title: Large prospective study of ovarian cancer screening in high-risk women: CA125 cut-point defined by menopausal status.
abstract: Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, whereas the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols. Baseline CA125 values and clinical and demographic data from 3,692 women participating in screening studies conducted by the National Cancer Institute-sponsored Cancer Genetics Network and Gynecologic Oncology Group were combined for this preplanned analysis. Because of the large effect of menopausal status on CA125 levels, statistical analyses were conducted separately in pre- and postmenopausal subjects to determine the impact of other baseline factors on predicted CA125 cut-points on the basis of 98th percentile. The primary clinical factor affecting CA125 cut-points was menopausal status, with premenopausal women having a significantly higher cut-point of 50 U/mL, while in postmenopausal subjects the standard cut-point of 35 U/mL was recapitulated. In premenopausal women, current oral contraceptive (OC) users had a cut-point of 40 U/mL. To achieve a 2% false positive rate in ovarian cancer screening trials and in high-risk women choosing to be screened, the cut-point for initial CA125 testing should be personalized primarily for menopausal status (50 for premenopausal women, 40 for premenopausal on OC, and 35 for postmenopausal women).
authors: Biostatistics Center, Massachusetts General Hospital, Boston, MA 02114, USA. dfinkelstein@partners.org
authors: Steven J
authors: SJ
authors: Skates
authors: Phuong
authors: P
authors: Mai
authors: Nora K
authors: NK
authors: Horick
authors: Marion
authors: M
authors: Piedmonte
authors: Charles W
authors: CW
authors: Drescher
authors: Claudine
authors: C
authors: Isaacs
authors: Deborah K
authors: DK
authors: Armstrong
authors: Saundra S
authors: SS
authors: Buys
authors: Gustavo C
authors: GC
authors: Rodriguez
authors: Ira R
authors: IR
authors: Horowitz
authors: Andrew
authors: A
authors: Berchuck
authors: Mary B
authors: MB
authors: Daly
authors: Susan
authors: S
authors: Domchek
authors: David E
authors: DE
authors: Cohn
authors: Linda
authors: L
authors: Van Le
authors: John O
authors: JO
authors: Schorge
authors: William
authors: W
authors: Newland
authors: Susan A
authors: SA
authors: Davidson
authors: Mack
authors: M
authors: Barnes
authors: Wendy
authors: W
authors: Brewster
authors: Masoud
authors: M
authors: Azodi
authors: Stacy
authors: S
authors: Nerenstone
authors: Noah D
authors: ND
authors: Kauff
authors: Carol J
authors: CJ
authors: Fabian
authors: Patrick M
authors: PM
authors: Sluss
authors: Susan G
authors: SG
authors: Nayfield
authors: Carol H
authors: CH
authors: Kasten
authors: Dianne M
authors: DM
authors: Finkelstein
authors: Mark H
authors: MH
authors: Greene
authors: Karen
authors: K
authors: Lu
mesh_terms: D000328:Adult; D000368:Aged; D018394:CA-125 Antigen / Q000096:biosynthesis*; D003276:Contraceptives, Oral / Q000494:pharmacology; D005006:Ethnicity; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D017698:Postmenopause; D017697:Premenopause; D011446:Prospective Studies; D012306:Risk
chemical_list: D018394:CA-125 Antigen; D003276:Contraceptives, Oral