BACKGROUND: Optimizing treatment through microarray-based molecular subtyping is 
a promising method to address the problem of heterogeneity in breast cancer; 
however, current application is restricted to prediction of distant recurrence 
risk. This study investigated whether breast cancer molecular subtyping 
according to its global intrinsic biology could be used for treatment 
customization.
METHODS: Gene expression profiling was conducted on fresh frozen breast cancer 
tissue collected from 327 patients in conjunction with thoroughly documented 
clinical data. A method of molecular subtyping based on 783 probe-sets was 
established and validated. Statistical analysis was performed to correlate 
molecular subtypes with survival outcome and adjuvant chemotherapy regimens. 
Heterogeneity of molecular subtypes within groups sharing the same distant 
recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was 
studied.
RESULTS: We identified six molecular subtypes of breast cancer demonstrating 
distinctive molecular and clinical characteristics. These six subtypes showed 
similarities and significant differences from the Perou-Sørlie intrinsic types. 
Subtype I breast cancer was in concordance with chemosensitive basal-like 
intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded 
survival outcome similar to those of CAF in this subtype. Subtype IV breast 
cancer was positive for ER with a full-range expression of HER2, responding 
poorly to CMF; however, this subtype showed excellent survival when treated with 
CAF. Reduced expression of a gene associated with methotrexate sensitivity in 
subtype IV was the likely reason for poor response to methotrexate. All subtype 
V breast cancer was positive for ER and had excellent long-term survival with 
hormonal therapy alone following surgery and/or radiation therapy. Adjuvant 
chemotherapy did not provide any survival benefit in early stages of subtype V 
patients. Subtype V was consistent with a unique subset of luminal A intrinsic 
type. When molecular subtypes were correlated with recurrence risk predicted by 
genes of Oncotype and MammaPrint predictors, a significant degree of 
heterogeneity within the same risk group was noted. This heterogeneity was 
distributed over several subtypes, suggesting that patients in the same risk 
groups require different treatment approaches.
CONCLUSIONS: Our results indicate that the molecular subtypes established in 
this study can be utilized for customization of breast cancer treatment.