Methods

EPIDEMIOLOGIC RISK

In 1989, Dr. Mitchell Gail, working at the National Cancer Institute developed a formula to calculate the “relative risk” of breast cancer.  He did this working from a study of over 250,000 women and focused on the then well-know clinical risk factors of age, race, age of first period and first pregnancy and the number of breast biopsies.  This evolved into a standard formula to calculate breast cancer risk called the “Gail Model” and has been validated in many follow-up studies as an accurate means to predict risk.

The Gail Model is important because it has been the basis for determining which individuals may benefit from risk reduction medication such as Tamoxifen.  The FDA has actually accepted a 5 year Gail Risk of >1.66 as a baseline to consider use of medication to reduce breast cancer risk.  It has been used in many important studies to determine the efficacy of medication or life style changes in reducing risk.  Obviously, since use of any medication involves risk of side effects – both good and bad effects- the same group at the National Cancer Institute has developed a tool to help determine who will benefit from use of medication.

Some of the very detailed questions that are asked on the patient registration forms are there in order to be able to calculate the Gail Risk, which has become a standard risk assessment tool.

FAMILIAL RISK

The number of family members with breast cancers, and the age at which they developed breast cancer, is a very important risk factor for breast cancer.  “Familial risk” is different from genetic risk, as it may depend more on an interplay between a number of genetic factors, or between genetic factors and the environment, whereas genetic risk is considered to result from a specific mutation in a single gene. 

Different risk assessment tools are used in this instance, since the standard risk assessment looks only at first degree relatives (mother, sister, daughter).  In addition, there are novel new technologies which are looking at a spectrum of genetic changes instead of just one gene, as a mechanism to determine risk.  One of these is the OncoVue test, which analyses changes in a number of high risk genes, and calculates a risk score.  This is still under development, but promises to become a standard risk assessment tool.  The Breast Center is one of fifty sites across the country involved in FDA approval studies for this new technique.  Click here for more information (OncoVue)

GENETIC RISK

There are 2 well described “breast cancer” genes called BRCA1 and BRCA2.  These are genes which normal help suppress the growth of tumors, and which can have subtle changes in genetic coding which allow for development of both breast and ovarian cancer.  The risk of cancer with mutations in these genes can range from 50-85% chance of developing breast cancer to 24-44% risk of ovarian cancer. 

A pattern of both breast and ovarian cancer in family can suggest a pattern based on one of these genetic mutations.  This can be a history on either the mother’s or the father’s side since these genes are inherited and passed on by both men and women.  A simple blood test will determine if such a mutation is present.  Because the information is so important, however, I always recommend that individuals speak with a genetic counselor before having to test, just to be sure that they understand all the implications of a positive result. 

BRCA1 and 2 testing is one of the major advances in our ability to precisely determine an individual’s future risk of developing breast cancer.  If you are at risk, you deserve the opportunity to at least review this is a genetic counselor.

HISTOLOGIC RISK

In years past, a biopsy was either benign or malignancy (“cancer or no cancer”.)  We now recognize that breast tissue reveals a spectrum of changes which are not just black or white, but rather show various shades of gray.  Today, pathologists classify tissues as completely benign, fibrocystic with nonproliferative or proliferative changes, atypical (“not normal”), or as noninvasive or invasive cancer.  In fact, today we know that some of the conditions previously called cancer, such as lobular carcinoma in situ, are not really breast cancer, but rather a risk factor for the future development of breast cancer.

The pathologist makes this distinction based on how the cells appear under the microscopic.  Certain specific changes area known to be associated with a substantially increased risk of breast cancer:

            Hyperplasia (typical)                 1.5 times the risk
            Hyperplasia (atypical)               4-5 times the risk
            Lobular carcinoma in situ          9-11 times the risk

The risk may further be magnified by a family history of breast cancer.

Fortunately, medication is extremely effective in this age group in reducing the future risk of breast cancer.