Clinical factors affecting HE4 and CA125 in women at high risk of developing ovarian cancer.

Abstract

1569 Background: CA125 is often used to screen high-risk patients (pts) for ovarian cancer (OC), but levels are affected by many factors, especially in premenopausal pts. In prior studies of low-risk pts, HE4 is more stable than CA125. The objective of this study was to determine how clinical variables affect CA125 and HE4 in pts at high risk for ovarian cancer. Methods: Serum from 373 pts at high risk of OC was collected every 3-12 mo from 2006-2012, for a total of 1081 samples. Serum CA125 and HE4 were measured in duplicate utilizing a commercially available multiplexed sandwich immunoassay (MagPlex). Multilevel regression models were used to examine the associations of clinical factors with CA125 and HE4, while considering the inter-correlated nature of outcomes measured periodically from the same subject. Results: The mean age was 44.6 years, 51.2% were premenopausal, 72.7% were white, 9.1% were Ashkenazi Jewish, 65.2% had a history of breast cancer, and 81.5% had a BRCA mutation. Log transformed CA125 was found to be 0.32 units higher in premenopausal pts compared to postmenopausal pts (p=0.0023), and 0.27 units higher in pts with active breast cancer (BC) compared to pts with no active BC (p=0.0044). In premenopausal pts, CA125 varied throughout the menstrual cycle, with highest levels noted at menstruation (p<0.0001). Age, smoking status, and hormone use did not affect CA125 levels. Interestingly, there was no significant association between HE4 levels and any of the evaluated variables, including age, menopausal status, active BC, smoking status, hormone use, or point in menstrual cycle (all p>0.05). Conclusions: In women at high-risk for OC, HE4 levels fluctuate less with the menstrual cycle and are less likely to be elevated in BC than CA125. This finding is important as many high-risk pts that undergo screening are pre-menopausal and have a BC history. HE4 may provide a valuable addition to the current screening regimen of high-risk pts.