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.

Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer

“…Both CTC clusters and younger age have been associated with worse prognosis and reduced survival rates [ 2 , 5 , 17 – 20 ]. In this case, it is unlikely that younger age represents an independent risk factor for CTC cluster formation, but rather it may reflect an association with tumor aggressiveness [ 21 ].…”

Hormone Receptor–Positive/Human Epidermal Growth Receptor 2–Negative Metastatic Breast Cancer in Young Women: Emerging Data in the Era of Molecularly Targeted Agents

“…More recently, a study of more than 25,000 patients in Japan (2% of whom had metastatic disease at onset) found that age <35 years was an independent negative prognostic factor for both overall survival (OS; hazard ratio: 1.58; 95% CI: 1.16-2.15; p = .004) and diseasefree survival (hazard ratio: 1.73; 95% CI: 1.42-2.10; p < .001) [4]. Age-based comparisons of the clinicopathologic features of early breast cancer have consistently found that younger women are more likely to be diagnosed with estrogen receptor-negative (ER−) tumors, to have higher-grade and larger tumors, and to have lymph node involvement [16][17][18].…”

Hormonal Receptors, Human Epidermal Growth Factor Receptor-2 and Triple Negative Immunohistochemical Typing of Women Breast Cancer in Kampala, Uganda.

“…Mwakigonja et al reported that, the expression of HER2 in the patients with BC aged ≤ 55 years was 41% compared to 10% for those aged > 55 years and the difference was statistically signi cant (p = 0.079) [12]. in another study done by Marketa et al it was also found that the expression of HER2 in patients with BC aged 20-39 years was higher than those aged more than 50 years [38].…”

“…This observation is similar to the ndings in the study by Jiayu et al which was done in China which found that, the prevalence of TNBC in patients aged ≤ 40 years was 13.8% compared to 7.1% found in patients with > 40 years but the difference in having TNBC between the two age groups was not statistically signi cant (p = 0.443) [43]. Marketa et al in Czech Republic also reported that 66% of the cases with TNBC were in the age group 20-29 years [38] In another study which was done in United Kingdom (UK), it was found that, patients with TNBC were carrying the worst prognosis than the rest of the molecular subtypes [40].…”