MRI Background Parenchymal Enhancement as a Risk Factor for Breast Cancer: The IMAGINg and Epidemiology (IMAGINE) Study

Proposed Study Methods Pertaining to the Population, Eligibility and Recruitment In this
multi-center hospital-based case-control study, cases will be women diagnosed with incident
breast cancer who have undergone or are about to undergo a bilateral breast MRI with contrast
to assess extent of disease. The cancer-free controls will be women at high-risk of breast
cancer undergoing a bilateral breast MRI with contrast for screening. The MRI collected for
the study may be post-biopsy and post-surgery (unilateral lumpectomy/mastectomy), but prior
to bilateral mastectomy, radiation, hormonal, and/or chemotherapy. Study participants also
need to have a bilateral mammogram available at the study site within 24 months prior to, or
up to 24 months after the study MRI (as long as prior to surgery, radiation, hormonal, and/or
chemotherapy), to be included in the secondary aim analysis. The MRI/mammogram selected for
this study do not need to be conducted at the recruitment site, the digital images just need
to be accessible from the patient medical records at the site. Questionnaire data, optional
saliva samples, MRIs, mammograms, and medical records will be collected over a 27 month
period from women at three NCI-designated comprehensive cancer centers (MSK, Penn, Utah).
Each site has demonstrated experience with recruitment, patient interviews and collection of
MRIs and mammograms.

Inclusion Criteria:

- Eligibility Criteria for Breast Cancer Cases (invasive)

Women with the following characteristics at MRI will be eligible as invasive cases:

1. have a diagnosed invasive unilateral breast cancer after 1/1/2010;

2. have a pre-treatment (prior to bilateral mastectomy, radiation, hormonal, and/or
chemotherapy) bilateral breast MRI with contrast available from the study site;

3. be ≥ 21 and <70 years old at time of diagnosis; and

4. have an intact contralateral breast at the time of study MRI.

Eligibility Criteria for Breast Cancer Cases (non-invasive)

Women with the following characteristics at MRI will be eligible as non-invasive cases:

have a diagnosed unilateral ductal carcinoma in situ (DCIS) preferably after 1/1/2013; 2)
have a pre-treatment (prior to bilateral mastectomy, radiation, hormonal, and/or
chemotherapy) bilateral breast MRI with contrast available from the study site; 3) be ≥ 21
and <70 years old at time of diagnosis; and 4) have an intact contralateral breast. The
contralateral breast needs to be intact and unaffected by an invasive carcinoma and/or DCIS
so the MRI reading can be done on the breast without cancer. Women with a history of
previous cancer diagnosis are excluded because treatment they may have received for these
cancers might affect the MRI readings.

Eligibility Criteria for Controls Controls will be women determined to be at high risk of
developing breast cancer (i.e., lifetime risk ≥20%

Controls must meet the following criteria:

1. have a bilateral breast MRI screening with contrast available from the study site;

2. be ≥ 21 and <70 years old at time of MRI; and

3. negative breast MRI screen.

Exclusion Criteria:

- For either cases or controls prior to study MRI date:

1. unable to speak and read English;

2. history of prophylactic mastectomy;

3. history of pre-pectoral breast implants in either breast (sub-pectoral are
acceptable);

4. history of breast reduction surgery;

5. currently taking, or in the previous 3 months: hormonal medication such as
Tamoxifen (Nolvadex), Raloxifene (Evista), aromatase inhibitors
(Anastrozole/Arimidex, Letrozole/Femara, and/or Exemestane/Aromasin); and/or
other postmenopausal hormonal therapy (PHT) medication; and/or hormonal
medication for fertility treatment; [Note: Women are INELIGIBLE if they report
taking pills orally, use a patch or ring, even if just intermittently used. Women
are ELIGIBLE if they report just taking hormone replacement therapy in the form
of a cream, suppository (or intra-vaginal), soy-based, or other natural product.]

6. currently, or in the preceding 6 months, pregnant or breast feeding; and

7. history of previous cancer including DCIS [Note: Women are ELIGIBLE if diagnosed
with non melanoma skin cancer lobular carcinoma in situ (LCIS) and/or cervical
cancer in situ ].

Notes: Women recently diagnosed with DCIS within the study period will be categorized as
non-invasive cases (preferable prospective recruitment only). Only one breast may be
affected by a recent diagnosis of invasive carcinoma and/or DCIS.