Document Type : Case Report(s)


Department of Hematopathology, Molecular Pathology and Cytogenetics, Shiraz University of Medical Sciences, Shiraz, Iran


The emerging era of personalized medicine makes it increasingly important to consider intratumoral heterogeneity, which has been found in some breast cancer cases. However, its identification criteria, form of reporting, and subsequent effects on the clinical course of this disease remain controversial and not fully defined. Here, we report and discuss a case of breast invasive ductal adenocarcinoma with substantial intratumoral heterogeneity, discrepancy between Her2/neu immunostaining and in situ hybridization, and disparity between estrogen receptor status before and after neoadjuvant therapy.


1-    Cho SH, Jeon J, Kim SI. Personalized medicine in breast cancer: a systematic review.  J Breast Cancer. 2012;15(3):265-72.
2-    Verma M. Personalized medicine and cancer. J Pers Med. 2012;2(1):1-14.
3-    Tang P, Tse GM. Immunohistochemical surrogates for molecular classification of breast carcinoma: A 2015 update. Arch Pathol Lab Med. 2016;140(8):806-14.
4-    Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med. 2014;138(2):241-56.
5-    Fitzgibbons PL, Dillon DA, Alsabeh R, Berman MA, Hayes DF, Hicks DG,  et al. Template for reporting results of biomarker testing of specimens from patients with carcinoma of the breast. Arch Pathol Lab Med. 2014;138(5):595-601.
6-    Varga Z, Tubbs RR, Moch H. Concomitant detection of HER2 protein and gene alterations by immunohistochemistry (IHC) and silver enhanced in situ hybridization (SISH) identifies HER2 positive breast cancer with and without gene amplification. PLoS One. 2014;9(8):e105961.
7-    Seol H, Lee HJ, Choi Y, Lee HE, Kim YJ, Kim JH, et al. Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance. Mod Pathol. 2012;25(7):938-48.
8-    Makroo RN, Chowdhry M, Kumar M, Srivastava P, Tyagi R, Bhadauria P, et al. Correlation between HER2 gene amplification and protein overexpression through fluorescence in situ hybridization and immunohistochemistry in breast carcinoma patients. Indian J Pathol Microbiol. 2012;55(4):481-4.
9-    Tamaki K, Sasano H, Ishida T, Miyashita M, Takeda M, Amari M, et al. Comparison of core needle biopsy (CNB) and surgical specimens for accurate preoperative evaluation of ER, PgR and HER2 status of breast cancer patients. Cancer Sci. 2010;101(9):2074-9.
10-                       Niikura N, Tomotaki A, Miyata H, Iwamoto T, Kawai M, Anan K, et al. Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21,755 patients from the Japanese breast cancer registry. Ann Oncol. 2016;27(3):480-7.