Possible Prognostic Role of HER2/Neu in Ductal Carcinoma In Situ and Atypical Ductal Proliferative Lesions of the Breast

  • Published : 2016.08.01


HER2/neu is a well-established prognostic and predictive factor for invasive breast cancer. However, the role of HER2/neu in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that it is mainly linked to in situ local recurrence. Although molecular data suggest that atypical ductal hyperplasia (ADH) and duct carcinoma in situ (DCIS) are related lesions, albeit with vastly different clinical implications, the role of HER2/neu expression in atypical ductal hyperplasia is not well defined either. The aim of this study was to evaluate over expression of HER2/neu in DCIS and cases of ADH in comparison with invasive breast carcinoma. Archival primary breast carcinoma paraffin blocks (n=15), DCIS only (n=10) and ductal epithelial hyperplasia and other breast benign lesions (n=25) were analyzed for HER2/neu immunoexpression. Follow up was available for 40% of the patients. HER2/neu was positive in 80%of both DCIS and invasive carcinoma, and 67% of atypical ductal hyperplasia (ADH) cases. Thus at least a subset of patients with preinvasive breast lesions were positive, which strongly suggests a role for Her2/neu in identifying high-risk patients for malignant transformation. Although these are preliminary data, which need further studies of gene amplification within these patients as well as a larger patient cohort with longer periods of follow up, they support the implementation of routine Her2/neu testing in patients diagnosed as pure DCIS and in florid ADH.


  1. AbdelGhani A. and Ghada E (2002) .Expression of c- erb, p53, Bcl-2, Bax,c-myc and Ki-67 in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast, Virchows Arch, 11-26, 441-9.
  2. Abdelhamid M, Abdelaziz S, Daoud S, et al (2014). Concordance of HER-2/Neu over expression with steroid receptor status in female breast cancers. Surgical Science, 5, 354-62.
  3. Abdurrahman Al Diab, S. Qureshi, Khalid A. Al Saleh, et al (2013). Studies on the methods of diagnosis and biomarkersused in early detection of breast cancer in the Kingdom of Saudi Arabia: an Overview. World J Med Sci, 8, 36-47,
  4. Al Mansour Z, Stockl T, Khan A (2013). Significance of HER2/ neu overexpression in pure ductal carcinoma in situ: A clinicopathologic study with long-term follow-up. J Clin Oncol, 31.
  5. Bezwoda W (2000). C-erb B-2 Expression and Response to Treatment in Metastatic Breast Cancer. Med Oncol, 22-28.
  6. Borgquist S, Zhou W, Jirstrom K (2015).The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study. BMC Cancer. 15. 468.
  7. Christopher JV, Khouri N, MD, Sbaity E (2013). Borderline atypical ductal hyperplasia/low-grade ductal carcinoma in situ on breast needle core biopsy should be managed conservatively. Am J Surg Pathol, 37, 913-923.
  8. Cohen J., Weiner D., Mori K (1989). Expression pattern of the neu gene. encoded growth factor receptor protein, P185, In normal and transformed epithelial tissues of the digestive tract. Oncogene, 4, 81-8.
  9. Doval D, Sharma A , Sinha R , et al (2015). Immunohistochemical profile of breast cancer patients at a tertiary care hospital in New Delhi, India. Asian Pac J Cancer Prev, 16, 4959-64,
  10. Drakaki A, Hurvitz S (2015). HER2-positive breast cancer: update on new and emerging agents. Am J Hemtol/Oncol, 11, 17-23.
  11. Fendly B., Winget M., Hudziak R, et al (1990). Characterization of murin monoclonal antibodies reactive to either the human epidermal growth factor receptor or HER-2/ neu gene product. Cancer Res, 3, 1550-8.
  12. Jimenez RE, Hussain M, Bianco FJ, et al (2001). Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors. Clin Cancer Res, 7, 2440-7.
  13. Johnson NB, Collins LC (2009). Update on percutaneous needle biopsy of nonmalignant breast lesions. Adv Anat Pathol, 16, 183-195.
  14. Krishnaswamy U, Balachandran P, I. Rajakumar, K. Balachandar and Mansoor M (2013). Correlation of Her-2 neu overexpression with clinico pathological features of carcinoma breast, 88-100.
  15. Latta E K, Tjan S, Parkes R K and O’Malley F P (2002). The Role of HER2/neu Overexpression/Amplification in the Progression of Ductal Carcinoma In Situ to Invasive Carcinoma of the Breast. Mod Pathol, 15, 1318-25
  16. Mitri Z, Constantine T, O'Regan, R (2012). The HER2 receptor in breast cancer: pathophysiology, clinical use, and new advances in therapy. s.
  17. Owens MA., Horten BC, Da Silva M (2004). HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer, 5-69.
  18. Pinder SE and Ellis IO (2003).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, 254-7.
  19. Rosen P (1997). Intraduct carcinoma. invasive duct carcinoma and morphological prognostic markers. biological markers of prognosis. Breast Pathology. Philadelphia. Lippincott- Raven, 227-320.
  20. Sapino A, Goia M, Recupero D, and Marchio C (2013). Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issues. Front Oncol, 3, 129.
  21. Sibel O, Cabioglu, Neslihan C, et al (2014). Factors predicting microinvasion in ductal carcinoma in situ. Asian Pac J Cancer Prev, 15, 55-60.
  22. Stark A, B. S. Hulka, S. Joens, et al (2000). HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer, J Clin, 18, 267-74.
  23. Tsutsumi Y, Naber S, Delellis R (1990). Neu oncoprotein and epidermal growth factor receptor are independently expressed in benign and malignant breast tissues. Hum Pathol, 21, 750-8.
  24. Wolff AC, Hammond ME, Schwartz JN, et al (2007). American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol, 25, 118-53.