Hereditary Factors in Breast Cancer

Jessica Ray, MS, CGCGenetic Counselor

OBJECTIVES:

• Discuss who should consider genetic counseling and genetic testing

• Discuss risks for cancers associated with BRCA1/2 mutation

• Cancer Risk Reduction Options• Important Points of Genetic Testing• Cost of Genetic Testing and Insurance

Issues

Reasons for Seeking Genetics Consultation

• To learn about• Personal risk for cancer• Children’s risk for cancer• Family’s risk for cancer• Risks for developing cancer if you have a “cancer

gene”• Recommendations for screening, surveillance,

and/or treatment• Educational information• To obtain genetic DNA testing

J Med Genet 2000; 37:866-874

Key Flags that Warrant Genetic Counseling

• Significant family medical history-breast, ovarian, prostate, colon, melanoma, pancreatic, or other cancers

• Cancer occurs in every generation• Early age of onset (< 50 years)• Male breast cancer• Bilateral cancer, or multiple primary cancers in one

individual• Known family genetic mutation• Ethnicity – Ashkenazi Jewish ancestry

A BRCA Mutation Increases Risk of Second Cancer

JNCI 1999;15:1310-6JCO 1998;16:2417-25

Lancet 1998;351:316-21JCO 2004;22:2328-35

Lancet 1994;3343:692-5

0

20

40

60

Ovarian Cancer Breast Cancerafter 5 yrs

Breast Cancer by age

70

General PopulationBRCA Mutation

16% Up to 11%

Up to

27% Up to 11%

Up to 64%

Risk

of C

ance

r (%

)

* no statistic available

*

Average Age of Diagnosis

Hereditary Sporadic

• Breast 41• Prostate

63• Ovarian 40-50

• Breast62

• Prostate71

• Ovarian 60

RISK REDUCTION OPTIONS• Surveillance

• Alternate Mammogram and Breast MRI every 6 months

• CA-125 and Pelvic/Ovarian Ultrasound annually• Prophylactic Surgeries

• Prophylactic Bilateral/Unilateral Mastectomy = 90% reduction in breast cancer risk

• Prophylactic Bilateral Oophorectomy = 96% reduction in ovarian cancer risk

• If PBO performed pre-menopausally, also gives a 50% reduction in breast cancer risk

• Chemoprevention• Tamoxifen, Raloxifene

When Do You Offer Testing?• American Society of Clinical Oncology recommends

offering genetic testing when:• The individual has a personal or family history of

features suggestive of a genetic cancer susceptibility condition

• The test can be adequately interpreted• The results will aid in diagnosis or influence the

medical or surgical management of the patient or family members at hereditary risk of cancer

ASCO recommends genetic testing only in the setting of pre- and post-test counseling, which should includes discussion of possible risks and benefits of cancer early detection and prevention modalities

Commercial BRCA testing• BRCA1 and BRCA2 testing is available only at

Myriad Genetic Laboratories• In 2001, added 5 specific large rearrangements

in BRCA1• August 2006, new panel added to detect large

rearrangement in both BRCA1 and BRCA2• Cost of full sequencing of both BRCA1 and

BRCA2 genes is $4,000, Cost of testing for a known family mutation is $475

GINA-Genetic Information Nondiscrimination Act

• Prohibits use of an individual’s genetic information in setting eligibility or premium or contribution amounts by group and individual insurers

• Prohibits health insurers from requesting or requiring an individual to take a genetic test

• Does not prohibit medical underwriting based on current health status

• Prohibits use of an individual’s genetic information by employers in employment decisions such as hiring, firing, job assignments, and promotions

• Prohibits employers from requesting, requiring, or purchasing information about an individual employee or family member

Final Take Home Message• Evidence that many women overestimate their risk of

developing breast cancer• Genetic testing may provide accurate risk assessments for

both breast and ovarian cancer• Not everyone found to have a BRCA1/2 mutation will

develop cancer!• Negative genetic test result DOES NOT mean

No Increased Risk!!• What do we offer women at high risk for breast and

ovarian cancer who test negative commercially for a BRCA1/2 mutation? • HIGH RISK BREAST CANCER CLINIC AT AZCC