C49
Molecular subtypes of breast cancer and prognosis
Fiona M Blows1, Kristy E Driver1, Montserrat Garcia-Closas3, Peter A Fasching4, Elena Provenzano2, Paul Pharoah1, Carlos Caldas2
1Department of Oncology, University of Cambridge, Cambridge, UK, 2Department of Histopathology, Addenbrooke's Hospital NHS Trust, Cambridge, UK, 3Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland, USA, 4University Breast Center for Franconia, University Hospital, Erlangon, Bavaria, Germany
Background
Immunohistochemical (IHC) markers can be used to define several breast cancer subtypes. Estrogen receptor (ER), Progesterone receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER2) are currently used in the clinical setting. Recent research suggests that basal markers may predict a poorer prognosis within the triple negative phenotype (TNP, tumours that are negative for ER/PR/HER2). To test this we have analysed data from twelve studies, totalling 10, 454 participants with 46, 700 person years of follow-up.
Method
All studies provided IHC data for ER, PR, HER2 and at least one basal marker (CK5-6 and/or EGFR). Five subtypes were defined by IHC markers expressed: ER+/PR+/HER2- (n=7426), ER+/PR+/HER2+ (n=1073), ER-/PR-/HER2+ (n=819), ER-/PR-/HER2-/basal+ (core basal, n=621), ER-/PR-/HER2-/basal- (n=695). The Cox proportional hazards model was used to evaluate the prognostic significance of these subtypes stratified by study, treating the covariates as time dependent.
Results
Strong time dependent effects were seen for ER, PR and HER2 (hazard ratios decreasing with time). The poorest prognosis was seen in the ER-/PR-/HER2+ cases (HR= 2.64 [95% C.I. 2.28-3.06] compared to the ER+/PR+/HER2- cases). The TNP cases had an intermediate prognosis. The TNP/basal+ had an elevated hazard ratio (HR 1.98 [1.69-2.32]) compared to the TNP/basal- cases (HR 1.69 [1.43-1.99]). The ER+/PR+/HER2+ cases had a similar prognosis to the TNP cases.
Conclusion
Different combinations of IHC markers have different effects on estimating prognosis and have marked time dependent effects. Adding basal markers to the TNP group, does suggest a difference, which may be useful for novel targeted treatment.
