TY - JOUR
T1 - Identifying post-menopausal women at elevated risk for epithelial ovarian cancer
AU - Urban, Nicole
AU - Hawley, Sarah
AU - Janes, Holly
AU - Karlan, Beth Y.
AU - Berg, Christine D.
AU - Drescher, Charles W.
AU - Manson, Joann E.
AU - Palomares, Melanie R.
AU - Daly, Mary B.
AU - Wactawski-Wende, Jean
AU - O'Sullivan, Mary J.
AU - Thorpe, Jason
AU - Robinson, Randal D.
AU - Lane, Dorothy
AU - Li, Christopher I.
AU - Anderson, Garnet L.
N1 - Funding Information:
NCI R21 CA179443 (to NU), NCI P50 CA083636 (to NU), NCI U01 CA152637 (to CL), ACS SIOP-06–258-COUN (to BK), the Canary Foundation. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.
Funding Information:
NCI R21 CA179443 (to NU), NCI P50 CA083636 (to NU), NCI U01 CA152637 (to CL), ACS SIOP-06–258-COUN (to BK), the Canary Foundation. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Support from NCI R21 CA179443 (to NU), NCI P50 CA083636 (to NU), NCI U01 CA152637 (to CL), ACS SIOP-06-258-COUN (to BK), the Canary Foundation, and a grant of no-charge study materials from Abbott Laboratories, are gratefully acknowledged. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Comments from Daniel Cramer, MD and several anonymous reviewers aswell as assistance fromKathy O''Briant, Hannah Purkey and Christine Poulin are much appreciated. Please see Appendix A for WHI investigators whose efforts have made this work possible; their contributions are greatly appreciated. None of the authors listed in the abovemanuscript has declared any conflict of interest with the above manuscript.
Funding Information:
Support from NCI R21 CA179443 (to NU), NCI P50 CA083636 (to NU), NCI U01 CA152637 (to CL), ACS SIOP-06-258-COUN (to BK), the Canary Foundation , and a grant of no-charge study materials from Abbott Laboratories , are gratefully acknowledged. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Comments from Daniel Cramer, MD and several anonymous reviewers as well as assistance from Kathy O'Briant, Hannah Purkey and Christine Poulin are much appreciated. Please see Appendix A for WHI investigators whose efforts have made this work possible; their contributions are greatly appreciated. None of the authors listed in the above manuscript has declared any conflict of interest with the above manuscript.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015
Y1 - 2015
N2 - 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 7.8 years 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 7 years 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.
AB - 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 7.8 years 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 7 years 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.
KW - CA125
KW - HE4
KW - Ovarian cancer
KW - Risk prediction
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U2 - 10.1016/j.ygyno.2015.08.024
DO - 10.1016/j.ygyno.2015.08.024
M3 - Article
AN - SCOPUS:84952631744
VL - 139
SP - 253
EP - 260
JO - Gynecologic Oncology
JF - Gynecologic Oncology
SN - 0090-8258
IS - 2
ER -