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Genetic Testing For Breast Cancer

   Each year, approximately two hundred thousand American women are diagnosed with breast cancer. Five to ten percent of them have a hereditary HEREDITARY. That which is inherited.  form of this disease.

   Changes in certain genes would make some women more susceptible to developing breast and other types of cancer. Inherited inherited

received by inheritance.


inherited achondroplastic dwarfism
see achondroplastic dwarfism.

inherited combined immunodeficiency
see combined immune deficiency syndrome (disease).
 changes in the genes called BRCA BRCA  

One of two genes (designated BRCA1 and BRCA2) that help repair damage to DNA, but when inherited in a defective state increase the risk of breast and ovarian cancer.
1 and BRCA2 [breast cancer 1 and breast cancer 2] are involved in many cases of hereditary breast and ovarian cancer ovarian cancer

Malignant tumour of the ovaries. Risk factors include early age of first menstruation (before age 12), late onset of menopause (after age 52), absence of pregnancy, presence of specific genetic mutations, use of fertility drugs, and personal history of breast
. Scientists are searching for other genes that may also increase a cancer risk.

   The likelihood that breast or ovarian cancer is associated with BRCA1 or BRCA2 is highest in families with a history of multiple cases of breast cancer, cases of both breast and ovarian cancer, one or more family members with two primary cancers at different sites or an Eastern European Jewish background. However, not every woman in these families carries an alteration in BRCA1 or BRCA2 and not every cancer linked to these genetic changes.

How do genetic changes are related to cancers?

   A chance of developing breast or ovarian cancer is greatly increased if there are inherited changes on the BRCA1 or BRCA2 genes. Women with an inherited alteration in one of them have an increased risk of developing these cancers at a young age, before menopause menopause (mĕn`əpôz) or climacteric (klīmăk`tərĭk, klī'măktĕr`ĭk)  and often have multiple close family members with the disease.

   These women may also have an increased chance of developing colon cancer colon cancer, cancer of any part of the colon (often called the large intestine). Colon cancer is the second most common cancer diagnosed in the United States. . Men with an altered BRCA1 or BRCA2 gene also have an increased risk of breast cancer, primarily if the alteration is in BRCA2, and possibly prostate cancer prostate cancer, cancer originating in the prostate gland. Prostate cancer is the leading malignancy in men in the United States and is second only to lung cancer as a cause of cancer death in men. . Changes in the BRCA2 gene have also been associated with an increased risk of lymphoma lymphoma, a cancer of the tissue of the lymphatic system. There are two categories of lymphomas. One type is termed Hodgkin's disease, the other, non-Hodgkin's lymphoma (see lymphoma, non-Hodgkin's). See also neoplasm. , melanoma melanoma: see skin cancer.
melanoma

Dark-coloured malignant tumour of skin cells that produce the protective skin-darkening pigment melanin.
 and cancers of the pancreas pancreas (păn`krēəs), glandular organ that secretes digestive enzymes and hormones. In humans, the pancreas is a yellowish organ about 7 in. (17.8 cm) long and 1.5 in. (3.8 cm) wide. , gallbladder, bile ducts Bile ducts
Tubes that carry bile, a thick yellowish-green fluid that is made by the liver, stored in the gallbladder, and helps the body digest fats.

Mentioned in: Liver Transplantation, Percutaneous Transhepatic Cholangiography
, and stomach in some men and women.

   According to according to
prep.
1. As stated or indicated by; on the authority of: according to historians.

2. In keeping with: according to instructions.

3.
 estimates of lifetime risk, about thirteen percent of women in the general population will develop breast cancer, compared with estimates of thirty five to eighty five percent of women with an altered BRCA1 or BRCA2 gene. In other words Adv. 1. in other words - otherwise stated; "in other words, we are broke"
put differently
, women with an altered BRCA1 or BRCA2 gene are three to seven times more likely to develop breast cancer than women without alterations in those genes.

   Lifetime risk estimates of ovarian cancer for women in the general population indicate that approximately two percent will get ovarian cancer, compared with sixteen to sixty percent of women with altered BRCA1 or BRCA2 genes.

   We must remember that these statistical figures are estimates that do not necessarily apply to individual situations. More long term studies are needed to have a clearer picture as to the actual correlation between genetic changes and cancers.

   Some evidence suggests that there are slight differences in patterns of cancer between individuals with alterations on BRCA1 and BRCA2 genes, and even between people with different alterations in the same gene. For example, one study found that alterations in a certain part of the BRCA2 gene were associated with a higher risk for ovarian cancer in women, and a lower risk for prostate cancer in men than alterations in other areas of BRCA2.

   Most research related to these two genes has been done on large families with many affected individuals. Estimates of breast and ovarian cancer risk associated with these genes have been calculated from studies of these families. Because family members share a proportion of their genes and often, their environment, it is possible that the large number of cancer cases seen in these families may be partly due to other genetic or environmental factors. Therefore, risk estimates that are based on families with many affected members may not accurately reflect the levels of risk in the general population.

   Specific gene alterations have been identified in different ethnic groups. For example, among individuals of Ashkenazi Jewish descent, researchers have found that about two percent have an altered BRCA1 or BRCA2 gene. This frequency is about five times higher than that of the general population.

   Among people with alterations in these genes, three particular changes have been found to be most common in the Ashkenazi Jewish population —two in the BRCA1 gene and one in the BRCA2.

   It is not known whether the increased frequency of these alterations is responsible for the increased risk of breast cancer in Jewish populations compared with non-Jewish populations. Other ethnic and geographic populations, such as the Norwegian, Dutch, and Icelandic people, also have a higher rate of certain genetic alterations in BRCA1 and BRCA2. This information about genetic differences between ethnic groups may help health care professionals determine the most appropriate genetic test to select.

What is the meaning of a 'positive' genetic test result?

   In a family with a history of breast or ovarian cancer, it may be most informative to first test a family member who has the disease. If that person is found to have an altered BRCA1 or BRCA2 gene, the specific change is referred to as a 'known mutation.' Other family members can then be tested to see if they also carry that specific alteration.

   In this scenario, a positive test result may indicate that a person has inherited a known mutation in BRCA1 or BRCA2 and has an increased risk of developing certain cancers, as described above. However, a positive result provides information only about a person’s risk of developing cancer. It cannot tell whether cancer will actually develop, or when. It is also impossible to predict the effectiveness of special screening or preventive medical procedures for people with alterations in BRCA1 or BRCA2.

   We should then conclude that not all women who inherit To receive property according to the state laws of intestate succession from a decedent who has failed to execute a valid will, or, where the term is applied in a more general sense, to receive the property of a decedent by will.


inherit v.
 an altered gene will develop breast or ovarian cancer. A 'positive' genetic test result may have important health and social implications for family members, including future generations. Unlike most other medical tests, genetic tests can reveal information not only about the person being tested, but also about that person’s relatives.

   Men and women who inherit an altered BRCA1 or BRCA2 gene, whether or not they get cancer themselves, may pass the alteration on to their children. A 'negative' test result will be interpreted differently, depending upon whether there is a known mutation in the family. If someone in a family has a known mutation in BRCA1 or BRCA2, testing other family members for that specific gene alteration can provide information about their cancer risk.

   In this case, if a family member tests negative for the known mutation in that family, it is highly unlikely that they have an inherited susceptibility to cancer. This test result is called a 'true negative.' Having a true negative test result does not mean that a person will not get cancer; it means that the person’s risk of cancer is the same as that of the general population.

   In cases where no known mutation in BRCA1 or BRCA2 has previously been identified in a family with a history of breast or ovarian cancer, a negative test is not informative. It is not possible to tell whether a person has an alteration in BRCA1 or BRCA2 that was not identified by the test —a false negative, or whether the result is a true negative. In addition, it is possible for people to have an alteration in a gene other than BRCA1 or BRCA2 that increases their cancer risk, but is not detectable by this test.

   If the genetic test shows a change in BRCA1 or BRCA2 that has not been associated with cancer in other people, that person’s test result may be interpreted as ambiguous or uncertain. One study found that ten percent of women who underwent BRCA1 and BRCA2 testing had this type of ambiguous genetic change. Because everyone has genetic alterations that do not increase the risk of disease, it is sometimes not known whether a specific change affects a person’s risk of developing cancer.

   As more research is conducted and more people are tested for genetic alterations, scientists will learn more about these genetic alterations and cancer risk.

What are the options for a person who have a positive genetic test result?

   Several approaches are available for managing cancer risk in individuals with alterations in their BRCA1 or BRCA2 genes. However, limited data exist on the effectiveness of these approaches. First, follow-up: if a cancer develops, it is important to detect it as soon as possible. Careful monitoring for symptoms of cancer may be able to catch the disease at an earlier stage. Surveillance methods for breast cancer may include mammography mammography, diagnostic procedure that uses low-dose X rays to detect abnormalities in the breasts. The early diagnosis of breast cancer made possible by the routine use of mammography for screening women increases a woman's treatment alternatives and improves her  and a clinical breast exam.

   Some health professionals also recommend breast self-exams, but this surveillance method should not be used in place of clinical exams conducted by an experienced physician. Studies are currently under way to test the effectiveness of other breast cancer screening This article or section recently underwent a major revision or rewrite and needs further review. You can help! X-ray mammography
Mammography is still the modality of choice for screening of early breast cancer, since it is relatively fast, reasonably accurate, and
 methods in women with an altered BRCA1 or BRCA2 gene. With careful surveillance, many cancers will be diagnosed early enough to be successfully treated.

   For ovarian cancer, surveillance methods may include transvaginal ultrasound Transvaginal Ultrasound Definition

Transvaginal ultrasound is a imaging technique used to create a picture of the genital tract in women. The hand-held device that produces the ultrasound waves is inserted directly into the vagina, close to the pelvic
, CA-125 blood testing, MRI 1. (application) MRI - Magnetic Resonance Imaging.
2. MRI - Measurement Requirements and Interface.
 [Magnetic Resonance Imaging magnetic resonance imaging (MRI), noninvasive diagnostic technique that uses nuclear magnetic resonance to produce cross-sectional images of organs and other internal body structures. ] and clinical exams. Surveillance can sometimes find cancer at an early stage, but it is uncertain whether these methods can reduce a person’s chance of dying from ovarian cancer.

   Prophylactic surgery prophylactic surgery Surgical oncology An excision of precancerous tissue–eg, mastectomy of a ♀ at high risk of developing breast CA–to minimize the risk of future malignancy  involves removing as much of the at-risk tissue as possible in order to reduce the chance of developing cancer. Preventive mastectomy mastectomy (măstĕk`təmē), surgical removal of breast tissue, usually done as treatment for breast cancer. There are many types of mastectomy. In general, the farther the cancer has spread, the more tissue is taken. , with removal of healthy breasts, and preventive salpingo-oophorectomy with removal of healthy fallopian tubes Fallopian tubes
The narrow ducts leading from a woman's ovaries to the uterus. After an egg is released from the ovary during ovulation, fertilization (the union of sperm and egg) normally occurs in the fallopian tubes.
 and ovaries Ovaries
The female sex organs that make eggs and female hormones.

Mentioned in: Choriocarcinoma

ovaries (ō´v
 do not, however, offer a guarantee against developing these cancers. Because not all at-risk tissue can be removed by these procedures, some women have developed breast cancer, ovarian cancer, or primary peritoneal peritoneal /peri·to·ne·al/ (per?i-to-ne´al) pertaining to the peritoneum.

peritoneal

pertaining to the peritoneum.
 'carcinomatosis' —a type of cancer similar to ovarian cancer, even after prophylactic surgery.

   Risk avoidance-behaviors that may decrease breast cancer risk include exercising regularly and limiting alcohol consumption. Research results on the benefits of these behaviors are based on studies in the general population. The effects of these actions in people with BRCA1 or BRCA2 alterations are not yet known.

   Chemoprevention che·mo·pre·ven·tion
n.
The use of chemical agents, drugs, or food supplements to prevent disease.


chemoprevention 
 —this approach involves the use of natural or synthetic substances to reduce the risk of developing cancer, or to reduce the chance that cancer will come back. For example, Tamoxifen tamoxifen (təmŏk`sĭfĕn'), synthetic hormone used in the treatment of breast cancer. Introduced in 1978, tamoxifen is used to prevent recurrences of cancer in women who have already undergone surgery to remove their tumors.  would reduce the risk of invasive breast cancer by almost fifty percent in women at increased risk for developing the disease.

   Studies have been performed to test the effectiveness of Tamoxifen in women with a BRCA1 or BRCA2 alteration. One study found that Tamoxifen reduced the incidence of breast cancer by sixty percent in women with alterations in BRCA2. However, the results showed no reduction in breast cancer incidence with Tamoxifen use among women with BRCA1 changes.

   How about 'gene therapy'? At present, altered BRCA1 and BRCA2 genes cannot be repaired. Someday some·day  
adv.
At an indefinite time in the future.

Usage Note: The adverbs someday and sometime express future time indefinitely: We'll succeed someday. Come sometime.
 it may be possible to fix or manipulate the genes or sets of genes that increase the risk of cancer.

   Are there benefits of genetic testing Genetic Testing Definition

A genetic test examines the genetic information contained inside a person's cells, called DNA, to determine if that person has or will develop a certain disease or could pass a disease to his or her offspring.
 in relation to the actual risks of developing cancers? There can be benefits to genetic testing, whether a person receives a positive or a negative result. The potential benefits of a negative result include a sense of relief and elimination of the need for special preventive checkups, tests, or surgeries.

   A positive test result can bring relief from uncertainty and allow people to make informed decisions about their future, including taking steps to reduce cancer risk. In addition, many people are able to participate in medical research that may, in the long run, decrease the risk of death from breast cancer.

   The direct medical risks of genetic testing are very small, but test results may have an impact on a person’s emotions, social relationships, finances, and medical choices. People who receive a positive test result may feel anxious, depressed, or angry. They may choose to undergo preventive measures that have serious long-term implications and whose effectiveness is uncertain.

   Individuals who receive a negative test result may experience 'survivor guilt' caused by avoiding a disease that affects a loved one. They may also be falsely reassured that they have no chance of developing cancer, even though people with a negative test result have the same cancer risk as the general population.

   Because genetic testing can reveal information about more than one family member, the emotions caused by test results can create tension within families. Test results can also affect personal choices, such as marriage and childbearing child·bear·ing
n.
Pregnancy and parturition.



childbearing adj.
. Issues surrounding the privacy and confidentiality of genetic test results are additional potential risks.

   Clinical test results are normally included in a person’s medical records, and the inclusion of genetic test results in a patient’s records may have serious implications. For example, when applying for medical, life, or disability insurance, individuals may be asked to sign forms that give the insurance company permission to access their medical records. The insurance company may take genetic test results into account when making decisions about coverage. An employer may also have the right to look at an employee’s medical records. Individuals considering genetic testing must understand that when test results are placed in their medical records, the results might not be kept private.

   Some physicians keep test results out of medical records. However, even if genetic test results are not included in a person’s medical records, there may still be some risk of discrimination. Information about a person’s genetic profile can sometimes be gathered from that person’s family medical history.

   What is 'genetic discrimination'? It may occur when people are treated differently by their insurance company or employer because they have a gene alteration that increases their risk of a disease, such as cancer. People who undergo genetic testing to find out whether they have an alteration in their BRCA1 or BRCA2 gene may be at risk for genetic discrimination.

   A positive genetic test result may affect health insurance coverage; it may be denied for medical expenses related to a genetic condition, an individual may be dropped from their current health plan, or be unable to qualify for new insurance. Some insurers view the affected individual as a potential cancer patient whose medical treatment would be costly to their company.

   The Health Insurance Portability and Accountability Act The Health Insurance Portability and Accountability Act (HIPAA) was enacted by the U.S. Congress in 1996.

According to the Centers for Medicare and Medicaid Services (CMS) website, Title I of HIPAA protects health insurance coverage for workers and their families when
 [HIPAA (Health Insurance Portability & Accountability Act of 1996, Public Law 104-191) Also known as the "Kennedy-Kassebaum Act," this U.S. law protects employees' health insurance coverage when they change or lose their jobs (Title I) and provides standards for patient health, ] of 1996 provides some protection for people who have employer-based health insurance. The Act prohibits group health plans from using genetic information as a basis for denying coverage if a person does not currently have a disease. However, the Act does not prohibit employers from refusing to offer health coverage as part of their benefits, or prevent insurance companies from requesting genetic information.

   The Department of Health and Human Services Noun 1. Department of Health and Human Services - the United States federal department that administers all federal programs dealing with health and welfare; created in 1979
Health and Human Services, HHS
 has released the HIPAA National Standards to Protect Patients’ Personal Medical Records. This regulation covers medical records maintained by health care providers, health plans, and health care clearinghouses. Although the standards are not specific to genetic information, they provide the first comprehensive Federal protection for the privacy of health information.

   A person who tests positive for a BRCA1 or BRCA2 alteration may also experience genetic discrimination in the workplace if an employer learns about the test result. Although there are currently no federal laws specific to genetic discrimination, some protection from discrimination by employers is offered through the Americans with Disabilities Act Americans with Disabilities Act, U.S. civil-rights law, enacted 1990, that forbids discrimination of various sorts against persons with physical or mental handicaps.  of 1990 [ADA Ada, city, United States
Ada (ā`ə), city (1990 pop. 15,820), seat of Pontotoc co., S central Okla.; inc. 1904. It is a large cattle market and the center of a rich oil and ranch area.
]. In 1995, the Equal Employment Opportunity Commission [EEOC EEOC
abbr.
Equal Employment Opportunity Commission

EEOC n abbr (US) (= Equal Employment Opportunities Commission) → comisión que investiga discriminación racial o sexual en el empleo
] expanded the definition of 'disabled' to include individuals who carry genes that put them at higher risk for genetic disorders The following is a list of genetic disorders and their origins. Beside most disorders is a code that indicates the type of fertilization and the chromosome involved.
  • P - Point mutation, or any insertion/deletion entirely inside one gene
. The extent of this protection, however, has not yet been tested in the courts.

   Several states also have laws that address genetic discrimination by employers and health insurance companies. The degree of discrimination protection varies from state to state. Therefore, the decisions that people make about genetic testing while living in one state may have repercussions repercussions nplrépercussions fpl

repercussions nplAuswirkungen pl 
 in the future if they move to another area.

   Testing for changes in a person’s BRCA1 or BRCA2 gene is done on a blood sample. The person’s blood is drawn in a laboratory, doctor’s office, hospital, or clinic, and the blood sample is sent to a laboratory to check for alterations in these genes. The cost for genetic testing can range from several hundred to several thousand dollars. Insurance policies vary with regard to whether the cost of genetic testing is covered.

   Because the results of genetic tests can affect a person’s health insurance coverage, some individuals may not want to use their insurance to pay for testing. Some people may choose to pay out-of-pocket for the test, even when their insurer would be willing to cover the cost.

   To protect their privacy, some may not even want their insurer to know they are thinking about genetic testing. Others may decide to ask their insurance company to cover these costs. People who are considering genetic testing may want to find out more about their particular insurance company’s policies and the privacy protection laws in their state before submitting the charge for the test.

   It can take several weeks or months for test results to become available; the length of time depends on the tests performed and other factors. Individuals who decide to get tested should check with their doctor or genetic counselor to find out when test results might be available.

   The following factors have been associated with increased breast or ovarian cancer risk in the general population. It is not yet known exactly how these factors influence risk in people with BRCA1 or BRCA2 alterations.

   The risk of breast and ovarian cancers increases with age. Most breast and ovarian cancers occur in women over the age of fifty. Women with an altered BRCA1 or BRCA2 gene often develop breast or ovarian cancer before age fifty. Family history is important; women who have a first-degree relative [mother, sister, or daughter] or other close relative with breast or ovarian cancer may be at increased risk for developing them.

   In addition, women with relatives who have had colon cancer are at increased risk of developing ovarian cancer.

   Women who already had breast cancer are at increased risk of developing it again, or of developing ovarian cancer. Women who have had colon cancer also have an increased risk of developing ovarian cancer.

   Estrogen is naturally produced by the body and stimulates the normal growth of breast tissue. It is suspected that excess estrogen may contribute to breast cancer risk because of its natural role in stimulating breast cell growth. Women who had their first menstrual menstrual /men·stru·al/ (men´stroo-al) pertaining to the menses or to menstruation.

men·stru·al or men·stru·ous
adj.
Of or relating to menstruation.
 period before the age of twelve or experienced menopause after age fifty-five have a slightly increased risk of breast cancer, as do women who had their first child after age thirty.

   Each of these factors increases the amount of time a woman’s body is exposed to estrogen. Removal of a woman’s ovaries, which produce estrogen, reduces the risk of breast cancer.

   Birth control pills birth control pill
n.
See oral contraceptive.


birth control pill Oral contraceptive, see there
: most studies show a slight increase or no change in breast cancer risk in women taking birth control pills. Some studies suggest that a woman who has taken birth control pills for a long period of time, and began taking them at an early age or before her first pregnancy, has a small increase in her risk for developing breast cancer. In contrast, taking birth control pills may decrease a woman’s risk of ovarian cancer.

   Hormone replacement therapy Hormone Replacement Therapy Definition

Hormone replacement therapy (HRT) is the use of synthetic or natural female hormones to make up for the decline or lack of natural hormones produced in a woman's body.
 [HRT HRT
abbr.
hormone replacement therapy


Hormone replacement therapy (HRT)
Also called estrogen replacement therapy, this controversial treatment is used to relieve the discomforts of menopause.
]: a woman’s risk for developing breast cancer may be increased by hormone replacement therapy, especially when it is used for a long period of time. Doctors may prescribe HRT to reduce the discomfort from symptoms of menopause, such as hot flashes hot flashes Hot flush Gynecology A symptom afflicting 80-85% of middle-aged ♀, first occurring during the perimenopause, continuing with ↓ intensity for yrs, manifesting itself as transient waves of erythema and uncomfortable warmth beginning in the . Some evidence suggests that women who use HRT after menopause may also have a slightly increased risk of developing ovarian cancer.

   HRT may have positive health effects as well, such as lowering a woman’s risk of heart disease and osteoporosis osteoporosis (ŏs'tēō'pərō`sĭs), disorder in which the normal replenishment of old bone tissue is severely disrupted, resulting in weakened bones and increased risk of fracture; osteopenia . These protective effects diminish after a woman discontinues therapy. The risks and benefits of HRT should be carefully considered by a woman and her family physician.

   Although early studies suggested a possible association between a high-fat diet high-fat diet A diet rich in fats, often saturated–animal or tropical oils—fats Adverse effects Arthritis, CA, vascular disease, DM, HTN, obesity, stroke. See Fat, Fatty acids, Saturated fat acis, Cf Low-fat diet.  and increased breast cancer risk, more recent studies have been inconclusive INCONCLUSIVE. What does not put an end to a thing. Inconclusive presumptions are those which may be overcome by opposing proof; for example, the law presumes that he who possesses personal property is the owner of it, but evidence is allowed to contradict this presumption, and show who is . It is not yet known whether a diet low in fat will lower breast cancer risk.

   Studies of the relationship between physical activity and breast cancer have had mixed results. However, some studies suggest that regular exercise, particularly in women age forty and younger, may decrease breast cancer risk.

   Alcohol use may increase breast cancer risk, but no biological mechanism for the relationship between alcohol and breast cancer risk has been established.

   Exposure to ionizing radiation i·on·i·zing radiation
n.
High-energy radiation capable of producing ionization in substances through which it passes.


Ionizing radiation 
, such as radiation therapy for Hodgkin’s disease or other disorders, is associated with an increased risk of breast cancer, especially when the exposure occurred at a young age. Evidence for the effect of occupational, environmental, or chemical exposure on breast cancer risk is limited. For example, there is some evidence to suggest that organochlorine or·gan·o·chlo·rine
n.
Any of various hydrocarbon pesticides, such as DDT, that contain chlorine.
 residues in the environment, such as those from insecticides insecticides, chemical, biological, or other agents used to destroy insect pests; the term commonly refers to chemical agents only. Chemical Insecticides
, might be associated with an increase in breast cancer risk. However, the significance of this evidence has been debated.

   Scientific research is currently in progress to study the effects of various environmental factors on breast cancer risk.

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Date:Nov 8, 2006
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