Hereditary Breast and Ovarian Cancer Syndrome

Question 1

What is Hereditary breast and ovarian cancer syndrome?

Answer 1

An inherited cancer-susceptibility syndrome. Hallmarks:

1. multiple family members with breast cancer or ovarian cancer or both
2. Presence of both breast cancer and ovarian cancer in a single individual
3. Early age of breast cancer onset

Question 2

Germline mutations in BRCA1 and BRCA2 account for vast majority of families with hereditary what cancer?

Answer 2

breast and ovarian cancer syndrome.

Question 3

In the general population, approximately ___ to ___ carry a mutation in BRCA1 or BRCA2

Answer 3

1 in 300 to 1 in 800 individuals

Question 4

What is the risk for a woman with BRCA1 mutation?

Answer 4

39-46% risk of ovarian cancer

Question 5

What is the risk for a woman with BRCA2 mutation?

Answer 5

risk of ovarian cancer is 12-20%

Question 6

What is the lifetime risk of breast cancerwith a BRCA1 or BRCA2 mutation?

Answer 6

65-74%

Question 7

who should be offered hereditary cancer risk assessment for hereditary breast and ovarian cancer syndrome?

Answer 7

Initial screening should involve asking specific questions about personal and family history of breast cancer and ovarian cancer.

Question 8

Criteria for Genetic Risk Assessment: Patients with greater than 20-25% chance of having an inherited predisposition to breast cancer and ovarian cancer and form whom genetic risk assessment is recommended:

Answer 8

1. Women with personal history of both breast cancer and ovarian cancer
2. Women with ovarianc ancer and a close relative with ovarian cancer or premenopausal breast cancer or both
3. Women with ovarian cancer who are of Ashkenazi Jewish ancestry
4. Women with breast cancer at 50 years or younger and a close relative with ovarian cancer or male breast cancer at any age
5. Women of Ashkenazi Jewish ancestry in whom breast cancer was diagnosed at age 40 years or younger
6. Women with a close relative with a known BRCA1 or BRCA2 mutation

Question 9

patients with approximate 5-10% chance of having inherited predisposition to breast cancer and ovarian cancer and form whom genetic risk assessment may be helpful:

Answer 9

1. women with breast cancer at age 40 years or younger
2. women with ovarian cancer, primary peritoneal cancer, or fallopian tube cancer of high grade, serous histology at any age
3. women with bilateral breast cancer (particularly if first case of breast cancer dx at age 50 years or younger)
4. women with breast CA at age 50 years of younger and a close relative with breast cancer at age 50 or younger
5. women of Ashkenazi Jewish ancestry with breast cancer at age 50 years or younger
6. Women with breast cancer at any age and two or more close relatives with breast cancer at any age (particularly if at least one case of breast CA dx at age 50 or younger)
7. unaffected women with a close relative that meets one of the previous criteria

Question 10

How should women with mutations in BRCA1 or BRCA2 be counseled to reduce the risk of ovarian cancer and fallopian tube cancer?

Answer 10

Current strategies to reduce the risk of developing ovarian cancer / fallopian tube cancer in women at high risk with known deleterious BRCA mutations include:

1. surveillance
2. chemoprevention
3. surgery.

Available screening procedures have limited ability to detect ovarian cancer at an early, more curable stage of disease, and patients should be informed that there is no evidence that screening has reduced the mortality or improved the survival associated with ovarian cancer in high-risk populations.

Question 11

How should screening be done in women with mutations in BRCA1 and bRCA2?

Answer 11

1. CA125
2. transvaginal ultrasonography beginning 30-35 yrs or 5-10 years earlier than the earliest age of first diagnosis of ovarian cancer in the family.

Question 12

How should women with mutations in bRCA1 or BRCA2 be counseled to reduce the risk of breast cancer?

Answer 12

1. surveillance- clinical breast examination semiannually as well as both annual mammogram and annual breast MRI beginning at age 25 or sooner based on earliest age onset in the family. (MRI is more sensitive for the detection of breast cancer than mammography.
2. chemoprevention- chemoprevention with tamoxifen may reduce breast CA by approx 62% in BRCA2 mutation carriers. In contrast, tamoxifen did not reduce breast cancer among BRCA1 mutation carriers.
3. surgery. - prophylactic surgery with bilateral mastectomy reduces the risk of breast CA by greater than 90-95% depending on the type of mastectomy procedure.

Question 13

what is total mastectomy

Answer 13

Entire breat tissue, nipple, and areola removed. It is most effective risk-reducingprocedure.

Question 14

what is subcutaneous mastectomy?

Answer 14

Removal of all breast tissue except the nipple and areola.

Question 15

Risk reducing salpingo-oophrectomy reduces the risk of breast cancer by what percentage?

Answer 15

40-70%. This protection likely occurs only if patients are premenopausal at the time of risk-reducing salpingo-oophrectomy. In addition, BRCA1 mutation carriers may have less of a protective effect from risk-reducing salpingo-oophrectomy on breast cancer risk than BRCA2 mutation carriers.

Question 16

At what age should risk-reducing salpingo-oophrectomy be considered in women with mutations in BRCA1 or BRCA2?

Answer 16

Women with BRCA1 or BRCA2 mutations should be offered risk-reducing salpingo-oophrectomy by age 40, or when childbearing is complete. Ovarian cancer detected in < 2-3% of women with BRCA1 or BRCA2 mutations before 40.