257P A low fT3/fT4 ratio as a negative prognostic factor in patients with metastatic breast cancer

Low levels of free triiodothyronine (fT3) predict worse outcomes across various medical conditions even in the absence of the so called non thyroidal illness syndrome. fT3/fT4 ratio better reflects peripheral deiodination activity and holds promise for stratifying patients (pts) with normal fT3 levels. A reduced fT3/fT4 ratio has been linked to worse outcomes in pts with various metastatic cancers. In this study, we aimed to explore the potential prognostic effect of fT3/fT4 in pts with metastatic breast cancer (mBC). We conducted a retrospective analysis of pts with mBC enrolled in phase I/II trials at the European Institute of Oncology. Clinical data and baseline blood test results were collected at the initiation of the experimental treatment. PFS and OS were analysed by means of Kaplan Meier. Study population was categorised in High vs Low levels of fT3/fT4 ratio groups using the median as the cutoff point. 36 pts with available fT3/fT4 ratio results were included. Median age at diagnosis was 43 years (IQR 26-67), median number of previous treatment lines was 2 (IQR 0-9). At diagnosis, 69% of pts had visceral metastases, 36% had hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) BC, while 22% and 36% had HER2+ and triple-negative BCs, respectively. The median value of fT3/fT4 was 0.267. Among pts with low fT3/fT4 ratio 88% had visceral metastasis compared to 52% in the group with high fT3/fT4 ratio (p=0.021). Neither age nor the number of previous lines of treatment or albumin levels were different across the fT3/fT4 ratio groups. Pts with a low fT3/fT4 ratio had a mPFS of 1.6 months and a mOS of 6.0 months compared to 1.8 and 20.0 months, respectively, for pts with a high fT3/fT4 ratio (PFS HR=0.81, 95%CI 0.41-1.58, p=NS; OS HR=0.43, 95%CI 0.20-0.94, p=.008). At MV analyses including the presence of visceral metastasis as covariate only fT3/fT4 ratio retained its significant association with OS (p=0.004). Our data suggest that fT3/fT4 ratio, may deserve further investigation as a negative prognostic marker in patients with mBC. Given the small sample size, these exploratory survival analyses as well as the associations with other well known prognostic features should be interpreted with caution.