Genes and Other Risk Factors for Second Primary Breast Cancer in Women With Breast Cancer and Their Female Family Members and Friends
Genes and Other Risk Factors for Second Primary Breast Cancer in Women With Breast Cancer and Their Female Family Members and Friends
RATIONALE: Studying samples of blood, urine, and tumor tissue in the laboratory from patients
 with cancer and their female relatives and friends may help doctors learn more about changes
 that occur in DNA and identify biomarkers related to cancer.

 PURPOSE: This research study is looking at genes and other risk factors for second primary
 breast cancer in women with breast cancer and in their female family members and friends.
OBJECTIVES:

 -  To identify new breast cancer susceptibility alleles in breast cancer patients and
 family controls.

 -  To compare the prevalence of known polymorphisms in genes involved in hormonal
 activation and degradation pathways in breast cancer patients and family controls.

 -  To correlate these polymorphisms with quantitative intermediate markers of
 susceptibility to breast cancer, such as circulating hormone levels and mammographic
 density.

 -  To perform linkage analysis to detect new susceptibility genes in larger multiple-case
 families combined with data on families previously collected by the Institute of Cancer
 Research.

 -  To evaluate the relationship between these polymorphisms and hormone levels in relatives
 and family controls.

 -  To compare average hormone levels in patients' unaffected first-degree relatives with
 family controls using urine samples from premenopausal women and urine and/or serum
 samples from postmenopausal women.

 -  To perform follow-up in a cohort of unaffected first-degree relatives at
 moderate-to-high risk of developing breast cancer with prospective questionnaire data
 and hormone measurements.

 OUTLINE: Unaffected and affected first-degree female relatives and family or friend controls
 undergo blood sample collection once during study. Genomic DNA is purified from the blood
 samples for genetic analyses. Within a cohort of unaffected first-degree relatives,
 postmenopausal women also provide a single urine sample for hormonal assays. Hormones
 analyzed in the serum and/or urine of postmenopausal women include estradiol, estrone,
 sulphate, prolactin, androstenedione, testosterone, progesterone, 17-hydroxyprogesterone, and
 SHBG. Unaffected premenopausal women within the cohort provide urine samples on 6 successive
 days around the midpoint of their menstrual cycle and on one day towards the luteal phase of
 their menstrual cycle. These samples are analyzed for luteinizing hormone and metabolites of
 estradiol and progesterone (i.e., creatinine ratios for estrone glucuronide and pregnanediol
 glucuronide).

 Access to case notes, mammograms, and archival tumor blocks and accompanying pathology
 reports of breast cancer patients and their affected relatives is requested. When tumor
 samples from both tumors in bilateral cases are available, these samples are analyzed to
 identify regions of loss of heterozygosity in which both tumors have lost the same
 chromosomal region.

 Cancer patients and controls, including affected or unaffected first-degree relatives,
 relatives by marriage, or friends complete a questionnaire at baseline to provide information
 on demographics (i.e., personal and family), cancer diagnosis and treatment (if applicable),
 and known risk factors for breast cancer (i.e., lifestyle, reproductive behavior, and family
 history).

 Study participants may be followed periodically for cancer incidence and cause-specific
 mortality.

 Peer Reviewed and Funded or Endorsed by Cancer Research UK.
DISEASE CHARACTERISTICS:

 -  Meets 1 of the following criteria:

 -  Women who have been diagnosed with contralateral or unilateral breast cancer

 -  Family controls, including sisters and adult daughters of contralateral cases,
 female relatives by marriage

 -  Unrelated controls (i.e., friends)

 -  Hormone receptor status not specified

 PATIENT CHARACTERISTICS:

 -  Pre- or postmenopausal

 PRIOR CONCURRENT THERAPY:

 -  Not specified