Protocol for Women at Increased Risk of Developing Breast Cancer

1. To correlate established risk biomarkers such as cytomorphology obtained from random
periareolar fine needle aspiration ( RPFNA), mammographic breast density, serum
bioavailable estradiol and IGF-1/IGFBP-3 with each other and with 5-10 year Gail risk
estimates. Where available, and with appropriate safe guards to maintain status for
breast cancer susceptibility genes may be included.

2. To determine the relative predictive value of established risk biomarkers for the
development of DCIS and/or invasive cancer.

3. To evaluate potential new breast tissue-based biomarkers including Ki-67, PCNA, ER,
COX-2, aromatase, methylation of key tumor suppressor genes (i.e., RAR, p16, etc),
proteomic patterns in RPFNA and nipple aspirate fluid (NAF), as well as NAF hormone
levels, and correlate them with other risk biomarkers listed in 1.

4. To determine the prevalence of polymorphisms of a panel of genes important in hormone
and xenobiotic metabolism as well as DNA repair and correlate these polymorphisms with
established risk biomarkers listed in 1, as well as with development of DCIS and
invasive cancer.

5. To maintain contact with this initially identified cohort of high risk women, acquire
demographic data, biologic specimens and data and follow them prospectively for the
development.

Inclusion Criteria:

- women with at least 2 times the normal risk of developing breast cancer

- between the ages of 30-65 (or within 10 years of youngest age at diagnosis in first
degree relative)

- greater than six months from ingestion of antihormonal therapy

- greater than 1 year from pregnancy, lactation, or chemotherapy

- willing to have a mammogram within six months prior to RPFNA

- willing to discontinue NSAIDS or herbal supplements

- willing to have blood drawn

Exclusion Criteria:

- no metastatic malignancy of any kind

- no breast implants or tram flap reconstructions

- no radiation to both breasts

- no women who have a current mammogram or clinical breast exam suspicious for cancer