Cancer Intervention and Surveillance Modeling Network (CISNET)

Principal Investigator: Donald A. Berry
Institution: M.D. Anderson Cancer Center
Grant Number: 5U01CA088278-04

Awarded under CA-99-013
Currently a CISNET Affiliate Member

Abstract: The last decade has seen an over-all decrease in breast cancer mortality within the United States (SEER 1998). This encouraging trend has also been observed in a number of other countries including Canada and the United Kingdom (IARC. 1999). Whilst there are a variety of possible explanations for this decline in mortality, two of the most likely reasons are earlier detection and improved treatment.

Substantial gains have been made in early detection through the use of screening mammography. This procedure has proven effective in identifying breast cancer at an earlier point in its development, subsequently shifting the stage of the disease for many women (Kricker 1999). Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) cancer statistics review (1998), shows a dramatic increase in stage-I and in-situ cancer during the last decade. Moreover, results from randomized trials have shown that screening mammography decreases breast cancer mortality (Jatoi 1999, Kerlikowske Jama 1995, Fletcher 1993). The prevalence of screening mammography has increased dramatically during the 1990's (Health, United States 1999) as has the use of clinical breast examination (MMWR 45(3) 1996).

During the same period, chemotherapy treatments have increased in both overall usage and in the number of cytotoxic agents now available (Early Breast Cancer Trialists' Parts 1&2 1992, Hortobagyi 1999). The focus of current chemotherapy research in breast cancer includes developing fine-tuned combination therapies, utilizing established drugs in more effective ways, and specifically selecting patients for treatment according to their prognostic characteristics. The late 1980's and 1990's have seen a dramatic increase in the use of adjuvant tamoxifen for patients whose tumors are hormone-receptor sensitive, especially for postmenopausal patients in the early part of this period (Early Breast Cancer Trialists' Collaborative Group, Lancet 1998).

Although breast cancer mortality, prevalence of screening, effectiveness of screening, therapy use patterns, and therapy effectiveness are not perfectly known, each can be estimated. However, estimates are subject to error. A principle goal of this project is to provide estimates of the relative contributions of screening and therapy (and the associated uncertainty) to the observed decrease in relation to breast cancer mortality in the United States. A corollary of this goal is assessing the benefits of screening mammography and therapy, based upon all of the available information. A further goal is to address the potential impact of changing guidelines for screening mammography and of the use of additional interventions, such as tamoxifen and other SERMs (selective estrogen-receptor modulators) as preventive agents. Methods to be used include statistical modeling and simulation. A variety of sources of information will be used in model development.