductal carcinoma of the breast. Virchows Arch 435:469–472CrossRefGoogle Scholar
  18. 18.
    Westbury C, Reis-Filho J, Dexter T, Mahler-Araujo B et al (2009) Genome-wide transcriptomic profiling of microdissected human breast tissue reveals differential expression of KIT (c-Kit, CD117) and oestrogen receptor-alpha (ERalpha) in response to therapeutic radiation. J Pathol 219:131–140CrossRefGoogle Scholar
  19. 19.
    Ghazani A, Arneson N, Warren K, Pintilie M et al (2007) Genomic alterations in sporadic synchronous primary breast cancer using array and metaphase comparative genomic hybridization. Neoplasia 9:511–520CrossRefGoogle Scholar
  20. 20.
    Hernandez L, Wilkerson P, Lambros M, Campion-Flora A (2012) Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection. J Pathol 227:42–52CrossRefGoogle Scholar
  21. 21.
    Kim S, Jung S, Kim M, Baek I et al (2015) Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer. Oncotarget 6:7597–7607Google Scholar
  22. 22.
    Kroigard A, Larsen M, Laenkholm A, Knoop A et al (2015) Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis. Oncotarget 6:5634–5649CrossRefGoogle Scholar
  23. 23.
    Koboldt D, Steinberg K, Larson D, Wilson R et al (2013) The next-generation sequencing revolution and its impact on genomics. Cell 155:27–38CrossRefGoogle Scholar
  24. 24.
    Newburger D, Kashef-Haghighi D, Weng Z, Salari R et al (2013) Genome evolution during progression to breast cancer. Genome Res 23:1097–1108CrossRefGoogle Scholar
  25. 25.
    Yates L, Gerstung M, Knappskog S, Desmet C et al (2015) Subclonal diversification of primary breast cancer revealed by multiregion sequencing. Nat Med 21:751–759CrossRefGoogle Scholar
  26. 26.
    Macklin P (2012) Essential ductal carcinoma in situ (DCIS) pathobiology for modelers. Accessed 1 Aug 2017
  27. 27.
    Ernster V, Barclay J, Kerlikowske K, Wilkie H et al (2000) Mortality among women with ductal carcinoma in situ of the breast in the population-based surveillance, epidemiology and end results program. Arch Intern Med 160:953–958CrossRefGoogle Scholar
  28. 28.
    Schopper D, de Wolf C (2007) Breast cancer screening by mammography: international evidence and the situation in Switzerland. Krebsliga Schweiz/Oncosuisse. Accessed 1 Aug 2017
  29. 29.
    Biller-Adorno N, Juni P (2014) Abolishing mammography screening programs? A view from the Swiss medical board. N Engl J Med 370:1965–1967CrossRefGoogle Scholar
  30. 30.
    Berger N, Schwizer S, Varga Z, Rageth C et al (2016) Assessment of the extent of microcalcifications to predict the size of a ductal carcinoma in situ: comparison between tomosynthesis and conventional mammography. Clin Imaging 50(6):1269–1273CrossRefGoogle Scholar
  31. 31.
    Nielsen M, Jensen J, Anderson J (1984) Precancerous and cancerous breast lesions during lifetime and at autopsy. A study of 83 women. Cancer 54:612–615CrossRefGoogle Scholar
  32. 32.
    Welch H, Black W (1997) Using autopsy series to estimate the disease “reservoir” for ductal carcinoma in situ of the breast: how much more breast cancer can we find? Ann Intern Med 127:1023–1028CrossRefGoogle Scholar
  33. 33.
    Rosen P, Snyder R, Foote F, Wallace T (1970) Detection of occult carcinoma in the apparently benign breast biopsy through specimen radiography. Cancer 26:944–952CrossRefGoogle Scholar
  34. 34.
    Fong J, Kurniawan E, Rose A, Mou A (2011) Outcomes of screening-detected ductal carcinoma in situ treated with wide excision along. Ann Surg Oncol 18:3778CrossRefGoogle Scholar
  35. 35.
    Van Zee K, Subhedar P, Olcese C, Patil S et al (2015) Relationship between margin width and recurrence of ductal carcinoma in situ: analysis of 2996 women treated with breast conserving surgery for 30 years. Ann Surg 262(4):623–631Google Scholar
  36. 36.
    Wapnir I. Dignam J, Fisher B, Mamounas E et al (2011) Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst 103(6):478–488CrossRefGoogle Scholar
  37. 37.
    Fisher B, Dignam J, Wolmark N et al (1998) Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from the national surgical adjuvant breast and bowel project B-17. J Clin Oncol 16:441–452CrossRefGoogle Scholar
  38. 38.
    Taylor C, Correa C, Duane F, Aznar M et al (2017) Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials. J Clin Oncol 35(15):1641–1649CrossRefGoogle Scholar
  39. 39.
    Jackson S, Frederick P, Pepe M, Nelson H et al (2017) Diagnostic reproducibility: what happens when the same pathologist interprets the same breast biopsy specimen at two points in time? Ann Surg Onc 24(5):1234–1241CrossRefGoogle Scholar
  40. 40.
    Amin M, Greene F, Edge S, Compton C et al (2017) The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA 67:93–99Google Scholar
  41. 41.
    Petkov V, Miller D, Howlader N, Gliner N et al (2016) Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study. Breast Cancer 2(16017):1–9Google Scholar
  42. 42.
    Sparano J, Gray R, Makower D, Pritchard K (2015) Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 373(21):2005–2014CrossRefGoogle Scholar
  43. 43.
    Stemmer S, Steiner M, Rizel S, Soussan-Gutman L et al (2016) Real -life analysis evaluating 1594 N0/Nmic breast cancer patients for whom treatment decisions incorporated the 21-gene recurrence score result: 5-year KM estimate for breast cancer specific survival with recurrence score results ≤ 30 is> 98%. Cancer Res 76(4S):P5–P08Google Scholar
  44. 44.
    Nitz U, Gluz O, Christgen M, Clemmons M et al (2017) Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial. Breast Cancer Res Treat 165:573CrossRefGoogle Scholar
  45. 45.
    Solin L, Gray R, Baehner F, Butler S 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):701–710CrossRefGoogle Scholar
  46. 46.
    Rakovitch E, Nofech-Mozes S, Hanna W, Baehner F et al (2015) A population-based validation study of the DCIS Score predicting recurrence risk in individuals treated by breast-conserving surgery alone. Breast Cancer Res Treat 152(2):389–398CrossRefGoogle Scholar
  47. 47.
    Rakovitch E, Gray R, Baehner F, Sutradhar R et al (2018) Refined estimates of local recurrence risks by DCIS score adjusting for clinicopathological features: a combined analysis of ECOG-ACRIN E5194 and Ontario DCIS cohort studies. Breast Cancer Res Treat 169:359–369CrossRefGoogle Scholar
  48. 48.
    Pilewskie M, Olcese C, Eaton A, Patil S et al (2014) Perioperative breast MRI is not associated with lower locoregional recurrence rates in DCIS patients treated with or without radiation. Ann Surg Oncol 21(5):1552–1560CrossRefGoogle Scholar
  49. 49.
    Hill M, Beeman J, Jhala K, Holubar S et al (2017) Relationship of breast MRI to recurrence rates in patients undergoing breast-conservation treatment. Breast Cancer Res Treat 163:615CrossRefGoogle Scholar
  50. 50.
    Khan S, Gatsonis C, Snyder B, Lehman C et al (2017) Prospective study of MRI and Multiparameter gene expression assay in DCIS: a trial of the ECOG-ACRIN Cancer Research Group (E4112). J Clin Oncol 35(15_suppl):534–534CrossRefGoogle Scholar
  51. 51.
    American Cancer Society. (2017) Breast Cancer Facts & Figs. 2017–2018. American Cancer Society, Inc., Atlanta. Accessed 26 July 2017

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kristin E. Rojas
    • 1
    Email author
  • Thais A. Fortes
    • 1
  • Patrick I. Borgen
    • 1
  1. 1.Department of SurgeryBrooklyn Breast Cancer Program of Maimonides Medical CenterBrooklynUSA

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