Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses.

Background: Breast cancer developed at a young age (≤45 years) is hypothesized to have unique biology; however, findings in this field are controversial. Methods: We compared the whole transcriptomic profile of young vs. old-age breast cancer using DNA microarray. RNA was extracted from 13 fresh estrogen receptor (ER)-positive primary breast cancer tissues of untreated patients (7 = young age ≤45 years and 6 = old age ≥55 years). In silico validation for the differentially expressed genes (DEGs) by young-age patients was conducted using The Cancer Genome Atlas (TCGA) database. Next, we analyzed the protein expression encoded by two of the significantly down-regulated genes by young-age patients, Glycine N-acyltransferase-like 1 (GLYATL-1) and Ran-binding protein 3 like (RANBP3L), using immunohistochemical analysis in an independent cohort of 56 and 74 ER-positive pre-therapeutic primary breast cancer tissues, respectively. Results: 12 genes were significantly differentially expressed by young-age breast cancers (fold change >2 or <2- with FDR p-value < 0.05). TCGA data confirmed the differential expression of six genes. Protein expression analysis of GLYATL-1 and RANBP3L did not show heterogeneous expression between young and old-age breast cancer tissues. Loss of expression of GLYATL-1 was significantly (p-value 0.005) associated with positive lymph node status. Higher expression of RANBP3L was significantly associated with breast cancers with lower histopathological grades (p-value 0.038). Conclusions: At the transcriptomic level, breast cancer developed in young and old age patients seems homogenous. The variation in the transcriptomic profiles can be attributed to the other clinicopathological characteristics rather than the age of the patient.

Angiopoietin-Like Protein 4 and Insulin-Like Growth Factor-1 Expression in Invasive Breast Carcinoma in Young Women.

Biomarker identification is imperative for invasive breast carcinoma, which is more aggressive and associated with higher mortality and worse prognosis in younger patients (<45 years) than in older patients (>50 years). The current study aimed to investigate angiopoietin-like protein 4 (ANGPTL4) and insulin-like growth factor-1 (IGF-1) protein expression in breast tissue from young patients with breast carcinoma. Immunohistochemical staining was applied in formalin-fixed, paraffin-embedded samples of breast carcinoma tissue from young patients aged <45 years at the time of diagnosis. Both proteins were expressed in the majority of cases. The highest frequency of positive ANGPTL4 and IGF-1 expression was observed in the luminal A subtype, whereas the HER2-overexpression subtype exhibited the lowest expression frequency for both proteins. There was no significant association between ANGPTL4 (p = 0.897) and IGF-1 (p = 0.091) expression and molecular subtypes of breast carcinoma. The histological grade was a significant predictor of ANGPTL4 expression (grade 1 vs. grade 3, adjusted odds ratio = 12.39, p = 0.040). Therefore, ANGPTL-4 and IGF-1 expressions are common in young breast carcinoma tissue. There is a potential use of them as biomarkers in breast carcinoma.

The Unique Biology behind the Early Onset of Breast Cancer.

Breast cancer commonly affects women of older age; however, in developing countries, up to 20% of breast cancer cases present in young women (younger than 40 years as defined by oncology literature). Breast cancer in young women is often defined to be aggressive in nature, usually of high histological grade at the time of diagnosis and negative for endocrine receptors with poor overall survival rate. Several researchers have attributed this aggressive nature to a hidden unique biology. However, findings in this aspect remain controversial. Thus, in this article, we aimed to review published work addressing somatic mutations, chromosome copy number variants, single nucleotide polymorphisms, differential gene expression, microRNAs and gene methylation profile of early-onset breast cancer, as well as its altered pathways resulting from those aberrations. Distinct biology behind early-onset of breast cancer was clear among estrogen receptor-positive and sporadic cases. However, further research is needed to determine and validate specific novel markers, which may help in customizing therapy for this group of patients.