Breast Cancer and genetics:
The breast is made up of glands called lobules that can make milk and thin tubes called ducts that carry the milk from the lobules to the nipple. Breast tissue also contains fat and connective tissue, lymph nodes, and blood vessels. The most common type of breast cancer is ductal carcinoma, which begins in the cells of the ducts. Breast cancer can also begin in the cells of the lobules and in
other tissues in the breast. Invasive breast cancer is breast cancer that has spread from where it began in the ducts or lobules to surrounding tissue.
In the U.S., breast cancer is the second most common cancer in women after skin cancer. It can occur in both men and women, but it is very rare in men. Each year there are about 2,300 new cases of breast cancer in men and about 230,000 new
cases in women.
osis → Screening and Testing → Genetic Testing
Genetic Testing:
Three of the most well-known genes that can mutate and raise the risk of breast and/or ovarian cancer are BRCA1, BRCA2, and PALB2. Women who inherit a mutation, or abnormal change, in any of these genes — from their mothers or their fathers — have a much higher-than-average risk of developing breast cancer and/or ovarian cancer. (Abnormal PALB2 genes are suspected to raise the risk of ovarian cancer, but larger studies need to confirm that risk.) Men with these mutations have an increased risk of breast cancer, especially if theBRCA2 gene is affected, and possibly of prostate cancer. Many inherited cases of breast cancer have been associated with mutations in these three genes.
The function of the BRCA and PALB2 genes is to keep breast cells growing normally and prevent any cancer cell growth. But when these genes contain the mutations that are passed from generation to generation, they do not function normally and breast cancer risk increases. Abnormal BRCA1, BRCA2, andPALB2 genes may account for up to 10% of all breast cancers, or 1 out of
every 10 cases.
Most people who develop breast cancer have no family history of the disease. However, when a strong family history of breast and/or ovarian cancer is present, there may be reason to believe that a person has inherited an abnormal gene linked to higher breast cancer risk. Some people choose to undergo genetic
testing to find out. A genetic test involves giving a blood or saliva sample that can be analyzed to pick up any abnormalities in these genes.
""Simply having a proven gene abnormality does not necessarily mean that a woman will develop breast cancer, or that her cancer will be any worse than cancer that does not stem from an inherited genetic flaw..""
The proteins produced from the
BRCA1 and BRCA2 genes are involved in fixing damaged DNA, which helps to maintain the stability
of a cell's genetic information. They are described as tumor suppressors because they help keep cells from
growing and dividing too fast or in an uncontrolled way. Mutations in these genes impair DNA repair,
allowing potentially damaging mutations to persist in DNA. As these defects accumulate, they can trigger cells to grow and divide without control or order to
form a tumor.
A significantly increased risk of breast cancer is also a feature of several rare genetic syndromes. These include Cowden syndrome, which is most often caused by mutations in the PTEN gene;hereditary diffuse gastric cancer, which results from mutations in the CDH1 gene; Li-Fraumeni syndrome, which is usually
caused by mutations in the TP53 gene; and Peutz-Jeghers syndrome, which typically results from mutations in the STK11 gene. The proteins produced from these genes act as tumor suppressors. Mutations in any of these genes can allow
cells to grow and divide unchecked, leading to the development of a cancerous tumor. Like BRCA1 and BRCA2, these genes are considered "high penetrance" because mutations greatly increase a person's chance of developing cancer. In addition to breast cancer, mutations in these genes increase the risk of several other types of cancer over a person's lifetime. Some of the conditions also include other signs and symptoms, such as the growth of noncancerous (benign) tumors.
Mutations in dozens of other genes have been studied as possible risk factors for breast cancer. These genes are described as "low
penetrance" or "moderate penetrance" because changes in each of these genes appear to make only a small or moderate contribution to overall breast cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations in these genes may significantly impact a person's risk of developing breast cancer.
In many families, the genetic changes associated with hereditary breast cancer are unknown. Identifying additional genetic risk factors for breast cancer is an active area of medical research.
In addition to genetic changes, researchers have identified many personal and environmental factors that contribute to a person's risk of developing breast cancer. These factors include gender, age, ethnic background, a history of previous breast cancer, certain changes in breast tissue, and hormonal and reproductive factors. A history of breast cancer in closely related family members is also an important risk factor, particularly if the cancer occurred in early
adulthood.
About 5% to 10% of breast cancers are thought to be hereditary,
caused by abnormal genes passed from parent to child. Genes are particles in cells, contained in chromosomes, and made of DNA
(deoxyribonucleic acid). DNA contains the instructions for building proteins. And proteins control the structure and function of all the cells that make up your body. Think of your genes as an instruction manual for cell growth and function. Abnormalities in the DNA are like typographical errors. They may provide the wrong set of instructions, leading to faulty cell growth or function. In any one person, if there is an error in a gene, that same mistake will appear in all the cells that contain the same gene. This is like having an instruction manual in which all the copies have the same typographical error.
BRCA1 and BRCA2 genes:
Having.an.abnormal BRCA1 or BRC A2 gene doesn't mean you will be diagnosed with breast cancer. Researchers are learning that other mutations in pieces
of chromosomes -- called SNPs (single nucleotide polymorphisms) -- may be
linked to higher breast cancer risk in women with an abnormal BRCA1 gene as well as women who didn't inherit an abnormal breast cancer gene. Women who are diagnosed with breast cancer and have an abnormal BRCA1 orBRCA2 gene often have a family history of breast cancer,
ovarian cancer, and other cancers. Still, most people who develop breast cancer did not inherit an abnormal breast cancer gene and have no family history of the disease.
Men with an abnormal BRCA1 gene have a slightly higher risk of prostate cancer. Men with an abnormal BRCA2 gene are 7 times more likely than men without the abnormal gene to develop prostate cancer. Other cancer risks, such as cancer of the skin or digestive tract, also may be slightly higher in men with
abnormal BRCA1 or BRCA2 genes.
Steps you can take:
If you know you have an abnormal gene linked to breast cancer, there are lifestyle choices you can make to keep your risk as low it can be:
maintaining a healthy weight
exercising regularly
limiting alcohol
eating nutritious food
never smoking (or quitting if you do smoke)
Along with these lifestyle choices, there are other risk-reduction options for women at high risk because of abnormal genetics.
Hormonal therapy:
medicines:
Two SERMs (selective estrogen receptor modulators) and two
aromatase inhibitors have been shown to reduce the risk of developing hormone-receptor-positive breast cancer in women at high risk. Tamoxifen has been shown to reduce the risk of first-time hormone-receptorpositive breast cancer in both postmenopausal and premenopausal women at high risk. Certain medicines may interfere with tamoxifen's protective effects. Evista (chemical name: raloxifene) has been shown to reduce the risk of first-time
hormone-receptor-positive breast cancer in postmenopausal women.
Hormonal therapy medicines do not reduce the risk of hormone-receptor-negative breast cancer.
More frequent screening:
If you're at high risk because of an abnormal breast cancer gene, you and your doctor will develop a screening plan tailored to your unique situation. You may start being screened when you're younger than 40. In addition to the recommended screening guidelines for women at average risk, a screening plan for a woman at high risk may include:
a monthly breast self-exam
a yearly breast exam by your doctor
a digital mammogram every year starting at age 30 or younger
an MRI scan every year starting at age 30 or younger
Protective surgery:
Removing the healthy breasts and ovaries -- called prophylactic surgery ("prophylactic" means "protective") -- are very aggressive, irreversible riskreduction options that some women with an abnormal BRCA1 orBRCA2 gene choose. Prophylactic breast surgery may be able to reduce a woman's risk of developing
breast cancer by as much as 97%. The surgery removes nearly all of the breast tissue, so there are very few breast cells left behind that could develop into a cancer.
How much does having a BRCA1 or BRCA2 gene mutation increase a woman’s risk of breast and ovarian cancer?
A woman’s lifetime risk of developing breast and/or
ovarian cancer is greatly increased if she inherits a harmful mutation in BRCA1 or BRCA2. Breast cancer: About 12 percent of women in the general population will develop breast cancer sometime during their lives (4). By contrast, according to the most recent estimates, 55 to 65 percent of women who inherit a harmful BRCA1 mutation and around 45 percent of women who inherit a harmful BRCA2 mutation will develop breast cancer by age 70 years (5, 6).
Abstract:
For many tumors, pathological subclasses exist which have to be further defined by genetic markers to improve therapy and follow-up strategies. In this study, cDNA array analyses of breast cancers have been performed to classify tumors into categories based on expression patterns. Comparing purified normal
ductal epithelial cells and corresponding tumour tissues, the expression of only a small fraction of genes was found to be significantly changed. A subset of genes repeatedly found to be differentially expressed in breast cancers was subsequently employed to perform a classification of 82 normal and malignant
breast specimens by cluster analysis. This analysis identifies a subgroup of transcriptionally related tumours, designated class A, which can be further subdivided into A1 and A2. Correlation with classical clinicopathological parameters revealed that subgroup A1 was characterized by a high number of nodepositive tumours (14 of 16). In this subgroup there was a disproportionate number of
patients who had already developed distant metastases at
the time of diagnosis (25% in this subgroup, compared with
5% among the rest of the samples). Taken together, the use of these differently expressed marker genes in conjunction with sample clustering algorithms provides a novel molecular classification of breast cancer specimens, which facilitates the identification of patients with a higher risk of recurrence.
The breast is made up of glands called lobules that can make milk and thin tubes called ducts that carry the milk from the lobules to the nipple. Breast tissue also contains fat and connective tissue, lymph nodes, and blood vessels. The most common type of breast cancer is ductal carcinoma, which begins in the cells of the ducts. Breast cancer can also begin in the cells of the lobules and in
other tissues in the breast. Invasive breast cancer is breast cancer that has spread from where it began in the ducts or lobules to surrounding tissue.
In the U.S., breast cancer is the second most common cancer in women after skin cancer. It can occur in both men and women, but it is very rare in men. Each year there are about 2,300 new cases of breast cancer in men and about 230,000 new
cases in women.
osis → Screening and Testing → Genetic Testing
Genetic Testing:
Three of the most well-known genes that can mutate and raise the risk of breast and/or ovarian cancer are BRCA1, BRCA2, and PALB2. Women who inherit a mutation, or abnormal change, in any of these genes — from their mothers or their fathers — have a much higher-than-average risk of developing breast cancer and/or ovarian cancer. (Abnormal PALB2 genes are suspected to raise the risk of ovarian cancer, but larger studies need to confirm that risk.) Men with these mutations have an increased risk of breast cancer, especially if theBRCA2 gene is affected, and possibly of prostate cancer. Many inherited cases of breast cancer have been associated with mutations in these three genes.
The function of the BRCA and PALB2 genes is to keep breast cells growing normally and prevent any cancer cell growth. But when these genes contain the mutations that are passed from generation to generation, they do not function normally and breast cancer risk increases. Abnormal BRCA1, BRCA2, andPALB2 genes may account for up to 10% of all breast cancers, or 1 out of
every 10 cases.
Most people who develop breast cancer have no family history of the disease. However, when a strong family history of breast and/or ovarian cancer is present, there may be reason to believe that a person has inherited an abnormal gene linked to higher breast cancer risk. Some people choose to undergo genetic
testing to find out. A genetic test involves giving a blood or saliva sample that can be analyzed to pick up any abnormalities in these genes.
""Simply having a proven gene abnormality does not necessarily mean that a woman will develop breast cancer, or that her cancer will be any worse than cancer that does not stem from an inherited genetic flaw..""
-- Marisa Weiss, M.D., chief medical officer, Breastcancer.org
The proteins produced from the
BRCA1 and BRCA2 genes are involved in fixing damaged DNA, which helps to maintain the stability
of a cell's genetic information. They are described as tumor suppressors because they help keep cells from
growing and dividing too fast or in an uncontrolled way. Mutations in these genes impair DNA repair,
allowing potentially damaging mutations to persist in DNA. As these defects accumulate, they can trigger cells to grow and divide without control or order to
form a tumor.
A significantly increased risk of breast cancer is also a feature of several rare genetic syndromes. These include Cowden syndrome, which is most often caused by mutations in the PTEN gene;hereditary diffuse gastric cancer, which results from mutations in the CDH1 gene; Li-Fraumeni syndrome, which is usually
caused by mutations in the TP53 gene; and Peutz-Jeghers syndrome, which typically results from mutations in the STK11 gene. The proteins produced from these genes act as tumor suppressors. Mutations in any of these genes can allow
cells to grow and divide unchecked, leading to the development of a cancerous tumor. Like BRCA1 and BRCA2, these genes are considered "high penetrance" because mutations greatly increase a person's chance of developing cancer. In addition to breast cancer, mutations in these genes increase the risk of several other types of cancer over a person's lifetime. Some of the conditions also include other signs and symptoms, such as the growth of noncancerous (benign) tumors.
Mutations in dozens of other genes have been studied as possible risk factors for breast cancer. These genes are described as "low
penetrance" or "moderate penetrance" because changes in each of these genes appear to make only a small or moderate contribution to overall breast cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations in these genes may significantly impact a person's risk of developing breast cancer.
In many families, the genetic changes associated with hereditary breast cancer are unknown. Identifying additional genetic risk factors for breast cancer is an active area of medical research.
In addition to genetic changes, researchers have identified many personal and environmental factors that contribute to a person's risk of developing breast cancer. These factors include gender, age, ethnic background, a history of previous breast cancer, certain changes in breast tissue, and hormonal and reproductive factors. A history of breast cancer in closely related family members is also an important risk factor, particularly if the cancer occurred in early
adulthood.
caused by abnormal genes passed from parent to child. Genes are particles in cells, contained in chromosomes, and made of DNA
(deoxyribonucleic acid). DNA contains the instructions for building proteins. And proteins control the structure and function of all the cells that make up your body. Think of your genes as an instruction manual for cell growth and function. Abnormalities in the DNA are like typographical errors. They may provide the wrong set of instructions, leading to faulty cell growth or function. In any one person, if there is an error in a gene, that same mistake will appear in all the cells that contain the same gene. This is like having an instruction manual in which all the copies have the same typographical error.
BRCA1 and BRCA2 genes:
Having.an.abnormal BRCA1 or BRC A2 gene doesn't mean you will be diagnosed with breast cancer. Researchers are learning that other mutations in pieces
of chromosomes -- called SNPs (single nucleotide polymorphisms) -- may be
linked to higher breast cancer risk in women with an abnormal BRCA1 gene as well as women who didn't inherit an abnormal breast cancer gene. Women who are diagnosed with breast cancer and have an abnormal BRCA1 orBRCA2 gene often have a family history of breast cancer,
ovarian cancer, and other cancers. Still, most people who develop breast cancer did not inherit an abnormal breast cancer gene and have no family history of the disease.
Men with an abnormal BRCA1 gene have a slightly higher risk of prostate cancer. Men with an abnormal BRCA2 gene are 7 times more likely than men without the abnormal gene to develop prostate cancer. Other cancer risks, such as cancer of the skin or digestive tract, also may be slightly higher in men with
abnormal BRCA1 or BRCA2 genes.
Steps you can take:
If you know you have an abnormal gene linked to breast cancer, there are lifestyle choices you can make to keep your risk as low it can be:
maintaining a healthy weight
exercising regularly
limiting alcohol
eating nutritious food
never smoking (or quitting if you do smoke)
Along with these lifestyle choices, there are other risk-reduction options for women at high risk because of abnormal genetics.
Hormonal therapy:
medicines:
Two SERMs (selective estrogen receptor modulators) and two
aromatase inhibitors have been shown to reduce the risk of developing hormone-receptor-positive breast cancer in women at high risk. Tamoxifen has been shown to reduce the risk of first-time hormone-receptorpositive breast cancer in both postmenopausal and premenopausal women at high risk. Certain medicines may interfere with tamoxifen's protective effects. Evista (chemical name: raloxifene) has been shown to reduce the risk of first-time
hormone-receptor-positive breast cancer in postmenopausal women.
Hormonal therapy medicines do not reduce the risk of hormone-receptor-negative breast cancer.
More frequent screening:
If you're at high risk because of an abnormal breast cancer gene, you and your doctor will develop a screening plan tailored to your unique situation. You may start being screened when you're younger than 40. In addition to the recommended screening guidelines for women at average risk, a screening plan for a woman at high risk may include:
a monthly breast self-exam
a yearly breast exam by your doctor
a digital mammogram every year starting at age 30 or younger
an MRI scan every year starting at age 30 or younger
Protective surgery:
Removing the healthy breasts and ovaries -- called prophylactic surgery ("prophylactic" means "protective") -- are very aggressive, irreversible riskreduction options that some women with an abnormal BRCA1 orBRCA2 gene choose. Prophylactic breast surgery may be able to reduce a woman's risk of developing
breast cancer by as much as 97%. The surgery removes nearly all of the breast tissue, so there are very few breast cells left behind that could develop into a cancer.
How much does having a BRCA1 or BRCA2 gene mutation increase a woman’s risk of breast and ovarian cancer?
A woman’s lifetime risk of developing breast and/or
ovarian cancer is greatly increased if she inherits a harmful mutation in BRCA1 or BRCA2. Breast cancer: About 12 percent of women in the general population will develop breast cancer sometime during their lives (4). By contrast, according to the most recent estimates, 55 to 65 percent of women who inherit a harmful BRCA1 mutation and around 45 percent of women who inherit a harmful BRCA2 mutation will develop breast cancer by age 70 years (5, 6).
Abstract:
For many tumors, pathological subclasses exist which have to be further defined by genetic markers to improve therapy and follow-up strategies. In this study, cDNA array analyses of breast cancers have been performed to classify tumors into categories based on expression patterns. Comparing purified normal
ductal epithelial cells and corresponding tumour tissues, the expression of only a small fraction of genes was found to be significantly changed. A subset of genes repeatedly found to be differentially expressed in breast cancers was subsequently employed to perform a classification of 82 normal and malignant
breast specimens by cluster analysis. This analysis identifies a subgroup of transcriptionally related tumours, designated class A, which can be further subdivided into A1 and A2. Correlation with classical clinicopathological parameters revealed that subgroup A1 was characterized by a high number of nodepositive tumours (14 of 16). In this subgroup there was a disproportionate number of
patients who had already developed distant metastases at
the time of diagnosis (25% in this subgroup, compared with
5% among the rest of the samples). Taken together, the use of these differently expressed marker genes in conjunction with sample clustering algorithms provides a novel molecular classification of breast cancer specimens, which facilitates the identification of patients with a higher risk of recurrence.
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