Suris-Swarm[5] reported that women younger than 50-year-old suffering from 4.3 times higher the possibility of getting bilateral primary breast cancer (BPBC) than women over the age of 50 year old. Award reported that women less than 40-year-old are in the population having a high risk of getting BPBC[6]. Among the patients studied in this paper, the diseased tissues are more frequently found in left breasts than the right breasts of patients in the younger group. Two (1.9%) patients get tumors on both of the left and right breasts in the young group, while no patient get tumors on both of the left and right breasts in the older group. The majority of patients have their incidence positions at the outer upper quadrant, followed by the inner upper quadrant and the nipple. Triple-negative breast cancer (TNBC) represents the major phenotype of basal-like molecular subtype of breast cancer, characterized by higher incidence in young women and a very poor prognosis. Svoboda[7] found that expression of miR-34b negatively correlates with an overall survival of TNBC patients.
Hutter[8] found that the number of lymph node metastasis is one of the decisive factors affecting the prognosis of breast cancer. Patients without lymph node metastasis have more favorable prognosis than those having lymph node metastasis. The more the number of metastatic lymph nodes, the worse the prognosis. Xu[9] found that claudin-6 is an important factor influencing lymphatic metastasis, whereas up-regulation of HDAC1 is associated with tumor progression and invasiveness in breast IDC. According to Liu et al.[10], the 3-year -and 5-year survival rates of young breast cancer patients with lymph node metastasis was 61.11%, 25% and the 3-year and 5-year survival rates of young breast cancer patients without lymph node metastasis was 100% and 83.33%, respectively. It is reported that young breast cancer patients have higher lymph node metastasis rates. More lesions are located in the internal mammary areas and the patients have late clinical stage, higher rate of infiltrating tumor occurrence, strong tumor invasiveness, easy transfer, and poor prognosis[11, 12]. According to our research, the younger group has more cases with tumor diameter greater than 5 cm than the older group (P < 0.05). The young group has more histological grade III tumors than the older group (P < 0.01),which is consistent with finding reported by Jimor[13] and Chen[14]. Since the pathological stage is a judgment made after visual inspection of the postoperative pathological specimens, and can more accurately reflect the severity and extent of breast cancer, it is more accurate than clinical staging.
In this study, according to the PTNM staging, the young group has less patients in phases 0 - I and phase II than the older group, and the numbers of patients in phase III was significantly more than the elderly group. Two groups have a significant statistical difference (P < 0.01). The younger group has higher axillary lymph node metastasis rates and the proportion of positive lymph node was significantly higher than the older group (P < 0.01), which is consistent with previous reports. In this study, we found young women with breast cancer have larger tumor mass, higher histological grade and lymph node metastasis rate than the elderly group. The majority of patients fall into the PTNM stage III.
As a tumor suppressor gene, the breast cancer susceptibility gene l (BRCA 1), not only inhibits cell growth, but is also involved in cell cycle regulation, gene transcription, DNA damage repair and apoptosis, and some other important cellular activities. It plays an important role in maintaining genetic stability. There is study found that the BRCA1 protein exits in the nucleus of normal mammary epithelial cell and the cytoplasm of tumor cells[15]. Chen et al.[16] find that dislocation of the cytoplasmic BRCA1 protein in breast cancer cells is related to the occurrence and metastasis of breast cancer, but the molecular mechanism is unclear. Fu[17] and Liu[18] found the BRCA1 protein is highly expressed in breast cancer, suggesting that the abnormal expression of the BRCA1 has some correlations with the occurrence and growth of breast cancer. Liu[18] also found BRCA1 protein expression and the patient age were negatively correlated. Younger patients have higher BRCA1 protein expression rate. In our study, BRCA1 protein is expressed in the cytoplasm of breast cancer cells of both of the young group and elderly group. The young group has higher positive expression rate than the old age group (< 0.01). BRCA1 protein expression is positively correlated with PTNM stage and axillary lymph node metastasis, which is consistent with the results reported by Chen[16] and Liu[18]. The younger group has a higher degree of malignancy and poor prognosis. The ectopic expression of BRCA1 in breast cancer is closely related to the happening, development and prognosis of young breast cancer patients.
Tomasz[19] found that methylation of the BRCA1 gene in PB DNA correlates with increased risk of breast cancer, suggesting that aberrant methylation of genes in PB and disease predisposition are related. Lv[20] observed that EGFR gene mutations were rare in breast carcinomas, but EGFR gene amplification was detected in about one third of the cases in this population. In their study, rare mutations in the EGFR gene in patients with breast cancer were detected, indicating that EGFR gene mutations are infrequent in this cohort of breast cancers. We carried out DNA sequencing on the gene mutation hot spots, the exon 2 and exon 20, in BRCA 1 gene. Fresh specimens of 10 cases of unrelated young invasive ductal carcinoma was compared by DNA sequencing to search for single nucleotide polymorphism (SNP) sites, the results found no sequence variation.
WWOX protein contains 414 amino acids. In its amino-terminal, there are two WW domains. The WW functional domains are related to the interaction between the proteins[21]. Protein interactions are necessary for the tumor suppressor genes to inhibit tumor growth through signal transduction pathways. The deletion and mutation of WWOX may inhibit apoptosis and promote tumor occurrence and development[22]. In this study, WWOX protein expression of the young group and old group were 86.9% and 86.6%, respectively. The difference was not statistically significant (P > 0.05), the experiments also showed no correlation (P > 0.05) between WWOX and age and other clinical indicators.
Patient age itself is not a major factor affecting the prognosis of breast cancer. In young patients with poor prognosis, it is mainly due to their adverse pathological parameters and invasive biological characteristics. Therefore, clinically, comprehensive analysis should be carried on age and tumor clinicopathological and biological indicators.