{'fraction_non_alphanumeric': 0.037907100907634814, 'fraction_numerical': 0.037907100907634814, 'mean_word_length': 4.528023598820059, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
PARP1 in triple-negative breast cancer: Expression and therapeutic potential.

1061 Background: Triple negative breast cancers (TNBC) are so named as they lack expression of ER, PR and do not exhibit overexpression of HER2. Consequently, targeted therapy is currently unavailable for this subgroup of patients. The aims of this study were to investigate the expression of poly (ADP-ribose) polymerase 1 (PARP1) in TNBC and test the effect of the PARP inhibitor, Olaparib, on the growth of TNBC cell lines in vitro.


METHODS
PARP1 protein was measured in 90 breast cancers using Western blotting. Pooled data from 22 published gene expression databases (N=approx 4,000 patients) was used to relate PARP1 mRNA to patient outcome. The effect of Olaparib on the growth of TNBC lines was investigated using the acid phosphatase assay and Calcusyn software.


RESULTS
Using Western blotting, 4 forms of PARP1 were found in extracts of breast cancer, migrating at 116 kDa (main form), 65 kDa (necrotic form), 50 kDa (necrotic form) and 27 kDa (apoptotic form). The parental form of PARP, ie, the 116 kDa form was detected in all of 12 TN and in 73/78 (94%) of non TN samples. Using Kaplan-Meier analysis, high PARP1 mRNA expression was significantly related to adverse patient outcome (p=0.002). IC50 values for the inhibitory effect of Olaparib on the growth of the TNBC cell lines, MDA 231 and BT20 were 1.1 and 3.2 μM, respectively, while IC50 values for 5 non TN cell lines varied from 4.4 μM to16.7 μM.


CONCLUSIONS
Our results suggest that PARP1 is expressed in the majority of TN and non-TN breast cancer and that high levels are associated with adverse outcome. Furthermore, our in vitro findings suggest that olaparib may be more effective in TN than non TN breast cancers. Acknowledgement: The authors thank SFI (SRC award, 08/SRC/B1410 to MTCI) for funding this work.