Background

Reducing the burden of cancer is important to women who have a mutation in the BReast CAncer susceptibility genes BRCA1 or BRCA2. It is estimated that 50-85% of these women will develop breast cancer by age 70; many will develop breast cancer before age 50. Women who have a BRCA mutation also have an increased risk of ovarian cancer. BRCA1 mutation carriers have a 40% chance of developing ovarian by age 70. Women with a BRCA2 mutation have about half this risk.

Breast Cancer Screening and Prevention

• Current recommendations for breast cancer screening in women at high genetic risk include:
1. Screening mammograms once or twice a year, beginning at age 25-35 (or at least 5 years before the earliest age at which a breast cancer has been diagnosed in the family).
2. Clinical breast examinations performed by a physician or nurse breast specialist, every 6 - 12 months starting at age 18.
3. Monthly breast self-examination beginning at age 18.


• There are both medical and surgical approaches to the prevention of breast cancer in high-risk women:
1. Medical prevention involves the use of Tamoxifen or other selective estrogen receptor modulators (also called "SERMs"). There is currently little information about whether the use of tamoxifen or other SERMs reduces the risk of breast cancer in women with BRCA mutations, as they do in women from the general population who are thought to be at increased risk of breast cancer.
2. Surgical prevention, risk-reducing ("prophylactic") mastectomy involves the removal of both of the breasts before there is any clinical evidence of cancer. This procedure, which appears to reduce the risk of breast cancer by about 90%, involves removing as much of the breast tissue (including the nipple) as possible. Small amounts of breast tissue are unavoidably left behind, so occasionally women may still develop breast cancer after having undergone this surgery. While this approach seems to produce the largest reduction in the risk of developing breast cancer, it is not clear whether it actually reduces the risk of dying from breast cancer compared with careful breast cancer screening. Surgical removal of the ovaries (see below) from pre-menopausal women has also been reported to reduce the risk of breast cancer (by about half, or 50%).
   

Ovarian Cancer Screening and Prevention

• Surveillance for ovarian cancer is recommended to begin between the ages of 25 and 35 (or five to ten before the earliest age at which an ovarian cancer has been diagnosed in the family). Current recommendations for ovarian cancer screening of women at high genetic risk include:
1. Pelvic examination once or twice a year.
2. CA-125 blood test once or twice a year.
3. Transvaginal ultrasound once or twice a year.


• There are also medical and surgical approaches to reducing the risk of ovarian cancer in high-risk women:
1. Surgical prevention is called risk-reducing (or “prophylactic”) salpingo-oophorectomy (RRSO). This involves removal of the ovaries and fallopian tubes before there is clinical evidence that cancer has developed. It has been estimated that this procedure results in a 95% reduction in the risk of ovarian cancer in women who carry a mutation. It is recommended that high-risk women consider this procedure when they complete their childbearing. Surgical removal of the ovaries from a woman who is still regularly having her periods results in loss of fertility and menopausal symptoms, such as hot flashes. The risks and benefits of menopausal hormone therapy for women who have undergone RRSO have not been clearly defined in women with a BRCA mutation. Tubal ligation (“tying the tubes”) may also help reduce the risk of ovarian cancer without removing the ovaries. It does not reduce cancer risk as much as RRSO does, but it avoids immediate menopause.
2. Medical prevention is for women who do not want or are not yet ready to have surgery to remove their ovaries. The use of oral contraceptives (birth control pills) has been shown to reduce the risk of ovarian cancer by about 50% among women in the general population, but information about the potential risks and benefits of oral contraceptives among BRCA1/2 mutation carriers is limited. While the risk of ovarian cancer may be reduced, the risk of breast cancer may be increased with oral contraceptive use in high-risk women.

Imaging of the Breast:

Mammography is currently the best available tool for detecting early breast cancer, but mammography fails to detect some breast cancers. Importantly, mammography may miss some breast cancers in younger women. This is of concern because much of the BRCA1- and BRCA2-related breast cancer occurs before age 50. In postmenopausal women, it is easier to detect a cancer, which appears as a white mass, or associated with white calcium spots, contrasted against a dark background. Before menopause, a woman's breasts are made up of relatively more supporting tissue (which appears "dense" or white on a mammogram) and less fatty tissue (which appears "radiolucent" or dark).

On the left is a picture of a mammogram of a woman with a breast lump. The location of the breast lump is indicated by the white dot on the mammogram. The mammogram failed to show the large breast cancer (indicated with the arrow), which was clearly seen on the MRI study of the breast (picture on the right).

Computer-assisted mammography reading and digital mammography are now being studied as ways to improve the accuracy of mammography interpretation. Magnetic resonance imaging (MRI), an imaging technique that does not involve radiation exposure, is also being evaluated as a way to improve detection of early breast cancers when screening women at high genetic risk of breast cancer.

Sampling Breast Duct Cells:

Over 95% of breast cancers develop from the cells that line the breast milk ducts.

There has been much interest in looking for ways to screen breast duct cells for early, pre-cancerous changes. Evaluating the breast in this way is still very much a research tool. While this approach may have promise, the benefit of this type of screening has not been proven. Breast duct lavage, in which cells are washed from the breast duct, and needle biopsy of the breast, are two of the techniques used to obtain breast duct cells for research purposes.

Visit our cancer.gov Web site for more information about breast cancer and gene mutations.