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OffLine Spring 2001

Volume 13 Number 2

Cancer prevention has been a research priority for Group Health Center for Health Studies since its inception in 1983. For example, the origin of Group Health's smoking cessation program, Free & Clear, can be traced to a 1984 CHS grant from the National Cancer Institute (NCI). In the mid 1980s, Center investigators played a pivotal role in the design and implementation of the Coop's Breast Cancer Screening Program, a program that has gained nationwide recognition as a model for cancer screening.

CHS's involvement in cancer-related research has continued to grow during the last 15 years. Free & Clear was just the first in a long line of smoking cessation studies that continue to this day (see Off Line Vol. 11 No. 2). Since 1994, CHS has been one of several U.S. sites funded by the NCI to establish a comprehensive breast cancer surveillance system (Stephen Taplin, Principal Investigator). Through database linkage, the Surveillance project provides important information on markers of breast cancer risk and prognosis, mammography screening accuracy, and patterns of care and cost. CHS investigator Bill Barlow directs the analysis of data gathered from all 7 participating sites.

CHS investigators have piloted a similar surveillance system for colorectal cancer screening at Group Health and are currently collaborating with the Fred Hutchinson Cancer Research Center and the University of Washington on the Seattle Gastrointestinal program project grant. The main research goals are to: 1) identify biologic markers that could aid in the early detection of cancers of the colon and pancreas; and 2) establish a registry of colonoscopy procedures, pathology results and tissue specimens to be used in longitudinal studies of colon cancer risk and development.

Participation in the Cancer Research Network (CRN) is another example of the breadth of CHS' cancer-related research. Led by Principal Investigator Ed Wagner of CHS, the CRN consists of the research programs, enrollee populations and databases of 10 HMO members of the HMO Research Network. The overall goal of the CRN is to determine the effectiveness of cancer control interventions in multiple, diverse health systems, in order to identify factors associated with better or worse outcomes or costs. Along with Group Health, the CRN is comprised of Harvard Pilgrim Health Care, Henry Ford Health System, HealthPartners Research Foundation, Meyers Primary Care Institute, and Kaiser Permanente divisions in Colorado, Hawaii, Oregon, Northern California, and Southern California.

These 10 geographically-dispersed health plans with nine million enrollees offer large diverse enrollee populations, rich automated databases and extensive research expertise. Founded on the principle that the whole is greater than the sum of the parts, the CRN seeks to pool data and expertise from these sites to increase our knowledge of optimal cancer treatment and control. For example, the "Tobacco Control in Managed Care: Implementation, Effectiveness and Impact on Cost of Care" project is examining characteristics and penetration of smoking cessation programs at the 10 plans by pooling data from providers, patients and plan leaders.

This issue of Off Line discusses some of the recent developments in the CHS cancer-prevention research program. (This article excludes the CHS smoking cessation studies as they have been covered previously).

Much of CHS' cancer research agenda focuses on prevention, specifically secondary prevention. This concept refers to preventive efforts, such as screening, that lead to the early detection and treatment of disease, which in turn should lead to a reduction in late-stage disease and cancer-related deaths. Evidence exists that screening programs have been successful in reducing fatalities due to cancer. After decades of little change in the morbidity and mortality of most adult cancers, recent data point to declines in breast and colorectal cancer mortality. A CHS study found that rates of late-stage breast tumors declined significantly between 1983 and 1992 among Group Health women aged 50 years and older. It is noteworthy that the Cooperative's Breast Cancer Screening Program was implemented in 1986.

Despite these advances and the availability of screening, some cases of advanced disease still occur. Why don't screening programs prevent all cases of late-stage disease? That is the question addressed by a CRN study that is looking at patient, provider and system factors that influence the occurrence of invasive breast and cervical cancer in HMO populations that have access to breast and cervical cancer screening.

Participation in cancer screening

Throughout the years, CHS investigators have conducted extensive research designed to improve the effectiveness of cancer screening. One avenue of research relates to participation. That is, if a significant segment of the target population does not participate in a screening program, the program by definition will not be very effective at preventing advanced disease. In an attempt to shed light on this issue, CHS investigators have examined participation rates in various Group Health screening programs and have also looked at factors that either positively or negatively impact participation.

For example, Center scientist Meg Mandelson looked at what factors were associated with fecal occult blood testing (FOBT) in a sample of older women. This test, an important screening test for colorectal cancer (CRC), is recommended annually for all men and women aged 50 years and older. The study found that among 931 women aged 50 and older, 75 percent reported ever-screening by FOBT and 48 percent reported having been screened in the prior 2 years. Participation in screening did not vary by demographic characteristics or perceived or actual risk for CRC. Women whose physicians strongly encouraged CRC screening and those who had a positive attitude toward screening were more likely to have had a recent FOBT. However, only 58 percent of the women reported that their physician recommended the test. Mandelson and colleagues cite the need for stronger and more consistent screening recommendations from primary care physicians.

In collaboration with researchers at the Memorial Sloan–Kettering Cancer Center, Mandelson is currently directing the Group Health clinical site for a randomized trial of the feasibility of screening colonoscopy. While colonoscopy is considered to be the "gold standard" for detection of CRC, it is an invasive procedure usually performed under anesthestic. One of the aims of this trial is to determine the level of participation in a screening colonoscopy trial among asymptomatic average risk men and women between the ages of 50 and 69.

In one of several studies examining factors predicting participation in breast cancer screening, CHS investigator Stephen Taplin found that having a false-positive mammogram did not adversely impact screening behavior in the next recommended interval. Taplin has also tested various methods designed to increase participation in breast cancer screening. These efforts are bolstered by the fact that, as of the mid-1990s, only 58 percent of Group Health women followed through on invitations sent by the Group Health screening program to get a mammogram. Recently, Taplin and colleagues compared 3 methods designed to increase participation in mammography: 1) a 10-minute motivational phone call addressing women's barriers to mammography; 2) a 3-minute phone call reminding women to schedule an appointment; and 3) a postcard reminder. The study found that the brief phone call was as effective as the longer motivational call in increasing mammography participation rates (and both were superior to the postcard reminder). As a result of this study, Group Health has integrated reminder phone calls into its protocol for the screening program.

Improving accuracy of mammography screening

Even if all targeted women did participate in mammography screening, not all late-stage breast cancers would be prevented. Mammograms are not always accurate for a variety of reasons, including: 1) rapid tumor growth patterns; 2) technical and interpretive errors; and 3) breast density. Dense breasts, as compared to fatty breasts, have a larger proportion of connective and epithelial tissue which appears opaque on a screening mammogram and can thus obscure a tumor. A CHS study led by Meg Mandelson and reported in the Journal of the National Cancer Institute helped quantify the degree to which breast density affects mammography accuracy. The investigators examined density as a risk factor for interval cancer, defined as cancer that is detected after a negative mammogram. The researchers compared the breast density of women whose cancer was detected following a "positive" screen with the breast density of women whose cancer was diagnosed following a "negative" screen (e.g., interval cancer). Women with extremely dense breasts were 6 times more likely to have their breast cancer missed by mammography compared to women with predominantly fatty tissue.

Since younger women have greater breast density on average than do older women, mammograms are less effective in the 40 to 49 year age group. A UW–CHS study found that among younger women, breasts tend to be less dense during the first 2 weeks of the menstrual cycle as opposed to the third and fourth week of the cycle. These results suggest that for pre-menopausal women in their 40s mammograms should be timed to coincide with the time in the menstrual cycle when breast density is at its lowest.

The relationship between breast density and hormone replacement therapy (HRT) was the subject of a recent article published in the Journal of the American Medical Association. CHS scientist Carolyn Rutter and colleagues reported that HRT initiation is associated with increases in breast density. Although previous studies had linked initiation of HRT to increases in breast density, this study was the first to show that this increase may be reversed when a woman stops taking the drug. While these findings may prompt questions about whether short-term cessation of HRT before a mammogram can improve breast cancer detection, CHS investigator Stephen Taplin cautioned that there may be serious health risks associated with starting and stopping HRT and it's too early to suggest that women stop taking the drug prior to their mammograms.

Interpretive errors when reading a mammogram can also adversely affect mammography accuracy. To improve screening accuracy, several studies have advocated that two radiologists interpret every case. A CHS study by Taplin and colleagues found that double-reading did not improve accuracy of readings overall. While double reading increased the detection of breast cancers by 7 percent, it resulted in an average decrease in specificity of 11 percent. That is, double-reading meant that women were more likely to be told they had breast cancer when they did not. The authors recommend exploring other ways of improving mammography accuracy, such as use of new computer-assisted reading devices.

This issue of Off Line has focused on CHS researchers' efforts to improve the early detection and treatment of certain types of cancers. Meg Mandelson sums up this work, saying, "The overall aim of our research in cancer screening is to identify ways to maximize cancer screening effectiveness locally, in the Group Health population, and nationally."

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