# US 2014/0193919 A1 · Methods of detecting ovarian cancer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0193919 A1 - Document ID: US20140193919A1 - Status: Published application - Kind: A1 - Application number: 14/147,941 - Filed: 2014-01-06 - Published: 2014-07-10 - Earliest claimed: 2013-01-04 - Assignees: Wisconsin Alumni Research Foudation; Wake Forest University Health Sciences - Applicants: Wisconsin Alumni Research Foundation - Inventors: Halcyon Gerald Skinner; Gary G. Schwartz - Web page: https://patentgrep.com/patent/US20140193919A1 ## CPC - G01N 33/84: involving inorganic compounds or pH - G01N 33/57545: of the ovaries - G01N 2333/765: Serum albumin, e.g. HSA - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Methods of screening human female subject for a risk of ovarian cancer are described. High levels of calcium in serum are shown to be significantly positively associated with the risk of ovarian cancer and can advantageously be used to triage women into risk categories for more intensive testing. Also included are preoperative methods of determining if an adnexal mass is likely to be malignant or benign. ## Claims ### Claim 1 A preoperative method of determining a greater likelihood that an adnexal mass in a female subject is malignant or benign, comprising providing a blood sample collected from the subject; determining a total serum calcium level and a serum albumin level in the blood sample; comparing the total serum calcium level and the serum albumin level of the blood sample to a predictive model that includes total serum calcium and serum albumin levels for a population; and determining that the adnexal mass is likely to be malignant when the total serum calcium level in the blood sample is high normocalcemic to hypercalcemic or deviates upward from normal based on the predictive model, or determining that the adnexal mass is likely to be benign when total serum calcium level in the blood sample is normocalcemic or lower, is normal based on the predictive model or deviates downward from normal based on the predictive model. ### Claim 2 (depends on 1) The method of claim 1, wherein it is determined that the adnexal mass is likely to be malignant and further comprising referring the subject to a gynecological surgeon for removal of the malignant adnexal ovarian mass. ### Claim 3 (depends on 1) The method of claim 1, wherein the predictive model further comprises a covariate and the covariate is age, body mass index, menopausal status, parity, or a combination thereof ### Claim 4 (depends on 1) The method of claim 1, wherein the total serum calcium level that deviates upward from normal is greater than or equal to 9.8 mg/dl ### Claim 5 A preoperative method of determining if an adnexal mass in a female subject is likely to be malignant or likely to be benign, comprising providing a blood sample collected from the subject; determining a total serum calcium level and an albumin level in the blood sample, and calculating an albumin-corrected calcium level of the blood sample from the subject, or determining the ionized serum calcium level of the blood sample from the subject; comparing the albumin-corrected calcium level of the blood sample from the subject to a predictive model that includes albumin-corrected calcium levels for a population, or comparing the ionized serum calcium level of the blood sample from the subject to a predictive model that includes ionized serum calcium levels for a population; and determining that the adnexal mass is malignant when the albumin-corrected calcium level in the blood sample is high normocalcemic to hypercalcemic or deviates upward from normal based on the predictive model, determining that the adnexal mass is benign when the albumin-corrected calcium level in the blood sample is normocalcemic or lower, is normal based on the predictive model or deviates downward from normal based on the predictive model, determining that the adnexal mass is likely to be malignant when the ionized serum calcium level in the blood sample is high normocalcemic to hypercalcemic or deviates upward from normal based on the predictive model, or determining that the adnexal mass is likely to be benign when the ionized serum calcium level in the blood sample is normocalcemic or lower, is normal based on the predictive model or deviates downward from normal based on the predictive model. ### Claim 6 (depends on 5) The method of claim 5, wherein ionized serum calcium is determined, and the method further comprises determining serum albumin. ### Claim 7 (depends on 5) The method of claim 5, wherein the albumen-corrected calcium level in the blood sample is calculated as (0.8 times the difference between 4.0 g/dL and the albumin level in the blood sampled)+(the total serum calcium level in the blood sample in mg/dL). ### Claim 8 (depends on 5) The method of claim 5, wherein it is determined that the adnexal mass is likely to be malignant and further comprising referring the subject to a specialist removal of the malignant adnexal ovarian mass. ### Claim 9 (depends on 5) The method of claim 5, wherein the predictive model further comprises a covariate and the covariate is age, body mass index, menopausal status, parity, or a combination thereof. ### Claim 10 (depends on 5) The method of claim 5, wherein the albumin-corrected calcium level that deviates upward from normal is greater than or equal to 9.8 mg/dl. ### Claim 11 A method of screening for an increased risk of ovarian cancer in a human female subject, comprising providing a blood sample collected from the subject; determining a level of total or ionized serum calcium in the blood sample; and determining that the subject has an increased risk of ovarian cancer when the level of total or ionized serum calcium in the blood sample is in the upper tertile compared to a normal distribution, wherein the subject is experiencing one or more symptoms of ovarian cancer and/or wherein the subject has a family history of breast or ovarian cancer. ### Claim 12 (depends on 11) The method of claim 11, wherein the increase in total or ionized serum calcium is not accompanied by an increase in serum parathyroid hormone, or is accompanied by a detectable level of parathyroid-hormone-related peptide. ### Claim 12 (depends on 11) The method of claim 11, wherein when said sample is in the upper tertile compared to a normal distribution, further detecting CA-125 in a blood sample from the subject, screening with ultrasound, or both. ### Claim 13 (depends on 11) The method of claim 11, wherein the increased level of total or ionized serum calcium is increased 0.25 mg/dl or more compared to a midpoint of normal distribution. ### Claim 13 (depends on 11) The method of claim 11, wherein when said sample is in the upper tertile compared to a normal distribution, further detecting beta-2 microglobulin, CA 125-II, apolipoprotein Al, prealbumin, and transferrin in a blood sample from the subject. ### Claim 14 (depends on 11) The method of claim 11, wherein the subject experiencing one or more symptoms of ovarian cancer and/or having a family history of breast or ovarian cancer has been tested for beta-2 microglobulin, CA 125-II, apolipoprotein Al, prealbumin, and transferrin in a blood sample from the subject. ### Claim 15 (depends on 11) The method of claim 11, wherein when the subject is found to be at risk of ovarian cancer, the method further assaying a blood sample for human epididymis protein 4. ### Claim 16 A method of screening for an increased risk of ovarian cancer in a human female subject, comprising providing a first blood sample and a second blood sample collected from the subject, wherein the first and second blood samples are taken at a first time interval; determining a level of total or ionized serum calcium in the first and second blood samples; and determining that the subject has an increased risk of ovarian cancer when the level of total or ionized serum calcium in the second blood sample is increased compared to the first blood sample, and the increase in total or ionized serum calcium is not accompanied by an increase in serum parathyroid hormone, and/or is accompanied by a detectable level of parathyroid-hormone-related peptide. ### Claim 17 (depends on 16) The method of claim 16, wherein increased total or ionized serum calcium in the second blood sample is increased by 10% or more. ### Claim 18 (depends on 16) The method of claim 16, wherein the time interval is 6 weeks. ### Claim 19 (depends on 16) The method of claim 16, wherein the subject has been tested for beta-2 microglobulin, CA 125-II, apolipoprotein Al, prealbumin, and transferrin in a blood sample from the subject.