Breast Cancer-1

a)General Description
b)Risk Factors
c)Anatomy Of The Breast
d)Types Of Breast Cancer
e)Special Manifistation Of Cancer
f)Breast Diseases
g)Screening Techniques
h)Screening Findings
i)Biopsies
j)Prognostic And Predictive Factors
k)Tests For Distant Metastases
l)Treatment
m)Preventing Metastasis
n)Other Considerations
o)Blood Testing
p)Summary

Most women share a common fear: developing breast cancer. This is not an unfounded fear when considering that, except for lung cancer, breast cancer is the most common cancer found in women, accounting for one of every three diagnoses. However, men are also affected by breast cancer. In 2002 the American Cancer Association estimate that 1500 men will be diagnosed with breast cancer, and 400 will die as a result. In 2001 an estimated 192,200 American women were diagnosed with breast cancer and 39,600 women died of the disease (The American Cancer Association). In 2004 an estimated 203,500 new cases of breast cancer will be diagnosed in America.

WHAT IS BREAST CANCER?


Breast cancer occurs when cells in the breast tissue divide and grow without control. The cell cycle is the natural mechanism that regulates the growth and death of cells. When the normal cell regulators malfunction and cells do not die at the proper rate, there is a failure of cell death (apoptosis) therefore cell growth goes unchecked. As a result, cancer begins to develop as cells divide without control, accumulating into a mass of extra tissue called a tumor. A tumor can be either non-cancerous (benign) or cancerous (malignant). As a tumor grows, it elicits new blood vessel growth from the surrounding normal healthy tissues and diverts blood supply and nutrients away from this tissue to feed itself. This process is termed “angiogenesis”- the development (genesis) of new blood vessels (angio). Unregulated tumor angiogenesis facilitates the growth of cancer throughout the body.

Cancer cells have the ability to leave the original tumor site, travel to distant locations, and recolonize. This process is called metastasis and it occurs in organs such as the liver, lungs, and bones. Both the bloodstream and lymphatic system (the network connecting lymph nodes throughout the body) serve as ideal vehicles for the traveling cancer. Although, these traveling cancer cells do not always survive beyond the tumor, if they do survive, the cancer cells will again begin to divide abnormally and will create tumors in each new location. A person with untreated or treatment-resistant cancer may eventually die of the disease if vital organs such as the liver or lungs are invaded, overtaken, and destroyed.

Cancerous tumors in the breast usually grow slowly. It is thought that by the time a tumor is large enough to be felt as a lump, it may have been growing for as long as 10 years. This has lead to the belief that undetectable spread of tumor cells (micrometastasis) may have already occurred by the time of the diagnosis. Therefore, preventive measures such as a healthy balanced diet and lifestyle, nutritional supplementation, and exercise are of primary importance against the development of cancer. Early diagnosis is the best way to reduce the risk of dying from breast cancer. This can be accomplished by monthly self-breast exams, annual clinical breast exams and screening mammography. If breast cancer is detected, a multimodality approach incorporating nutritional supplementation, dietary modification, detoxification, and one or more of the following may be considered: surgery, chemotherapy, radiation, hormone therapy, or vaccine therapy.


RISK FACTORS
A wide variety of factors may influence an individual's likelihood of developing breast cancer; these factors are referred to as risk factors. The established risk factors for breast cancer include: female gender, age, previous breast cancer, benign breast disease, hereditary factors (family history of breast cancer), early age at menarche (first menstrual period), late age at menopause, late age at first full-term pregnancy, obesity, low physical activity, use of postmenopausal hormone replacement therapy, use of oral contraceptives, exposure to low-dose ionizing radiation in midlife and exposure to high-dose ionizing radiation early in life.

Correlated risk factors for breast cancer include never having been pregnant, having only one pregnancy rather than many, not breast feeding after pregnancy, diethylstilbestrol (DES), certain dietary practices (high intake of fat and low intakes of fiber, fruits, and vegetables), tobacco, smoking, abortion, breast trauma, breast augmentation, large breast size, synthetic estrogens, electromagnetic fields, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and alcohol consumption. Alcohol is known to increase estrogen levels. Alcohol use appears to be more strongly associated with risk of lobular carcinomas and hormone receptor-positive tumors than it is with other types of breast cancer (Li et al. 2003).

A novel growth inhibitor recently identified as estrogen down-regulated gene 1 (EDG1) was found to be switched off (down-regulated) by estrogens. Inhibiting EDG1 expression in breast cells resulted in increased breast cell growth, whereas over-expression of EDG1 protein in breast cells resulted in decreased cell growth and decreased anchorage-independent growth, supporting the role of EDG1 in breast cancer (Wittmann et al. 2003).

ANATOMY OF THE BREAST

The breast is composed mainly of fat (adipose tissue) and breast tissue, along with connective tissue, nerves, veins, and arteries. Breast tissue is a complex network known as the mammary gland. Within the mammary gland, there are 15-20 lobes or compartments separated by adipose tissue. Within each lobe are several smaller compartments called lobules.

Lobules are composed of grapelike clusters of milk-secreting glands termed alveoli, which are found embedded in connective tissue. Spindle-shaped cells called myoepithelial cells, whose contractions help propel milk toward the nipple, surround the alveoli. There are about one million lobules contained within each breast (Spratt et al. 1995). The lobules are connected by tiny ducts that are joined together (much like a grape stem) into increasingly larger ducts. Within each breast there are between five and ten ductal systems, each with its own opening at the nipple.

Surrounding the nipple is a darkly shaded circle of skin called the areola. The areola appears rough because it contains modified sebaceous (oil) glands. These glands secrete small amounts of fluid to lubricate the nipple during breast-feeding.

Of all breast cancers, about 80% originate in the mammary (lactiferous) ducts, while about 20% arise in the lobules (IOM 1997). One of the most important distinctions to understand is the difference between invasive breast cancer and carcinoma in situ.

TYPES OF BREAST CANCER

a)Invasive Cancer
b)Carcinoma In Situ
c)Ductal Carcinoma In Situ
d)Lobular Carcinoma In Situ

Invasive Cancer
When abnormal cells from within the lobules or mammary ducts break out into the surrounding tissue the condition is referred to as invasive breast cancer. However, this term does not necessarily mean that metastases have been found anywhere beyond the breast.


Carcinoma In Situ
Carcinoma in situ is referred to as precancerous condition because it can increase the risk of developing cancer. When abnormal cells grow within the lobules or mammary ducts and there is no sign that the cells have spread into the surrounding tissue or beyond, the condition is called carcinoma in situ. The term in situ means “in place”. There are two main categories of carcinoma in situ: ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS).

Non-invasive cancer is grouped into four subcategories, based on how the cancer cells grow relative to each other within the center of the milk duct:

Solid: There is wall-to-wall cell growth

Cribiform: There are holes between groups of cancer cells, making it look like Swiss cheese.

Papillary: The cells grow in fingerlike projections, toward the inside of the duct.

Comedo: There are areas of "necrosis," which is debris from dead cancer cells; this indicates that a tumor is growing so fast that some tumor cells die because there is insufficient blood supply.

Carcinoma in situ is generally considered a slow-growing cancer. The solid, cribiform, and papillary growth patterns are also referred to as "low-grade" cancers. However, Comedo is considered a faster growing cancer and is referred to as a "high-grade" non-invasive cancer, but is more likely than other categories to become invasive.


Ductal Carcinoma In SituMammary ducts are hollow to allow fluid to pass through. However, with ductal carcinoma in situ (DCIS) excess cells grow inside the mammary ducts. DCIS is not invasive cancer. It is a precancerous condition that has the potential to develop into breast cancer. DCIS is, however, a risk factor for breast cancer.


Lobular Carcinoma In Situ
The lobules of the breast tissue have open space inside them much like the mammary ducts. Lobular carcinoma in situ (LCIS) is the growth and accumulation of large numbers of abnormal cells within the lobules. LCIS is often referred to as lobular neoplasia in situ. LCIS is not a direct cancer precursor. The abnormal cells found inside the lobules are not likely to mutate into cancer. LCIS is, however, a risk factor for breast cancer.


SPECIAL MANIFESTATIONS OF CANCER

Paget's Disease of the Nipple
Inflammatory Breast Cancer

Paget's Disease of the Nipple
Paget's disease is a rare, slowly growing cancer of the nipple. Paget's disease is usually associated with in situ or invasive cancer. One of the biggest problems with Paget's disease of the nipple is that its symptoms appear to be harmless. It is frequently thought to be a skin inflammation or infection, leading to unfortunate delays in disease detection, diagnosis and treatment. Symptoms of Paget's disease include persistent redness, itching, oozing, crusting, and fluid discharge from the nipple or a sore on the nipple that does not heal. Typically, only one nipple is affected. Treatment and prognosis for the disease are directly related to the type and extent of the underlying cancer.


Inflammatory Breast Cancer (IBC)
Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer that is usually not detected by mammograms or ultrasounds. IBC usually grows in nests or sheets rather than as a confined solid tumor and can be diffuse throughout the breast with no palpable mass. The cancer cells clog the lymphatic system just below the skin, resulting in lymph node involvement. Increased breast density compared to prior mammograms should be considered suspicious.

However, the main symptoms of IBC are breast swelling, inflammation, pink, red, or a dark colored area (erythema), sometimes with texture similar to the skin of an orange (peau d'orange), ridges and thickened areas of the breast skin, an area of the breast that is warm to the touch, what appears to be a persistent bruise, itching (pruritus) that is unrelenting and unaffected by medicated creams and ointments, increase in breast size over a short period of time, nipple flattening, retraction, or discharge, breast pain that is not cyclic in nature and may be constant or stabbing, or swollen lymph nodes in the armpit or above the collar bone. Since many of these symptoms mimic a breast infection, doctors frequently treat inflammatory breast cancer merely as an infection. When symptoms do not improve after antibiotic treatment for the suspected “infection” only then is the inflammatory breast cancer diagnosed.

IBC has an extremely high risk of recurrence and a very poor prognosis. It is the most lethal form of breast cancer. To improve the chances of survival it is important that symptoms are recognized early, resulting in an immediate diagnosis and treatment. Chemotherapy is usually begun within days of diagnosis. Without treatment, chances of 5-year survival for individuals with inflammatory breast cancer are very poor. With treatment, about 50% of patients will be living 5 years after diagnosis.


BREAST DISEASES

a)Calcifications
Cysts
b)Fibroadenomas
c)Hyperplasia
d)Atypical Hyperplasia

There are a variety of breast diseases, ranging from infections to excessive cell growth (neoplasms). Unfortunately, many breast diseases mimic the symptoms of cancer and therefore require tests and possibly surgical biopsy to obtain an accurate diagnosis. The majority of biopsies are found to be benign (non-cancerous) forms of breast disease. While most breast diseases are not dangerous in themselves, they may increase the risk of developing breast cancer. Hyperplasia, cysts, fibroadenomas, and calcifications are the common benign breast diseases.


Calcifications
Calcifications are randomly scattered residues of calcium that in older women may have left the bones to appear in other parts of the body, such as the joints or breasts. Microcalcifications are small, tight clusters of tiny calcifications in the ducts that can be seen on a mammogram and may indicate a precancerous or cancerous condition.


Cysts
Cysts are sacs filled with fluid; they are almost always benign. Although most are too small to feel, approximately a third of women between the ages of 35-50 have cysts in their breasts. If large enough, cysts may feel like lumps in the breast. Normally, cysts are left untreated. However, if a cyst becomes painful, it can be aspirated or drained of its fluid. Some women may prefer to have a cyst removed if, after being aspirated repeatedly, it continues to recur.

Cysts are not associated with an increased risk of cancer; yet, they are more common in women as they approach menopause and occur much less frequently after menopause (Donegan 1995). What causes cysts to develop is unknown; however, certain dietary factors, such as the intake of caffeine have been proposed as possible risk factors for the development of breast cysts.


Fibroadenomas
Fibroadenomas are a type of benign lump most commonly found in younger women. They are usually not removed since they pose no risk. If a fibroadenoma is large, uncomfortable, and produces a lump, it may be removed. In older women, fibroadenomas are generally removed to ensure that they are not malignant tumors. Fibroadenomas do not pose an increased risk of cancer.

Hyperplasia
Hyperplasia is not a precancerous condition. It is the excessive accumulation or proliferation of normal cells typically found on the inside of the lobules or the ducts in the breast tissue. Hyperplasia is associated with approximately a two-fold risk of breast cancer.

Atypical Hyperplasia
Atypical hyperplasia occurs when excess cells in the lobules or ducts are abnormal. This condition falls between hyperplasia (too many normal cells) and carcinoma in situ (too many abnormal cells). However, atypical hyperplasia is associated with an approximately 3.5-5 times increased risk of developing breast cancer (Page et al. 1985; Colditz 1993; Marshall et al. 1997).