Annals of Surgical Oncology

, Volume 20, Issue 9, pp 2850–2857

A Model to Predict the Risk of Upgrade to Malignancy at Surgery in Atypical Breast Lesions Discovered on Percutaneous Biopsy Specimens

  • Catherine Uzan
  • Chafika Mazouni
  • Malek Ferchiou
  • Laura Ciolovan
  • Corinne Balleyguier
  • Marie-Christine Mathieu
  • Philippe Vielh
  • Suzette Delaloge
Breast Oncology



When any atypical feature is identified on a percutaneous biopsy specimen of a suspicious breast lesion, surgical excision is mandatory, leading to unnecessary surgeries in 70–90 % of the cases. The purpose of this study was to develop a model to predict the presence of cancer at surgery that would be applicable to all atypical lesions.


We collected complete clinical, radiological, and double-reading histological data concerning all patients with a diagnosis of a pure atypical lesion on image-guided biopsy performed at the One-Stop Breast Care Unit between 2004 and 2011.


Among the 204 eligible patients, 49 cancers (24 %) had been diagnosed at definitive surgery (20 ductal carcinoma in situ, 20 invasive ductal, and 9 invasive lobular carcinoma). The univariate analysis retrieved age (p = 0.03), the focus size in mm (p = 0.02), the number of biopsy cores (p = 0.02), the disappearance of radiological anomalies after biopsy (p = 0.05), the mean number of atypical foci (p = 0.05) and the percentage of atypical lobules and ducts for lobular neoplasia (p = 0.04) as factors associated with cancer at surgery, whereas neither Ki67 nor ALDH1 expression was significantly correlated. The final most informative nomogram comprised information on patient age, the disappearance of radiological anomalies after biopsy and a focus size >15 mm. For the optimal threshold (risk of cancer = 21 %), sensitivity, specificity, positive predictive value, and negative predictive value were 78, 66, 36, and 90 %, respectively.


After validation, this model could help to identify a subset of patients with premalignant disease who could be spared surgery.

Supplementary material

10434_2013_2989_MOESM1_ESM.doc (46 kb)
Supplementary material 1 (DOC 46 kb)
10434_2013_2989_MOESM2_ESM.doc (58 kb)
Supplementary material 2 (DOC 58 kb)


  1. 1.
    Hartmann LC, Sellers TA, Frost MH, et al. Benign breast disease and the risk of breast cancer. N Engl J Med. 2005;353:229–37.PubMedCrossRefGoogle Scholar
  2. 2.
    Page DL, Dupont WD. Anatomic indicators (histologic and cytologic) of increased breast cancer risk. Breast Cancer Res Treat. 1993;28:157–66.PubMedCrossRefGoogle Scholar
  3. 3.
    Allred DC. Molecular biomarkers of risk in premalignancy and breast cancer prevention. Cancer Prev Res (Phila). 2011;4:1947–52.PubMedCrossRefGoogle Scholar
  4. 4.
    Winchester DJ, Bernstein JR, Jeske JM, et al. Upstaging of atypical ductal hyperplasia after vacuum-assisted 11-gauge stereotactic core needle biopsy. Arch Surg. 2003;138:619–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Polat AK, Kanbour-Shakir A, Andacoglu O, Polat AV, Johnson R, Bonaventura M, Soran A. Atypical hyperplasia on core biopsy: is further surgery needed? Am J Med Sci. 2012;344:28–31.PubMedCrossRefGoogle Scholar
  6. 6.
    Jain RK, Mehta R, Dimitrov R, et al. Atypical ductal hyperplasia: interobserver and intraobserver variability. Mod Pathol. 2011;24:917–23.PubMedCrossRefGoogle Scholar
  7. 7.
    Darvishian F, Singh B, Simsir A, Ye W, Cangiarella JF. Atypia on breast core needle biopsies: reproducibility and significance. Ann Clin Lab Sci. 2009;39:270–6.PubMedGoogle Scholar
  8. 8.
    Kohr JR, Eby PR, Allison KH, DeMartini WB, Gutierrez RL, Peacock S, Lehman CD. Risk of upgrade of atypical ductal hyperplasia after stereotactic breast biopsy: effects of number of foci and complete removal of calcifications. Radiology. 2010;255:723–30.PubMedCrossRefGoogle Scholar
  9. 9.
    Ingegnoli A, d’Aloia C, Frattaruolo A, Pallavera L, Martella E, Crisi G, Zompatori M. Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate. Breast J. 2010;16:55–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Ely KA, Carter BA, Jensen RA, Simpson JF, Page DL. Core biopsy of the breast with atypical ductal hyperplasia: a probabilistic approach to reporting. Am J Surg Pathol. 2001;25:1017–21.PubMedCrossRefGoogle Scholar
  11. 11.
    de Mascarel I, Brouste V, Asad-Syed M, Hurtevent G, Macgrogan G. All atypia diagnosed at stereotactic vacuum-assisted breast biopsy do not need surgical excision. Mod Pathol. 2011;24:1198–206.PubMedCrossRefGoogle Scholar
  12. 12.
    Uzoaru I, Morgan BR, Liu ZG, Bellafiore FJ, Gaudier FS, Lo JV, Pakzad K. Flat epithelial atypia with and without atypical ductal hyperplasia: to re-excise or not. Results of a 5-year prospective study. Virchows Arch. 2012;461:419–23.PubMedCrossRefGoogle Scholar
  13. 13.
    Yamaguchi R, Tanaka M, Tse GM, et al. Pure flat epithelial atypia is uncommon in subsequent breast excisions for atypical epithelial proliferation. Cancer Sci. 2012;103:1580–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Bianchi S, Bendinelli B, Castellano I, et al. Morphological parameters of flat epithelial atypia (FEA) in stereotactic vacuum-assisted needle core biopsies do not predict the presence of malignancy on subsequent surgical excision. Virchows Arch. 2012;461:405–17.PubMedCrossRefGoogle Scholar
  15. 15.
    Peres A, Barranger E, Becette V, Boudinet A, Guinebretiere JM, Cherel P. Rates of upgrade to malignancy for 271 cases of flat epithelial atypia (FEA) diagnosed by breast core biopsy. Breast Cancer Res Treat. 2012;133:659–66.PubMedCrossRefGoogle Scholar
  16. 16.
    Solorzano S, Mesurolle B, Omeroglu A, El Khoury M, Kao E, Aldis A, Meterissian S. Flat epithelial atypia of the breast: pathological-radiological correlation. AJR Am J Roentgenol. 2011;197:740–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Simpson PT, Gale T, Reis-Filho JS, et al. Columnar cell lesions of the breast: the missing link in breast cancer progression? A morphological and molecular analysis. Am J Surg Pathol. 2005;29:734–46.PubMedCrossRefGoogle Scholar
  18. 18.
    Schnitt SJ, Vincent-Salomon A. Columnar cell lesions of the breast. Adv Anat Pathol. 2003;10:113–24.PubMedCrossRefGoogle Scholar
  19. 19.
    Feeley L, Quinn CM. Columnar cell lesions of the breast. Histopathology. 2008;52:11–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Verschuur-Maes AH, de Bruin PC, van Diest PJ. Epigenetic progression of columnar cell lesions of the breast to invasive breast cancer. Breast Cancer Res Treat. 2012;136:705–15.PubMedCrossRefGoogle Scholar
  21. 21.
    Ko E, Han W, Lee JW, et al. Scoring system for predicting malignancy in patients diagnosed with atypical ductal hyperplasia at ultrasound-guided core needle biopsy. Breast Cancer Res Treat. 2008;112:189–95.PubMedCrossRefGoogle Scholar
  22. 22.
    Bendifallah S, Defert S, Chabbert-Buffet N, et al. Scoring to predict the possibility of upgrades to malignancy in atypical ductal hyperplasia diagnosed by an 11-gauge vacuum-assisted biopsy device: an external validation study. Eur J Cancer. 2012;48:30–6.PubMedCrossRefGoogle Scholar
  23. 23.
    American College of Radiology. Breast imaging reporting and data system (BI-RADS), 4th edn. Reston: American College of Radiology, 2003.Google Scholar
  24. 24.
    Mazouni C, Sneige N, Rouzier R, et al. A nomogram to predict for malignant diagnosis of BI-RADS Category 4 breast lesions. J Surg Oncol. 2010;102:220–4.PubMedCrossRefGoogle Scholar
  25. 25.
  26. 26.
    Harrell FE. Regression modeling strategies. New York: Springer, 2001.CrossRefGoogle Scholar
  27. 27.
    McGhan LJ, Pockaj BA, Wasif N, Giurescu ME, McCullough AE, Gray RJ. Atypical ductal hyperplasia on core biopsy: an automatic trigger for excisional biopsy? Ann Surg Oncol. 2012;19:3264–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Puliti D, Duffy SW, Miccinesi G, de Koning H, Lynge E, Zappa M, Paci E, EUROSCREEN Working Group. Overdiagnosis in mammographic screening for breast cancer in Europe: a literature review. J Med Screen. 2012;19:42–56.PubMedCrossRefGoogle Scholar
  29. 29.
    Villa A, Tagliafico A, Chiesa F, Chiaramondia M, Friedman D, Calabrese M. Atypical ductal hyperplasia diagnosed at 11-gauge vacuum-assisted breast biopsy performed on suspicious clustered microcalcifications: could patients without residual microcalcifications be managed conservatively? AJR Am J Roentgenol. 2011;197:1012–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Rendi MH, Dintzis SM, Lehman CD, Calhoun KE, Allison KH. Lobular in-situ neoplasia on breast core needle biopsy: imaging indication and pathologic extent can identify which patients require excisional biopsy. Ann Surg Oncol. 2012;19:914–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Catteau X, Simon P, Noël JC. Predictors of invasive breast cancer in mammographically detected microcalcification in patients with a core biopsy diagnosis of flat epithelial atypia, atypical ductal hyperplasia or ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy. Pathol Res Pract. 2012;208:217–20.PubMedCrossRefGoogle Scholar
  32. 32.
    Kunju LP, Cookingham C, Toy KA, Chen W, Sabel MS, Kleer CG. EZH2 and ALDH-1 mark breast epithelium at risk for breast cancer development. Mod Pathol. 2011;24:786–93.PubMedCrossRefGoogle Scholar
  33. 33.
    Santisteban M, Reynolds C, Barr Fritcher EG, et al. Ki67: a time-varying biomarker of risk of breast cancer in atypical hyperplasia. Breast Cancer Res Treat. 2010;121:431–7.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Catherine Uzan
    • 1
    • 6
  • Chafika Mazouni
    • 1
    • 6
  • Malek Ferchiou
    • 2
    • 6
  • Laura Ciolovan
    • 3
    • 6
  • Corinne Balleyguier
    • 3
    • 6
  • Marie-Christine Mathieu
    • 2
    • 6
  • Philippe Vielh
    • 2
    • 4
    • 6
  • Suzette Delaloge
    • 5
    • 6
  1. 1.Department of SurgeryInstitut Gustave Roussy and University Paris SudVillejuif CedexFrance
  2. 2.Department of PathologyInstitut Gustave RoussyVillejuifFrance
  3. 3.Department of ImagingInstitut Gustave RoussyVillejuifFrance
  4. 4.Integrated BiobankInstitut Gustave RoussyVillejuifFrance
  5. 5.Department of Medical OncologyInstitut Gustave RoussyVillejuifFrance
  6. 6.Breast Cancer UnitInstitut Gustave RoussyVillejuifFrance

Personalised recommendations