updated May 20, 2011
Content in this section includes:
Background
- Family histories of breast cancer or ovarian cancer can be classified as:
- sporadic (70-75%), or
- multifactorial (20-25%), or
- hereditary (5-10%)
- Only those with personal or family histories that suggest an inherited predisposition should be referred to the Hereditary Cancer Program. See Assessing Family History for examples.
Hereditary Breast and/or Ovarian Cancer
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- There are currently two genes known to be associated with hereditary breast and/or ovarian cancer (HBOC): BRCA1 and BRCA2.
- Approximately 1:500 to 1:1000 people in the general population are born with an inherited mutation in either the BRCA1 or BRCA2 genes.
- The frequency of BRCA1 or BRCA2 gene mutations is approximately 1:40 for people with Ashkenazi Jewish heritage.
- HBOC is inherited in an autosomal dominant manner.
Genetic assessment and counselling is offered to individuals and families who meet referral criteria. Genetic testing for HBOC is offered on a clinical basis to individuals who meet specific testing criteria.
Referral Criteria - see criteria page
Features of Hereditary Breast and/or Ovarian Cancer
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Individuals with HBOC are at increased risk for the following cancers over their lifetime.
Cancer risk and ages at diagnosis vary between individuals and between families.
| Type of cancer |
General Population Risk |
BRCA1 carrier risk |
BRCA2 carrier risk |
| breast - women |
11% |
47-66% |
40-57% |
| breast - men |
0.1% |
up to 6% |
6% |
| ovarian |
1-2% |
35-46% |
13-23% |
| prostate |
12% |
2-3 times higher |
2-3 times higher |
| other |
varies |
see notes below |
see notes below |
Other cancers:
1) Some studies have shown increased colon cancer risk among BRCA1 and BRCA2 mutation carriers, while other research has not supported this association.
2) A number of other types of cancer (pancreas, larynx, esophagus, stomach, gall bladder, bile duct, hematopoetic, melanoma) have been observed in some families with BRCA2 gene mutations.
Genetic Testing for BRCA1 and BRCA2 (Refer also to general information about genetic testing.)
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- BRCA1/2 testing is available in BC through the Hereditary Cancer Program for individuals/families who meet eligibility criteria
- carrier testing is offered if a BRCA1 or BRCA2 gene mutation has already been identified in the family
- expedited BRCA1/2 testing
can be arranged in selected cases, where the result will alter immediate clinical management in a meaningful way
- the approach to BRCA1/2 genetic testing for Ashkenazi Jewish families may be different and will be discussed with the genetic counsellor
- "index" testing for a family usually begins with a blood sample from:
- a woman with ovarian cancer, or
- the woman with the youngest diagnosis of breast cancer
- possible BRCA1/BRCA2
index test results:
- positive - a mutation is identified in either BRCA1 or BRCA2. Relatives are eligible for "carrier" testing for the specific familial mutation.
- uninformative - a mutation is not identified in either BRCA1 or BRCA2. Carrier testing is not available to family members. Does not rule out an inherited predisposition in the family. Further assessment is required and may include testing of additional affected family members.
- unclassified variant - a change in the gene that is not yet understood and may or may not be related to an increased risk of cancer. Carrier testing is not available to family members. Does not rule out an inherited predisposition. Further assessment is required.
Cancer screening and risk reduction
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For those with a confirmed BRCA1 or BRCA2 gene mutation (or who are at 50% risk of having inherited the mutation known in their family), current screening recommendations include:
- WOMEN:
- annual screening mammogram beginning at age 30
- annual screening breast MRI from late 20s to age 65 - scheduled to alternate every 6 months with mammogram
- careful clinical examination of breasts and regional lymph nodes every 6 months, in conjunction with appropriate imaging
- monthly breast self-exam is an option chosen by some women
- MEN:
- regular physical examination by a doctor
- careful attention to any changes in the chest/breasts
- population screening guidelines for prostate cancer, unless family history suggests otherwise
- not currently recommended:
- screening mammograms for men
- ovarian cancer screening due to lack of evidence to support its effectiveness
The above recommendations are based on Canadian guidelines published in JOGC, January 2007.
Women who are confirmed to carry a BRCA1 or BRCA2 gene mutation may also consider risk-reducing surgery:
- Bilateral prophylactic mastectomy with breast reconstruction:
- associated with at least a 90% reduction in breast cancer risk
- may be a complex personal decision due to potential long-term impact on body image, sexuality and other aspects of quality of life
- currently covered by MSP
- must include expert pathology review of excised breast tissue for the presence of cancer
- Bilateral prophylactic salphingo-oophorectomy:
- should be strongly considered due to the lack of effective ovarian cancer screening
- must include expert pathology review of excised ovaries and fallopian tubes for the presence of cancer
- in addition to reducing risk of ovarian and fallopian tube cancers, BSO is associated with 50% reduction in breast cancer risk if completed prior to menopause
- most effective if done at age 35-40, and/or when childbearing is complete
- impact of surgical menopause is important to address in decision-making and in post-op followup. Unless otherwise contraindicated, HRT is usually an important component of symptom management.
Options for chemoprevention may also be discussed. Oral contraceptives have been shown in some studies to reduce ovarian cancer risk; this may be an important consideration for BRCA1/2+ women of child-bearing age. Tamoxifen is not currently prescribed on a regular basis for reduction of breast cancer risk in BRCA1/2+ women.
HBOC Case Examples
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pedigrees will be added to illustrate these cases
1) A 55-year-old woman is diagnosed with a non-mucinous epithelial ovarian cancer. Her two daughters, one brother and both parents are alive and well with no known cancer history. One of her daughters is concerned about her risks to develop ovarian cancer over her lifetime and requests a referral for genetic counselling to discuss genetic testing. The most appropriate woman to refer to the Hereditary Cancer Program would be the mother, who would be offered BRCA1/2 index genetic testing after giving informed consent.
2) A 37-year-old woman is diagnosed with invasive breast cancer. Her two younger sisters are well and their maternal family history is non-contributory. The patient’s father is living at age 72, and he has one sister who was diagnosed with breast cancer at age 51, and another sister who was diagnosed with ovarian cancer at age 42. He also has a paternal female cousin, through an uncle, with breast cancer at age 58. A referral is appropriately made for the 37 year old to the Hereditary Cancer Program. Medical record review reveals the ovarian cancer to be a cervical malignancy, but all reported breast cancers are confirmed. Genetic testing is offered to the patient as there are three breast cancers in this family, with one diagnosis under the age of 50. Although the third diagnosis is in a fourth degree relative to the patient, the intervening relatives are all male. This woman therefore qualifies as a “close” relative to the patient.