Age-associated prognostic and predictive biomarkers in patients with breast cancer

Abstract

To date, no comprehensive prognostic or predictive marker profiling analysis has been performed in association with the age of patients with breast cancer. In the present study, 632 breast cancer tissue samples were analyzed for expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), B-cell lymphoma (Bcl)-2 protein, HER2 gene amplification, proliferation [as evaluated by proliferating cell nuclear antigen (PCNA) and Ki-67 index], tumor grade, histological type and molecular subtype. The data revealed correlations with the age of patients. A statistically significant positive correlation was identified between patient age and expression of ER (P<0.0001). There was no significant association between patient age and PR, HER2 protein expression, HER2 gene amplification or PCNA. A significant negative correlation between age and Ki-67 expression (P<0.0001) as well as grade of tumor (P=0.007) was identified. The spectrum of molecular subtypes differed according to age (P=0.0003). The highest incidence of aggressive triple-negative and HER2-positive breast cancer was present in patients aged between 20 and 39 years. Luminal A subtype was the most frequent cancer subtype in patients from age 40 onwards, where proliferation activity declined with age and expression of hormone receptors increased along with Bcl-2 expression. Aggressive forms of breast cancer were more common in younger patients. Prognostic and predictive markers have a complex age-specific distribution. The findings of less aggressive luminal A and B subtypes in older patients, and the positive correlation with ER, PR and Bcl-2 expression reveal the potential efficacy of Bcl-2 as a marker of hormone responsiveness in these patients.

Keywords: B-cell lymphoma 2; age-associated expression; biomarkers; breast cancer; molecular subtypes.

Figure 1.

Mean histological score (H-score) of PCNA, Ki-67, PR, HER2, Bcl-2 and ER in age decades. PCNA, proliferating cell nuclear antigen; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; Bcl, B-cell lymphoma; ER, estrogen receptor.

Figure 2.

Graphical presentation of age-associated distribution of molecular subtypes. HER2, human epidermal growth factor receptor 2; TNBC, triple-negative breast cancer.