Using known risk factors for breast cancer, mathematical models can be developed to help answer important questions. These mathematical models are useful tools for researchers and for patients as follows:
1.Research on risk factors The Claus risk assessment model was used to discover the subpopulation of people who had an autosomal dominant genetic allele that increased their risk from 10% to 92%. This led to the discovery of the BRCA genes associated with breast, ovarian, and prostate cancer.
2.Clinical trial eligibility The Gail risk assessment model was developed to help researchers determine who to enroll in the NSAPB Breast Cancer Prevention Trials
where chemoprevention was shown to reduce breast cancer risk.
3.Guidelines for doing BRCA testing BRCA testing is very expensive and practically worthless if done on everyone (because it is so rare to be homozygous for BRCA1 or BRCA2). Mathematical models such as the BRCAPRO, BOADICEA, and Tyrer-Cuzick models can help determine what patients should undergo BRCA testing. The decision for testing is usually made when one of these models predicts a 10% or greater chance that there is a mutation of the BRCA1, BRCA2, or both genes.
4.Guidelines for doing MRI screening for breast cancer – MRI screening for breast cancer is not a cost effective screening test for the general population, but in specific groups, there are clear cut reasons to do so. In general, screening MRI is recommended for women with 20-25% or greater lifetime risk of breast cancer. The BRCAPRO and Tyrer-Cuzick models have been used to help make clinical decisions about ordering MRIs for breast cancer screening.
5.Guidelines for breast cancer therapy The Gail model is used clinically to help
determine who should be put on tamoxifen or raloxifene for chemoprevention. Other models have been used to help make decisions about breast cancer risk reduction with prophylactic mastectomy.
For these reasons, it is important to understand these models. These models are collectively refered to as risk assessment tools. The following paragraphs summarize the most popular and most widely used risk assessment tools. Keep in mind that none of these risk assessment tools apply to breast cancer survivors. No mathematical model has been widely accepted to determine cancer risk in cancer survivors.
General Risk Assessment Tools
Gail Model: The Gail model is a validated risk-assessment model that focuses primarily on nonhereditary risk factors, with limited information on family history. It was developed by scientists at the National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to assist health care providers in discussing breast cancer risk to determine their eligibility for the Breast Cancer Prevention Trial. The tool allows one to project a woman’s individual estimate of breast cancer risk over a five-year period of time and over her lifetime. It also compares the woman’s risk calculation with the average risk for a woman of the same age. The Gail Model is an on-line quiz that has 13 questions and is interactive. This calculator is based on published risk statistics and methods gathered from peer-reviewed journals, and has been extensively tested for its validity.
The major limitation of the Gail model is the inclusion of only first-degree relatives, which results in underestimating risk in the 50% of families with cancer in the paternal lineage and also takes no account of the age of onset of breast cancer. It may underestimate risk in certain groups, such as obese patients.
National Cancer Institute Model: The NCI risk assessment tool is essentially a simplified Gail Model that also factors in race. Race is a factor in determining breast cancer risk but is excluded when determining eligibility for clinical trials. This tool is probably the most popular risk assessment tool available to the public as an on-line, interactive risk calculator. The on-line quiz is a shorter, nine-point questionnaire that includes multiple factors, giving a woman her future five-year risk of breast cancer and her lifetime risk of breast cancer.
The NCI tool does not account for a lot of risk factors that can be modified. For this reason, it is difficult to use this test as a motivation tool to show people how lifestyle can alter their risk of breast cancer. It also cannot be used in breast cancer survivors, in patients with DCIS, LCIS, or people who carry one of the BRCA genes.
BRCAPRO model: This is a statistical model available as a computer program that uses two different algorithms to evaluate family history and helps a doctor determine the likelihood of finding either a BRCA1 mutation or a BRCA2 mutation in a family. The results of this can be used to determine if BRCA testing is indicated. This is very useful in light of the high cost of BRCA testing ($3,000). None of the nonhereditary risk factors can yet be incorporated into the model, however. In a comparison of four different methods for estimating breast cancer risk in patients with a family history of breast cancer, the BRCAPRO model was the least accurate. It predicted only 49% of the breast cancers that actually occurred in the screened group of patients with a family history of breast cancer.
Harvard Center for Cancer Prevention Risk Assessment Tool: This is another breast cancer risk assessment tool that includes more lifestyle factors than the NCI or Gail Model tools. It has not been studied as extensively as the Gail Model or the simplified NCI model, but it is promising in that it includes many lifestyle factors that people can do to modify their risk of developing cancer. It is also an on-line questionnaire that can be used by both women and men to estimate their breast cancer risk.
Making all this practical
Now after a thorough and confusing discussion of all these statistical models, its time to make all this information practical. What is the best way to help a patient accurately assess her risk of breast cancer and if possible, show her what positive factors are reducing her risk and what negative factors can be changed to reduce her risk? If possible, it would also be great to show the patient the value and indications for testing, imaging, chemoprevention, and in some cases surgery. A discussion of the practical aspect of each of these is addressed in a Q & A format below:
Q: What (free) online programs can be used to help a patient assess their risk of breast cancer?
A: Several of the risk assessment tools mentioned above can be accessed for free by the public. Here are the tests and their websites:
1.Your Disease Risk English version: http://www.diseaseriskindex.harvard.edu
Spanish version: http://www.diseaseriskindex.harvard.edu/spanish
This is a great interactive questionnaire that calculates five-year and lifetime risk of breast cancer developed by the Harvard Center for Cancer Prevention and made public online in 2000. In 2005, they launched the Spanish version of the site, Cuidar de su Salud. The risk calculator includes lifestyle factors such as weight, dietary vegetables, alcohol intake, as well as Jewish ethnicity. It does not include other ethnicities, however, and is not accurate for BRCA mutation carriers or breast cancer survivors. Despite these issues, this is by far the best free online risk calculator since it is very interactive and gives you a personalized description of your risk in the form of a colored bar graph, which they can electronically manipulate to experience “virtual” risk reduction. The bar graph is a seven-level scale that compares users to a typical man or woman your age. Users learn where to focus their prevention efforts and how to make lifestyle changes by “clicking on” personalized strategies. With each click, the bar graph shrinks, and the user watches his/her predicted risk drop. This is a great concept to motivate people to participate and comply with lifestyle modification measures.
2.The NCI Risk Assessment Tool regular web: http://www.cancer.gov/bcrisktool
Mobile web: http://www.cancer.gov/bcrisktoolmobile
This is the easy to use, on-line questionnaire based on a modified Gail model that also includes ethnicity. It does not factor in a personal history of breast cancer, DCIS, or LCIS. It does not account for other factors such as BRCA status, hormonal replacement therapy, lifestyle factors, breast feeding, menopause, or mammographic density. Despite these issues, it is a very useful tool that gives a woman her five-year and lifetime risk of breast cancer. It is the only risk assessment tool that can be used via mobile handheld devices (any type). A version of this can be downloaded for PDAs with Windows Pocket PC operating system as well.
Q: What programs can be used to help a doctor make decisions about ordering a breast MRI?
A: The American Cancer Society has developed some very good guidelines for breast cancer screening with MRI. It should be emphasized that MRI is an adjunct to mammography, not a replacement. Four programs can be used to help in clinical decision making. They are as follows:
1.A Cancer Journal for Clinicians http://caonline.amcancersoc.org/cgi/content/full/57/2/75
2.BRCPRO ver.4.3 available @ http://www4.utsouthwestern.edu/breasthealth/cagene/default.asp
3.Claus Model available as a palm based software product version 1.0 at
4.IBIS – Breast Cancer Risk Evaluation Tool, RiskFileCalc version 1.0. This is the Tyrer-Cuzick model that includes hereditary and nonhereditary risk factors. Contact: