ERCC1 Expression and Complete Pathologic Response to Platinum-Based Therapy for Patients with Triple Negative Breast Cancer
Carmen Gomez-Fernandez, Maureen Cioffi-Lavina, Jude Hurley, Gail Walker, Jennifer J Hu, Merce Jorda. Jackson Memorial Hospital, Miami, FL; University of Miami School of Medicine, Miami, FL; Sylvester Comprehensive Cancer Center, Miami, FL
Background: Platinum-based chemotherapy exerts its cytotoxic effects by forming intra-strand DNA adducts that inhibit replication. Excision Repair Cross Complementing group 1 protein (ERCC1) plays a critical, yet undesirable, role in repair of DNA damage induced by platinum. Absence of immunohistochemical expression of ERCC1 has been shown to be associated with response to platinum-based chemotherapy regimens in non small cell lung carcinomas. Experimental data suggests that triple negative breast cancers (TNBC) may have increased sensitivity to platinum-based chemotherapy, particularly in BRCA1 mutation carriers, whose cancers cluster among the basal-like subtype, as defined by gene expression profiling. We investigated the immunohistochemical expression of ERCC1 in relation to response to neoadjuvant platinum-based chemotherapy in a cohort of patients with TNBC.
Design: We reviewed the diagnostic core biopsies of 80 TNBC patients treated with neoadjuvant docetaxel plus platinum-based salts at our institution between 1999 and 2007. Twenty-eight (35%) study patients had pathologic complete response (pCR), defined by the absence of invasive carcinoma in the breast and axilla. Immunohistochemistry for ERRC1 (ABCAM) was performed in all cases using the LSAB method. A nuclear immunohistochemical reaction in >1% of the tumor cells was scored as positive for ERCC1. Fisher's exact test was used to compare pCR rates by ERCC1 status.
Results: Of 80 TNBC, 55 (69.75%) were positive for ERCC1 by immunohistochemistry. Reactivity was present in 10 to 100% of the tumor cell nuclei. The remaining 25 (31.25%) carcinomas were definitively negative for ERCC1. A higher pCR rate was found among patients with ERCC1(−) tumors, 12/25 (48%), compared to 16/55 (29.1%) patients with ERCC1(+) tumors, but did not reach statistical significance p=0.131. A one-sided test for higher pCR rates among ERCC1(-) patients was marginally significant, p=0.083, Fisher's exact test.
Conclusions: Absence of immunohistochemical expression for ERCC1 was marginally predictive of higher pathologic complete response to platinum-based neoadjuvant chemotherapy for patients withTNBC. A larger study is needed to further elucidate the relationship between ERCC1 expression and response to platinum-based therapy for patients with TNBC.
Monday, March 19, 2012 1:00 PM
Poster Session II # 64, Monday Afternoon