A Trial Using Novel Markers to Predict Malignancy in Elevated-Risk Women

Inclusion Criteria

• •Risk Group 1, Women ages 25 - 80:
• •The subject has tested positive for a deleterious germ line mutation in BRCA1 or BRCA2.
• •Risk Group 2, Women ages 35 - 80, Pedigree conditions can be satisfied by multiple primary cancers in the same person:
• •The subject has a personal history of breast cancer diagnosed before or at age 50.
• •OR the subject has a personal history of bilateral breast cancer
• •OR the subject has one first-degree relative with breast cancer diagnosed before or at age 50.
• •OR the subject has two breast cancers in the first or second degree relatives, same lineage, with at least one breast cancer diagnosed before or at age 50.
• •OR the subject has three or more first or second degree relatives, same lineage, with breast cancer diagnosed at any age.
• •OR The family contains at least one ovarian cancer diagnosed at any age in the first or second degree relatives.
• •OR the subject is of Ashkenazi ancestry and has had breast cancer diagnosed at any age.
• •OR The subject is of Ashkenazi Jewish ethnicity and has one first or second degree relative with breast cancer diagnosed at any age (must be in the same lineage as the Ashkenazi ancestry)
• •OR The subject has a male relative with breast cancer diagnosed at any age
• •OR The subject has a personal history of a positive genetic test result for a deleterious germline mutation in the P53 gene.
• •OR The subject has tested positive for a deleterious germline mutation in one of the DNA mismatch repair (MMR) genes associated with the Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, also known as Lynch Syndrome) The MMR genes include MLH1, MSH2, MSH6 and PMS2.
• •OR the subject has a first or second degree relative with an identified deleterious germline BRCA1 or BRCA2 mutation, but has not yet undergone testing herself.
• •OR the subject has a first or second degree relative with an identified deleterious germline MMR gene mutation, but has not yet undergone testing herself.
• •OR Probability of carrying a BRCA1 or BRCA2 mutation given family pedigree of breast and ovarian cancers exceeds 20% by any existing BRCA mutational probability model.
• •Risk Group 3, Women ages 45 - 80:
• •Have measurement of CA125, HE4, MMP7 or Mesothelin exceeding the 95th percentile;
• •OR have a relative risk of at least 2 based on the EpiRisk logistic regression model including age, family history, and other risk factors.