Breast cancer is the most common form of cancer diagnosed among American women. Breast cancer ranks second behind lung cancer in terms of the number of total deaths attributable to the disease. Each year approximately 180,000 women will be told they have breast cancer and about 46,000 women will die. Unfortunately unlike most cancers, the incidence (number of new cases per year) has been increasing. About one in nine women will develop breast cancer throughout their lifetime; this is assuming they will live to be about 80 years old. There appears to be a hereditary component to breast cancer, and this accounts for about 5 to 10% of all cases. Two genes have been identified called BRCA I and BRCA II. Alterations (mutations) in these genes significantly increase a woman's chance of getting cancer. Her risk of ovarian cancer increases as well.

What are some risk factors that increase a woman's chance of getting breast cancer?

Breast cancer risk certainly increases with age. The average age at diagnosis being approximately 60 years old.

Women who have had a previous history of cancer in the other breast are at high risk for developing another breast lesion.

Hormonal influences - a woman who began her 1^st menses at an early age and went through menopause at a late age is at high risk. A slightly increased risk of breast cancer is seen in women who have had their 1^st child after age 30. Longer exposure to estrogen in her reproductive years increases breast cancer risk, because estrogen stimulates the breast cells to grow.

Oral Contraceptives - Oral contraceptives have many health benefits such as reducing the risk of ovarian and uterine cancer, but prolonged use (over an 8 year period) may slightly increase a woman's risk for breast carcinoma.

Hormone replacement therapy - Prolonged use of estrogen during the menopausal years may slightly increase a woman's chances of getting breast cancer. Prolonged use is defined as more than 10 years. The data from numerous studies are conflicting and more research needs to be done in this area. The benefits from hormone replacement therapy are overwhelmingly positive.

Dietary fat and a sedentary lifestyle has been associated with patients who have breast cancer. Women who are overweight tend to have higher levels of circulating estrogen.

Alcohol may slightly increase a woman's risk, but no biological mechanism for the relationship between alcohol and breast cancer risk has been established. Ionizing radiation to the breasts at an early age markedly increases a woman's chance of getting breast cancer. Evidence is limited on occupational, environmental, chemical exposures (insecticides), or organochlorine residues. Scientific research is currently in progress to verify any truths to these propositions.

What is a gene?

A gene is made up of DNA which acts as a blue print for an organism's appearance and function. Every animal or organism has DNA which codes for their physical attributes and metabolism. As humans, we have 23 pairs of chromosomes and on each chromosome there are roughly a few thousand genes. An alteration of a gene can cause diseases from cystic fibrosis to cancer depending on the location of the gene, type of alteration, and the location of the alteration.

What is hereditary breast cancer?

Breast cancer has long been known to run in families. Women whose mothers or sisters that have had the disease are at substantially higher risk. Women who have had hereditary breast cancer generally develop cancer at an earlier age; before they reach menopause. Researchers who have studied large families have isolated a gene on chromosome 17 which is responsible for breast cancer. An alteration in the BRCA I or BRCA II genes is responsible for breast cancer. This gene is inherited in a dominant fashion. So a woman's risk of receiving the gene is 50% if one parent carries the gene. If a woman with the altered gene is diagnosed with cancer, her prognosis (outlook) is no different than that of a woman who has developed breast cancer spontaneously.

In a general population about 1 in 800 individuals will have an alteration in the BRCA I or BRCA II genes. In Ashkenazi (Eastern European) Jewish descent, 2.5 percent will carry the altered gene. Three different mutation (alterations) have been found in the Ashkenazi population. Researchers are still looking for mutation in other populations and ethnic groups.

What is a woman's risk for developing breast cancer and ovarian cancer if she has the altered gene?

In a normal population approximately one in nine women will get breast cancer during her lifetime. Women who have the altered BRCA I and BRCA II gene have a 50-85% chance of developing breast cancer. A woman without an alteration has about a 1.5% chance of developing ovarian cancer over her lifetime. With the altered BRCA I, gene it jumps to 5-40% and 10-20% with the defective BRCA II gene.

What should a woman think about before getting tested?

Being tested for breast cancer risk does not give you a yes or no answer. If an altered gene runs through a woman's family, she may have feelings of guilt if she tests negative. Some women may not want to know their genetic status. The cost of genetic testing runs over one thousand dollars so its quite expensive. Most insurance companies will not cover it. If a woman is found to be positive, it could affect the status of a person's health, life, and disability insurance by causing that individual to be unable to qualify for a new insurance policy. An insurance company would surely view a potential cancer patient as high risk and not a good liability. A woman with an altered gene may experience discrimination if an employer learns about the test results. Even if a physician keeps the test results out of the records, it is hard to justify the need for increase surveillance (i.e. mammograms and ultrasounds) or prophylactic surgery without disclosing this information to the insurance company. Some protection may be offered through the American's with Disabilities Act or the Equal Opportunity Commission which expands the definition of the disabled, but the extent of this protection has not been tested in the legal arena.

What steps can a woman take if she tests positive for the altered gene?

1. Avoid behaviors which may increase breast cancer risk. This includes shying away from fatty diets and alcoholic beverages and starting a regular exercise program.

2. If a cancer arises, it is important to find it early. A woman should not overlook the importance of clinical breast exams every month or yearly physician breast exams. Routine mammography at close intervals may heighten surveillance. For ovarian cancer, pelvic ultrasound, CA-125 levels (an ovarian tumor marker), and pelvic exams are routine surveillance measures.

3. Removing the organ at risk is an option. Prophylactic mastectomy or oopherectomy has been offered to women with the defective BRCA I and BRCA II gene. This does not guarantee a cure for cancer, because some women have gone on to develop cancer. Removal of health tissue not only places the patient at risk during surgery, but can be emotionally disfiguring.

4. Certain compounds may decrease a woman's chance of breast cancer. Tamoxifen has recently been shown to lower the incidence of breast cancer in healthy patient compared to their age matched controls (those who received a placebo). Raloxifene is another selective estrogen modulator that may play a role in this area, but more studies are needed. Dietary retinoids, Vitamin E, soy protein (tofu), and selenium have been shown to be active against breast cancer.

Currently, there is no treatment or gene therapy to fix these defective genes. Most doctors outside of large University settings are not routinely screening patients, because the test is relatively new and the benefits of the test have not been clearly established. If a person has tested positive for the altered gene or if she is considering genetic testing, she can call 1-800-4-CANCER for more information.

Ryan K. Lee is a physician specializing in Obstetrics and Gynecology. He is currently in private practice in Glendale and Los Angeles, California.