Supplemental Table 1. Quality assessment scoring algorithm

Parameter Score

2 1 0

Time span Describes the time frame of surgical

excision from initial CBN for all cases

Describes the time frame of surgical

excision from initial CBN for some cases

No time frame description

Percent Excised >75% of reported FEA cases surgically

excised

50-75% of reported FEA cases excised

<50% of reported FEA cases excised

Assessment of outcome

Follow-up and outcomes reported for

all of those not excised

Follow-up and outcomes reported for

some of those not excised

No follow up described in those not

excised

Ascertainment bias Full description of how the cohort was identified to confirm

ascertainment

Vague description of how to the cohort was identified to confirm

ascertainment

No description of cohort ascertainment

Supplemental Table 2. Reports on FEA that were excluded from meta-analysis.

Abstracts (n=59)

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Lee AHS. Columnar cell lesions of the breast: A practical approach. J Pathol. Apr 2013;229:S3.

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Articles Not Available in English (N=3)

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Papers mentioning FEA but did not meet inclusion criteria (N=156)

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D'Alfonso TM, Wang K, Chiu YL, Shin SJ. Pathologic upgrade (PU) rates on subsequent excisional biopsy (EXBX) when lobular carcinoma in situ (LCIS) is found in a needle core biopsy (NCB) with emphasis on radiologic correlation. Lab Invest. Feb 2012;92:32A.

D'Alfonso TM, Wang K, Chiu YL, Shin SJ. Pathologic upgrade rates on subsequent excision when lobular carcinoma in situ is the primary diagnosis in the needle core biopsy with special attention to the radiographic target. Arch Pathol Lab Med. Jul 2013;137(7):927-935.

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de Mascarel I, MacGrogan G, Mathoulin-Pelissier S, et al. Epithelial atypia in biopsies performed for microcalcifications. Practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up. Virchows Arch. Jul 2007;451(1):1-10.

Degnim AC, King TA. Surgical management of high-risk breast lesions. Surg Clin N Am. Apr 2013;93(2):329-340.

Demiralay E, Demirhan B, Sar A. Immunohistochemical and morphologic findings in columnar cell lesions coexisting with invasive breast carcinomas. Virchows Arch. Aug 2007;451(2):303.

Dooley WC, Wang J, Thor A, Parker J. Clinical significance of columnar cell hyperplasia in breast tissue specimens. Breast Cancer Res Treat. 2003;82:S99.

Drotman MB, Eisen CS, Vazquez MF, Wechsler E, Rosenblatt R. Columnar cell alteration diagnosed at stereotactic core biopsy of breast calcifications: Mammographic findings and results at subsequent surgical excision. Radiology. Nov 2001;221:519-520.

Edelweiss M, Brogi E, Nehhozina T, Akram M, Norton L, Corben AD. Extravasated mucin pools in breast core needle biopsy: Ten year experience at a single institution. Lab Invest. Feb 2010;90:44A-45A.

Elif A, Burcu S, Nazan C, Sumru CZ, Kemal AN. Columnar cell lesions of the breast: Radiological features and histological correlation. Med Ultrason. Jun 2015; 17(2):147-154.

Ellis IO. Intraductal proliferative lesions of the breast: morphology, associated risk and molecular biology. Mod Pathol. May 2010;23 Suppl 2:S1-7.

Eradat J, Shamonki JM, Bassett LW, Apple S. Columnar cell lesions in breast core needle biopsy and the predictive value for unsampled ductal carcinoma. Mod Pathol. Mar 2007;20:30A-30A.

Erdogan G, Bilgin G, Ozbey C, Pestereli EH, Karaveli SF. Mucinous cystadenocarcinoma and columnar cell mucinous carcinoma of the breast. Virchows Arch. Aug 2009;455:181-182.

Garijo MF, Val-Bernal JF, Vega A, Val D. Postoperative spindle cell nodule of the breast: Pseudosarcomatous myofibroblastic proliferation following endo-surgery. Pathol Int. Dec 2008;58(12):787-791.

Georgian-Smith D, Lawton TJ. Controversies on the management of high-risk lesions at core biopsy from a radiology/pathology perspective. Radiol Clin N Am. Sep 2010;48(5):999-1012.

Georgian-Smith D, Lawton TJ. Variations in physician recommendations for surgery after diagnosis of a high-risk lesion on breast core needle biopsy. AJR Am J Roentgenol. Feb 2012;198(2):256-263.

Goodman S, Kandil D, Khan A. Diagnosis of breast needle core biopsies using whole slide imaging. Lab Invest. Feb 2014;94:399A.

Graesslin O, Antoine M, Chopier J, et al. Histology after lumpectomy in women with epithelial atypia on stereotactic vacuum-assisted breast biopsy. Eur J Surg Oncol. Feb 2010;36(2):170-175.

Gurung A, Zhou C, Rahemtulla A, et al. Centralized breast cancer biomarker testing: A value-added role in guiding patient management. Am J Clin Pathol. Sept 2013;140:A093.

Ha D, Dianani V, Mehta TS, Keefe W, Iuanow E, Slanetz PJ. Mucocele-like lesions in the breast diagnosed with percutaneous biopsy: Is surgical excision necessary? AJR Am J Roentgenol. Jan 2015; 204(1):204-210.

Hayes BC, Quinn CM. Pathology of B3 lesions of the breast. Diagn Histopathol. Oct 2009; 15(10):459-469.

Heller SL, Hernandez O, Moy L. Radiologic-pathologic correlation at breast MR imaging what is the appropriate banagement for high-risk lesions? Magn Reson Imaging Clin N Am. Aug 2013;21(3):583-599.

Ichihara S, Moritani S, Hasegawa M, et al. Pseudo-micropapillary structures associated with columnar cell lesions of the breast are an artifact due to traumatic epithelial detachment: A potential pitfall which can lead to overtreatment. Virchows Arch. 2013;463(1):93-95.

Jacobs TW, Connolly JL, Schnitt SJ. Nonmalignant lesions in breast core needle biopsies: to excise or not to excise? Am J Surg Pathol. Sep 2002;26(9):1095-1110.

Jara-Lazaro AR, Tse GM, Tan PH. Columnar cell lesions of the breast: an update and significance on core biopsy. Pathology. Jan 2009;41(1):18-27.

Joshi M, Reddy SJ, Nanavidekar M, Russo JP, Russo AV, Pathak R. Core biopsies of the breast: diagnostic pitfalls. Indian J Pathol Microbiol. Oct-Dec 2011;54(4):671-682.

Kanbour-Shakir A, Teh YC, Bonaventura M, Soran A. Significance of radial scar diagnosis in breast core biopsy and correlation with follow up surgical excision. Lab Invest. Jan 2009;89:49A.

Kandel S, Kumar P, Liu Q, Liu S, Khoury T. Non-mass like enhancement (NMLE) in breast magnetic resonance imaging: A proposal of pathological-radiological correlation. Lab Invest. Feb 2013;93:48A.

Kapucuoglu N, Bircan S, Ciris M, Inan G. Estrogen receptor expression and Ki67 proliferative activity in normal breast, columnar cell lesions and DCIS grade I: A pilot study. Virchows Arch. Aug 2007;451(2):304-304.

Khoury T, Turner B, Chen X, Wang D, Kandel S, Liu S. Nomograms to predict the likelihood of upgrade of atypical ductal hyperplasia diagnosed on a core needle biopsy in mammographically detected lesions. Lab Invest. Feb 2014;94:59A.

Kim MJ, Kim EK, Oh KK, Park BW, Kim H. Columnar cell lesions of the breast: Mammographic and US features. Eur J Radiol. Nov 2006;60(2):264-269.

Krishnamurthy S, Bevers T, Kuerer H, Yang WT. Multidisciplinary considerations in the management of high-risk breast lesions. AJR Am J Roentgenol. Feb 2012;198(2):W132-140.

Kryvenko ON, Chitale DA, VanEgmond EM, Gupta NS, Schultz D, Lee MW. Angiolipoma of the female breast: clinicomorphological correlation of 52 cases. Int J Surg Pathol. Feb 2011;19(1):35-43.

Kumaroswamy V, Liston J, Shaaban AM. Vacuum assisted stereotactic guided mammotome biopsi es in the management of screen detected microcalcifications: experience of a large breast screening centre. J Clin Pathol. Jun 2008;61(6):766-769.

Kunju LP, Kleer CG. Tubular carcinoma and grade 1 (well differentiated) invasive ductal carcinoma: Comparison of associated flat epithelial atypia and other intra-epithelial lesions. Mod Pathol. Mar 2007;20:39A.

Kunju LP, Kleer CG. ER/PR positive and ER/PR negative DCIS: Morphologic characterization in a cohort of age-matched cases. Lab Invest. Jan 2009;89:52A-53A.

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Supplemental Table 3. Meta-regression showing impact of moderators on heterogeneity between studies for the outcome of upgrade to cancer.

Coefficient (95% CI) p-value

Outcome: Upgrade to cancer

Quality score 0.06 (-0.11, 0.23) 0.48

Did not adhere to WHO criteria in defining FEA -0.03 (-0.98, 0.91) 0.95

Year published -0.21 (-0.33, -0.08) 0.001

Study included cases prior to 2003 1.13 (0.60, 1.66) <0.0001

Outcome: Upgrade to ADH

Quality score 0.33 (0.01, 0.66) 0.046

Did not adhere to WHO criteria in defining FEA 1.77 (-0.09, 3.62) 0.06

Year published -0.16 (-0.37, 0.04) 0.12

Study included cases prior to 2003 -0.41 (-1.35, 0.52) 0.38

Supplemental Table 4. Followup for patients with FEA who did not undergo immediate surgical excision.

Author, Year Duration of F/U

Number of patients with F/U

Number of Subsequent Excisional Biopsies

Number Upgraded to Cancer

Noel, 2010 6-12 months 37 0 NA

Sohn, 2011 3 years 12 0 NA

Soloranzo, 2011

1.5 years 5† 0 N/A

Verschuur-Maes, 2011

8 years 45 7‡ 5

Peres, 2012 13 months 0 0 NA

Uzoaru, 2012 5 years 33 0 NA

Yamaguchi, 2012

1.5 years 9 * 0 NA

NA

Khoumais, 2013

3 years 10 0 NA

Chi-Chang, 2 years 135 0 NA

Dialani 2-7 years 0 0 NA

†1/5 patients had a follow up vacuum assisted biopsy that yielded columnar change with no atypia with no change on 1 year US. 4/5 patients under went mammography at 12, 12, 12, and 18 months with no change documented. ‡Follow up for 7 patients, 1 – CCL, 1 ADH, 5 Invasive Cancer* 9 had no change in BiRADs grading (Mammography and/or US) since initial biopsy