Abstract P6-05-23: An immunohistochemical study of folate receptor alpha status in breast cancers in Asian vs. North American women

Abstract

Abstract Background: Folate receptor α (FRα) has been found to be over-expressed in several cancers, including lung, ovary, and breast cancers. Studies have also shown that over-expression of FRα in breast cancer strongly correlated with early recurrence and decreased median survival; thus, FRα has emerged as a potentially promising therapeutic target. Breast cancer rates among Chinese women have been shown to be much lower than women in many other racial groups. The breast cancer incidence in China per 100,000 people is only 18.7. China is ranked 142th in the world for this disease, compared to the top-ranking United States, which reaches 101.1 breast cancers per 100,000 people of all races and ethnicities. The disparity between the two groups led us to investigate and compare the immunohistochemical expression of FRα in breast cancers. Design: A new, highly specific clone of a mouse monoclonal FRα antibody, [26B3.F2], suitable for IHC, has been developed and well characterized on formalin-fixed paraffin-embedded tissue. A tissue microarray of 75 cases of breast cancer patients from China and 168 cases of whole tissues from North American patients were collected. Tissue was evaluated by immunohistochemistry (IHC) and stained for ER, PR, Her2 and FRα. A >1% cut-off value for ER/PR positive staining and a >10% cut-off value for FRα was adopted to determine positivity. Only 3+ Her2 positive cases were used in this study. Results: FRα expression was identified in 23.5% (57/243) of all breast cancers, with an increased incidence in ER-/PR- cases, and no significant difference between North American and Chinese populations (Tables 1&2). In ER-/PR- patients, FRα expression was observed in 51.9% (14/27) and 40% (18/45) of cases from North American and Chinese populations, respectively, and only 6.7% (7/105) and 12.5% (3/24) of ER+/PR+ patients, respectively. FRα expression was also found to be significantly increased in ER-/PR-/HER2- (triple negative) cases across both populations; and FRα was positive in 52.4% (22/44) triple negative cases, compared to 30% (15/50) of HER2+ cases (p = 0.01). FRα was positive in 15.5% of ER+/PR+ vs. 44.4% of ER-/PR- cases, (p = 0.0001), and ER+/PR- cases also demonstrated higher FRα vs. ER+/PR+ in North American women. Table 1: North American women (n = 168)Antibody# casesHER2+FRα+ER+/PR+105 (62.5%)11 (10.5%)7 (6.7%)ER+/PR-28 (16.7%)9 (32.1%)14 (50.0%)ER-/PR-27 (16.1%)5 (18.5%)14 (51.9%)HER2+26 (15.5%)N/A9 (34.6%)ER-/PR-/HER2-22 (13.1%)N/A13 (59.1%) Conclusion: This study represents the first IHC FRα comparison study of breast cancers in Chinese and North American women. Our findings demonstrated that both ethnic groups demonstrated high expression of FRα in triple negative breast cancers and may identify a molecular subset of patients that would benefit from an anti-folate targeted therapy, including hormone receptor, or Her2 positive patients that have failed to respond to prior treatment, or triple negative patients for whom limited treatment options are available. Table 2: Chinese women (n = 75)Antibody# casesHER2+FRa+ER+/PR+24 (32.0%)3 (12.5%)3 (12.5%)ER+/PR-6 (8.0%)1 (16.7%)0 (0.0%)ER-/PR-45 (60.0%)20 (44.4%)18 (40.0%)HER2+24 (32.0%)N/A6 (25.0%)ER-/PR-/HER2-19 (25.3%)N/A9 (45%) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-23.