319Early Diagnosis of Ovarian Cancer
Two tumor biomarkers, CA125 and one approved by FDA called HE4, are used to
track whether chemotherapy is working or cancer is recurring. A one-time CA125
test cannot screen seemingly healthy women because levels rise with benign cysts,
endometriosis, even normal menstruation, but Fujirebio’s triage test uses HE4 and
CA125 to assess who most likely has a benign cyst and whose has cancer.
OVA1 ® (Vermillion Inc) is a simple blood test cleared by the FDA to help physi-
cians assess the likelihood that an ovarian mass is malignant prior to a planned
surgery. OVA1 ® is not a screening test, but it is to be used together with a physi-
cian’s overall assessment. OVA1 ® measures the levels of fi ve proteins found in the
blood and then uses proprietary software called OvaCalc ® to calculate a single
score. A woman’s risk of cancer is measured by using a 0–10 scale versus predeter-
mined cut-off points. Women who are pre-menopausal have a cut off score of 5
whereas postmenopausal women have a 4.4 cutoff. A high OVA1 ® score is not a
diagnosis of cancer, rather it indicates an increased risk. An elevated OVA1 ® test
score helps the physician to decide on referral to a gynecologic oncologist and
increases the likelihood of optimal surgery, treatment and follow up for ovarian
cancer patients.
A prospective, multi-institutional trial enrolled female patients scheduled to
undergo surgery for an adnexal mass (Bristow et al. 2013 ). The multivariate index
assay correctly identifi ed 83.3 % malignancies missed by clinical impression and
70.8 % cases missed by CA125-II. Multivariate index assay was superior in predict-
ing the absence of an ovarian malignancy, with a negative predictive value of
98.1 %. The study concluded that multivariate index assay demonstrated higher
sensitivity and negative predictive value for ovarian malignancy compared to clini-
cal impression and CA125-II in an intended-use population of non-gynecologic
oncology practices.
Determining Response to Chemotherapy in Ovarian Cancer
Gene expression profi les can predict response of ovarian cancer patients to chemo-
therapy. The method may enable clinicians to identify patients who are candidates
for additional and/or novel chemotherapy drugs, and effectively choose appropriate
cancer treatment. A variant in the 3′UTR of the KRAS oncogene, referred to as the
KRAS variant, is associated with both cancer risk and altered tumor biology. KRAS
variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC).
A study has shown that postmenopausal EOC patients with the KRAS variant are
signifi cantly more likely to die of ovarian cancer by multivariate analysis and are
signifi cantly more likely to be platinum resistant (Ratner et al. 2012 ). In addition,
direct targeting of the KRAS variant leads to a signifi cant reduction in EOC cell
growth and survival in vitro. These fi ndings confi rm the importance of the KRAS
variant in EOC, and indicate that the KRAS variant is a biomarker of poor outcome
in EOC likely due to platinum resistance. In addition, this study supports the
Personalized Management of Cancers of Various Organs