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 7.8 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 253-260 |
| Number of pages | 8 |
| Journal | Gynecologic Oncology |
| Volume | 139 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2015 |
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Keywords
- CA125
- HE4
- Ovarian cancer
- Risk prediction
ASJC Scopus subject areas
- Obstetrics and Gynecology
- Oncology
Cite this
Identifying post-menopausal women at elevated risk for epithelial ovarian cancer. / Urban, Nicole; Hawley, Sarah; Janes, Holly; Karlan, Beth Y.; Berg, Christine D.; Drescher, Charles W.; Manson, Joann E.; Palomares, Melanie R.; Daly, Mary B.; Wactawski-Wende, Jean; O'Sullivan, Mary J.; Thorpe, Jason; Robinson, Randal D.; Lane, Dorothy; Li, Christopher I.; Anderson, Garnet L.
In: Gynecologic Oncology, Vol. 139, No. 2, 2015, p. 253-260.Research output: Contribution to journal › Article
}
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.
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
UR - http://www.scopus.com/inward/record.url?scp=84952631744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84952631744&partnerID=8YFLogxK
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 -