Study of Radiation Exposure and Bilateral Breast Cancer

This study expands upon an existing case-control study we call the Women's Environment Cancer
and Radiation Epidemiology (WECARE) Study. For simplicity, in this protocol, we will refer to
that study as the "parent" study. The goal of both studies is to examine the interaction of
radiation exposure and genetic susceptibility factors in the etiology of breast cancer. A
subset of study participants who consented to 'future contact' in the GWA Study (and those in
the 'parent' study from selected sites) will be included in an analysis of radiation-related
heart disease and related conditions.

Inclusion Criteria:

- Eligibility for Cases: All women who meet the following eligibility requirements will
be recruited as cases for the WECARE:GWA Study if they are not already cases (or
refusers) from the parent WECARE Study:

- Diagnosed since 1/1/1990 with a histologically confirmed first primary breast cancer
(only invasive stage 1 or 2) while residing in one of the study enrollment site
(cancer registry);

- Diagnosed since 1/1/1992 with CBC (invasive only any stage) while residing in the same
enrollment site (cancer registry);

- Two years or longer time interval between first and second primaries; Between the ages
of 18 and 54 at the time of diagnosis of the first primary;

- Alive at time of contact; and

- No history of previous or intervening cancer diagnosis, except cervical cancer in situ
(CIS) or non-melanoma skin cancer.

- Without bilateral mastectomy or prophylactic mastectomy of the contralateral breast
following diagnosis of their first primary.

Eligibility for Controls: Women who meet all of the following requirements will be eligible
as controls. One matched control will be recruited for each participating case:

- Diagnosed since 1/1/1990 with their first primary breast cancer (only invasive stage 1
or 2) while residing in one of the study enrollment site (i.e., cancer registry);

- Between the ages of 18 and 54 at the time of diagnosis of the first primary;

- Residing in the same study enrollment site (cancer registry) as when they were
diagnosed with their breast cancer;

- Alive at time of contact;

- Never diagnosed (at reference date (date of first diagnosis plus "at risk interval" of
matched case)) as having had CBC or any other cancer diagnosis other than the original
breast cancer; with the exception of CIS or non-melanoma skin cancer.

- Without bilateral mastectomy or prophylactic mastectomy of the contralateral breast
following diagnosis of their first primary.

Matching of Controls: Controls eligible for inclusion in this study will be individually
matched (1:1) to cases on:

- Enrollment site (cancer registry);

- Age at diagnosis of the cases first primary(within 5-year age groups);

- Year of diagnosis of the cases first primary;(within 4-year categories);

- Race/ethnicity (white, black, Latina, Asian, other).

Exclusion Criteria:

Exclusion for Cases: Women with any of the following characteristics will be ineligible as
a case:

- Unable to speak English in U.S. or Canadian enrolling sites or Spanish in the
California site, and Danish in Denmark

- Unable to sign informed consent

- Stage IV distant metastases for either the first or second primary (lymph node
metastasis is acceptable, but there should be no organ involvement

- Simultaneous diagnosis of invasive in one breast and in situ in the other breast

Exclusion for Controls: Women with any of the following characteristics will be ineligible
as a control:

- Unable to speak English in U.S. and Canadian enrolling sites, or Spanish in the
California site and Danish in Demark

- Unable to sign informed consent

- Stage IV distant metastases (lymph node metastasis is acceptable, but there should be
no organ involvement