Age-Dependent Heterogeneity of Lymph Node Metastases and Survival Identified by Analysis of a National Breast Cancer Registry

Abstract

Background: For several cancers, including those of the breast, young age at diagnosis is associated with an adverse prognosis. Although this effect is often attributed to heritable mutations such as BRCA1/2, the relationship between pathologic features, young age of onset, and prognosis for breast cancer remains unclear. In the present study, we highlight links between age-of onset and lymph node metastasis (LNM) in US women with breast cancer. Methods: Case listings from Surveillance, Epidemiology, and End Result (SEER) 18-population-based registry data for women with breast cancer, which include information on race, were used. LNM and its associated outcomes were evaluated for a subset of women with receptor subtype information and then compared against a larger, pre-subtype validation set of data from the same registry. Age of diagnosis was a 5-category variable; under 40 years, 40-49 years, 50-59 years, 60-69 years and 70+ years. Univariate and adjusted multivariate survival models were applied to both sets of data. Results: As determined with adjusted logistic regression models, women under 40 years old at diagnosis had 1.55 times the odds of LNM as women 60-69 years of age. The odds of LNM for (HR = hormone receptor) HR+/ HER2+, HR-/HER2+, and triple-negative breast cancer subtypes were significantly lower than those for HR+/HER2-. In subtype-stratified adjusted models, age of diagnosis had a consistent trend of decreasing odds of LNM by age category, most noticeable for HR+ subtypes of luminal A and B. Univariate 5-year survival by age was worst for women under 40 years, with LNM attributable for 49% of the hazard of death from cancer in adjusted multivariate models. Conclusions: Lymph node metastasis is age-dependent, yet not all molecular subtypes are clearly affected by this relationship. For <40-yr- old women, LNM is a major cause for shorter survival. When stratified by subtype, the strongest associations were in HR+ groups, suggesting a possible hormonal connection between young age of breast cancer onset and LNM.