Breast, Ovarian and Endometrial Cancer Case-Control Study in Poland

Trial Information

Breast, Ovarian and Endometrial Cancer Case-Control Study in Poland

The Polish breast, ovarian and endometrial cancer study is a molecular epidemiologic study
conducted in two cities in Poland (Warsaw and L6dz) that enrolled 2,386 breast, 347 ovarian
and 555 endometrial cancer cases, and 2,798 controls. This large population-based study
combines state-of-the art techniques of exposure assessment and collection of biological
specimens to allow for the study of a wide range of biomarkers. For a subset of cases we
also obtained the pre-treatment mammograms to obtain mammographic density measures. Subject
enrollment started in February 1, 2000. The last day of diagnosis for eligible breast cancer
cases was January 31, 2003 and for ovarian and endometrial cancer cases was December 31,
2003.The final response rates to the interview for the breast cancer component of the study
are 79% for breast cancer cases and 69% for controls. Among women who agree to the
interview, most of them agree to provide biological specimens (84% of breast cancer cases
and 92% of controls agree to provide a blood sample; 82% of cases and 89% of controls agree
to provide a urine sample), anthropometric measurements (95% of breast cancer cases and 93%
controls) and wear a physical activity monitor (76% of breast cancer cases and 84% of
controls from the Warsaw study site). The final participation rates to the interview for the
ovarian and endometrial component of the study are 78% for ovarian, 80% for endometrial
cancer cases. Of these women, 85% of ovarian and 86% of endometrial cancer cases agreed to
provide a blood sample. We are continuing to obtain follow-up information and mortality
information from breast, ovarian and endometrial cancer cases in the study using the Death
Certificate Office database in Poland. The main research projects being conducted or planned
for the near future include:

1. Analyses of questionnaire-based factors and anthropometric measurements in relation to
cancer risk and prognosis. This work has been addressed within the consent form
documents as follows: "If you agree to participate, a trained interviewer from the
Polish Sociological Association will administer a questionnaire about your reproductive
history, diet, occupation, physical activity, and other factors related to health."

2. Association between genetic susceptibility markers and cancer risk, mammographic
density, risk factors, survival, and treatment using candidate gene and genome-wide
association (GWAS) approaches. Genomic-wide association data has been acquired for the
ER negative breast cancer cases, ovarian cancer cases, endometrial cancer cases and a
subset of matched controls to evaluate genetic risk factors for these diseases. This
work has been addressed within the consent form documents as follows: "The saliva,
blood, urine, and tissue samples obtained will be used to look at factors that might be
related to breast [ovarian/endometrial] disease. These factors include genes that are
uncommon in the population but may dramatically increase the risk of breast
[ovarian/endometrial] disease, and more common genes that are likely to cause a modest
increase in breast [ovarian/endometrial] disease risk."

3. Analyses of breast tissue/tumor markers to evaluate relationships with cancer risk
factors (known or suspected), and their impact on predicting recurrence and survival
after diagnosis. Biomarkers currently being evaluated include autoantibody profiles in
plasma, metabolomic profiles in serum, levels of endogenous hormones and their
metabolites in serum and adipose tissue, hormone levels in urine and breast tissue
samples. Tumor markers are being analyzed using formalin fixed tissue samples
(individual blocks or tissue cores in tissue microarrays) collected from about 2,000
breast, 200 ovarian and 400 endometrial cancer cases, and frozen tissue samples
collected from a subset of about 300 breast cancer cases. Current tumor markers being
analyzed include immunohistochemestry markers, DNA methylation, micro RNA profiling,
mRNA profiling, cytogenetic changes using SNP arrays, and somatic mutations. This work
has been addressed within the consent form documents as follows: "The saliva, blood,
urine, and tissue samples obtained will be used to look at factors that might be
related to breast [ovarian/endometrial] disease". In addition to tumor samples, we are
collaborating with investigators to look at non-invasive tissues collected from the
study.

4. Confirmation of genetic associations and evaluation of risk factors for uncommon tumor
subtypes requires large numbers of cases and controls that can only be attained in
analyses of pooled data across individual studies. Therefore, we are collaborating with
consortia of studies, particularly the Breast Cancer Association Consortium, the breast
cancer CGEMS project, the Ovarian Cancer Association Consortium and the E2C2 Consortium
of endometrial cancer studies.