Dynamic and subtype-specific interactions between tumor burden and prognosis in breast cancer

Purpose Recent updates of the AJCC staging system in breast cancer incorporated biologic characteristics along with the traditional anatomic tumor burden for outcome prediction. However, potential interactions between the prognostic effect of anatomic factors and the biologic characteristics are not reflected in the new system. In this study, we evaluated the interactions between the prognostic relevance of anatomic tumor burden and the molecular subtypes. Methods From the Korean Breast Cancer Registry Database, we investigated the relationship between the prognostic importance of anatomic tumor burden and molecular subtypes in patients with invasive breast carcinoma who were treated between 1980 and 2014. Tumors were classified into four different molecular subtypes based on the hormonal receptor status and HER2 expression status. (1) HR+/HER2- subtypes; (2) HR+/HER2+ subtypes; (3) HR-/HER2+ subtypes; (4) HR-/HER2- subtypes. Results Breast cancers with different molecular subtypes had unique outcome patterns in relation to anatomic tumor burden. In HR+/HER2+ and HR-/HER2- tumors, the increase in T stages exhibited profound rise in the hazard of death, while the presence of metastatic node was more important in HR+/HER2+ and HR-/HER2+ tumors in 131,178 Stage I to III breast cancer patients. The patterns for increasing risk of deaths along with tumor growth (per centimeter) and metastatic nodes (per one node) were examined in 67,038 patients with tumors 7cm or smaller and less than 8 metastatic nodes. HR+/HER2- and HR-/HER2- tumors showed persistent increase in risk of deaths as tumors grow while the effect was modest in HER2+ tumors. In contrast, the increased number of metastatic nodes was accompanied with persistent rise of risk in HR-/HER2+ tumors while the effect was minimal after 3 or 4 nodes in HR-/HER2- tumors. The interactions between the prognostic significance of anatomic tumor burden and molecular subtypes were statistically significant. Conclusion Our data demonstrates that the prognostic implication of tumor growth and spread, measured by the increase in tumor size and number of metastatic nodes, shows significant association with the molecular subtypes of the breast cancer. Additionally, our data suggest that the association between the prognostic impact and the anatomic tumor burden is rather dynamic that linear within a specific molecular subtype. Citation Format: Hong-Kyu Kim, Sae Byul Lee, Yunhee Choi, Young Wook Ju, Han-Byoel Lee, Wonshik Han, Dong-Young Noh, Jong Won Lee, Hyeong-Gon Moon, Jihye Choi. Dynamic and subtype-specific interactions between tumor burden and prognosis in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-37.