Breast Cancer Health Article

Demographics

On average, a North American woman faces a lifetime risk of approximately one in nine (11%) to develop breast cancer. Most cases of breast cancer occur in women past the age of 50, and more commonly in individuals of North American descent.

The prevalence of BRCA alterations in the general population is estimated to be between one in 500 and one in 1,000. However, there are specific alterations that are commonly found in certain ethnic groups. In the Ashkenazi (Eastern European) Jewish population, two specific BRCA1 alterations and one BRCA2 alteration are commonly seen and range in prevalence from 0.1% to 1.0% in this group. As a result, hereditary forms of breast and ovarian cancer are more predominant in people of Ashkenazi Jewish ethnicity. A common BRCA1 alteration has been found in the Dutch population; a specific BRCA2 alteration exists in about 0.6% of people from Iceland. Additionally, common alterations have been identified in both BRCA1 and BRCA2 in French Canadians, and a BRCA1 alteration has often been seen in West Africans.

Signs and symptoms

Various symptoms may bring someone to medical attention in order to investigate the possibility of breast cancer. These may include a breast lump that persists, as opposed to one that only appears at certain times of a woman's menstrual cycle (which is more common). Other signs include changes from the normal breast shape, pain, itchiness, fluid leaking from the nipple (especially if a woman is not pregnant), a turned-in nipple, fatigue, or unexplained weight loss. Sometimes individuals may feel a breast lump or change while examining their own breasts, or a physician may note it on a CBE. Additionally, it may be seen on a screening mammogram. It is important to note not all breast lumps or breast changes signify cancer—they may be benign growths or cysts that need to be removed or drained.

Signs of a possible BRCA1 or BRCA2 alteration in a family, signifying hereditary breast or ovarian cancer, include:

• several relatives with cancer
• close genetic relationships between people with cancer, such as parent-child, sibling-sibling
• earlier ages of cancer onset, such as before ages 45-50
• an individual with both breast and ovarian cancer
• an individual with bilateral or multi-focal breast cancer
• the presence of ovarian, prostate, colon, or pancreatic cancers in the same family
• case(s) of breast cancer in men

Suspicion of a BRCA alteration may be raised if someone has the above features in their family and is of a particular ethnic group, such as an Ashkenazi Jew. This is because specific BRCA1 and BRCA2 alterations are known to be more common in this group of individuals.

Diagnosis

Once a suspicious breast abnormality has been found, the next step is determining if it is breast cancer. A mammogram can identify an area of increased breast density, which is a common sign of a malignant tumor. Women in their 20s to 30s naturally have denser breasts, so mammograms may not be as effective in this age group because the increased breast density associated with a tumor is difficult to see. Breast ultrasound, a way of visualizing the breast tissue using sound waves, can be helpful in younger women because breast density is not a large factor in its effectiveness. A breast biopsy can determine specifically whether the breast tissue has undergone a benign or malignant change because the breast tissue is studied directly under a microscope. Sometimes biopsies are performed with a very thin needle (known as fine needle aspiration), or with x ray guidance using a thicker needle (known as a core needle biopsy).

Newer techniques have improved breast cancer screening and diagnosis. Direct digital imaging in mammograms ends the need for film, and the digital images provide finer detail and allow the images to be rotated in order to get several different views of the breasts. Magnetic resonance imaging (MRI) uses magnetic energy to create an image. Its effectiveness is currently the subject of research studies, but MRI often provides very detailed imaging of tumors. MRI is expensive though, and this is another reason it is not widely used.

There is DNA-based genetic testing to identify a BRCA1 or BRCA2 alteration in an individual. In the United States, Myriad Laboratories in Utah is the only place to offer this costly testing. A blood sample is used and both BRCA genes are studied for alterations. There is also targeted testing for people in high-risk ethnic groups (such as the Ashkenazi Jews) in which only the common BRCA alterations can be tested; this testing is much less costly. Even with current technology, only certain regions of the BRCA genes can be studied, which leaves some alterations unlocated.

With either method of testing, it is best to begin the testing process with an individual who has survived breast and/or ovarian cancer. This is because tests are more likely to find an alteration a cancer survivor than someone who has not had cancer. A result is abnormal (or "positive") if a known cancer-causing BRCA alteration is found. If an alteration is found, it is assumed to have caused the cancer(s) in the tested, affected individual. That individual may also identify new cancer risks from the positive result. For example, if a woman survived breast cancer and was found to have a BRCA alteration through testing, she would now be at an increased risk to develop ovarian cancer, as well as a second breast cancer.

For people who go through testing and are not found to have a BRCA alteration (a "negative" result), this result is not informative. There are several possibilities for a negative result. First, there could be a BRCA alteration in the family and the person did not inherit it. In this case, the cancer would be due to reasons unrelated to BRCA1 and BRCA2. Additionally, they could have an alteration in an unknown gene (such as BRCA3), for which there is no testing available. Lastly, they could have a BRCA1 or BRCA2 alteration that is undetectable by available testing methods.

There is a possibility that individuals may have an "unknown alteration" in one of their BRCA genes. In this scenario, a change in the DNA is identified, but its significance is unclear. Therefore, it is unknown whether the gene change causes cancer. In these situations, the results are most often considered uninformative, until more information about the alteration becomes available in the future.

Once an alteration is identified, other at-risk relatives, both affected and unaffected, can pursue targeted analysis for the confirmed familial alteration. This is much quicker and far less expensive than the initial analysis.

Unaffected individuals who test positive for a known alteration in the family are at a significantly increased risk to develop the associated cancers. A woman's risks associated with a BRCA1 alteration are: 3-85% for breast cancer by age 70, 40–60% for ovarian cancer by age 70. A man's risk with a BRCA1 alteration is about 8% for prostate cancer by age 70. A woman's risks with a BRCA2 alteration are: 4–86% for breast cancer by age 70, and 16–27% for ovarian cancer by age 70. Less than 1% of men with BRCA 2 alteration develop breast cancer but they are at a slight or moderate increased risk for prostate cancer. For BRCA2 in men and women, there is an increased risk for colon and pancreatic cancers. Cancers of the larynx (structure in neck that helps with breathing), esophagus (tube-like structure that connects mouth to stomach), stomach, gallbladder (structure that makes bile), bile duct (tube that transports bile between liver and intestine), blood, and melanoma (a form of skin cancer) have been seen in families with BRCA2 alterations.

When a person who has not had cancer tests negative for a known, familial BRCA alteration, they are lowered to the general risk to develop the associated cancers, such as the lifetime risk of 11% for a woman to develop breast cancer. This is because he or she did not inherit the genetic alteration causing cancer in his or her family.

Everyone should receive proper genetic counseling before pursuing any BRCA1 and BRCA2 testing. This should include asking them what they hope to learn from the testing. Many people are not aware of the testing limitations, and may be expecting a clear "yes/no" answer from the results. Asking people what they hope to learn from testing allows the opportunity to provide them with accurate facts, such as the possibility of a result that is not informative. Common motivations to be tested include the need to make informed medical decisions, financially planning for the future, or just "wanting to know" about cancer risk.

Genetic testing for cancer susceptibility often triggers strong emotional responses. It is important to find out about an individual's "support system" before they begin testing. Having a close friend, family member, or religious leader to talk with is often helpful for people pursuing testing. Someone who tests positive may be concerned because his or her risks for cancer are now higher than they were before the testing. Additionally, someone may feel "empowered" by the knowledge because they can better plan for medical procedures. Someone with a family history of a BRCA alteration may feel relief if they test negative, because they initially assumed they would develop cancer. Alternatively, someone who tests negative in this situation may feel "survivor guilt" for not having inherited the altered gene in the family. All of these feelings may change the way an individual interacts with his or her family and friends. People may not be aware of the emotional changes that can occur from learning about cancer risk through genetic testing.

It is important to discuss the possibility of insurance coverage for the testing, particularly because it is so expensive. Insurance companies may not routinely cover the testing unless a physician or genetic counselor

describes the need for testing in a letter. Some companies are willing to cover the testing without wanting to know the results.

Issues of potential "genetic discrimination" should be discussed. Unaffected individuals who test positive for a BRCA1 or BRCA2 mutation may face difficulty when trying to obtain health, life, and/or disability insurance. Fortunately, there are laws in place that can help protect American individuals who have group health insurance, but the exact laws vary by state. There are no laws to protect individuals from life and disability insurance discrimination, nor employer discrimination.