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

Nicole Urban, Sarah Hawley, Holly Janes, Beth Y. Karlan, Christine D. Berg, Charles W. Drescher, Joann E. Manson, Melanie R. Palomares, Mary B. Daly, Jean Wactawski-Wende, Mary J. O'Sullivan, Jason Thorpe, Randal D. Robinson, Dorothy Lane, Christopher I. Li, Garnet L. Anderson

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)253-260
Number of pages8
JournalGynecologic Oncology
Volume139
Issue number2
DOIs
StatePublished - 2015

Fingerprint

Women's Health
Epidemiologic Factors
Observational Studies
Fallopian Tubes
Biomarkers
Ovarian Neoplasms
Clinical Trials
Breast Neoplasms
Ovarian epithelial cancer
Population
Hormones
Carcinoma
Neoplasms

Keywords

  • CA125
  • HE4
  • Ovarian cancer
  • Risk prediction

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Urban, N., Hawley, S., Janes, H., Karlan, B. Y., Berg, C. D., Drescher, C. W., ... Anderson, G. L. (2015). Identifying post-menopausal women at elevated risk for epithelial ovarian cancer. Gynecologic Oncology, 139(2), 253-260. https://doi.org/10.1016/j.ygyno.2015.08.024

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 journalArticle

Urban, N, Hawley, S, Janes, H, Karlan, BY, Berg, CD, Drescher, CW, Manson, JE, Palomares, MR, Daly, MB, Wactawski-Wende, J, O'Sullivan, MJ, Thorpe, J, Robinson, RD, Lane, D, Li, CI & Anderson, GL 2015, 'Identifying post-menopausal women at elevated risk for epithelial ovarian cancer', Gynecologic Oncology, vol. 139, no. 2, pp. 253-260. https://doi.org/10.1016/j.ygyno.2015.08.024
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. / Identifying post-menopausal women at elevated risk for epithelial ovarian cancer. In: Gynecologic Oncology. 2015 ; Vol. 139, No. 2. pp. 253-260.
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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.",
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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

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