Today, breast cancer, like other forms of cancer, is considered to be the final outcome of multiple environmental and hereditary factors. Some of these factors include:
Lesions to DNA such as genetic mutations. Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure. Beyond the contribution of estrogen, research has implicated viral oncogenesis and the contribution of ionizing radiation in causing genetic mutations.
Failure of immune surveillance, a theory in which the immune system removes malignant cells throughout ones life.
Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth. For example, tumors can induce blood vessel growth (angiogenesis) by secreting various growth factors further facilitating cancer growth.
Inherited defects in DNA repair genes, such as BRCA1, BRCA2
Although many epidemiological risk factors have been identified, the cause of any individual breast cancer is often unknowable. In other words, epidemiological research informs the patterns of breast cancer incidence across certain populations, but not in a given individual. The primary risk factors that have been identified are sex, age, childbearing, hormones, a high-fat diet, alcohol intake, obesity, and environmental factors such as tobacco use and radiation.
No etiology is known for 95% of breast cancer cases, while approximately 5% of new breast cancers are attributable to hereditary syndromes. In particular, carriers of the breast cancer susceptibility genes, BRCA1 and BRCA2, are at a 30-40% increased risk for breast and ovarian cancer, depending on in which portion of the protein the mutation occursperspective of.
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Tumor immunology - Destroy 97% of cancer causing causing cells
Another important role of the immune system is to identify and eliminate tumors. The transformed cells of tumors express antigens that are not found on normal cells. To the immune system, these antigens appear foreign, and their presence causes immune cells to attack the transformed tumor cells. The antigens expressed by tumors have several sources; some are derived from oncogenic viruses like human papillomavirus, which causes cervical cancer,while others are the organism's own proteins that occur at low levels in normal cells but reach high levels in tumor cells. One example is an enzyme called tyrosinase that, when expressed at high levels, transforms certain skin cells (e.g. melanocytes) into tumors called melanomas.A third possible source of tumor antigens are proteins normally important for regulating cell growth and survival, that commonly mutate into cancer inducing molecules called oncogenes.
The main response of the immune system to tumors is to destroy the abnormal cells using killer T cells, sometimes with the assistance of helper T cells.Tumor antigens are presented on MHC class I molecules in a similar way to viral antigens. This allows killer T cells to recognize the tumor cell as abnormal.NK cells also kill tumorous cells in a similar way, especially if the tumor cells have fewer MHC class I molecules on their surface than normal; this is a common phenomenon with tumors.Sometimes antibodies are generated against tumor cells allowing for their destruction by the complement system.
Clearly, some tumors evade the immune system and go on to become cancers.Tumor cells often have a reduced number of MHC class I molecules on their surface, thus avoiding detection by killer T cells.Some tumor cells also release products that inhibit the immune response; for example by secreting the cytokine TGF-â, which suppresses the activity of macrophages and lymphocytes.In addition, immunological tolerance may develop against tumor antigens, so the immune system no longer attacks the tumor cells.
Paradoxically, macrophages can promote tumor growth when tumor cells send out cytokines that attract macrophages which then generate cytokines and growth factors that nurture tumor development. In addition, a combination of hypoxia in the tumor and a cytokine produced by macrophages induces tumor cells to decrease production of a protein that blocks metastasis and thereby assists spread of cancer cells.
Worldwide, breast cancer is the fifth most common cause of cancer death (after lung cancer, stomach cancer, liver cancer, and colon cancer). In 2005, breast cancer caused 502,000 deaths (7% of cancer deaths; almost 1% of all deaths) worldwide. Among women worldwide, breast cancer is the most common cause of cancer death.
In the United States, breast cancer is the third most common cause of cancer death (after lung cancer and colon cancer). In 2007, breast cancer is expected to cause 40,910 deaths (7% of cancer deaths; almost 2% of all deaths) in the U.S. Among women in the U.S., breast cancer is the most common cancer and the second-most common cause of cancer death (after lung cancer). Women in the U.S. have a 1 in 8 lifetime chance of developing invasive breast cancer and a 1 in 33 chance of breast cancer causing their death. In the U.S., both incidence and death rates for breast cancer have been declining in the last few years. Nevertheless, a U.S. study conducted in 2005 by the Society for Women's Health Research indicated that breast cancer remains the most feared disease, even though heart disease is a much more common cause of death among women.
The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world. Because the breast is composed of identical tissues in males and females, breast cancer also occurs in males, though it is less common.
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Time line of breast cancer suggesting probable heterogeneity. Primary breast cancers begin as single (or more) cells which have lost normal regulation of differentiation and proliferation but remain confined within the basement membrane of the duct or lobule. As these cells go through several doublings, at some point they invade through the basement membrane of the duct or lobule and ultimately metastasize to distant organs.Breast cancers are described along four different classification schemes, each based on different criteria and serving a different purpose.
Pathology:
The pathologist will categorize each tumor based on its histological appearance and other criteria. The most common pathologic types of breast cancer are invasive ductal carcinoma and invasive lobular carcinoma. In the future, this pathologic classification may be changed. For example, a subset of ductal carcinomas may be re-named basal-like carcinoma (part of the "triple-negative" tumors). See Pathology classification section below.
Grade of tumor
the histological grade is determined by the pathologist under a microscope. A well-differentiated (low grade) tumor resembles normal tissue. A poorly differentiated (high grade) tumor is composed of disorganized cells and, therefore, does not look like normal tissue. Moderately differentiated (intermediate grade) tumors are somewhere in between.
Protein & gene expression status:
Currently, all breast cancers should be tested for expression of the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu proteins. These tests are usually done by immunohistochemistry and reported in the pathologist's report. The profile of expression of a given tumor helps predict its prognosis and helps the oncologist chose the most appropriate treatment. More genes & proteins may be tested in the future.
FACT: One in every three Americans will develop cancer. 1.2 million cancer cases are diagnosed every year in this country, and that number is going up, not down. Of these, six of ten people will die within five years.
FACT: One in every four deaths (over 500,00 each year) is attributable to cancer, and the rate is rising. The good news is that the National Cancer Institute estimates that over 75% of all cancer cases are preventable.
FACT: According to some experts at the National Cancer Institute, we are losing our battle with cancer because we’ve been on the wrong track. Prevention rather than cure should become our new emphasis.
What is cancer? It is a disease characterized by the uncontrolled growth of abnormal cells permitted to reproduce due to extensive immune collapse. Cancer is allowed to grow because our immune surveillance system falls asleep.
Our immune watch guards single out identify and destroy carcinogenic agents that enter the body daily. Immune cells such as B-lymphocytes produce antibodies designed to attack and eradicate malignant cells, and a variety of immune chemicals keep tumors in check.
Given the multifaceted defense strategy of our immune system, it is remarkable that in some people, cancer cells grow without any detection. Why? Because people with faulty immune responses are at a much higher risk of developing cancer.
Because many of us cannot avoid exposure to pollution, pesticides, additives, ultra-violet rays, etc., it is crucial that we boost our natural immune defenses to protect us against cancer.
Vivienne Matalon, M.D.
Dr. Matalon graduated from the Utesa School of medicine. Currently she serves as the medical director of TLC Healthcare, Health Map and as a member of the Board of Directors for the South Jersey PPA. Her hospital appointments include four facilities in the state of New Jersey. She has been actively involved in teaching, researching and publishing throughout her career in healthcare.
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