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Gynecol Oncol. 2015 Nov;139(2):253-60. doi: 10.1016/j.ygyno.2015.08.024. Epub 2015 Sep 3.

Identifying post-menopausal women at elevated risk for epithelial ovarian cancer.

Author information

  • 1Fred Hutchinson Cancer Research Center, Seattle, WA, United States. Electronic address: nurban@fhcrc.org.
  • 2Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
  • 3Cedars-Sinai Medical Center, Los Angeles, CA, United States.
  • 4Johns Hopkins Medicine, Baltimore, MD, United States.
  • 5Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
  • 6Cancer Prevention, Inc., Las Vegas NV and Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
  • 7Fox Chase Cancer Center, Philadelphia PA, United States.
  • 8University at Buffalo, SUNY, Buffalo, NY, United States.
  • 9University of Miami, Miami, FL, United States.
  • 10University of Texas Health Science Center, San Antonio TX, United States.
  • 11Stony Brook University, Stony Brook, NY, United States.

Abstract

OBJECTIVE:

We developed and validated a hybrid risk classifier combining serum markers and epidemiologic risk factors to identify post-menopausal women at elevated risk for invasive fallopian tube, primary peritoneal, and ovarian epithelial carcinoma.

METHODS:

To select epidemiologic risk factors for use in the classifier, Cox proportional hazards analyses were conducted using 74,786 Women's Health Initiative (WHI) Observational Study (OS) participants. To construct a combination classifier, 210 WHI OS cases and 536 matched controls with serum marker measurements were analyzed; validation employed 143 cases and 725 matched controls from the WHI Clinical Trial (CT) with similar data.

RESULTS:

Analyses identified a combination risk classifier composed of two elevated-risk groups: 1) women with CA125 or HE4 exceeding a 98% specificity threshold; and 2) women with intact fallopian tubes, prior use of menopausal hormone therapy for at least two years, and either a first degree relative with breast or ovarian cancer or a personal history of breast cancer. In the WHI OS population, it classified 13% of women as elevated risk, identifying 30% of ovarian cancers diagnosed up to 7.8years post-enrollment (Hazard Ratio [HR]=2.6, p<0.001). In the WHI CT validation population, it classified 8% of women as elevated risk, identifying 31% of cancers diagnosed within 7years of enrollment (HR=4.6, p<0.001).

CONCLUSION:

CA125 and HE4 contributed significantly to a risk prediction classifier combining serum markers with epidemiologic risk factors. The hybrid risk classifier may be useful to identify post-menopausal women who would benefit from timely surgical intervention to prevent epithelial ovarian cancer.

KEYWORDS:

CA125; HE4; Ovarian cancer; Risk prediction

PMID:
26343159
PMCID:
PMC4664187
DOI:
10.1016/j.ygyno.2015.08.024
[PubMed - indexed for MEDLINE]
Free PMC Article

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