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

Abstract

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.

Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Breast Cancers

“…Moreover, different clinical behaviors and histopathologic characteristics of HR+/HER2+ breast cancers and HR–/HER2+ breast cancers have been reported [28,29]. In this study, we found that HR–/HER2+ breast cancers were significantly associated with a higher histologic grade, higher nuclear grade, and abundant amount of TILs when compared to HR+/HER2+ breast cancers, consistent with previous studies.…”

Clinical and prognostic relevance of EZH2 in breast cancer: A meta-analysis

“…Biological behaviors and prognoses of BC with different molecular phenotypes are different [26]. The luminal type was proved to be well differentiated with more of histological grade 1, small size, and negative axillary lymph node [26,27], while HER-2 enriched type and TNBC were considered to be poorly differentiated with higher histological grades, larger tumors, greater lymph involvements and more advanced stages [27,28]. Furthermore, some researches investigated the relationships between the subtypes of BC and distant metastases [29,30].…”

Prognostic Significance of Tumor-Infiltrating Lymphocytes and the Tertiary Lymphoid Structures in HER2-Positive Breast Cancer Treated With Adjuvant Trastuzumab

“…We previously analyzed surgically resected, HER2-positive breast cancers from patients treated with adjuvant chemotherapy and trastuzumab and found that hormone receptor-negative/HER2positive (HR−/HER2+) tumors had more diffuse and intense lymphocytic infiltration, a higher nuclear grade, less tubule formation, a higher histologic grade, more frequent apocrine features, stronger HER2 immunohistochemical staining, a higher average HER2 copy number and HER2/CEP17 ratio, the absence of HER2 genetic heterogeneity, and more p53 expression than hormone receptor-positive/HER2-positive (HR+/HER2+) tumors. 1 HR-/HER2+ tumors also have a higher pathologically complete response rate to neoadjuvant systemic therapy than HR+/HER2+ tumors, and the patterns of relapse, metastatic spread, and patient survival also differ between these subtypes. [2][3][4] The prognostic and predictive values of tumor-infiltrating lymphocytes (TILs) have been determined for breast cancer.…”