Pilot Study of Glucocorticoid Metabolism in Triple Negative Breast Cancers (TNBC)

Program: Abstracts - Orals, Poster Previews, and Posters
Session: SUN 203-235-Steroid Hormone Actions, Biosynthesis and Metabolism (posters)
Bench to Bedside
Sunday, April 3, 2016: 1:15 PM-3:15 PM
Exhibit/Poster Hall (BCEC)

Poster Board SUN 222
Keely M McNamara*1, Tiffany Mori2, Minoru Miyashita2, Noriko Nemoto2, Kentaro Tamaki3, Takanori Ishida4, Noriaki Ohuchi4 and Hironobu Sasano5
1Tohoku University, Sendai, Japan, 2Tohoku University, 3Nahanishi Clinic, 4Tohoku Univ Sch of Med, Sendai, Japan, 5Tohoku University Graduate School of Medicine, Sendai, Japan
Glucocorticoids partially function as dampeners of various systemic stress responses including inflammation and emesis. This physiological role has been utilised in pharmacologically treatment aimed improve the quality of life of breast cancer patients during chemotherapy. Despite being a commonly used drug little is been known regarding their direct actions upon breast cancers. In particular, glucocorticoid actions may be especially relevant in TNBCs given their therapeutic reliance on non-directed therapeutic modes such as chemotherapy and radiotherapy, and hence potential higher exposure to glucocorticoids administration. Therefore in this study antibodies directed against the GR receptor and importantly the two most directly related steroid metabolising enzymes 11βHSD1 and 2 were used to immunolocalize these protein in a pilot cohort of 44 TNBC retrieved from surgical pathology files of  Tohoku University Hospital, Sendai, Japan.  The correlations between the status of these molecules above, clinicopathological factors and other steroidogenic pathway components were then evaluated in order to understand the biological and clinical significance of glucocorticoid pathways in TNBC. GR immunoreactivity was detected in the nuclei of adjacent histologically normal breast epithelia, carcinoma cells as well as stromal cells and adipocytes.  We detected all three proteins at varying proportions and intensities in carcinoma cells of subsets of the TNBC cohort (GR 56% cases, 11βHSD1 33% cases, 11βHSD2 11% cases) although no statistically significant overlaps were present between GR and enzymes (GR/11β1+ 18% cases, GR/11β2+ 4% cases).  FOXA1 has been proposed as a pioneer factor for GR in addition to it well characterised role with AR but no significant association between either AR or FOXA1 and GR was detected in carcinoma cells. However, of interest, the percentage of positive cases for both enzymes was higher in FOXA1 positive cases and the difference reached statistical significance in 11βHSD2 (p<0.03). While the survival curves did not cross, with GR positive patients having a lower survival rate, this trend did not reach statistical significance. This pilot study did reveal the presence of GR and relevant enzymes within a significant subset of TNBCs. While possibly underpowered due to the relatively small number of the cases examined, results did suggest the possible interactions between differentiation (FOXA1) and glucocorticoid metabolism and GR and clinical outcome of the patients. This is important both in terms of biological significance of glucocorticoids administration during chemotherapy, as mentioned above and also of potential intersections between carcinoma development and chronic stress and inflammation (e.g. obesity), conditions well known to be associated with elevated circulating glucocorticoids. However further studies are required for clarification.

Nothing to Disclose: KMM, TM, MM, NN, KT, TI, NO, HS

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