Atypical Hyperplasia: High Risk or Precursor for Breast Cancer

By Priyanka Varma

BURLINGAME, Calif. Dec 23rd, 2021

Atypical hyperplasia of the breast is defined as the presence of abnormal epithelial, proliferative cell populations in the breast that are classified as premalignant  and contain some of but not all the features needed to qualify as carcinoma in situ [1]. It can be either atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH). ADH is typically an incidental finding on biopsy (5-20% of breast biopsies) and once identified, it increases the risk of developing breast cancer by five fold [1, 2]. ALH is also shown to increase the risk of developing cancer by four to five fold [1].

The biology of atypical hyperplasia is poorly defined. Genomic change is one of the theories to explain the proliferation of abnormal epithelial cells[1]. Therefore a better understanding of the genomic aspect of the Breast Atypical Hyperplasia will help delineate its progression to carcinogenesis and eventually to a better clinical management. The genes affecting cell proliferation, signal transduction, and apoptosis like RB1, VEGF, STAT5A, CCND1, TP53, ESR1 (ER-α), and ERBB have been found to be closely related to the occurrence and development of atypical hyperplasia in breast [3].

Atypical Hyperplasia - Normal Duct and Duct with ADH

An increased exposure to estrogen (early menarche, nulliparity, late first full-term pregnancy, oral contraceptive pills, late menopause, post menopausal obesity) is believed to potentially lead to a higher risk to developing cancer by increasing the genomic instability and more extensive genomic changes, quantitatively and qualitatively [4].

Even though the immunohistochemical and molecular studies point to ADH being a potential precursor of breast cancer, epidemiological statistics suggest it is only a high risk factor and the opinion of ADH being premalignant is still conflicted [5]. ALH is considered to only be a high risk lesion [1].

Surgical excision is considered to be standard of care management for ADH; however, the surgical excision management of ALH is controversial and can be omitted if there is no mass lesion, no accompanying ADH, excellent sampling was done [6]. It is recommended to assess the management options after evaluating the clinical picture and the high risk factors, have open and clear communication between patient and their primary care provider and manage the patient via a multidisciplinary collaboration.


  1. Myers DJ, Walls AL. Atypical Breast Hyperplasia. [Updated 2021 Sep 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from:
  2. Tomlinson-Hansen S, Cassaro S. Atypical Ductal Hyperplasia. 2020 Aug 20. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 32965915.)
  3. Ma W, Shi B, Zhao F, Wu Y, Jin F. Systematic analysis of breast atypical hyperplasia-associated hub genes and pathways based on text mining. Eur J Cancer Prev. 2019 Nov;28(6):507-514. doi: 10.1097/CEJ.0000000000000494. PMID: 30394935; PMCID: PMC6784767
  4. Danforth DN Jr. Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer. Breast Cancer (Auckl). 2016;10:109-146. Published 2016 Aug 17. doi:10.4137/BCBCR.S39384
  5. Lavoué V, Bertel C, Tas P, Bendavid C, Rouquette S, Foucher F, Audrain O, Bouriel C, Levêque J. Hyperplasie épithéliale atypique du sein : bilan des connaissances et pratique clinique [Atypical epithelial hyperplasia of the breast: current state of knowledge and clinical practice]. J Gynecol Obstet Biol Reprod (Paris). 2010 Feb;39(1):11-24. French. doi: 10.1016/j.jgyn.2009.09.007. Epub 2009 Oct 22. PMID: 19853386.
  6. Surgical management of ADH, ALH, and LCIS | The Bulletin (

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