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 mammogram once a year beginning at age 25 or at least 5 years before the earliest age at which breast cancer has been diagnosed in the family
  2. Breast MRI once a year starting at the same age as the mammogram
  3. Clinical breast exams performed by a clinician every 6 – 12 months starting at age 25
  4. Monthly breast self-exam beginning at age 18.

  Mammography and breast MRI are currently the best method for early detection of breast cancer. However, they may not detect all breast cancers. Additional studies (ultrasound or biopsy) may be needed for further evaluation as necessary.

• There are both medical and surgical approaches to the prevention of breast cancer in high-risk women:
  
  
  1. Medical prevention: Two different medicines can lower the risk of breast cancer among women at increased risk. These medicines - tamoxifen and raloxifene - belong to a class of drugs called selective estrogen receptor modulators (SERMs).
     
     A recent breast cancer prevention study (called the STAR trial) compared the effectiveness of the two drugs among women with elevated breast cancer risk; a prior study had shown that tamoxifen reduced breast cancer risk by about 50%. The STAR trial showed that raloxifene is as effective as tamoxifen in reducing the number of invasive breast cancer cases, and that it has fewer serious side effects.
     
     However, the benefit of these medications in women with known BRCA mutations is not well established. There are no data regarding the benefits of raloxifene in BRCA mutation carriers, and only a limited amount of information regarding tamoxifen. BRCA1 and BRCA2 mutation carriers who had a breast cancer diagnosis had over 50% reduction in their risk of developing breast cancer in the other breast when treated with tamoxifen. The largest studies of tamoxifen as a breast cancer prevention agent in mutation carriers without a previous breast cancer diagnosis have yielded conflicting results, but there is some suggestion that there is a reduction in risk, so tamoxifen may be a reasonable option for high-risk women to consider. In addition, tamoxifen has been associated with an increased risk of blood clots and endometrial cancer, so we encourage discussion of the risks and benefits of use with your healthcare provider.
     
  
  
  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 at age 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. A transvaginal ultrasound and CA-125 blood test every 6-12 months, starting at age 35, or 5 to 10 years earlier than the earliest age of first ovarian cancer diagnosis in the family. Note that the effectiveness of this screening schedule has not been proven.


• 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. The Premature Menopause Pamphlet, Health Care Maintenance for Women Undergoing Risk-Reducing Ovarian Surgery provides useful information for women who have undergone RRSO, as well as for their health care providers.
   
   
2. 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.
   
   
3. 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 and breast magnetic resonance imaging (MRI) are currently the best available tools for detecting early breast cancer. Mammography may fail 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 by mammography, 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).

The picture on the left is 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. Annual breast MRI, an imaging technique that does not involve radiation exposure, is now routinely recommended 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, nipple aspiration, which uses gentle suction to collect fluid from the nipple, and needle biopsy of the breast, are examples of techniques used to obtain breast duct cells and fluid for research purposes.

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