- INCLUSION CRITERIA:
Individuals with breast cancer are being ascertained from among the patient population at
National Naval Medical Center (NNMC) as well as other referring institutions. Individuals
from the Clinical Center may also be eligible. There will be three groups of participants,
which include a control group, individuals with a documented history of breast cancer, and
individuals identified to be at high risk of developing breast cancer. The purpose of the
high risk group is to look for potential similarities and differences between the cancer
and control populations that may start to be exhibited in the high risk group. This will
potentially allow the research team to identify high risk women by markers of risk. After
providing informed consent, individuals are asked to donate a blood sample, undergo nipple
fluid sampling, and complete epidemiological, dietary and family history questionnaires
and grant access to their medical records. The questionnaires will be completed and/or
reviewed by the research team.
1. . Individuals with a documented history of invasive breast cancer.
2. . Individuals with a documented history of ductal carcinoma in situ.
Control and High Risk Populations:
We will use two primary methods for establishing risk status in individuals who are not
affected with cancer.
1. . Individuals found to harbor a mutation in BRCA1 or BRCA2 face up to a 50-85 percent
lifetime risk for developing breast cancer as well as an increased risk for ovarian
and other cancers that vary dependent on the gene involved. Therefore, individuals
with a documented BRCA1 or BRCA2 mutation will be assigned to the high risk
2. . For all participants without a history of breast cancer and no documented BRCA1 or
BRCA2 mutation, the computerized Pedigree Assessment Tool (PAT) will be used to
establish control or high risk group assignment. The PAT is capable of identifying
women from families with features suggesting transmission of an autosomal dominant
breast cancer susceptibility allele. The PAT is a simple point scoring system which
assigns point values for each case of breast or ovarian cancer within a family.
Pedigree Assessment Tool Scoring System
Diagnosis Points Assigned
Breast Cancer at age 50 or higher 3
Breast cancer prior to age 50 4
Ovarian Cancer at any age 5
Male Breast Cancer at any age 8
Ashkenazi Jewish heritage 4
The PAT score is calculated by adding the points assigned to every family member with a
breast or ovarian cancer diagnosis, including 2nd and 3rd degree relatives. A separate
score is calculated for both the maternal and paternal lineage and the higher of the 2
scores is assigned to the participant. Validation data from this model demonstrate that
the PAT score was more accurate than the modified Gail model at identifying women with a
hereditary risk of breast cancer. Area under the ROC curve for the PAT was 0.9625 compared
to 0.389 and 0.5861 for 5-year and lifetime Gail estimates respectively. a PAT score of
greater than or equal to 8 provided the most accurate discrimination between "high risk"
and "not high risk" women with a sensitivity of 100 percent specificity of 93 positive
predictive value of 63 percent and negative predictive value of 100 percent.
The control participants have been ascertained from among the low risk screening
population, and from non-cancer clinics and practices of the NNMC and must meet both of
the following criteria.
1. Individuals with no prior history of any malignancy excluding skin cancers (except
melanoma) and cervical cancer in situ.
2. A PAT score less than 8.
3. Gail risk less than 1.67.
High Risk Population:
In order for individuals to be in the high-risk for breast cancer group a subject must
satisfy criterion 1 AND at least one of criteria 2 through 6.
1. Have no prior history of any malignancy excluding skin cancers (except melanoma) and
cervical cancer in situ.
2. Gail Model - an estimated risk of greater than 1.66 of developing breast cancer over
the next five years.
3. A documented deleterious mutation in BRCA1 or BRCA2.
4. A PAT score greater than or equal to 8 .
5. History of lobular carcinoma in situ (LCIS).
6. History of atypical lobular or ductal hyperplasia.
Inability to give informed consent.
Individuals with any active infection or superficial inflammation of the breast, or who
are currently lactating or who are less than 6 months post-lactation will not be eligible
to undergo nipple fluid sampling, however they may still participate in the rest of the