Breast Cancer

Women's Interview Study of Health (WISH), Case-Control Study of Breast Cancer Among Younger Women

A population-based case-control study of breast cancer was undertaken to address a number of etiologic hypotheses best addressed among younger women, including effects on risk of oral contraceptive usage, dietary and physical activity patterns early in life, and prenatal factors. The study was conducted in three different geographic areas: Atlanta, New Jersey, and Seattle. Controls were identified through random digit dialing, although one site also employed a series of women identified through a complex area survey sampling technique. The majority of the subjects were younger than 45 years of age, although the age range was extended at one site to 55 years to allow a broader perspective on several issues. Detailed interviews and anthropometric measurements were undertaken. Pre-operative blood samples were obtained at one site from early stage cases and controls. More information, Louise Brinton.

The BREAST Stamp Project

Investigators in DCEG’s Hormonal and Reproductive Epidemiology Branch are currently collaborating with extramural colleagues in NCI’s Breast Cancer Surveillance Consortium at the University of Vermont, the University of California at San Francisco, and in NCI’s Division of Cancer Control and Population Sciences, on the Breast Radiology Evaluation and Study of Tissues (or “BREAST”) Stamp Project. A total of 466 women ages 40-65 years who were clinically referred to radiologically-guided breast biopsy were enrolled from Fall 2007 through Summer 2010. The BREAST Stamp Project aims to characterize the radiologic, histologic, molecular, and biochemical features of dense breast tissue and to understand how the microenvironment of dense breasts promotes neoplastic transformation of the breast epithelium. Risk factor data and biological specimens (blood, buccal cells, tissue fluids, and tissue) required to discover mechanisms and biomarkers that link high mammographic density (as measured quantitatively using computerized methods) to breast cancer risk were collected from study participants. More information, Gretchen Gierach.

BCDDP Follow-Up Study

The Breast Cancer Detection Demonstration Project Follow-up Study involves approximately 64,000 women who were participants in the Breast Cancer Detection Demonstration Project, a 5-year screening program conducted between 1973 and 1980 at 29 centers throughout the United States. The follow-up study began in 1980 and follow-up continued through 2005. Information on cancer diagnoses, benign breast procedures, and exposure to established and hypothesized cancer risk factors has been ascertained through questionnaires administered over the course of the follow-up study. Researchers are analyzing exogenous hormones, lifestyle factors, and other risk factors for breast, ovarian, endometrial, and colorectal cancers. More information, Gretchen Gierach.

Breast Cancer Case-Control Study in Poland

This population-based case-control study was conducted from 2000-2003 in two major cities in Poland, Warsaw and Lodz, and enrolled 2,386 breast cancer cases and 2,798 age and site matched 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. Exposure information is obtained through detailed personal interviews, anthropometric measurements, physical activity monitors, and collection of dust samples from the participants’ homes. The collection of biological specimens includes blood samples processed as cryopreserved whole blood, serum+ blood clot, plasma+buffy coat+red blood cells; 12-hour overnight urine; paraffin embedded tumor and normal tissue; and fresh tissue from tumors, non-neoplastic breast tissue and mammary fat tissue. We obtained five year follow-up information from medical records for approximately 1,300 breast cancer cases recruited in Warsaw and 300 cases recruited in Lodz, as well as mortality data on most cases in the study using the Cancer Registry and Death Certificate Office database in Poland. The main research projects being conducted include: Analyses of questionnaire-based factors and anthropometric/physical activity measurements in relation to cancer risk and clinical outcomes; identifying genetic susceptibility markers of cancer risk and clinical outcomes using candidate gene and genome-wide association (GWAS) approaches; 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; and analyses of biomarkers in DNA (somatic changes), cryopreserved blood cells, serum/plasma, and urine in relationship to cancer risk and clinical outcomes. More information, Jonine Figueroa.

The Collaborative Breast Cancer Study in the U.S.

The Collaborative Breast Cancer Study (CBCS) is an extramurally-funded population-based case-control study of breast cancer in the states of Wisconsin, Massachusetts and New Hampshire. The main goal of this study is to evaluate susceptibility factors for breast cancer risk and their interactions with environmental risk factors. Enrollment and data collection started in June 1998 and was completed in April 2001. The CBCS obtained risk factor information from cases of invasive and in-situ breast cancer and from population controls through a telephone interview. At the end of the telephone interview, women were invited to participate in the buccal cell component of the study. Approximately 82 percent of eligible breast cancer cases and 78 percent of eligible controls agreed to participate in the study interview. A total of 7,833 subjects, representing approximately 75 percent of cases and 70 percent of controls that completed the interview, provided a cytobrush or mouthwash buccal cell sample. The main research projects being conducted include identification of genetic susceptibility loci for breast cancer, including evaluation of gene-gene interactions, and in combination with other risk factor information to evaluate gene-environment interactions. We are also collecting mortality information from breast cancer cases in the study using the National Death Index to evaluate determinants of survival. More information, Jonine Figueroa.

Male Breast Cancer Pooling Project

The etiology of male breast cancer has been difficult to clarify, given its relative rarity. Most previous studies have been of case-control designs, raising questions about the influence of recall biases. The identification of risk factors through prospective analyses is needed, although it is difficult to assemble sufficient numbers of cases in any individual study. A consortial approach is therefore underway, in which data from a number of studies will be pooled to derive sufficient power to fully explore the role of a variety of potential risk factors. Cohorts with biologic material collected prior to disease onset will be especially valuable for clarifying biologic mechanisms underlying identified risk factors. Of specific interest, given our current knowledge of male breast cancers, is the assessment of endogenous hormones and genetic markers. Questionnaire data and biologic samples (sera, DNA) are being sought for contribution to this consortial effort. This study is a valuable resource for adding to our knowledge of the etiology of male breast cancers. More information, Louise Brinton.

Markers of Risk Using Normal Breast Tissues From Healthy Volunteers: The Susan G. Komen® for the Cure Tissue Bank

Invasive breast cancers are believed to arise from normal breast structures specifically, the potential milk secreting units called terminal duct lobular units (TDLU). The last decade of breast cancer research has resulted in several established breast cancer risk factors, yet the biological mechanisms and markers associated with these risk factors remain poorly defined. We hypothesize that altered histomorphology in TDLUs, levels of proliferation, levels of apoptosis, and levels of the ER and PR in TDLUs, may be associated with known breast cancer risk factors. Previous efforts to characterize mechanisms of carcinogenesis for known risk factors have been limited by small sample sizes and incomplete epidemiologic characterization of the subjects. We are collaborating with the Susan G. Komen® for the Cure Tissue Bank at the IU Simon Cancer Center (KTB), which offers a rich and unique opportunity for identifying links between biologic markers and breast cancer risk factors. This repository includes questionnaire data, breast tissue, saliva, serum, and whole blood collected from over 1000 healthy women volunteers that exhibited no evidence of breast cancer. The current project offers the possibility of determining the mechanisms by which risk factors act on epithelial cells prior to tumor development. More information, Jonine Figueroa .

Columbia, Missouri Serum Bank Follow-up Study

The Columbia, MO serum bank was established as part of the National Cancer Institute’s Biological Markers Project to identify serum markers for breast cancer. A total of 7,224 women living in and around Columbia, MO who were free of cancer other than non-melanoma skin cancer, donated blood to the serum bank on one or more occasions between 1977 and 1987. Approximately 25% of the women were premenopausal. At the time of each blood collection, interview information was obtained from participants on the major known breast cancer risk factors including age, height, weight, reproductive and menstrual histories, family history of breast cancer, medical conditions, and drug use, including oral contraceptives and menopausal hormone therapy. Date of last menstrual period was obtained for women who were premenopausal at the time of each blood collection. Approximately 30% of the women donated multiple samples over the first 10 years of the study, including 20% who had 3 or more samples, with collections occurring on average one year apart. In 1989, the first follow-up ascertained 107 breast cancers among women who were cancer-free at blood collection. A subset of these breast cancers was included in a number of biomarker studies, including the measurement of sex steroid hormones, carotenoids, alpha-tocopherol, selenium, organochlorine pesticides and PCBs. A more recent follow-up was completed in 2002, at which time an additional 279 breast cancers were identified. More information, Louise Brinton.

The Ultrasound Study of Tamoxifen

Mammographic breast density, the radiological representation of the fibroglandular composition of the breast, is one of the strongest risk factors for breast cancer. Epidemiologic evidence suggests that changes in breast density are related to changes in breast cancer risk. Ultrasound tomography (UST) is a novel radiological method that provides a three-dimensional image of the breast (as opposed to mammography which is two-dimensional). Our collaborators at Karmanos Cancer Institute have developed a UST device which allows the calculation of sound speed, an objective physical measurement which is positively correlated with breast density. Thus, UST offers the possibility of determining breast density serially over time as a volume, without compression of the breast or exposure to potentially harmful ionizing radiation. In collaboration with researchers at Karmanos Cancer Institute and the University of Toronto, HREB investigators will use UST to define the time course of volumetric breast density changes among women receiving tamoxifen treatment. Tamoxifen is known to reduce breast density and breast cancer risk. Over three years, we will enroll 150 women receiving tamoxifen monotherapy for atypical lobular or ductal hyperplasia, lobular or ductal carcinoma in situ, or invasive breast cancer at Karmanos Cancer Institute to undergo repeated volumetric breast density assessment with UST. We will assess whether UST examinations performed as early as 1-3 months following initiation of tamoxifen can identify women whose breast density is demonstrated to have declined at one year using mammography. For comparison, we will enroll 150 age-, race-, and menopausal status-matched women without breast cancer to assess changes in UST density over time without tamoxifen exposure. Risk factor data and blood will also be collected from study participants. The broader study objective is to assess the concept of breast density as a biosensor of tamoxifen response and UST as a useful tool for making this determination. More information, Gretchen Gierach.