Two histopathologically different diseases: hormone receptor-positive and hormone receptor-negative tumors in HER2-positive breast cancer

• Published in: Breast cancer research and treatment 2014-06, Vol.145 (3), p.615-623
• Main Authors: Lee, Hee Jin, Park, In Ah, Park, So Yeon, Seo, An Na, Lim, Bora, Chai, Yun, Song, In Hye, Kim, Na Eun, Kim, Joo Young, Yu, Jong Han, Ahn, Jin-Hee, Gong, Gyungyub
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer; Cancer research; Cancer therapies; Carcinoma, Intraductal, Noninfiltrating; Care and treatment; Chemotherapy; Disease-Free Survival; Epidermal growth factor; Female; Gene Amplification; Histopathology; Hormones; Hormones, Sex; Humans; Immunohistochemistry; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Grading; Oncology; Preclinical Study; Receptor, ErbB-2 - biosynthesis; Receptor, ErbB-2 - genetics; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Retrospective Studies; Trastuzumab; Tumor proteins; Tumor Suppressor Protein p53 - biosynthesis; Young Adult
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-014-2983-x

The clinical behavior of human epidermal growth factor 2 (HER2)-positive breast cancer, including pathologic complete response rate and pattern of relapse and metastasis, differs substantially according to hormone receptor (HR) status. We investigated various histopathologic features of HER2-positive breast cancer and their correlation with HR status. We retrospectively analyzed tumors of 450 HER2-positive breast cancer patients treated with chemotherapy and 1 year of trastuzumab. HR−/HER2+ tumors showed higher nuclear grade, less tubule formation, higher histologic grade, frequent apocrine features, diffuse and abundant lymphocytic infiltration, strong HER2 immunohistochemical staining (3+), higher average HER2 copy number and HER2 / CEP17 ratio, the absence of HER2 genetic heterogeneity, and greater p53 expression than HR+/HER2+ tumors. An inverse correlation was observed between estrogen receptor or progesterone receptor Allred score and average HER2 copy number or HER2 / CEP17 ratio. The percentage of ductal carcinoma in situ (DCIS) within the tumor was negatively correlated with ER Allred score, but positively correlated with average HER2 copy number and HER2 / CEP17 ratio. Pathologic tumor size and DCIS percentage also showed a significant inverse correlation. Ratio of metastatic to total examined lymph node number was significantly correlated with average HER2 copy number and HER2 / CEP17 ratio. High pT stage (hazard ratio, 2.370; p  = 0.027), the presence of lymphovascular invasion (hazard ratio, 2.806; p  = 0.005), and HR negativity (hazard ratio, 2.202; 1.074–4.513; p  = 0.031) were found to be independent prognostic indicators of poor disease-free survival. In conclusion, HR+/HER2+ and HR−/HER2+ breast cancer showed distinct histopathologic features that may be relevant to their distinct clinical behavior.