Skip to main content
NCBI home page
Cancer Biomarkers: Section A of Disease Markers logoLink to Cancer Biomarkers: Section A of Disease Markers
. 2016 Sep 26;17(3):293–300. doi: 10.3233/CBM-160641

The role of molecular biomarkers for predicting adjacent breast cancer of Atypical Ductal Hyperplasia diagnosed on core biopsy

Ayfer Kamali Polat a,b, Atilla Soran a,*, Amal Kanbour-Shakir c, Ebru Menekse a, Fatih Levent Balci a, Ronald Johnson a
PMCID: PMC13020501  PMID: 27802205

Abstract

BACKGROUND:

Atypical Ductal Hyperplasia (ADH) is a disease of the proliferative breast lesion characterized with atypia and when diagnosed on core needle biopsy (CNB), excisional biopsy is the current management to exclude adjacent cancer, which may found 10 to 20%.

OBJECTIVE:

The purpose of the study is to investigate the role of biomarkers on surgical decision after the diagnosis of ADH on CNB.

METHODS:

Patients with pure ADH on core biopsy were retrospectively selected, and categorized according to final pathology after excision into three groups: Group I (n: 39) ADH; Group II (n: 27) ductal carcinoma in situ (DCIS), and Group III (n: 9) invasive cancer (IC). Immunohistochemical analyses were performed using biomarkers MUC1, Ki67, Cyclin B1, and Cyclin D1.

RESULTS:

Only Cyclin D1 was significant in between group analysis by one-way ANOVA (64.74, 49.44, and 51.11, respectively; p= 0.01). However when appropriate cut-off levels (2%-50%) were used for each biomarkers using X2 test, no statistical significance was found.

CONCLUSION:

MUC1, Ki67, Cyclin B, and Cyclin D1have failed to predict adjacent cancer on core biopsy specimens with ADH. Further surgery is warranted for all ADH cases diagnosed on core biopsies until a new predictor is identified.

Keywords: Atypical ductal hyperplasia, breast cancer, biomarker, MUC1, cyclin, Ki67

References

  • [1]. Pinder SE, Ellis IO, The diagnosis and management of pre-invasive breast disease: ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH)-current definitions and classification, Breast Cancer Res 5 (2003), 254-257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [2]. Dupont WD, Parl FF, Hartmann WH, Brinton LA, Winfield AC, Worrell JA, et al., Breast cancer risk associated with proliferative breast disease and atypical hyperplasia, Cancer 71 (1993), 1258-1265. [DOI] [PubMed] [Google Scholar]
  • [3]. Page DL, Dupont WD, Rogers LW, Landenberger M, Intraductal carcinoma of the breast: follow-up after biopsy only, Cancer 49 (1982), 751-758. [DOI] [PubMed] [Google Scholar]
  • [4]. Polat AK, Kanbour-Shakir A, Andacoglu O, Polat AV, Johnson R, Bonaventura M, et al., Atypical Hyperplasia on Core Biopsy: Is Further Surgery Needed? Am J Med Sci 344 (2012), 28-3. [DOI] [PubMed] [Google Scholar]
  • [5]. Darling ML, Smith DN, Lester SC, Kaelin C, Selland DL, Denison CM, et al., Atypical ductal hyperplasia and ductal carcinoma in situ as revealed by large-core needle breast biopsy: results of surgical excision, Am J Roentgenol 175 (2000), 1341-1346. [DOI] [PubMed] [Google Scholar]
  • [6]. Degnim AC, King TA, Surgical management of high-risk breast lesions, Surg Clin North Am 93 (2013), 329-40. [DOI] [PubMed] [Google Scholar]
  • [7]. Gam LH, Breast cancer and protein biomarkers, World J Exp Med 20 (2012), 86-89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8]. Rosen PP, Ductal hyperplasia, In: Rosen's Breast Pathology, 2nd ed. Philadelphia, PA: Lippincott Williams &Wilkins, 2001, pp. 201-228. [Google Scholar]
  • [9]. Schnitt SJ, Vincent-Salomon A, Columnar cell lesions of the breast, Adv Anat Pathol 10 (2003), 113-124. [DOI] [PubMed] [Google Scholar]
  • [10]. American College of Radiology. Breast Imaging Reporting and Data System Atlas. 2003. Available at: http://www. acr.org/departments/stand_accred/birads/ contents.html. Accessed August 19, 2004.
  • [11]. Rassidakis GZ, Goy A, Medeiros LJ, Jiang Y, Thomaides A, Remache Y, Cabanillas F, et al., Prognostic significance of MUC-1 expression in systemic anaplastic large cell lymphoma, Clin Cancer Res 9 (2003), 2213-2220. [PubMed] [Google Scholar]
  • [12]. Andacoglu O, Kanbour-Shakir A, Teh YC, Bonaventura M, Ozbek U, Anello M, et al., Rationale of Excisional Biopsy After the Diagnosis of Benign Radial Scar on Core Biopsy: A Single Institutional Outcome Analysis, Am J Clin Oncol 36 (2013), 7-11. [DOI] [PubMed] [Google Scholar]
  • [13]. Krishnamurthy S, Bevers T, Kuerer H, Yang WT, Multidisciplinary considerations in the management of high-risk breast lesions, AJR Am J Roentgenol 198 (2012), 132-140. [DOI] [PubMed] [Google Scholar]
  • [14]. Eby PR, Ochsner JE, DeMartini WB, Allison KH, Peacock S, Lehman CD, Frequency and upgrade rates of atypical ductal hyperplasia diagnosed at stereotactic vacuum-assisted breast biopsy: 9-versus 11-gauge, AJR Am J Roentgenol 192 (2009), 229-234. [DOI] [PubMed] [Google Scholar]
  • [15]. Houssami N, Ciatto S, Ellis I, Ambrogetti D, Underestimation of malignancy of breast core-needle biopsy: concepts and precise overall and category-specific estimates, Cancer 109 (2007), 487-495. [DOI] [PubMed] [Google Scholar]
  • [16]. Forgeard C, Benchaib M, Guerin N, Thiesse P, Mignotte H, Faure C, et al., Is surgical biopsy mandatory in case of atypical ductal hyperplasia on 11-gauge core needle biopsy? A retrospective study of 300 patients, Am J Surg 196 (2008), 339-345. [DOI] [PubMed] [Google Scholar]
  • [17]. Khoury T, Chen X, Wang D, Kumar P, Qin M, Liu S, et al., Nomogram to predict the likelihood of upgrade of atypical ductal hyperplasia diagnosed on a core needle biopsy in mammographically detected lesions, Histopathology 67 (2015), 106-20. [DOI] [PubMed] [Google Scholar]
  • [18]. Nguyen CV, Albarracin CT, Whitman GJ, Lopez A, Sneige N, Atypical ductal hyperplasia in directional vacuum-assisted biopsy of breast microcalcifications: Considerations for surgical excision, Ann Surg Oncol 18 (2011), 752-761. [DOI] [PubMed] [Google Scholar]
  • [19]. Deshaies I, Provencher L, Jacob S, Côté G, Robert J, Desbiens C, et al., Factors associated with upgrading to malignancy at surgery of atypical ductal hyperplasia diagnosed on core biopsy, Breast 20 (2011), 50-55. [DOI] [PubMed] [Google Scholar]
  • [20]. Viacava P, Naccarato AG, Bevilacqua G, Different proliferative patterns characterize different preinvasive breast lesions, J Pathol 188 (1999), 245-251. [DOI] [PubMed] [Google Scholar]
  • [21]. Xu R, Perle MA, Inghirami G, Chan W, Delgado Y, Feiner H, Amplification of Her-2/neu gene in Her-2/neu-overexpressing and -nonexpressing breast carcinomas and their synchronous benign, premalignant, and metastatic lesions detected by FISH in archival material, Mod Pathol 15 (2002), 116-124. [DOI] [PubMed] [Google Scholar]
  • [22]. Lacunza E, Baudis M, Colussi AG, Segal-Eiras A, Croce MV, Abba MC, MUC1 oncogene amplification correlates with protein overexpression in invasive breast carcinoma cells, Cancer Genet Cytogenet 201 (2010), 102-110. [DOI] [PubMed] [Google Scholar]
  • [23]. Liu T, Niu Y, Feng Y, Niu R, Yu Y, Lv A, et al., Methylation of CpG islands of p16 (INK4a) and cyclinD1 overexpression associated with progression of intraductal proliferative lesions of the breast, Hum Pathol 39 (2008), 1637-46. [DOI] [PubMed] [Google Scholar]
  • [24]. Radisky DC, Santisteban M, Berman HK, Gauthier ML, Frost MH, Reynolds CA, et al., p16(INK4a) expression and breast cancer risk in women with atypical hyperplasia. Cancer Prev Res (Phila) 4 (2011), 1953-1960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [25]. Fackler MJ, Rivers A, Teo WW, Mangat A, Taylor E, Zhang Z, et al., Hypermethylated genes as biomarkers of cancer in women with pathologic nipple discharge, Clin Cancer Res 15 (2009), 3802-3811. [DOI] [PubMed] [Google Scholar]
  • [26]. Umbricht CB, Evron E, Gabrielson E, Ferguson A, Marks J, Sukumar S, Hypermethylation of 14-3-3 sigma (stratifin) is an early event in breast cancer, Oncogene 20 (2001), 3348-3353. [DOI] [PubMed] [Google Scholar]
  • [27]. Zagouri F, Sergentanis TN, Nonni A, Papadimitriou CA, Michalopoulos NV, Domeyer P, et al., Hsp90 in the continuum of breast ductal carcinogenesis: Evaluation in precursors, preinvasive and ductal carcinoma lesions, BMC Cancer 10 (2010), 353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [28]. Polyak K, Is breast tumor progression really linear? Clin Cancer Res 15 (2008), 339-341. [DOI] [PubMed] [Google Scholar]
  • [29]. Chai H, Brown RE, Field effect in cancer-an update, Ann Clin Lab Sci 39 (2009), 331-337. [PubMed] [Google Scholar]
  • [30]. Larson PS, de las Morenas A, Cupples LA, Huang K, Rosenberg CL, Genetically abnormal clones in histologically normal breast tissue, Am J Pathol 152 (1998), 1591-1598. [PMC free article] [PubMed] [Google Scholar]
  • [31]. Kaneko M, Arihiro K, Takeshima Y, Fujii S, Inai K, Loss of heterozygosity and microsatellite instability in epithelial hyperplasia of the breast, J Exp Ther Oncol 2 (2002), 9-18. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Biomarkers: Section A of Disease Markers are provided here courtesy of SAGE Publications

RESOURCES