Advertisement

Annals of Surgical Oncology

, Volume 24, Issue 12, pp 3549–3558 | Cite as

Flat Epithelial Atypia on Core Biopsy and Upgrade to Cancer: a Systematic Review and Meta-Analysis

  • Anatoliy V. Rudin
  • Tanya L. Hoskin
  • Aodhnait Fahy
  • Ann M. Farrell
  • Aziza Nassar
  • Karthik Ghosh
  • Amy C. Degnim
Breast Oncology

Abstract

Background

No consensus exists on whether flat epithelial atypia (FEA) diagnosed percutaneously should be surgically excised. A systematic review and meta-analysis of the frequency of upgrade to cancer or an atypical ductal hyperplasia (ADH) at surgical excision of FEA was performed.

Methods

Embase, MEDLINE, Scopus, and Web of Science databases from January 2003 to November 2015 were searched. The inclusion criteria required a manuscript in English with original data on FEA diagnosed percutaneously, data including the presence or absence of other concurrent high-risk lesions, and data including outcome of cancer at surgical excision. Studies were assessed for quality, and two reviewers extracted data. Random-effects meta-analysis was used to pool estimates. The impact of study-level characteristics was assessed by stratified meta-analysis and meta-regression.

Results

The inclusion criteria was met by 32 studies. A total of 1966 core needle biopsies showed pure FEA, and 1517 (77%) showed surgical excision. The proportions of patients with upgrade to cancer varied from 0 to 42%, with an overall pooled estimate of 11.1%. Heterogeneity was observed, with the greatest impact based on whether a study included cases of FEA diagnosed before 2003. With restriction of the investigation to 16 higher-quality studies, the cancer upgrade pooled estimate was 7.5% (95% confidence interval [CI], 5.4–10.4%), and the rate of invasive cancer was 3% (95% CI 1.9–4.5%). For upgrade to ADH, data from 22 studies including 937 patients were analyzed. The proportion of patients upgraded to ADH ranged from 0 to 60%, with a pooled estimate of 17.9% overall and 18.6% among high-quality studies.

Conclusions

With patient management change potential for approximately 25% of patients, this analysis supports a general recommendation for surgical excision of FEA diagnosed by core biopsy.

Notes

Acknowledgment

We sincerely thank to Marilyn Churchward for assistance with manuscript preparation.

Conflict of interest

There are no conflicts of interest.

Supplementary material

10434_2017_6059_MOESM1_ESM.docx (42 kb)
Supplementary material 1 (DOCX 42 kb)

References

  1. 1.
    Becker AK, Gordon PB, Harrison DA, et al. Flat ductal intraepithelial neoplasia 1A diagnosed at stereotactic core needle biopsy: is excisional biopsy indicated? AJR Am J Roentgenol. 2013;200:682–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Tavassoli FA, Hoefler H, Rosai JH, Ellis RIO. Intraductal proliferative lesions. In: Tavassoli FA, Devilee P, editors. World Health Organization classification of tumours: pathology and genetics of tumours of the breast and female genital organs. Lyon: IARC Press; 2003, pp 63–73.Google Scholar
  3. 3.
    Kunju LP, Kleer CG. Significance of flat epithelial atypia on mammotome core needle biopsy: should it be excised? Hum Pathol. 2007;38:35–41.CrossRefPubMedGoogle Scholar
  4. 4.
    Said SM, Visscher DW, Nassar A, et al. Flat epithelial atypia and risk of breast cancer: a Mayo cohort study. Cancer. 2015;121:1548–55.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Mooney KL, Bassett LW, Apple SK. Upgrade rates of high-risk breast lesions diagnosed on core needle biopsy: a single-institution experience and literature review. Mod Pathol. 2016;29:1471–84.CrossRefPubMedGoogle Scholar
  6. 6.
    Schnitt SJ, Vincent-Salomon A. Columnar cell lesions of the breast. Adv Anat Pathol. 2003;10:113–24.CrossRefPubMedGoogle Scholar
  7. 7.
    Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.CrossRefPubMedGoogle Scholar
  8. 8.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Br Med J. 2003;327:557–60.CrossRefGoogle Scholar
  9. 9.
    Schwarzer G, Carpenter JR, Rucker G. META: general package for meta-analysis. R Package Version 4.3-2. Cham: Springer International Publishing; 2015.Google Scholar
  10. 10.
    Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48.CrossRefGoogle Scholar
  11. 11.
    National Comprehensive Cancer Center. National Comprehensive Cancer Network Clinical Guidelines, Breast Cancer Risk Reduction, v1, 2017. https://www.nccn.org/professionals/physician_gls/PDF/breast_risk.pdf. Accessed 16 Dec 2016.
  12. 12.
    Baum JK, Hanna LG, Acharyya S, et al. Use of BI-RADS 3: probably benign category in the American College of Radiology Imaging Network Digital Mammographic Imaging Screening Trial. Radiology. 2011;260:61–7.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Esserman L, Yau C. Rethinking the standard for ductal carcinoma in situ treatment. JAMA Oncol. 2015;1:881–3.CrossRefPubMedGoogle Scholar
  14. 14.
    Park TS, Hwang ES. Current trends in the management of ductal carcinoma in situ. Oncology Williston Park. 2016;30:823–31.PubMedGoogle Scholar
  15. 15.
    Hartmann LC, Degnim AC, Santen RJ, Dupont WD, Ghosh K. Atypical hyperplasia of the breast: risk assessment and management options. N Engl J Med. 2015;372:78–89.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hartmann LC, Radisky DC, Frost MH, et al. Understanding the premalignant potential of atypical hyperplasia through its natural history: a longitudinal cohort study. Cancer Prev Res Phila. 2014;7:211–7.CrossRefGoogle Scholar
  17. 17.
    Degnim AC, Dupont WD, Radisky DC, et al. Extent of atypical hyperplasia stratifies breast cancer risk in 2 independent cohorts of women. Cancer. 2016;122:2971–8.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Coopey SB, Mazzola E, Buckley JM, et al. The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions. Breast Cancer Res Treat. 2012;136:627–33.CrossRefPubMedGoogle Scholar
  19. 19.
    King TA, Pilewskie M, Muhsen S, et al. Lobular carcinoma in situ: a 29-year longitudinal experience evaluating clinicopathologic features and breast cancer risk. J Clin Oncol. 2015;333945–52.Google Scholar
  20. 20.
    Villa A, Chiesa F, Massa T, et al. Flat epithelial atypia: comparison between 9-gauge and 11-gauge devices. Clinl Breast Cancer. 2013;13:450–4.CrossRefPubMedGoogle Scholar
  21. 21.
    Lavoue V, Roger CM, Poilblanc M, et al. Pure flat epithelial atypia (DIN 1a) on core needle biopsy: study of 60 biopsies with follow-up surgical excision. Breast Cancer Res Treat. 2011;125:121–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Darling ML, Smith DN, Lester SC, et al. Atypical ductal hyperplasia and ductal carcinoma in situ as revealed by large-core needle breast biopsy: results of surgical excision. AJR Am J Roentgenol. 2000;175:1341–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Lim CN, Ho BC, Bay BH, Yip G, Tan PH. Nuclear morphometry in columnar cell lesions of the breast: is it useful? J Clin Pathol. 2006;59:1283–6.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Martel M, Barron-Rodriguez P, Tolgay Ocal I, Dotto J, Tavassoli FA. Flat DIN 1 (flat epithelial atypia) on core needle biopsy: 63 cases identified retrospectively among 1751 core biopsies performed over an 8-year period (1992–1999). Virchows Arch. 2007;451:883–91.CrossRefPubMedGoogle Scholar
  25. 25.
    Piubello Q, Parisi A, Eccher A, Barbazeni G, Franchini Z, Iannucci A. Flat epithelial atypia on core needle biopsy: which is the right management? Am J Surg Pathol. 2009;33:1078–84.CrossRefPubMedGoogle Scholar
  26. 26.
    Chivukula M, Bhargava R, Tseng G, Dabbs DJ. Clinicopathologic implications of “flat epithelial atypia” in core needle biopsy specimens of the breast. Am J Clin Pathol. 2009;131:802–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Senetta R, Campanino PP, Mariscotti G, et al. Columnar cell lesions associated with breast calcifications on vacuum-assisted core biopsies: clinical, radiographic, and histological correlations. Mod Pathol. 2009;22:762–9.PubMedGoogle Scholar
  28. 28.
    Hayes BD, Quinn CM. Pathology of B3 lesions of the breast. Diagn Histopathol. 2009;15:459–69.CrossRefGoogle Scholar
  29. 29.
    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
  30. 30.
    Tomasino RM, Morello V, Gullo A, et al. Assessment of “grading” with Ki-67 and c-kit immunohistochemical expressions may be a helpful tool in management of patients with flat epithelial atypia (FEA) and columnar cell lesions (CCLs) on core breast biopsy. J Cell Physiol. 2009;221:343–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Noske A, Pahl S, Fallenberg E, et al. Flat epithelial atypia is a common subtype of B3 breast lesions and is associated with noninvasive cancer but not with invasive cancer in final excision histology. Hum Pathol. 2010;41:522–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Lee TY, Macintosh RF, Rayson D, Barnes PJ. Flat epithelial atypia on breast needle core biopsy: a retrospective study with clinical-pathological correlation. Breast J. 2010;16:377–83.CrossRefPubMedGoogle Scholar
  33. 33.
    Ingegnoli A, d’Aloia C, Frattaruolo A, et al. Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate. Breast J. 2010;16:55–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Noel JC, Buxant F, Engohan-Aloghe C. Immediate surgical resection of residual microcalcifications after a diagnosis of pure flat epithelial atypia on core biopsy: a word of caution. Surg Oncol. 2010;19:243–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Flegg KM, Flaherty JJ, Bicknell AM, Jain S. Surgical outcomes of borderline breast lesions detected by needle biopsy in a breast screening program. World J Surg Oncol. 2010;8:78.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Sohn V, Porta R, Brown T. Flat epithelial atypia of the breast on core needle biopsy: an indication for surgical excision. Mil Med. 2011;176:1347–50.CrossRefPubMedGoogle Scholar
  37. 37.
    Rakha EA, Lee AH, Jenkins JA, Murphy AE, Hamilton LJ, Ellis IO. Characterization and outcome of breast needle core biopsy diagnoses of lesions of uncertain malignant potential (B3) in abnormalities detected by mammographic screening. Int J Cancer. 2011;129:1417–24.CrossRefPubMedGoogle Scholar
  38. 38.
    Solorzano S, Mesurolle B, Omeroglu A, et al. Flat epithelial atypia of the breast: pathological-radiological correlation. AJR Am J Roentgenol. 2011;197:740–6.CrossRefPubMedGoogle Scholar
  39. 39.
    Verschuur-Maes AH, Witkamp AJ, de Bruin PC, van der Wall E, van Diest PJ. Progression risk of columnar cell lesions of the breast diagnosed in core needle biopsies. Int J Cancer. 2011;129:2674–80.CrossRefPubMedGoogle Scholar
  40. 40.
    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.CrossRefPubMedGoogle Scholar
  41. 41.
    Uzoaru I, Morgan BR, Liu ZG, et al. 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.CrossRefPubMedGoogle Scholar
  42. 42.
    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.CrossRefPubMedGoogle Scholar
  43. 43.
    Biggar MA, Kerr KM, Erzetich LM, Bennett IC. Columnar cell change with atypia (flat epithelial atypia) on breast core biopsy-outcomes following open excision. Breast J. 2012;18:578–81.CrossRefPubMedGoogle Scholar
  44. 44.
    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.CrossRefPubMedGoogle Scholar
  45. 45.
    Polom K, Murawa D, Murawa P. Flat epithelial atypia diagnosed on core needle biopsy: clinical challenge. Rep Pract Oncol Radiother. 2012;17:93–6.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Khoumais NA, Scaranelo AM, Moshonov H, et al. Incidence of breast cancer in patients with pure flat epithelial atypia diagnosed at core-needle biopsy of the breast. Ann Surg Oncol. 2013;20:133–8.CrossRefPubMedGoogle Scholar
  47. 47.
    Ceugnart L, Doualliez V, Chauvet MP, et al. Pure flat epithelial atypia: is there a place for routine surgery? Diagn Interv Imaging. 2013;94:861–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Uzan C, Mazouni C, Ferchiou M, et al. A model to predict the risk of upgrade to malignancy at surgery in atypical breast lesions discovered on percutaneous biopsy specimens. Ann Surg Oncol. 2013;20:2850–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Dialani V, Venkataraman S, Frieling G, Schnitt SJ, Mehta TS. Does isolated flat epithelial atypia on vacuum-assisted breast core biopsy require surgical excision? Breast J. 2014;20:606–14.CrossRefPubMedGoogle Scholar
  50. 50.
    Calhoun BC, Sobel A, White RL, et al. Management of flat epithelial atypia on breast core biopsy may be individualized based on correlation with imaging studies. Mod Pathol. 2015;28:670–6.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2017

Authors and Affiliations

  • Anatoliy V. Rudin
    • 1
  • Tanya L. Hoskin
    • 2
  • Aodhnait Fahy
    • 1
  • Ann M. Farrell
    • 3
  • Aziza Nassar
    • 4
  • Karthik Ghosh
    • 5
  • Amy C. Degnim
    • 1
  1. 1.Department of SurgeryMayo ClinicRochesterUSA
  2. 2.Biomedical Statistics and InformaticsMayo ClinicRochesterUSA
  3. 3.Mayo Clinic LibrariesMayo ClinicRochesterUSA
  4. 4.Laboratory Medicine and PathologyMayo ClinicJacksonvilleUSA
  5. 5.Breast Clinic, General Internal MedicineMayo ClinicRochesterUSA

Personalised recommendations