Exploratory study of clonality determined by expression of tumor markers in intrinsic subtypes of breast cancers.

Abstract

Abstract Abstract #5060 [Background] However expression profile-based intrinsic subtypes revealed heterogeneity of breast cancer, several biological issues are not clarified yet, especially in tumor development. [Objectives] In order to clarify the relationship between intrinsic subtypes and positivity of tumor markers (TMs), CEA, CA15-3, BCA225 and NCC-ST439 were measured from sera taken from patients at the relapse retrospectively. In addition to the analysis of positivity of TMs, migration of TMs were analyzed in each intrinsic subtype, especially focused on changes of CA15-3 (equivalent to soluble MUC1) to identify the heterogeneity and development to other subtypes in the meaning of TMs expression. [Methods] Sera were collected from seventy five patients of newly diagnosed metastatic breast cancer. Intrinsic subtypes were simply determined by immunohistochemical staining as Luminal A (LA) ,B (LB), HER2 and TN. The positivity of TM was defined if it elevated 20% higher than normal upper limit. [Results] The positive rate of any TMs were higher in order of LA, LB, HER2 and TN. There was significant difference between Luminal (LA+LB) and TN in positive rate of TMs(p<0.05). If focused on mammary epithelium development marker MUC1 (CA15-3 as a soluble form), it was significantly elevated in Luminal (LA+LB) than HER2 and TN(p<0.05). Interestingly, 18 of 23 (72.3%) TN tumors showed all TMs negative at the relapse, although 4 of 18 (22.2%) TN tumors developed to TMs positive after palliative chemotherapies. [Conclusion] Luminal type showed higher expression of TMs at the relapse. It might be explained by the fact that common TMs were selected as responsive serum proteins to the tumor volume of dominant population of breast cancer by chance. But if we integrate the idea that CA15-3 as a development marker, luminal cancer was developed from ER+ highly developed progenitor and HER2 and TN might be developed from ER- progenitor lineage. The migration of TMs of TN after palliative chemotherapies might be illustrated with clonal selection by chemosensitivity. These phenomenon will be understood by further biological experiments and prospective clinical trials to improve the outcome of metastatic breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5060.