Breast cancer

Definition

Breast cancer is a disease in which abnormal breast cells begin to grow uncontrollably, forming tumors. It often shows up as a breast lump, breast thickening, or skin change.

Description

The breasts are areas of tissue located on the front chest wall, and are essentially part of the skin. They are like "specialized sweat glands" in their structure and function, in that they can produce and secrete fluids, like milk. They are made of ductal tissue, supporting connective tissue, and fat. The breasts naturally drain fluid through the lymph channels to the axillary lymph nodes, located in the armpit areas. Within the breasts are intricate structures of ducts and lobules, which are channels and areas that create and transport milk during lactation.

Excluding skin cancers, breast cancer is the most common cancer among women and the leading cause of death in women in their middle years of life. Male breast cancer, though rare, accounts for less than 1% of all breast cancers. Both genetic and environmental factors are thought to cause breast cancer. Of all breast cancer diagnoses, only approximately 5-10% are caused by hereditary factors like specific alterations in breast cancer susceptibility genes, or by a genetic cancer syndrome. In these instances, individuals may have a strong family history of cancer and the cancers may be diagnosed at an earlier age than usual.

Breast cancers vary in their type and size, and this can be determined by a breast biopsy. Breast cancer may commonly be detected by a mammogram, a physician's clinical breast examination (CBE), or a patient's own breast self-examination (BSE). Breast cancer, if it is the first cancer diagnosed, may sometimes metastasize (spread) to other organs, such as the liver, bone, lungs, skin, or brain. The breasts may also be the site of metastasis from other primary cancers.

Breast cancer may present as a lump or other change within the breast. As with other types of cancer, the initial diagnosis may be unexpected. Each cancer has a unique prognosis, and this will affect the patient's concern. If an individual has a very strong family history of breast cancer, the diagnosis may be somewhat expected, but no less emotionally taxing. Treatment and management of the cancer may be extremely exhausting, painful, and stressful for the patient and his or her family.

Genetic profile

Cells in breast tissue normally divide and grow, according to controls and instructions of various genes. If these genes have changes within them, the instructions for cellular growth and division may go awry. Abnormal, uncontrolled cell growth may occur, causing breast cancer. Therefore, all breast cancers are genetic because they all result from changes within genes. However, most breast cancers occur later in life after years of exposure to various environmental factors that can cause alterations (such as the body's own hormones, asbestos exposure, or smoking).

A small proportion of breast cancers is caused by inherited genetic alterations. In 1994 a breast cancer susceptibility gene, known as BRCA1 (location 17q21), was identified. The discovery of BRCA2 (location 13q12) followed shortly in 1995. Women with alterations in these genes have an increased risk for breast and ovarian cancer, and men have an increased risk for prostate cancer. Men with a BRCA2 alteration have an increased risk for breast cancer. Slightly increased risks for colon and pancreatic cancers (in men and women) are associated with BRCA2 alterations.

BRCA1 and BRCA2 alterations are inherited in an autosomal dominant manner; an individual has one copy of a BRCA alteration and has a 50% chance of passing it on to each of his or her children, regardless of that child's gender. Nearly all individuals with BRCA alterations have a family history of the alteration, usually a parent. In turn, they also may have a very strong family history of breast, ovarian, prostate, colon, and/or pancreatic cancers. Aside from BRCA1 and BRCA2, there likely are other breast cancer susceptibility genes that are still unknown (such as BRCA3). Additionally, there may be other genes that convey increased risks solely for other cancers, such as ovarian cancer.

BRCA1 and BRCA2 are thought to function as "tumor-suppressor genes," meaning that their normal role is to prevent tumors from forming. Specifically, they control cellular growth and division, all the while preventing the over-growth that may lead to cancer. Alterations in tumor-suppressor genes, such as BRCA1 and BRCA2, would naturally lead to an increased risk of developing cancer. However, this risk is not 100%.

There are rare, genetic cancer syndromes that may include breast cancer. As a group, these comprise less than 1% of all breast cancer diagnoses. In these instances, an individual may have other health problems (unrelated to cancer) and a family history of a wide variety of cancers and symptoms. These health problems can initially appear unrelated, but may be caused by alterations in a specific gene. As an example, Cowden syndrome typically involves early-onset thyroid and breast cancers, as well as specific tissue growths on the face, limbs, and mouth. An individual with Cowden syndrome may have all or some of these symptoms. It is now known that alterations in the PTEN gene cause Cowden syndrome. Other known cancer syndromes are caused by specific alterations in different genes. These genes are responsible for the various symptoms and cancers in an individual.

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.

Treatment and management

Breast cancer treatment is determined by the exact size and type of cancer, so it is often unique to an individual. Treatment may include surgeries, such as a lumpectomy (removal of the breast lump) or mastectomy (removal of the entire breast). Breast reconstruction (recreation of the breast) by plastic surgery is an option some individuals may pursue.

Chemotherapy, or using strong chemicals to kill fast-growing cells, is a common treatment. Side effects from chemotherapy may include nausea, vomiting, hair loss, exhaustion, and sores in the mouth. Symptoms associated with menopause (such as "hot flashes" and the absence of menstrual periods) may occur, or menopause may actually begin because of chemotherapy. Radiation therapy is another common form of treatment, in which directed radioactive waves are used to kill fast-growing cells. Some side effects of radiation therapy are dry and itchy skin, rashes, exhaustion, nausea, and vomiting.

Sometimes, medications such as Tamoxifen are used to prevent a breast cancer from coming back. Tamoxifen is often used for five years following a breast cancer diagnosis to actively prevent a recurrence. Tamoxifen is only effective in specific types of breast cancer, which again are unique to each individual. Some side effects of Tamoxifen include beginning menopause, as well as an increased risk for uterine cancer. Other drugs, such as Raloxifene, are currently being studied for breast cancer prevention because it may be able to do the same things as Tamoxifen, without the side effects. Research studies are under way to determine whether Tamoxifen or Raloxifene can reduce the risk of breast cancer in women with BRCA alterations.

An example of a screening program for women at high risk to develop breast cancer includes:

BSEs monthly starting in early adulthood (about 20–25 years of age)
CBEs every six months or yearly starting at age 25–35
mammograms yearly starting at age 25–35

Exact screening guidelines may vary between physicians. For men with a BRCA2 alteration, breast cancer screening is recommended, though no formal program is specifically recommended.

In addition to screening, women with BRCA1 or BRCA2 alterations should know about their preventive surgery options. They may consider having their healthy breasts and/or ovaries removed, in order to reduce their risks of developing breast and/or ovarian cancer. Women may be more agreeable to an oophorectomy because ovarian cancer is difficult to detect. Surgeries may greatly reduce a woman's cancer risk, but they can never eliminate the risk entirely.

For people with cancer or at high risk, there are support and discussion groups available. These may be invaluable to those who feel alone in their situation.

Prognosis

The type and size of breast cancer developed largely determines the overall prognosis for an individual. Those with larger tumors and those with a type of breast tumor that does not usually respond to treatment may have a poorer outcome. Additionally, once cancer has spread to other areas of the body the prognosis worsens because the cancer is more difficult to treat. The cancer may also be more likely to continue spreading to other areas of the body.

Those with BRCA alterations who develop breast cancer have a similar prognosis to those without BRCA alterations that have equivalent cancers. In addition, people with BRCA alterations are treated for their cancers using the same methods as those without alterations.

For cancer-free individuals identified to have BRCA alterations, it is important to remember that they are at an increased risk to develop the associated cancers, but that the risk is not 100%. Though people with BRCA alterations may feel "destined" to develop cancer, it is by no means a certainty. It is also important to emphasize that breast cancer screening techniques and treatments are constantly being evaluated and improved.

Breast cancer

Definition

Description

Genetic profile

Demographics

Signs and symptoms

Diagnosis

Treatment and management

Prognosis

Resources

BOOKS

ORGANIZATIONS

WEBSITES