Breast cancer is a heterogeneous group of disease that can be characterized into clinically, morphologically and biologically distinct subgroups
[14, 23]. By gene expression profiling and IHC markers, breast cancers can be classified into five major subtypes: luminal A (ER + and/or PR+, HER2-), luminal B (ER + and/or PR+, HER2+), HER2-overexpressing (ER-, PR-, HER2+), basal-like (ER-, PR-, HER2-, CK5/6+ and/or EGFR+) and normal breast-like tumors
[1, 8, 12, 24, 25]. Of particular importance is the basal-like subtype, which accounts for 15 to 20% of all breast cancers and confers a markedly poor prognosis
[1, 4, 5]. Recent studies have shown that basal-like breast cancers are likely to be mitotically active high-grade invasive tumors that are associated with a younger patient age
[4, 26, 27]. A population-based study also identified this subtype to be more prevalent in premenopausal African American women and highly associated with BRCA-1 mutation
[4, 12, 26, 27]. Due to their lack of ER, PR and HER2 expression, basal-like breast cancers are also unlikely to respond to anti-estrogen hormonal therapies or trastuzumab
To date, the gold standard for identifying basal-like breast cancers is based on gene expression profiling. However, cost and technical issues have rendered gene expression profiling impractical as a routine diagnostic tool in the clinical setting. In the Western population, approximately 70 to 90% of “triple-negative” breast cancers (ER-, PR-, HER2-) express basal markers, resulting in the triple-negative subtype commonly used as a surrogate marker for the basal-like subtype
[1, 4, 8, 18, 29–37]. Relatively little is known about this disease entity within Asian populations, and in particular Malaysian populations.
Within the small cohort of 340 breast cancer patients described in this study, a total of 42 cases (12.4%) were identified as triple-negative. This proportion was slightly lower than the recent studies in the Malaysian, Japanese, Chinese and Korean populations that estimated the prevalence of TNBC to be around 15 to 20%
[23, 38–41]. Consistent with earlier studies, our results showed that TNBC in Malaysian women was strongly associated with a younger age and high grade tumors compared to non-TNBC
[5, 10, 14, 15, 38, 42]. However, no significant differences in tumor size, histology (IDC vs DCIS) and lymph node infiltration rates were observed between TNBC and non-TNBC in the current study.
Further analysis was carried out to investigate the expression of EGFR, CK5/6 and c-KIT in TNBC and non-TNBC specimens. Due to the lack of information on HER2 amplification, only tumors with HER2 scores of 0 were included in the TNBC cohort. Our results demonstrated that TNBC in Malaysian women was strongly associated with EGFR, CK5/6 and c-KIT expression. Our results also showed that TNBC had a significantly higher Ki-67 proliferation index than non-TNBC, suggesting that TNBC could be more progressive.
Numerous studies have also shown that basal-like breast cancer can be specifically identified using IHC surrogate panels including ER, PR and HER2 negativity and either EGFR or CK5/6 positivity (ER-, PR-, HER2-, CK5/6+ and/or EGFR+)
[8, 19, 26, 43, 44]. Using such surrogates, our study showed that 78% (14/18) of TNBC can be categorized as basal-like breast cancers. This proportion is consistent with previous studies that also show that 71.5% of TNBC are basal-like by gene expression profiling