Abstract
e24129 Background: E is approved for the treatment of mBC pts after previous exposure to antracyclines and taxanes. E interferes with microtubule leading to apoptosis and cell cycle arrest in G2/M. E reverses epithelial mesenchimal transition (EMT) in human cancer cell lines and in mice. Moreover, reduces metastatization in mice. TGFβ is an immunosuppressive cytokine, is a growth factor for cancer-associated fibroblasts (CAFs) and promotes EMT. TNFα synergizes with TGFβ to promote EMT. EMT permits cancer cells trafficking thus driving metastatization. Our study investigates the interference among E and TGFβ and TNFα levels in pts and the correlation with the outcome and the metastatic spread. Methods: Blood levels of TGFβ and TNFα were determined at baseline, before cycle (C) 3, 5 and at disease progression in mBC pts treated with E at 1.23 mg/m2, d 1–8 every 21 d. Results: We report data on 24 pts who completed 5 C or progressed before C 5. We did not observe changes of TNFα during treatment. The median (M) basal TGFβ value was higher in pts than in 4 healthy volunteers (M concentrations: 232 pg/ml vs 114 pg/ml respectively). We divided our population according to basal TGFβ levels upper or lower the M value. M PFS was similar in the two groups (112 vs 100 d). TGFβ increased in 9 pts from basal to C 5, and decreased in 15 pts. We observed a numerical difference in M PFS between the pts with decreased and increased values (107 vs 82 d respectively). In 8 pts TGFβ decreased at each subsequent point. M PFS in these pts was 167 vs 84 d in the remaining. Notwithstanding the continuous decline of TGFβ, 2 of these pts progressed at C 5 (both at CNS). In pts with continuous TGFβ decline the M value approaches healthy controls (160 pg/ml [range 303-90] vs 114 pg/ml [range 120-85] respectively). At C 5 9 pts did not progress: 3 PR and 6 SD (M PFS 175 d). TGFβ decreased in all but 2 pts (1PR+1SD). In these 2 pts PD occurred as early as 21 and 30 d respectively from C 5. The behaviour of pts with SD suggests that there is no correlation between tumor burden and TGFβ level. Conclusions: Basal TGFβ does not predict outcome. TGFβ changed during treatment with E regardless of tumor load. Our results suggest that TGFβ changes correlate with outcome.
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