Managing Cancer Risk

What are the cancer risks for people with mutations in BRCA1 and BRCA2?

A positive BRCA1 or BRCA2 test result means that a person has an inherited mutation in either gene and is at increased risk for certain cancers. The cancers most commonly associated with BRCA mutations are breast (male and female), ovarian, prostate and pancreatic cancers, as well as melanoma.

Why are cancer risks presented as ranges? Why are cancer risks different, depending on the source?

The cancer risks associated with BRCA1 and BRCA2 in men and women carrying mutations are presented as ranges since cancer risk may vary in different families or population groups. As more individuals undergo genetic testing and more studies to assess cancer risk are published, our understanding of cancer risk in individuals with BRCA1 and BRCA2 mutations will continue to evolve. For these reasons, risk estimates may vary from one source to the next and as research advances.

Where in the range of risk do I fall?

At this time, we cannot predict where any individual will fall in the risk range. There are other genetic and lifestyle factors that can influence, or modify cancer risk associated with mutations in BRCA1 and BRCA2. Discovering these factors and refining our understanding of the risk associated with them may help us provide a more accurate individual risk assessment. The Basser Center is actively working on studies to uncover the factors that may help individualize risk assessment.

Do all people with BRCA mutations develop cancer?

People with mutations in BRCA1 or BRCA2 may develop one or more cancers, or they may not develop cancer at all. Unfortunately, being diagnosed with one type of cancer does not mean that other cancer risks no longer apply. For example, women with a BRCA mutation with breast cancer are at increased risk of developing a second breast cancer. The risk for a second new breast cancer may depend on a person’s age at diagnosis of the first breast cancer, family history, and whether a person has a BRCA1 or BRCA2 mutation.

Are there other cancer risks for BRCA mutation carriers?

In addition to the cancers commonly associated with BRCA mutations (breast, ovarian, prostate, pancreatic, melanoma), men and women with BRCA mutations appear to have a slightly increased risk of developing cancers in general. Therefore, regular medical follow-up with prompt attention to symptoms is strongly encouraged. For example, unexplained weight loss, unexplained and persistent pain, swollen lymph nodes, and sores that do not heal should be evaluated by a physician.

General cancer screening recommendations, such as colonoscopy and cervical cancer screenings, should also be followed in addition to the more intensive cancer screening recommended for BRCA1/2 -related cancers.

What is cancer risk management?

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 . You and your doctors will ultimately decide what plan makes the most sense for you. Cancer risk management generally includes the following categories:

• Intensive screening to increase the chances of early detection, should cancer develop.
• Prophylactic or risk reducing surgical removal of ovaries and consideration of prophylactic removal of the breasts.
• Chemoprevention, which is taking a medicine shown to lower the chances of developing cancer.

Men and women with BRCA1 and BRCA2 mutations should also undergo yearly skin checks with a dermatologist. A more personalized plan can be created for individuals with a family or personal history of melanoma.

BRCA mutation carriers, particularly those with a strong family history of pancreatic cancer, may consider the option of screening. Currently, there is limited data that pancreatic cancer screening is effective. For those interested in pancreatic screening or with a family history, we recommend annual endoscopic ultrasound (EUS). We highly recommend that pancreatic screening be performed by someone with significant experience, preferably as part of an ongoing clinical study.

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

What are risk reducing surgical options that are available to BRCA mutation carriers?

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.

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  BRCA1/2  mutations. Breast awareness means a woman is familiar with her breasts and promptly reports changes to her health care provider.

How is breast cancer screening done for male BRCA carriers?

Starting at age 35, male BRCA carriers should begin self-breast exams and undergo clinical breast exams every 12 months with a physician. A mammogram may be recommended on an individual basis. Mammograms are done the same way in men as they are done in women.

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 BRCA1/2 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 medications reduce breast cancer risk?

Chemoprevention, taking a medicine in an attempt to lower cancer risk, can provide additional choices for high-risk women. There is very limited, if any, data on these medications specifically in BRCA1 and BRCA2 mutation carriers. There are several medications available; tamoxifen, raloxifene, and aromatase inhibitors are three common examples.

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 prostate cancer screenings are recommended for men with BRCA1 or BRCA2 mutations?

At age 40, prostate cancer screenings are recommended for BRCA2 mutation carriers and considered for BRCA1 mutation carriers. Prostate cancer screenings may include prostate-specific antigen (PSA) blood tests and digital rectal exams.

Are there effective ways to screen for pancreatic cancer?

BRCA mutation carriers, particularly those with a strong family history of pancreatic cancer, may consider the option of screening. The goal of screening is to identify cancer at an early, more treatable stage. Currently, there is limited data that pancreatic cancer screening is effective. However, this is an active area of research. For those interested in pancreatic screening or with a family history, we recommend annual endoscopic ultrasound (EUS). We highly recommend that pancreatic screening be performed by someone with significant experience, preferably as part of an ongoing clinical study.

How do I manage my risk for melanoma?

Melanoma is a serious type of skin cancer. BRCA mutation carriers, like the general population, should practice sun safety and see a dermatologist yearly for a full body skin check. Any new or changing moles should be evaluated by a doctor. People with a personal or family history of melanoma should speak to a physician about personalized options.

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 how breast cancer risk evolves over the course of lifetime. The graphs of breast cancer risk by age are from a meta-analysis, which is a study that combines results from many studies to gain the best estimate of risks. They show the risk of breast cancer developing by different ages.

You may notice that the average breast 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 while other studies show risk to later ages. The graphs of risk by decade are helpful for understanding the trends in cancer risk over a lifetime.

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.

What medications reduce breast cancer risk?

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.

Watch Basser Young Leadership Council Co-Chair, Jenny Sorin, and fertility expert, Dr. Jaime Knopman, discuss the process of freezing eggs and embryos and undergoing pre-implantation genetic testing (PGT) in the video below.

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.