BRCA in Women

A complete personal and family history, including at least three generations of relatives on both you mother and father’s side of the family, should be examined to determine if a mutation is present in a high risk cancer gene. Consider genetic risk evaluation if you or a family member has had*:

• Breast cancer at age 65 or younger
• Triple negative breast cancer at any age
• Ovarian or fallopian tube cancer at any age
• More than one breast cancer diagnosis
• Male breast cancer
• Pancreatic cancer
• Metastatic prostate cancer
• Anyone of Ashkenazi Jewish ancestry
• A known mutation in a cancer risk gene
• Breast, ovarian, pancreatic, or high grade prostate cancer diagnosed in multiple individuals on the same side of the family

* A genetics specialist can help to determine if your personal and/or family history meets these or other criteria.

Are breast and ovarian cancer inherited?

Only about 5-10% of breast cancers and 10-15% of ovarian cancers are strongly related to mutations in single high cancer risk genes. Breast cancer is a common disease, affecting about 13%, or 1 in 8 women in the United States. Ovarian cancer is less common, affecting about 1-2%, or 1 in 70 women in this country. While most women who develop breast or ovarian cancer have sporadic (random, non-hereditary) cancers, a small number develop cancer because they inherited a significant risk of developing these cancers due to a mutation in a cancer risk gene.

How is breast cancer screening done for female BRCA carriers?

Screening for breast cancer will not decrease the chance that cancer will develop. However, intensive screening for breast cancer helps to detect breast cancer early when it is most treatable.

Over the years, researchers have developed specialized breast cancer screening strategies for BRCA carriers. This involves starting screening at an earlier age and using several different methods at regular intervals. Intensive breast cancer screening typically starts at age 25 for women with a BRCA-mutation; it might be recommended at an earlier age if there is a particularly young breast cancer diagnosis in the family. Intensive screening may also be done in combination with preventive medications.

Clinical breast exam is recommended every 6-12 months starting at age 25. Between ages 25 and 29, it is recommended that annual breast MRI (or mammogram if breast MRI is unavailable) be performed. Between age 30 and 75, annual breast MRI AND mammography is recommended. Sometimes, the imaging studies- mammogram and breast MRI- are staggered so that a breast MRI is followed by a mammogram 6 months later. For women older than 75, breast cancer surveillance should be managed on an individual basis.

It is recommended that women who carry BRCA mutations have "breast awareness" which includes breast self-exams, beginning at age 18. Given that many women will not undergo genetic testing until 25, breast self-exams can be considered by all women from families with  BRCA1 or BRCA2  mutations. Breast awareness means a woman is familiar with her breasts and promptly reports changes to her health care provider.

What is a mammogram?

A mammogram is a low-dose X-ray procedure that produces images of the inside of the breasts. Mammography can detect some suspicious breast changes that are too small or too deep to be felt on breast examination.

A newer technology, called 3-dimensional (3D) mammography, or breast tomosynthesis, can be done as part of mammography screening. Although some studies have suggested that breast tomosynthesis may find more breast cancers and have fewer false positives than standard mammography, it remains unclear whether this is a better approach. All women should discuss this screening option in more detail with their doctor.

What is a breast MRI?

A breast MRI (Magnetic Resonance Imaging) uses a magnetic field to create clear detailed pictures of the inside of the breasts. A woman lies on her stomach during the procedure to mildly compress the breast tissue. An intravenous injection is necessary for the best imaging.

Do mammograms increase cancer risk in BRCA carriers?

Deciding on a cancer screening regimen involves weighing the benefit of diagnosing a cancer early against the risks of the screening test. Mammograms use radiation to image the breasts and radiation exposure can theoretically increase cancer risk. Therefore, the benefit of detecting a breast cancer early with a mammogram must outweigh the small risk that the radiation could cause harm in order for a mammogram to be recommended.

Some studies indicate that for  BRCA1 or BRCA2  carriers under age 30, the risks of mammography are greater than the benefits. This is in part because there are few breast cancers in BRCA mutation carriers under 30, with breast cancer risk before age 30 ranging from 1-2%. Guidelines for managing BRCA positive women recommend that between the ages of 25-29, annual breast MRI-or mammogram if breast MRI is not available-be performed. Starting at age 30, annual breast mammography is recommended in conjunction with annual breast MRI and clinical breast exam every 6-12 months.

Screening regimens are individualized based on family history and should always be discussed with your doctor.

What is ovarian cancer screening and is it effective?

Currently available methods for ovarian cancer screening often fail to detect ovarian cancer at an early stage. Therefore, it is at the discretion of the doctor and woman whether transvaginal ultrasound and CA-125 blood tests are used to screen for ovarian cancer before a woman has surgery to remove her ovaries and fallopian tubes. A risk-reducing bilaterial salpingo-oophorectomy, or the removal of healthy ovaries and fallopian tubes, is strongly recommended after completion of childbearing to reduce ovarian cancer risk.

What is a transvaginal ultrasound?

Ultrasound is an imaging technique that uses sound waves to create picture. By inserting an ultrasound probe into a woman's vagina, doctors can get a relatively good look at her ovaries. However, transvaginal ultrasound often fails to detect ovarian cancer at an early stage and can detect changes in the ovaries that are not actually cancer.

What is a CA-125 level?

CA-125 is a protein in the blood that is shed from damaged ovary cells and is often elevated in ovarian cancer. However, CA-125 can also be elevated for other reasons unrelated to cancer. Also, many early stage ovarian cancers do not cause an elevated CA-125.

What experimental or research cancer screening options do I have?

There are multiple research studies currently being conducted through the Basser Center for BRCA that aim to find better methods for detecting BRCA-related cancers early. It is hoped that these studies will find even better ways to manage high-risk individuals. Current cancer screening opportunities for which you are eligible can be discussed with your local BRCA specialist. Pancreatic cancer screening is not yet proven but is frequently offered to BRCA carriers, especially those who have a history of pancreatic cancer. Watch informational videos created by our team on pancreatic cancer commonly asked questions.

A personalized cancer risk management program can be developed for individuals known to be at increased cancer risk due to a mutation in BRCA1 or BRCA2. Cancer risk management can include intensive screening to increase the chance of early detection, prophylactic or risk reducing surgical removal of ovaries and consideration of prophylactic removal of the breasts, and chemoprevention, which is taking a medicine shown to lower the chances of developing cancer.

Some women may want to consider risk-reducing surgical removal of the breasts, also called a prophylactic mastectomy, to reduce breast cancer risk. This is the most aggressive and effective strategy available to reduce breast cancer risk. However, breast cancer screening is a reasonable alternative to risk-reducing mastectomy, as screening for breast cancer is usually effective in finding breast cancer at an early stage.

Risk-reducing bilateral salpingo-oophorectomy (BSO) is the removal of healthy ovaries and fallopian tubes. Risk-reducing BSO surgery is highly recommended after completion of childbearing because screening methods have not been proven effective at detecting ovarian cancer.

What is a risk-reducing, or prophylactic, mastectomy? How should I decide whether to have one?

A risk-reducing (prophylactic) mastectomy is the surgical removal of healthy breast tissue. It is the most aggressive and effective strategy available to reduce breast cancer risk. Some women with BRCA mutations choose this option. Studies have shown that this procedure lowers breast cancer risk by at least 90 percent in women with  BRCA 1 and BRCA2  mutations. Therefore, breast cancer risk is significantly lowered by this procedure.

However, breast cancer screening is a valid alternative to prophylactic mastectomy, as screening for breast cancer is usually effective in finding breast cancer at an early stage, particularly when MRI is used as one of the screening components. Even if breast cancer is detected at an early stage, chemotherapy may still be required, which can impact some women’s decisions. Intensive screening can also be used in combination with preventive medications.

Surgery is a very personal decision and we recommend women fully investigate all their options. Some women considering a prophylactic mastectomy may find it helpful to consult with a plastic surgeon to learn about options for breast reconstruction. We encourage all women who would consider this option to take the time they need to make a thoughtful decision.

How does breast cancer risk change over time?

In determining when to start breast cancer screening and in considering risk reducing surgery, it can be helpful to understand that in the general popular, breast cancer risk increases by age up to 70 years of age. The lifetime risk numbers on this website (see below) reflect studies done in carriers of BRCA1 and BRCA2, who have an increased risk for breast cancer as compared to the general population. 

What is a risk-reducing, or prophylactic, bilateral salpingo-oophorectomy and when is it recommended?

Risk-reducing bilateral salpingo-oophorectomy (BSO) is the removal of healthy ovaries and fallopian tubes. It is strongly recommended that women who carry BRCA mutations remove their ovaries and fallopian tubes after childbearing has been completed. The major decision is related to the timing of the procedure.

Current guidelines recommend oophorectomy by age 35-40. Recent studies suggest that this approach will reduce ovarian cancer incidence by as much as 90 percent. Fallopian tube cancers are very rare, but occur more frequently in women with BRCA1 and BRCA2 mutations. It is routine for the fallopian tubes to be removed at the time of oophorectomy.*

In addition to dramatically reducing ovarian cancer risk, it appears that removing the ovaries from pre-menopausal women also reduces breast cancer risk by 30-60 percent. Therefore, the overall benefit of this surgery is very significant. This is important since screening for ovarian cancer is very limited and usually does not detect ovarian cancer in the early stages.

A small number of women will still develop cancer of the lining of the abdomen, known as primary peritoneal cancer. This is a disease that behaves like advanced ovarian cancer.

* Removal of only the fallopian tubes, known as salpingectomy, is not currently recommended to reduce the risk for fallopian tube and ovarian cancer in BRCA mutation carriers. This is currently being studied but is not standard of care at this time. Those women who wish to learn more are encouraged to discuss with a specialist.

How does ovarian cancer risk change over time?

The risk of ovarian cancer and the average age of developing ovarian cancer differ between BRCA1 and BRCA2 mutation carriers. Therefore, it is important to discuss with your providers these issues and how they relate to the timing of the procedure. Current guidelines recommend oophorectomy by age 35-40 after finishing childbearing.

You may notice that the average ovarian cancer risk to age 70 in these graphs is on the lower end of the range for lifetime cancer risks in carriers cited earlier. The lifetime risk numbers on this website are still correct; they simply reflect different studies done in carriers of BRCA1 and BRCA2. Furthermore, these graphs only capture risk to age 70 and other studies have captured risk to later ages. The graphs of risk by decade are most helpful for understanding the trends in cancer risk in the course of a lifetime.

Should I remove my uterus also?

Some women choose to have their uterus removed at the same time their ovaries are removed. Removal of the uterus is called a hysterectomy. Women may consider removing their uterus in addition to ovaries and fallopian tubes for the following reasons: 

• Tamoxifen is a medication that some BRCA carriers elect to take in order to reduce their risk of breast cancer. It is associated with a slightly increased risk for uterine cancer.
• The type of hormone replacement therapy (HRT) prescribed for premenopausal women who have had their ovaries removed depends on whether a woman still has her uterus. HRT can be simplified if no uterus is present.
• There is a small risk of developing cancer where the fallopian tube was connected to the uterus.
• There may be a very small increased risk of uterine cancer in BRCA1 carriers, particularly in women who have taken tamoxifen.

However, the recovery time for surgery involving the uterus, ovaries, and fallopian tubes is longer than that for surgery to remove only the ovaries and fallopian tubes. The only “required” surgery for BRCA mutation carriers is the removal of the ovaries and the fallopian tubes. We encourage you to discuss these issues in more detail with your providers.

What are the effects of oophorectomy if I have not gone through menopause yet?

Removing the ovaries of a pre-menopausal woman will cause her to enter menopause, since the ovaries provide a woman with her major source of estrogen. Because of this, prophylactic oophorectomy is only considered after a woman is sure she has completed her family.

What are the effects of oophorectomy if I have gone through menopause already?

Once a woman has gone through natural menopause (no periods for over a year), her ovaries are not expected to produce estrogen. Therefore, removing healthy ovaries in a woman who has naturally gone through menopause will usually not have an impact on her symptoms of menopause.

What are the risks of pre-menopausal oophorectomy?

While risk-reducing bilateral salpingo-oophorectomy reduces ovarian and breast cancer risk, there are additional health issues that need consideration. Estrogen provides women with major protection from bone loss (osteoporosis), a condition where the bones are weakened and more easily fractured. In addition, estrogen deprivation at a young age increases a woman’s risk of heart disease. Pre-menopausal women who undergo prophylactic oophorectomy may also experience some effects of menopause, such as hot flashes, vaginal dryness, mood swings and sleep disturbances.

Can a pre-menopausal BRCA carrier take hormone replacement therapy (HRT) after prophylactic oophorectomy?

Women with a BRCA mutation and no history of breast cancer typically have the option of hormone replacement therapy (HRT) after having their ovaries removed. Many women at high risk of breast cancer may feel anxious about taking hormonal medications. Discussions with your physicians are usually helpful in making these difficult decisions. Lastly, pre-menopausal women who have had breast cancer are discouraged from using HRT.

Can a post-menopausal BRCA carrier take hormone replacement therapy (HRT) after prophylactic oophorectomy?

Women who have gone through natural menopause with a BRCA mutation are not good candidates for traditional HRT. Therefore, post-menopausal women should discuss non-hormonal options with their doctor. Avoiding use of HRT in post-menopausal BRCA mutation carriers is the most cautious approach at present. Lastly, post-menopausal women with a previous breast cancer diagnosis are discouraged from using HRT.

Chemoprevention, taking a medicine in an attempt to lower cancer risk, can provide additional choices for high-risk women. There is very limited data on these medications specifically in BRCA1 and BRCA2 mutation carriers. Three common examples are tamoxifen, raloxifene (Evista) and aromatase inhibitors (AIs).

What is tamoxifen?

Tamoxifen has been used in both treatment and to reduce the risk of breast cancer. A national study of over 13,000 healthy women at increased risk determined tamoxifen can lower the risk of developing breast cancer by up to 50%. Tamoxifen was also associated with some protection from bone loss in postmenopausal women. Drawbacks to taking tamoxifen include a small increased risk for early stage uterine cancer and a small increase in the risk for pulmonary embolism (a blood clot in the lung), deep vein thrombosis (a blood clot in a major vein), and cataracts.

What is raloxifene?

In post-menopausal women, raloxifene (also called Evista) has been shown to decrease the risk of breast cancer and to benefit bone and cholesterol levels. Therefore, this option can be an excellent choice for women with bone loss. Raloxifene is not associated with an increased risk of uterine cancer. Like tamoxifen, raloxifene has risks that must be weighed against the benefits in consultation with your physician.

What are aromatase inhibitors?

Aromatase inhibitors (AI's) are another class of medications being investigated for their ability to prevent breast cancer.

Do birth control pills affect cancer risk in BRCA carriers?

There have been several studies published examining the safety of birth control pills in women who have BRCA mutations. Birth control pills, also known as oral contraceptives, work in part by preventing a woman from ovulating. Preventing a woman from ovulating is usually associated with a decreased risk for ovarian cancer. Some studies suggest that the risk reduction for ovarian cancer can be as much as 50%.

There are some conflicting findings about the association between birth control pills and breast cancer risk. Some studies have shown there may be a small increased risk of breast cancer associated with these medications. However, many of these studies included women who were on higher dosages of hormones prior to the 1970's. Current formulations of birth control pills have lower hormone levels, and may therefore be associated with lower risks. More research is underway to help answer these important questions.

Ultimately, balancing the risk of breast cancer (for which we do have effective screening), against the significantly reduced risk for ovarian cancer, and the potential need for effective birth control is complex. Discussion of the benefits and risks on an individual basis is strongly encouraged.

How likely is it for a BRCA1 and BRCA2  mutation to be passed down?

A man or woman who has a mutation in  BRCA1  or  BRCA2  has a 50% chance of passing the mutated gene on to each of their children (son or daughter), and a 50% chance of passing along the normal copy of the gene to each of their children (son or daughter). A parent with a BRCA mutation may pass the mutation along to one, some or none of their children.

Gene mutations in  BRCA1  and  BRCA2  do not skip a generation. A child who does not inherit a BRCA mutation from a parent cannot then pass a BRCA mutation to the next generation.

What if I don't want to pass BRCA on to my children?

Many BRCA carriers accept the 50% risk of passing on a BRCA mutation to their children. The decision to use reproductive technologies to avoid passing on genetic diseases is a very personal decision.

Preimplantation genetic diagnosis testing (PGT) is a reproductive technology that may be an option for individuals who wish to minimize the chance of passing a known gene mutation to a child. This procedure is used in combination with in vitro fertilization (IVF) to test embryos (fertilized eggs) for a specific gene mutation, such as a BRCA1 or BRCA2 mutation.

PGT does not guarantee transferred embryos will lead to a full-term, healthy pregnancy. PGT is costly and coverage can vary greatly depending on insurance plan. Those who are interested in PGT may discuss in greater detail with their genetics providers and may be referred to a fertility clinic specializing in this service for more information.

Find a Fertility Clinic Near You
 

Susan M. Domchek, MD, Executive Director, Basser Center for BRCA, and Clarisa Gracia, MD, MSCE, Chief of the Division of Reproductive Endocrinology and Infertility at the University of Pennsylvania discuss fertility preservation, egg freezing, pre-implantation genetic testing (PGT), and more:
 

What is Fanconi Anemia?

Fanconi Anemia is a rare condition, occurring in 1 in 360,000 births, characterized by skeletal differences, developmental delays, bone marrow failure, and risks for certain types of cancer. Inheriting two BRCA2 mutations (one from the mother and one from the father) is one cause of Fanconi Anemia. This type of inheritance is called autosomal recessive.