Abstract P6-09-11: Independent prognostic value of age depends on breast cancer subtype
Authors: Poppe A , Brouckaert O , Laenen A , Soubry A , Remmerie C , Floris G , Leunen K , Berteloot P , Amant F , Vergote I , Nevelsteen I , Smeets A , Christiaens M-R , Weltens C , Peeters S , Van Limbergen E , Wildiers H , Neven P 
Published: May 2016

Abstract
Background: Young women present more often with aggressive breast cancer phenotypes and have worse prognosis. It remains controversial whether age is an independent prognostic factor in early stage breast cancer. Arbitrarily chosen age cut-off values have been proposed in different studies. Furthermore, few studies have examined the impact of breast cancer subtypes on the prognostic value of age. This abstract represents an update of a prior analysis (San Antonio Breast Cancer Symposium, December 4-8 2012, P06-07-29).
Methods: We included all primary operable female breast cancer patients from our prospectively managed database in UZ Leuven, Belgium. We assessed the effect of age on locoregional free interval (LRRFI), distant metastasis interval (DMFI) and breast cancer specific survival (BCSS). In univariate analysis, using Cox regression models, we determined the best categorization of age at diagnosis into two or three age groups by considering all possible combinations of cut-off values. Best categorization was obtained with three age groups. We further determined, using multivariate analysis (correcting for phenotype, tumor size, nodal status, adjuvant chemo -, hormone – and radiotherapy, type of surgery and procedure of axillary staging), whether age at diagnosis remains an independent predictor of outcome (LRRFI, DMFI and BCSS). We further explored whether age at diagnosis is an independent predictor of event risk (LRRFI, DMFI and BCSS) in different breast cancer subtypes. Luminal A-like (grade I or II, ER and/or PR positive, HER 2 positive), Luminal B-like (idem but grade III), Luminal HER 2 like (ER and/or PR positive, HER 2 positive), HER 2 like (ER/PR negative, HER 2 positive), triple negative (ER/PR negative, HER 2 negative).
Results: We included 4180 patients with a mean/median age of 58/57 year and with a median follow up of 8.9 year. Multivariate analysis confirmed age as an independent prognostic variable for LRRFI, DMFI and BCSS.
Results multivariable analysis with age in 3 groups (HR (95% CI) P-VALUE) LRRFIDMFIBCSSYoungest versus middle1.61 (1.18-2.18) 0.00251.54 (1.23-1.93) 0.00021.72 (1.26-2.36) 0.0007Youngest versus oldest3.45 (1.85-6.45) 0.00011.25 (0.89-1.77) 0.19821.31 (0.85-2.02) 0.2220Middle versus oldest2.15 (1.22-3.79) 0.00820.81 (0.61-1.09) 0,17060.76 (0.55-1.06) 0.1014
We found optimal cut-off values for LRRFI at 44y and 72y, for DMFI at 47y and 71y and for BCSS at 41y and 70y.
In an exploratory analysis, with age as continuous variable, by subtype we found a significant independent association between age and LRRFI (P=0.0169), DMFI (P=0.0344) in luminal A-like, LRRFI (P=0.0022) in luminal B-like and DMFI (P=0.0010) and BCSS (P=0.0053) in triple negative breast cancer. No significant associations were found in luminal HER2 and HER2 like breast cancers.
Conclusion:
This study has shown that young age is an independent prognostic factor for LRRFI, DMFI and BCSS after correction for the most important clinical prognostic factors. The prognostic effect is most important in luminal A and triple negative subtypes. Additional analyses for subtypes with age as a categorical variable will be performed and optimal cut off values will be defined.
Citation Format: Poppe A, Brouckaert O, Laenen A, Soubry A, Remmerie C, Floris G, Leunen K, Berteloot P, Amant F, Vergote I, Nevelsteen I, Smeets A, Christiaens M-R, Weltens C, Peeters S, Van Limbergen E, Wildiers H, Neven P. Independent prognostic value of age depends on breast cancer subtype. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-09-11.