03-10-2012, 04:27 PM
BREAST CANCER
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DEFINITION:
Breast cancer is a cancer that starts in the tissues of the breast. There are two main types of breast cancer:
• Ductal carcinoma starts in the tubes (ducts) that move milk from the breast to the nipple. Most breast cancers are of this type.
• Lobular carcinoma starts in the parts of the breast, called lobules, that produce milk.
Breast cancer may be invasive or noninvasive. Invasive means it has spread from the milk duct or lobule to other tissues in the breast. Noninvasive means it has not yet invaded other breast tissue. Noninvasive breast cancer is called "in situ."
• Ductal carcinoma in situ (DCIS), or intraductal carcinoma, is breast cancer in the lining of the milk ducts that has not yet invaded nearby tissues. It may progress to invasive cancer if untreated.
• Lobular carcinoma in situ (LCIS) is a marker for an increased risk of invasive cancer in the same or both breasts.
Many breast cancers are sensitive to the hormone estrogen. This means that estrogen causes the breast cancer tumor to grow. Such cancers have estrogen receptors on the surface of their cells. They are called estrogen receptor-positive cancer or ER-positive cancer.
Some women have what's called HER2-positive breast cancer. HER2 refers to a gene that helps cells grow, divide, and repair themselves. When cells (including cancer cells) have too many copies of this gene, they grow faster. Experts think that women with HER2-positive breast cancer have a more aggressive disease and a higher risk that the disease will return (recur) than women who do not have this type.
CAUSES AND RISK FACTORS:
• Age and gender -- Your risk of developing breast cancer increases as you get older. Most advanced breast cancer cases are found in women over age 50. Women are 100 times more likely to get breast cancer than men.
• Family history of breast cancer -- You may also have a higher risk for breast cancer if you have a close relative who has had breast, uterine, ovarian, or colon cancer. About 20 - 30% of women with breast cancer have a family history of the disease.
• Genes -- Some people have genes that make them more likely to develop breast cancer. The most common gene defects are found in the BRCA1 and BRCA2 genes. These genes normally produce proteins that protect you from cancer. If a parent passes you a defective gene, you have an increased risk for breast cancer. Women with one of these defects have up to an 80% chance of getting breast cancer sometime during their life.
• Menstrual cycle -- Women who got their periods early (before age 12) or went through menopause late (after age 55) have an increased risk for breast cancer.
Other risk factors include:
• Alcohol use -- Drinking more than 1 - 2 glasses of alcohol a day may increase your risk for breast cancer.
• Childbirth -- Women who have never had children or who had them only after age 30 have an increased risk for breast cancer. Being pregnant more than once or becoming pregnant at an early age reduces your risk of breast cancer.
• DES -- Women who took diethylstilbestrol (DES) to prevent miscarriage may have an increased risk of breast cancer after age 40. This drug was given to the women in the 1940s - 1960s.
• Hormone replacement therapy (HRT) -- You have a higher risk for breast cancer if you have received hormone replacement therapy with estrogen for several years or more.
• Obesity -- Obesity has been linked to breast cancer, although this link is controversial. The theory is that obese women produce more estrogen, which can fuel the development of breast cancer.
• Radiation -- If you received radiation therapy as a child or young adult to treat cancer of the chest area, you have a much higher risk for developing breast cancer. The younger you started such radiation and the higher the dose, the higher your risk -- especially if the radiation was given during breast development.
Breast implants, using antiperspirants, and wearing under wire bras do not raise your risk for breast cancer. There is no evidence of a direct link between breast cancer and pesticides.
SYMPTOMS:
Early breast cancer usually does not cause symptoms. This is why regular breast exams are important.
As the cancer grows, symptoms may include:
• Breast lump or lump in the armpit that is hard, has uneven edges, and usually does not hurt
• Change in the size, shape, or feel of the breast or nipple -- for example, you may have redness, dimpling, or puckering that looks like the skin of an orange
• Fluid coming from the nipple -- may be bloody, clear to yellow, green, and look like pus
• Men can get breast cancer, too. Symptoms include breast lump and breast pain and tenderness.
Symptoms of advanced breast cancer may include:
• Bone pain
• Breast pain or discomfort
• Skin ulcers
• Swelling of one arm (next to the breast with cancer)
• Weight loss
PATHOPHYSIOLOGY:
Breast cancer, like other cancers, occurs because of an interaction between the environment and a defective gene. Normal cells divide as many times as needed and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when mutations destroy their ability to stop dividing, to attach to other cells and to stay where they belong. When cells divide, their DNA is normally copied with many mistakes. Error-correcting proteins fix those mistakes. The mutations known to cause cancer, such as p53, BRCA1 and BRCA2, occur in the error-correcting mechanisms. These mutations are either inherited or acquired after birth. Presumably, they allow the other mutations, which allow uncontrolled division, lack of attachment, and metastasis to distant organs.
Normal cells will commit cell suicide (apoptosis) when they are no longer needed. Until then, they are protected from cell suicide by several protein clusters and pathways. One of the protective pathways is the PI3K/AKT pathway; another is the RAS/MEK/ERK pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of committing suicide when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the PTENprotein turns off the PI3K/AKT pathway when the cell is ready for cell suicide. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not commit suicide.
Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.
Failure of immune surveillance, the removal of malignant cells throughout one's life by the immune system.
BREAST CANCER SURGERY
Operations used to treat breast cancer include:
• Removing the breast cancer (lumpectomy). During lumpectomy, which may be referred to as breast-sparing surgery or wide local excision, the surgeon removes the tumor and a small margin of surrounding healthy tissue. Lumpectomy is typically reserved for smaller tumors that are easily separated from the surrounding tissue.
• Removing the entire breast (mastectomy). Mastectomy is surgery to remove all of your breast tissue. Mastectomy can be simple, meaning the surgeon removes all of the breast tissue — the lobules, ducts, fatty tissue and some skin, including the nipple and areola. Or mastectomy can be radical, meaning the underlying muscle of the chest wall is removed along with breast tissue and surrounding lymph nodes in the armpit. Radical mastectomies are less commonly done today. Some women may be able to undergo a skin-sparing mastectomy, which leaves the skin overlying the breast intact and may help with reconstruction options.
• Removing one lymph node (sentinel node biopsy). Breast cancer that spreads to the lymph nodes may spread to other areas of the body. Your surgeon determines which lymph node near your breast tumor receives the lymph drainage from your cancer. This lymph node is removed using a procedure called sentinel node biopsy and tested for breast cancer cells. If no cancer is found, the chance of finding cancer in any of the remaining lymph nodes is small and no other nodes need to be removed.
• Removing several lymph nodes (axillary lymph node dissection). If cancer is found in the sentinel node, your surgeon may remove additional lymph nodes in your armpit. However, there is good evidence that removal of additional affected lymph nodes does not improve survival in cases of early breast cancer following a lumpectomy, chemotherapy and whole-breast irradiation for tumors less than 2 inches (5 centimeters) in size, and where the cancer has spread to just a few lymph nodes in the armpit. In such cases, chemotherapy and radiation treatment after the lumpectomy have proved to be equally effective. This avoids the serious side effects, including chronic swelling of the arm (lymphedema), that often occur after lymph node removal.
However, axillary lymph node dissection may still be performed if the sentinel lymph node contains cancer following a mastectomy, in the case of larger breast tumors or when a lymph node is large enough to be felt on physical exam. It may also be performed in situations when a woman elects to receive partial breast irradiation.
Complications of breast cancer surgery depend on the procedures you choose. Surgery carries a risk of bleeding and infection.
Some women choose to have breast reconstruction after surgery. Discuss your options and preferences with your surgeon. Consider a referral to a plastic surgeon before your breast cancer surgery. Your options may include reconstruction with a synthetic breast implant or reconstruction using your own tissue. These operations can be performed at the time of your mastectomy or at a later date.
RADIATION THERAPY
Radiation therapy uses high-powered beams of energy, such as X-rays, to kill cancer cells. Radiation therapy is typically done using a large machine that aims the energy beams at your body (external beam radiation). But radiation can also be done by placing radioactive material inside your body (brachytherapy).
External beam radiation is commonly used after lumpectomy for early-stage breast cancer. Doctors may also recommend radiation therapy after mastectomy for larger breast cancers. When external beam radiation is used after a woman has tested negative on a sentinel node biopsy, there is evidence that the chance of cancer occurring in other lymph nodes is significantly reduced.
Side effects of radiation therapy include fatigue and a red, sunburn-like rash where the radiation is aimed. Breast tissue may also appear swollen or more firm. Rarely, more-serious problems may occur, including arm swelling (lymphedema), broken ribs, and damage to the lungs or nerves.
CHEMOTHERAPY
Chemotherapy uses drugs to destroy cancer cells. If your cancer has a high chance of returning or spreading to another part of your body, your doctor may recommend chemotherapy to decrease the chance that the cancer will recur. This is known as adjuvant systemic chemotherapy.
Chemotherapy is sometimes given before surgery in women with larger breast tumors. Doctors call this neoadjuvant chemotherapy. The goal is to shrink a tumor to a size that makes it easier to remove with surgery. This may also increase the chance of a cure. Research is ongoing into neoadjuvant chemotherapy to determine who may benefit from this treatment.
Chemotherapy is also used in women whose cancer has already spread to other parts of the body. Chemotherapy may be recommended to try to control the cancer and decrease any symptoms the cancer is causing.
Chemotherapy side effects depend on the drugs you receive. Common side effects include hair loss, nausea, vomiting, fatigue and a small increased risk of developing infection.