News reports of medical advances in genetics are appearing in the lay press almost daily. These reports, coupled with women's fear of breast cancer, mean that more women are asking about screening for mutations in the breast cancer susceptibility genes BRCA1 and BRCA2.

When to screen

Ordinarily, the BRCA genes produce proteins that prevent abnormal growth within cells. When certain mutations are present, however, the risk that breast and ovarian cancers will develop increases by 60% to 85% and by 10% to 26%, respectively. 1 Current estimates indicate that BRCA mutations affect approximately 1 in every 300 to 500 persons.¹

Although 20% to 30% of patients with breast cancer have a positive family history for the disease, genetic abnormalities account for only 5% to 10%2—and BRCA mutations for 2% to 3%3—of all breast cancers. Given this background, universal screening for mutations in BRCA1 or BRCA2 cannot be justified. The US Preventive Services Task Force (USPSTF) has confirmed this.⁴ However, the USPSTF did say there was fair evidence to support genetic testing for women whose family history suggests a mutation in BRCA1 or BRCA2. ⁴

A woman may be at risk for a BRCA mutation if she has biological family members with any of the following: breast cancer diagnosed before age 50 years; bilateral breast cancer; breast cancer in a male; recurrent breast cancer with a different tumor type; breast cancer associated with ovarian cancer; both ovarian and breast cancer; multiple cases of breast or ovarian cancer; breast or ovarian cancer in a first-degree or second-degree relative of Ashkenazi Jewish heritage.

Components of genetic counseling

There are technologic, medical, emotional, and social issues that must be explored before a woman undergoes testing. Testing, even by DNA sequencing, is not absolutely reliable. The incidence of false-positive results is approximately 13%, and false-negatives results range from 12% to 15%.¹ Not all women with mutations in BRCA1 or BRCA2 develop cancer, and there is no way to identify which patients will. Furthermore, there are no data to indicate that testing reduces morbidity or mortality.¹ Positive results on genetic testing may lead to a number of undesirable consequences, including additional interventions. Negative results on genetic testing can reduce a woman's anxiety. However, she can still acquire breast cancer.

Options for women with a mutation

The recommendations presented here are based on metaanalysis, data extracted from secondary analysis of studied populations, and observational studies, not on clinical trials.

Surgery Prophylactic bilateral mastectomy appears to be associated with an 85% to 100% reduction in the incidence of breast cancer.³ Prophylactic bilateral oophorectomy appears to decrease the incidence of ovarian cancer by 85% to 100% and that of breast cancer by 53% to 68%.³

Chemoprevention Tamoxifen or raloxifene decreases the risk of primary and secondary breast cancers in women with a family history of breast cancer that is estrogen-receptorpositive. However, these drugs may increase the risk of other diseases, and women interested in chemoprevention should be referred to appropriate ongoing clinical trials for treatment.⁵

Increased surveillance Evaluation must occur more frequently than annually because of the aggressive nature of carcinomas associated with BRCA mutations; MRI has the greatest sensitivity (approximately 77%), followed by mammography (36%), breast ultrasonography (33%), and clinical breast examination (9%), in detecting cancers in women with BRCA gene mutations. The combination of MRI, mammography, and ultrasonography has a sensitivity of 95%.³

Bottom line

Genetic counseling and BRCA gene mutation testing should be offered to all women at risk for this genetic defect. JAAPA

For information that can be photocopied and handed to patients, please see the next page. 

REFERENCES

1. Nelson HD, Huffman LH, Fu R, Harris EL. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: systematic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2005:143(5):362-379.

2. American Cancer Society. Detailed guide: breast cancer. What are the risk factors for breast cancer? Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_What_are_the_risk_factors_for_breast_cancer_5.asp. Accessed May 3, 2006.

3. Eccles DM, Pichert G. Familial non-BRCA1/BRCA2-associated breast cancer. Lancet Oncol. 2005;6(9):705-711.

4. US Preventive Services Task Force (USPSTF). Recommendation statement: Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility. Available at: http://www.ahrq.gov/clinic/uspstf05/brcagen/brcagenrs.htm. Accessed May 3, 2006.

5. National Cancer Institute, National Institutes of Health. Genetic testing for breast and ovarian cancer risk: it's your choice. Available at: http://www.cancer.gov/cancertopics/genetic-testing-breast/allpages/print. Accessed May 3, 2006.

PATIENT INFORMATION

BRCA1 and BRCA2 are shorthand for BReast CAncer gene 1 and BReast CAncer gene 2. These are genes that everyone has. Genes are the blueprint for life. They determine what your body will look like and how it will work. They also determine whether you might get certain diseases. Genes come in pairs, one from your mother and one from your father. That is why the health problems that blood relatives have on both sides of your family put you at risk for some diseases, like breast cancer or ovarian cancer.

When they work the way they should, BRCA1 and BRCA2 help protect your body from cancer. But if there is a mistake in one of these genes, it does not work as it should. Then, instead of protecting you from breast cancer, it raises your risk of getting breast cancer. These mistakes are called mutations.

Not everyone who has a mutated BRCA1 or BRC2 gene gets breast or ovarian cancer. Right now, we are not sure why some women do and some women don't.

Who should be tested?

Mutations in BRCA1 and BRCA2 are seen in only 2% to 3% of all breast cancers. So most women do not need to be tested for these mutations. But you should talk to your physician assistant (PA) or doctor about being tested if any of your blood relative has had

• A positive result on a test for a BRCA1 or BRCA2 mutation
• Breast cancer that was found before the age of 50 years
• Breast cancer that was found in both breasts
• Breast cancer that returned but was of a different type
• Breast cancer in a male relative
• Breast cancer in a close family member and you are of Ashkenazi-Jewish heritage.

Other factors can also put you at higher risk. These include having more than one relative with breast cancer and having both ovarian and breast cancer in your family.

What are the pros and cons of being tested?

The biggest concern is that the test result is not always 100% right. So your test result could be negative and you could still have the gene mutation. Or your result could be positive and you might not really have the mutation. Your PA or doctor will discuss all of the pros and cons with you to help you decide whether to have the test done.

He or she might also ask you to see a genetic counselor before having the test done. A genetic counselor is a person specially trained to discuss the pros and cons of testing for any genetic abnormality. A counselor can help you decide whether genetic testing is right for you.

How can I lower my risk of breast cancer?

Being tested for the BRCA1 and BRCA2 mutations is not the only way to fight breast cancer. There are also ways to find breast cancer early, when it is easiest to cure.

First, know the risk factors for breast cancer. Some of them cannot be changed. However, you should let your PA or doctor know that you have them. He or she might want to start checking you for breast cancer sooner or more often than is usually done.

These are the risk factors that cannot be changed:
• Being a woman
• Getting older
• Having a blood relative with breast cancer
• Already having breast cancer yourself
• Having a breast biopsy that was negative for cancer but still not “normal”
• Starting your periods before the age of 12 years
• Going through menopause after age 55 years
• Taking a drug called DES while pregnant (You or your mom may have taken this between 1940 and 1970 to keep from losing the baby. DES stands for diethylstilbestrol.)
• Having radiation treatment to the chest.
You can change these risk factors:
• Drinking alcohol
• Being overweight or fat
• Eating lots of foods that are high in fats
• Not exercising regularly
• Smoking cigarettes
• Not breast feeding your babies
• Never having children
• Having your first child after age 30 years

If you want to discuss any of these with your PA or doctor, he or she will be glad to help.

There are some things you can do to increase the chance that breast cancer will be found early. You can

• Examine your breasts every month starting when you are 20 years old. If you do not know how to do one, ask your PA or doctor to show you how. If you find any changes when you perform an exam, make an appointment right away to see your PA or doctor.

• Have your PA or doctor examine your breasts every year if you are older than 40. If you are 20 to 40 years old, this exam should be done at least every 3 years.

• Have a breast x-ray (mammogram) every year after you are 40. Mammograms can find breast cancers up to 2 years before you can feel a mass.

Finally, talk to your PA or doctor about any concern you have about breast cancer. He or she is there to help you. JAAPA