Prevention and early detection of ovarian cancer

mission impossible?

Robert C. Bast, Molly Brewer, Changping Zou, Mary A. Hernandez, Mary Daley, Robert Ozols, Karen Lu, Zhen Lu, Donna Badgwell, Gordon Mills, Steven Skates, Zhen Zhang, Dan Chan, Anna Lokshin, Yinhua Yu

Research output: Contribution to journalReview article

91 Citations (Scopus)

Abstract

Epithelial ovarian cancer is neither a common nor a rare disease. In the United States, the prevalence of ovarian cancer in postmenopausal women (1 in 2,500) significantly affects strategies for prevention and detection. If chemoprevention for ovarian cancer were provided to all women over the age of 50, side effects would have to be minimal in order to achieve an acceptable ratio of benefit to risk. This ratio might be improved by identifying subsets of individuals at increased risk or by bundling prevention of ovarian cancer with treatment for other more prevalent conditions. Approximately 10% of ovarian cancers are familial and relate to mutations of BRCA1, BRCA2, and mismatch repair genes. More subtle genetic factors are being sought in women with apparently sporadic disease. Use of oral contraceptive agents for as long as 5 years decreases the risk of ovarian cancer in later life by 50%. In one study, fenretinide (4-HPR) delayed development of ovarian cancer in women at increased risk of developing breast and ovarian cancer. Accrual to confirmatory studies has been prohibitively slow and prophylactic oophorectomy is recommended for women at increased genetic risk. Vaccines may have a role for prevention of several different cancers. Breast and ovarian cancers express mucins that could serve as targets for vaccines to prevent both cancers. Early detection of ovarian cancer requires a strategy with high sensitivity (> 75% for stage I disease) and very high specificity (> 99.6%) to achieve a positive predictive value of 10%. Transvaginal sonography (TVS) has achieved these values in some studies, but is limited by the cost of annual screening in a general population. Two-stage strategies that incorporate both serum markers and TVS promise to be more cost-effective. An algorithm has been developed that calculates risk of ovarian cancer based on serial CA125 values and refers patients at highest risks for TVS. Use of the algorithm is currently being evaluated in a trial with 200,000 women in the United Kingdom that will critically test the ability of a two-stage screening strategy to improve survival in ovarian cancer. Whatever the outcome, additional serum markers will be required to detect all patients in an initial phase of screening. More than 30 serum markers have been evaluated alone and in combination with CA125. Recent candidates include: HE4, mesothelin, M-CSF, osteopontin, kallikrein(s) and soluble EGF receptor. Proteomic approaches have been used to define a distinctive pattern of peaks on mass spectroscopy or to identify a limited number of critical markers that can be assayed by more conventional methods. Several groups are placing known markers on multiplex platforms to permit simultaneous assay of multiple markers with very small volumes of serum. Mathematical techniques are being developed to analyze combinations of marker levels to improve sensitivity and specificity. In the future, serum markers should improve the sensitivity of detecting recurrent disease as well as facilitate earlier detection of ovarian cancer.

Original languageEnglish (US)
Pages (from-to)91-100
Number of pages10
JournalRecent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer
Volume174
StatePublished - Mar 28 2007
Externally publishedYes

Fingerprint

Early Detection of Cancer
Ovarian Neoplasms
Biomarkers
Fenretinide
Ultrasonography
Vaccines
Breast Neoplasms
Costs and Cost Analysis
Osteopontin
Kallikreins
DNA Mismatch Repair
Macrophage Colony-Stimulating Factor
Chemoprevention
Ovariectomy
Mucins
Oral Contraceptives
Rare Diseases
Contraceptive Agents
Epidermal Growth Factor Receptor
Proteomics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prevention and early detection of ovarian cancer : mission impossible? / Bast, Robert C.; Brewer, Molly; Zou, Changping; Hernandez, Mary A.; Daley, Mary; Ozols, Robert; Lu, Karen; Lu, Zhen; Badgwell, Donna; Mills, Gordon; Skates, Steven; Zhang, Zhen; Chan, Dan; Lokshin, Anna; Yu, Yinhua.

In: Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer, Vol. 174, 28.03.2007, p. 91-100.

Research output: Contribution to journalReview article

Bast, RC, Brewer, M, Zou, C, Hernandez, MA, Daley, M, Ozols, R, Lu, K, Lu, Z, Badgwell, D, Mills, G, Skates, S, Zhang, Z, Chan, D, Lokshin, A & Yu, Y 2007, 'Prevention and early detection of ovarian cancer: mission impossible?', Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer, vol. 174, pp. 91-100.
Bast, Robert C. ; Brewer, Molly ; Zou, Changping ; Hernandez, Mary A. ; Daley, Mary ; Ozols, Robert ; Lu, Karen ; Lu, Zhen ; Badgwell, Donna ; Mills, Gordon ; Skates, Steven ; Zhang, Zhen ; Chan, Dan ; Lokshin, Anna ; Yu, Yinhua. / Prevention and early detection of ovarian cancer : mission impossible?. In: Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer. 2007 ; Vol. 174. pp. 91-100.
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AU - Bast, Robert C.

AU - Brewer, Molly

AU - Zou, Changping

AU - Hernandez, Mary A.

AU - Daley, Mary

AU - Ozols, Robert

AU - Lu, Karen

AU - Lu, Zhen

AU - Badgwell, Donna

AU - Mills, Gordon

AU - Skates, Steven

AU - Zhang, Zhen

AU - Chan, Dan

AU - Lokshin, Anna

AU - Yu, Yinhua

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N2 - Epithelial ovarian cancer is neither a common nor a rare disease. In the United States, the prevalence of ovarian cancer in postmenopausal women (1 in 2,500) significantly affects strategies for prevention and detection. If chemoprevention for ovarian cancer were provided to all women over the age of 50, side effects would have to be minimal in order to achieve an acceptable ratio of benefit to risk. This ratio might be improved by identifying subsets of individuals at increased risk or by bundling prevention of ovarian cancer with treatment for other more prevalent conditions. Approximately 10% of ovarian cancers are familial and relate to mutations of BRCA1, BRCA2, and mismatch repair genes. More subtle genetic factors are being sought in women with apparently sporadic disease. Use of oral contraceptive agents for as long as 5 years decreases the risk of ovarian cancer in later life by 50%. In one study, fenretinide (4-HPR) delayed development of ovarian cancer in women at increased risk of developing breast and ovarian cancer. Accrual to confirmatory studies has been prohibitively slow and prophylactic oophorectomy is recommended for women at increased genetic risk. Vaccines may have a role for prevention of several different cancers. Breast and ovarian cancers express mucins that could serve as targets for vaccines to prevent both cancers. Early detection of ovarian cancer requires a strategy with high sensitivity (> 75% for stage I disease) and very high specificity (> 99.6%) to achieve a positive predictive value of 10%. Transvaginal sonography (TVS) has achieved these values in some studies, but is limited by the cost of annual screening in a general population. Two-stage strategies that incorporate both serum markers and TVS promise to be more cost-effective. An algorithm has been developed that calculates risk of ovarian cancer based on serial CA125 values and refers patients at highest risks for TVS. Use of the algorithm is currently being evaluated in a trial with 200,000 women in the United Kingdom that will critically test the ability of a two-stage screening strategy to improve survival in ovarian cancer. Whatever the outcome, additional serum markers will be required to detect all patients in an initial phase of screening. More than 30 serum markers have been evaluated alone and in combination with CA125. Recent candidates include: HE4, mesothelin, M-CSF, osteopontin, kallikrein(s) and soluble EGF receptor. Proteomic approaches have been used to define a distinctive pattern of peaks on mass spectroscopy or to identify a limited number of critical markers that can be assayed by more conventional methods. Several groups are placing known markers on multiplex platforms to permit simultaneous assay of multiple markers with very small volumes of serum. Mathematical techniques are being developed to analyze combinations of marker levels to improve sensitivity and specificity. In the future, serum markers should improve the sensitivity of detecting recurrent disease as well as facilitate earlier detection of ovarian cancer.

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