Trial Information

The British Breast Cancer Study - National Cancer Research Network Cohort (BBC-NCRN)

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.