title: 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.
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: In Ah
authors.initials: IA
authors.lastname: Park
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: An Na
authors.initials: AN
authors.lastname: Seo
authors.forename: Bora
authors.initials: B
authors.lastname: Lim
authors.forename: Yun
authors.initials: Y
authors.lastname: Chai
authors.forename: In Hye
authors.initials: IH
authors.lastname: Song
authors.forename: Na Eun
authors.initials: NE
authors.lastname: Kim
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Yu
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Gyungyub
authors.initials: G
authors.lastname: Gong
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012189:Retrospective Studies; D000068878:Trastuzumab; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; D016159:Tumor Suppressor Protein p53; C508053:ERBB2 protein, human