This study is being done to find out what factors may be related to the risk of getting a second breast cancer among women who already have breast cancer in one breast. It will look at how genes, treatment for breast cancer; including radiation therapy, and the effects of different lifestyle activities, may affect the risk of breast cancer. It will use different processes to find genes that might increase the risk of breast cancer. The results of this study may help to develop better ways to detect, treat and prevent breast cancer. This study will compare women who have breast cancer in both breasts to women who have breast cancer in only one breast.

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

All of the WECARE:GWA Study participants (new cases and individually matched controls) will be identified, recruited, and interviewed by investigative teams in the five population-based cancer registries (NCC, OCR, FHCRC, Iowa, and DCS).