10603 Background: BC in young women is associated with poor prognosis, which has been attributed to the higher incidence of aggressive BC subtypes. Whether the performance of prognostic gene expression signatures (GS) varies by BC subtype across age groups is unknown.
METHODS
We used publically available datasets and normalized microarray data as published by the original studies. Eligible patients were those with known age who received no adjuvant systemic therapy. Patients were assigned to 3 molecular subtypes (ER+, HER2+, ER-/HER2-). For each data set, we evaluated the following published signatures: Proliferation GS (GGI, GENE70, GENE76), stroma GS (DCN, SDPP, PLAU) and immune GS (IRM). We examined their interaction with age and relapse free survival in a Cox regression model. Improvements in their prognostic value over Adjuvant online! (AOL) were assessed by the change in the likelihood ratio value across different age groups (≤40, 41-60, >60).
RESULTS
1254 patients (373 events) from 12 datasets were eligible; of whom 194 (15%) were ≤ 40 years. 64%, 15% and 21% had ER+, HER2+ and ER-/HER2- BC respectively. Younger (≤40) had significantly higher incidence of ER-/HER2- (29% vs. 20% vs. 18%) and HER2+ subtypes (21% vs. 15% vs. 9%) (p<0.0001). In ER+ group, there was no interaction between age and the prognostic performance of GS except for SDPP (p=0.03), which was not prognostic in patients >60. Adding proliferation GS to AOL significantly improved prognostication (overall effect, GGI: HR 2.9 [95% CI 2.2-3.9]; GENE70: 3.2 [2.2-4.5]; GENE76: 2.6 [2.1-3.3], all p<0.0001). However, in ER-/HER2-, only DCN and PLAU showed significant interaction with age (p=0.007 and 0.004). High DCN and PLAU levels were associated with poor prognosis only in patients ≤ 40 and improved prognostication when added to AOL (HR: 3.3 [1.1-9.4] and 3.0 [1.1-8.0]; all p=0.03). In ER-/HER2-, other GS did not add prognostic value to AOL in all age groups.
CONCLUSIONS
Proliferation GS add significant prognostic information in ER+ BC irrespective of age. However, in ER-/HER2-, stroma GS added prognostic value only in patients ≤40. This data underscores the importance of understanding the tumor-stroma interactions especially in young BC patients.