1. Hereditary Factors in Breast Cancer
Jessica Ray, MS, CGC
Genetic Counselor

2. 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

3. 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:

10. 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

14. A BRCA Mutation Increases Risk of Second Cancer
Up to 64%
General Population 60
BRCA Mutation
Up to 27% 40
Risk of Cancer (%)
Up to
11% 20
16%
Up to
11% *
Slide 8 : A BRCA Mutation Increases the Risk of a Second Cancer
Women who have developed breast cancer are at greatly increased risk of a second cancer if they carry a mutation in BRCA1 or BRCA2. Their risk of developing ovarian cancer is 10 times higher than women with early-onset breast cancer who do not have mutations, 1 or at least 16% in their lifetime.2 There are no current statistics for the general population.
In addition, mutations in these genes greatly increase the risk of a second breast cancer.3-5 The risk of a contralateral breast cancer is increased up to 64% by age 70, 3 or 27.1% within five years of the initial diagnosis5 in women with BRCA1 mutations. Mutations in BRCA2 increase these risks to about 50% by age 70,4 or 23.5% within five years of the first breast cancer. 5
References:
1. Frank TS, Manley SA, Olopade OI, et al. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. JCO 1998;16:
2. The Breast Cancer Linkage Consortium. Cancer Risks in BRCA2 Mutation Carriers. JNCI 1999;15:
3 Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, Breast Cancer Linkage Consortium. Risks of cancer in BRCA1-mutation carriers. Lancet 1994;343:
4. Verhoog LC, Brekelmans CTM, Seynaeve C, et al. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 1998;351:
5. Metcalfe K, Lynch HT, Ghadirian P, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. JCO 2004;22:
Ovarian Cancer
Breast Cancer
Breast Cancer by
after 5 yrs
age 70
* no statistic available
JNCI 1999;15:1310-6
JCO 1998;16:
Lancet 1998;351:316-21
JCO 2004;22:
Lancet 1994;3343:692-5

16. Average Age of Diagnosis Hereditary Sporadic
Breast 62
Prostate 71
Ovarian 60
Breast 41
Prostate 63
Ovarian 40-50

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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