[339] Expression of Id4, a BRCA1 Downregulator, in Triple Negative Breast Cancer

YH Wen, M Akram, T Nehhozina, Z Bowser, L Norton, E Brogi. Memorial Sloan-Kettering Cancer Center, New York, NY

Background: Somatic BRCA1 mutations are rare in sporadic breast cancer (BC). Id4, a transcription factor downregulating BRCA1 in vitro, could contribute to epigenetic BRCA1 inactivation in sporadic BC. To test this hypothesis, we compared the expression of Id4 in a series of triple negative breast carcinoma (TN) versus control (C) BC, and correlated the results with basal markers and clinical follow-up (F/U).
Design: We assessed the morphology of 54 TNBC and 105 CBC treated at our center (2002-4). Immunostains for Id4, CK14, calponin and p63 were performed on a representative section of TNBC and on tissue microarrays of CBC. Fisher's exact test and t-test were used for statistical analysis.
Results: Table 1 summarizes the clinicopathologic characteristics of our cases. All TNBC were invasive ductal (12 with a large central acellular zone (LCAZ), 5 apocrine, 1 with medullary features,1 matrix producing). CK14 was positive in 24 (44%) TNBC. Id4 occurred in 37 TNBC (69%) and involved >50% of tumor cells in 14 (26%), 5-50% in 14 (26%) and <5% in 9 (17%). Id4 expression in >5% of tumor cells correlated with LCAZ (36% vs 8%, p=0.021) and CK14 positivity (71% vs 15%, p=0.0001). Ten of the 13 TNBC with distant metastases were Id4+ (p=0.0001). In contrast, only 4 (4%) CBC had rare Id4+ cells (p=0.0001) and all 4 CBC with distant metastases were Id4-.

TN (n=54)Control (n=105)p
Median age5551
Size (cm)2.7 (0.3-28)2.6 (1.1-18.5)
Grade11 (2%)16 (15%)0.006
212 (22%)39 (37%)0.033
341 (76%)44 (42%)0.0002
N/A06 (6%)
LCAZ1200.0001
LN met25 (46%)68 (65%)0.028
TreatmentChemotherapy50 (93%)86 (82%)
Hormone therapy alone014 (13%)
Surgery alone4 (7%)5 (5%)
F/Un=51n=103
Median F/U (y)45
Mets13 (25%)6 (6%)0.001
Brain4 (8%)2 (2%)
Lung5 (10%)3 (3%)
Bone4 (8%)4 (4%)
Liver7 (14%)0
Id437 (69%)4 (4%)0.0001
CK1424 (44%)4 (4%)0.0001



Conclusions: Id4 expression is frequent in TNBC and correlates with basal phenotype and distant metastases. Evaluation of Id4 in additional cases and correlation with BRCA1 status is in progress. The results of our study could help to identify TNBC with sporadic BRCA1 inactivation, suitable for treatment with PARP inhibitors.
Category: Breast

Tuesday, March 23, 2010 11:00 AM

Platform Session: Section C, Tuesday Morning

 

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