Analysis of the Clinicopathologic Features and Prognosis in Triple-Negative Breast Cancer

Discussion

Sorlie et al. ^[1] reported that breast cancers can be segregated into prognostic categories based on hierarchical cluster analysis of gene expression. The ER positive group can be divided into luminal A and luminal B. Whereas the ER negative group can be divided into ERBB2+, basal-like and normal-like. Of these types, ERBB2+ and basal-like have a poorer prognosis ^[4]. Nielsen et al. ^[5] developed a panel for identifying basal-like breast cancers based on immunohistochemical profiles. They defined basal-like carcinomas as negative for ER and Her-2, in addition to being positive for either EGFR or cytolceratin (CK) 5/6. The specificity is 100% and the sensitivity is 76%.

Triple-negative breast cancers are a type of breast cancer that does not express ER, PR or Her2. Triple negative and basal-like breast cancer have similar clinical characteristics. For example, studies have shown that 67% of CK5/6-positive breast cancers were shown to be triple-negative, while 12% of CK5/6-negative breast cancers were triple-negative breast cancer. Most of basal-like breast cancers were also triple negative. However, they are not homogenous ^[6]. Use of immunohistochemical markers can classify the majority of basal-like breast cancer with accuracy. Therefore, a basal-like characteristic can be defined by triple-negative breast cancer ^[7].

Triple-negative breast cancers have rarely been reported in China. Our results showed that triple negative breast cancers accounted for 21.4% of the cases. The average age was 51.3 and the average tumor diameter was 3.8 cm and 57.8% of the triple-negative breast cancers were in a premenopausal status. In a previous study, Dent et al.^[7] found that 11.2% of their cases were triple negative. Compared with non-triplenegative breast cancer, patients in the triple-negative group had a lower average age (53 years vs. 57.5 years), larger tumor size (3.0 cm vs. 2.0 cm), higher rates of node positivity (54.6% vs. 45.6%) and a higher rate of Grade III (66% vs. 28%). However, tumor size was not correlated with lymph node status, even as patients with small tumor had higher rates of positive node. In our current study, the proportion of Grade III tumors and a medullary type was higher compared to non-triple negative breast cancers. However, no significant difference in other clinicopatholgical features was found between the 2 groups, perhaps due to the lower number of cases. In another report ^[8], the triple-negative group had a higher proportion of patients with a family history of cancer and patients in this group were more likely to be African American. A total of 99 breast cancer patients were tested for the BRCA gene. Of 10 BRCA1 patients, 8 were triple negative, whereas only 1 of 7 BRCA2 patients was triple negative. These results indicated that the BRCA1 mutation was correlated with triple negative breast cancers.

Haffty et al.^[8] selected 482 cases of breast cancer between 1980 and 2003 with 7.9 years of follow-up. The-5 year DFS in triple-negative patients was 67%, while for non-triple-negative cases of was 82%. Triple negative was an independent predictor of distant metastasis. In another study, Dent^[7] demonstrated that during follow-up triple negative breast cancer had increased the likelihood of distant metastasis compared to non-triple negative breast cancer. Among the triple-negative group, the risk of a distant recurrence gradually increased in the first 2 years, peaking at the third year and then declining rapidly thereafter, reaching the lowest in the fifth year. No distant metastases were found after 8 years follow-up. Among the other group, the recurrence risk seemed to be constant over the period of follow-up ^[7]. In our current study, the 5-year DFS was higher than other reports, probably because of early detection and both early treatment and comprehensive treatment.

Tissue microarrays were prepared and immunohistochemically stained for biomarkers. Rakha et al.^[9] reported that associations were found with loss of expression of the androgen receptor and E-cadherin, and positive expression of basal cytokeratins, P-cadhrein, p53, and EGFR. The tumor size, lymph node status, androgen receptor and basal phenotype can be used to select high-risk and low-risk patients. Other researchers have found that a number of genes and biomarkers are related with hormone receptors or HER2 gene, which can be helpful in clinical therapy.

BI-1 (Bax inhibitor-1) is an apoptotic inhibitory gene that plays an important role in the development and progression of breast cancer. The positive expression of BI-1 in ER negative tumors was higher than that in ER positive tumors ^[10]. Shi et al reported that the expression of MUC 1 in breast cancer was significantly higher than in the normal and benign breast tissues. MUC1 expression was positively correlated with HER2 expression. Detection of MUC 1 and HER2 protein expression can be used to evaluate the degree of malignancy, axillary lymph node involvement, prognosis and treatment for breast cancer patients^[11]. Interaction between the ERβ and MAPK signal transduction pathways contributes to the development of breast cancer, apoptosis and endocrine therapy resistance. These proteins may become new targets of endocrine and chemical therapies for breast cancer ^[12].

In summary, triple-negative breast cancers have an increased likehood of local relapse and metastasis. These tumors do not benefit from a targeted therapy. Detection of biomarkers and pathways may be helpful to improve clinical therapy.