Molecular Classification of Breast Cancer
Dina Ali Ali Somaie;
Abstract
Breast cancer is the most common cancer in women in developed western countries and is becoming even more significant in many developing countries. In Egypt, breast cancer is the most common cancer among women, representing 18.9% of total cancer cases with an age-adjusted rate of 49.6 per 100,000 populations.
Owing to advances both in early detection and in adjuvant systemic therapy, mortality rates from breast cancer have been decreasing steadily in most Western countries since the early 1990s. However, it is still the leading cause of cancer death in women in both developing and developed regions.
Review of modifiable risk factors shows that long-term use of oral contraceptives, low body mass index (BMI) and high animal fat diet consumption are associated with increased risk of premenopausal breast cancer. Decreased physical activity and obesity increase risks of breast cancer in postmenopausal women, but data on premenopausal women rather shows that high BMI is associated with decreased risk of breast cancer.
Non-modifiable risk factors such as family history and genetic mutations do account for increased risks of breast cancer in premenopausal women. Breast cancer in young women is associated with adverse pathological factors, including high grade tumors, hormone receptor negativity, and HER2 over-expression. This has a significant negative impact on the rate of local recurrence and overall survival.
Cancer develops through a multistep process in which normal, healthy cells in the body go through stages that eventually change them to abnormal cells that multiply out of control. In most cases, cancer takes many years to develop.
Part of the multistep process to cancer includes acquiring damage (mutations) to genes that normally regulate cell proliferation. Buildup of damage in these genes can result in uncontrolled cell proliferation. In some cases, further damage can lead to cells that can break away from the primary tumor and form cancers at other sites in the body (metastasis).
It is estimated that approximately 5 to 10% of all breast cancers have a strong hereditary component. The families of these patients often show an apparently dominant inheritance pattern of breast cancer and are often characterized by early age of onset and presence of ovarian cancer, bilateral breast cancer, and male breast cancer.
Germline mutations in BRCA1 and BRCA2 are detected in up to 28% of these breast-cancer families. In addition, inherited mutations in two other genes, p53 and PTEN, are associated with familial syndromes (LiFraumeni and Cowden's respectively) that include a high risk of breast cancer but both are rare. There are almost certainly other (as yet unidentified) genes that increase the risk of disease by only a degree—perhaps three or fourfold above the general population level.
Recent attention has focused on the use of whole-genome linkage disequilibrium studies to map common disease genes. These studies use single nucleotide polymorphisms to detect associations between a marker/gene and a particular disease. Single nucleotide polymorphisms are an abundant form of genetic variants and are distinguished from rare variants by a requirement for the least abundant variant allele to have a frequency of 1% or more. The use of single nucleotide polymorphisms, in conjunction with a range of studies involving animal models and genetic epidemiologic methodology, will facilitate the genetic analysis of complex diseases, such as breast cancer.
Breast cancer is a clinically heterogeneous disease. Histologically similar tumors may have different prognoses and may respond to therapy differently. It is believed that these differences in clinical behavior are due to molecular differences between histologically similar tumors. DNA microarray technology is ideally suited to reveal such molecular differences.
A novel molecular classification of breast cancer based on gene expression profiles was proposed Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The basal-like (mostly estrogen receptor negative) and erbB2+ (mostly HER-2 amplified and estrogen receptor negative) subgroups had the shortest relapse-free and overall survival, whereas the luminal-type (estrogen receptor– positive) tumors had a more favorable clinical outcome.
The different molecular classes of breast cancer not only have different prognoses but also show distinct sensitivities to preoperative chemotherapy. The basal-like and erbB2+ subtypes of breast cancer are more sensitive to preoperative chemotherapy than the luminal and normal-like cancers.
Efforts to improve treatment and early detection resonate strongly with clinicians and patients alike. Breast cancer prevention has received far too little attention but holds tremendous promise. Overall, we estimate that more than half of all breast cancers could be prevented through healthy behaviors and chemoprevention.
Of the primary prevention strategies that have been identified thus far, studies advocate those that are applicable to all women (maintenance of a healthy body weight, regular physical activity, and moderation of alcohol intake), as well as chemoprevention—a strategy that has a large effect in high-risk women and is currently underused.
Multidisciplinary treatment planning involving at least a breast surgeon, radiologist, pathologist, and medical and radiation oncologists should be used to integrate local and systemic therapies for breast cancer and their sequence. The possibility of hereditary cancer should be explored and, if needed, prophylactic procedures discussed following adequate genetic counseling and testing of the patient.
Most patients with breast cancer undergo surgery to remove the cancer from the breast. These include Breast conserving surgery and Mastectomy.
Breast conserving surgery, an operation to remove the cancer but not the breast itself, includes lumpectomy, a surgery to remove a tumor (lump) and a small amount of normal tissue around it. Patients who are treated with breast-conserving surgery may also have some of the lymph nodes under the arm removed for biopsy. This procedure is called lymph node dissection. It may be done at the same time as the breast-conserving surgery or after. Lymph node dissection is done through a separate incision.
Total mastectomy is also used as a measure of breast cancer therapy. It is surgery to remove the whole breast that has cancer. Some of the lymph nodes under the arm may be removed for biopsy at the same time as the breast surgery or after. This is done through a separate incision.
Another surgery is Modified radical mastectomy, which is surgery to remove the whole breast that has cancer, many of the lymph nodes under the arm, the lining over the chest muscles, and sometimes, part of the chest wall muscles.
Chemotherapy is generally given to stop the growth of drug, which may be given before surgery to remove the tumor. Chemotherapy will shrink the tumor and reduce the amount of tissue that needs to be removed during surgery if is given before surgery. Treatment, which is given before surgery is called neoadjuvent therapy. Treatment, which is given after the surgery, to lower the risk of recurrent breast cancer, is called adjuvant therapy, if anything is left behind after surgery.
Another approach is sentinel lymph node biopsy. The sentinel lymph node is the first lymph node to receive lymphatic drainage from a tumor. It is the first lymph node the cancer is likely to spread from the tumor. A radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through the lymph ducts to the lymph nodes. The first lymph node to receive the substance or dye is removed. A pathologist observes the tissue under a microscope to look for cancer cells. If cancer cells are not found, it may not be necessary to remove more lymph nodes. After the sentinel lymph node biopsy, the surgeon removes the tumor (breast-conserving surgery or mastectomy).
Another method of treatment is radiation therapy which uses high energy x-rays or other types of radiation to kill cancer cells or retard their growth. Radiation therapy may be external that uses a machine outside the body to send radiation toward the cancer or internal which uses a radioactive substance sealed in needles, seeds, wires or catheters are placed directly into or near the cancer. This therapy depends on the type and stage of the cancer.
Hormone therapy removes hormones or blocks their action and stops cancer cells from growing. Some hormones can cause certain cancers to grow. If tests show that the cancer cells have places where hormones can attach (receptors), drugs, surgery, or radiation therapy is used to reduce the production of hormones or block them from working.
Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibodies and tyrosine kinase inhibitors and PARP inhibitors are types of targeted therapies used in the treatment of breast cancer.
The prognosis of patients with breast cancer depends on biological characteristics of the cancer and the patient and on appropriate therapy. In general terms, the annual hazard of recurrence peaks in the second year after diagnosis but remains at 2–5% in years 5–20.
The aims of follow-up are to detect early in-breast and local recurrences or contra-lateral breast cancer, to evaluate and treat therapy related complications (such as menopausal symptoms, osteoporosis and second cancers) and to provide psychological support and information in order to enhance returning to normal life after breast cancer.
Owing to advances both in early detection and in adjuvant systemic therapy, mortality rates from breast cancer have been decreasing steadily in most Western countries since the early 1990s. However, it is still the leading cause of cancer death in women in both developing and developed regions.
Review of modifiable risk factors shows that long-term use of oral contraceptives, low body mass index (BMI) and high animal fat diet consumption are associated with increased risk of premenopausal breast cancer. Decreased physical activity and obesity increase risks of breast cancer in postmenopausal women, but data on premenopausal women rather shows that high BMI is associated with decreased risk of breast cancer.
Non-modifiable risk factors such as family history and genetic mutations do account for increased risks of breast cancer in premenopausal women. Breast cancer in young women is associated with adverse pathological factors, including high grade tumors, hormone receptor negativity, and HER2 over-expression. This has a significant negative impact on the rate of local recurrence and overall survival.
Cancer develops through a multistep process in which normal, healthy cells in the body go through stages that eventually change them to abnormal cells that multiply out of control. In most cases, cancer takes many years to develop.
Part of the multistep process to cancer includes acquiring damage (mutations) to genes that normally regulate cell proliferation. Buildup of damage in these genes can result in uncontrolled cell proliferation. In some cases, further damage can lead to cells that can break away from the primary tumor and form cancers at other sites in the body (metastasis).
It is estimated that approximately 5 to 10% of all breast cancers have a strong hereditary component. The families of these patients often show an apparently dominant inheritance pattern of breast cancer and are often characterized by early age of onset and presence of ovarian cancer, bilateral breast cancer, and male breast cancer.
Germline mutations in BRCA1 and BRCA2 are detected in up to 28% of these breast-cancer families. In addition, inherited mutations in two other genes, p53 and PTEN, are associated with familial syndromes (LiFraumeni and Cowden's respectively) that include a high risk of breast cancer but both are rare. There are almost certainly other (as yet unidentified) genes that increase the risk of disease by only a degree—perhaps three or fourfold above the general population level.
Recent attention has focused on the use of whole-genome linkage disequilibrium studies to map common disease genes. These studies use single nucleotide polymorphisms to detect associations between a marker/gene and a particular disease. Single nucleotide polymorphisms are an abundant form of genetic variants and are distinguished from rare variants by a requirement for the least abundant variant allele to have a frequency of 1% or more. The use of single nucleotide polymorphisms, in conjunction with a range of studies involving animal models and genetic epidemiologic methodology, will facilitate the genetic analysis of complex diseases, such as breast cancer.
Breast cancer is a clinically heterogeneous disease. Histologically similar tumors may have different prognoses and may respond to therapy differently. It is believed that these differences in clinical behavior are due to molecular differences between histologically similar tumors. DNA microarray technology is ideally suited to reveal such molecular differences.
A novel molecular classification of breast cancer based on gene expression profiles was proposed Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The basal-like (mostly estrogen receptor negative) and erbB2+ (mostly HER-2 amplified and estrogen receptor negative) subgroups had the shortest relapse-free and overall survival, whereas the luminal-type (estrogen receptor– positive) tumors had a more favorable clinical outcome.
The different molecular classes of breast cancer not only have different prognoses but also show distinct sensitivities to preoperative chemotherapy. The basal-like and erbB2+ subtypes of breast cancer are more sensitive to preoperative chemotherapy than the luminal and normal-like cancers.
Efforts to improve treatment and early detection resonate strongly with clinicians and patients alike. Breast cancer prevention has received far too little attention but holds tremendous promise. Overall, we estimate that more than half of all breast cancers could be prevented through healthy behaviors and chemoprevention.
Of the primary prevention strategies that have been identified thus far, studies advocate those that are applicable to all women (maintenance of a healthy body weight, regular physical activity, and moderation of alcohol intake), as well as chemoprevention—a strategy that has a large effect in high-risk women and is currently underused.
Multidisciplinary treatment planning involving at least a breast surgeon, radiologist, pathologist, and medical and radiation oncologists should be used to integrate local and systemic therapies for breast cancer and their sequence. The possibility of hereditary cancer should be explored and, if needed, prophylactic procedures discussed following adequate genetic counseling and testing of the patient.
Most patients with breast cancer undergo surgery to remove the cancer from the breast. These include Breast conserving surgery and Mastectomy.
Breast conserving surgery, an operation to remove the cancer but not the breast itself, includes lumpectomy, a surgery to remove a tumor (lump) and a small amount of normal tissue around it. Patients who are treated with breast-conserving surgery may also have some of the lymph nodes under the arm removed for biopsy. This procedure is called lymph node dissection. It may be done at the same time as the breast-conserving surgery or after. Lymph node dissection is done through a separate incision.
Total mastectomy is also used as a measure of breast cancer therapy. It is surgery to remove the whole breast that has cancer. Some of the lymph nodes under the arm may be removed for biopsy at the same time as the breast surgery or after. This is done through a separate incision.
Another surgery is Modified radical mastectomy, which is surgery to remove the whole breast that has cancer, many of the lymph nodes under the arm, the lining over the chest muscles, and sometimes, part of the chest wall muscles.
Chemotherapy is generally given to stop the growth of drug, which may be given before surgery to remove the tumor. Chemotherapy will shrink the tumor and reduce the amount of tissue that needs to be removed during surgery if is given before surgery. Treatment, which is given before surgery is called neoadjuvent therapy. Treatment, which is given after the surgery, to lower the risk of recurrent breast cancer, is called adjuvant therapy, if anything is left behind after surgery.
Another approach is sentinel lymph node biopsy. The sentinel lymph node is the first lymph node to receive lymphatic drainage from a tumor. It is the first lymph node the cancer is likely to spread from the tumor. A radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through the lymph ducts to the lymph nodes. The first lymph node to receive the substance or dye is removed. A pathologist observes the tissue under a microscope to look for cancer cells. If cancer cells are not found, it may not be necessary to remove more lymph nodes. After the sentinel lymph node biopsy, the surgeon removes the tumor (breast-conserving surgery or mastectomy).
Another method of treatment is radiation therapy which uses high energy x-rays or other types of radiation to kill cancer cells or retard their growth. Radiation therapy may be external that uses a machine outside the body to send radiation toward the cancer or internal which uses a radioactive substance sealed in needles, seeds, wires or catheters are placed directly into or near the cancer. This therapy depends on the type and stage of the cancer.
Hormone therapy removes hormones or blocks their action and stops cancer cells from growing. Some hormones can cause certain cancers to grow. If tests show that the cancer cells have places where hormones can attach (receptors), drugs, surgery, or radiation therapy is used to reduce the production of hormones or block them from working.
Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibodies and tyrosine kinase inhibitors and PARP inhibitors are types of targeted therapies used in the treatment of breast cancer.
The prognosis of patients with breast cancer depends on biological characteristics of the cancer and the patient and on appropriate therapy. In general terms, the annual hazard of recurrence peaks in the second year after diagnosis but remains at 2–5% in years 5–20.
The aims of follow-up are to detect early in-breast and local recurrences or contra-lateral breast cancer, to evaluate and treat therapy related complications (such as menopausal symptoms, osteoporosis and second cancers) and to provide psychological support and information in order to enhance returning to normal life after breast cancer.
Other data
| Title | Molecular Classification of Breast Cancer | Other Titles | التصنيف الجزيئي لسرطان الثدي | Authors | Dina Ali Ali Somaie | Issue Date | 2014 |
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